Input: Effect of nondopaminergic drugs on L - dopa - induced dyskinesias in MPTP - treated monkeys. A group of four monkeys was rendered parkinsonian with the toxin MPTP. They were then treated chronically with L - DOPA / benserazide 50 / 12. 5 mg / kg given orally daily for 2 months. This dose produced a striking antiparkinsonian effect, but all animals manifested dyskinesia. A series of agents acting primarily on neurotransmitters other than dopamine were then tested in combination with L - DOPA to see if the dyskinetic movements would be modified. Several drugs, including clonidine, physostigmine, methysergide, 5 - MDOT, propranolol, and MK - 801, markedly reduced the dyskinetic movements but at the cost of a return of parkinsonian symptomatology. However, yohimbine and meperidine reduced predominantly the dyskinetic movements. Baclofen was also useful in one monkey against a more dystonic form of dyskinesia. Atropine converted the dystonic movements into chorea.

L - dopa

MPTP

MPTP

L - DOPA / benserazide

dopamine

L - DOPA

clonidine

physostigmine

methysergide

5 - MDOT

propranolol

MK - 801

yohimbine

meperidine

Baclofen

Atropine

dyskinesias

parkinsonian

dyskinesia

dyskinetic

dyskinetic

parkinsonian

dyskinetic

dystonic

dyskinesia

dystonic

chorea

L - DOPA / benserazide

dyskinesias

L - DOPA / benserazide

dyskinesia

L - DOPA / benserazide

dyskinetic

L - DOPA / benserazide

dyskinetic

L - DOPA / benserazide

dyskinetic

L - DOPA / benserazide

dyskinesia

MPTP

parkinsonian

MPTP

parkinsonian

MPTP

parkinsonian

MPTP

parkinsonian


Input: CCNU (lomustine) toxicity in dogs: a retrospective study (2002 - 07). OBJECTIVE: To describe the incidence of haematological, renal, hepatic and gastrointestinal toxicities in tumour - bearing dogs receiving 1 - (2 - chloroethyl) - 3 - cyclohexyl - 1 - nitrosourea (CCNU). DESIGN: The medical records of 206 dogs that were treated with CCNU at the Melbourne Veterinary Specialist Centre between February 2002 and December 2007 were retrospectively evaluated. RESULTS: Of the 206 dogs treated with CCNU, 185 met the inclusion criteria for at least one class of toxicity. CCNU was used most commonly in the treatment of lymphoma, mast cell tumour, brain tumour, histiocytic tumours and epitheliotropic lymphoma. Throughout treatment, 56. 9% of dogs experienced neutropenia, 34. 2% experienced anaemia and 14. 2% experienced thrombocytopenia. Gastrointestinal toxicosis was detected in 37. 8% of dogs, the most common sign of which was vomiting (24. 3%). Potential renal toxicity and elevated alanine transaminase (ALT) concentration were reported in 12. 2% and 48. 8% of dogs, respectively. The incidence of hepatic failure was 1. 2%. CONCLUSIONS: CCNU - associated toxicity in dogs is common, but is usually not life threatening.

CCNU

lomustine

1 - (2 - chloroethyl) - 3 - cyclohexyl - 1 - nitrosourea

CCNU

CCNU

CCNU

CCNU

alanine

CCNU

toxicity

haematological, renal, hepatic and gastrointestinal toxicities

haematological, renal, hepatic and gastrointestinal toxicities

renal, hepatic and gastrointestinal toxicities

hepatic and gastrointestinal toxicities

gastrointestinal toxicities

toxicity

lymphoma

mast cell tumour

brain tumour

histiocytic tumours

epitheliotropic lymphoma

neutropenia

anaemia

thrombocytopenia

Gastrointestinal toxicosis

vomiting

toxicity

hepatic failure

toxicity

CCNU

haematological, renal, hepatic and gastrointestinal toxicities

CCNU

gastrointestinal toxicities

CCNU

Gastrointestinal toxicosis

lomustine

haematological, renal, hepatic and gastrointestinal toxicities

lomustine

gastrointestinal toxicities

lomustine

Gastrointestinal toxicosis

1 - (2 - chloroethyl) - 3 - cyclohexyl - 1 - nitrosourea

haematological, renal, hepatic and gastrointestinal toxicities

1 - (2 - chloroethyl) - 3 - cyclohexyl - 1 - nitrosourea

gastrointestinal toxicities

1 - (2 - chloroethyl) - 3 - cyclohexyl - 1 - nitrosourea

Gastrointestinal toxicosis

CCNU

haematological, renal, hepatic and gastrointestinal toxicities

CCNU

gastrointestinal toxicities

CCNU

Gastrointestinal toxicosis

CCNU

haematological, renal, hepatic and gastrointestinal toxicities

CCNU

gastrointestinal toxicities

CCNU

Gastrointestinal toxicosis

CCNU

haematological, renal, hepatic and gastrointestinal toxicities

CCNU

gastrointestinal toxicities

CCNU

Gastrointestinal toxicosis

CCNU

haematological, renal, hepatic and gastrointestinal toxicities

CCNU

gastrointestinal toxicities

CCNU

Gastrointestinal toxicosis

CCNU

haematological, renal, hepatic and gastrointestinal toxicities

CCNU

gastrointestinal toxicities

CCNU

Gastrointestinal toxicosis

CCNU

hepatic failure

lomustine

hepatic failure

1 - (2 - chloroethyl) - 3 - cyclohexyl - 1 - nitrosourea

hepatic failure

CCNU

hepatic failure

CCNU

hepatic failure

CCNU

hepatic failure

CCNU

hepatic failure

CCNU

hepatic failure

CCNU

thrombocytopenia

lomustine

thrombocytopenia

1 - (2 - chloroethyl) - 3 - cyclohexyl - 1 - nitrosourea

thrombocytopenia

CCNU

thrombocytopenia

CCNU

thrombocytopenia

CCNU

thrombocytopenia

CCNU

thrombocytopenia

CCNU

thrombocytopenia

CCNU

renal, hepatic and gastrointestinal toxicities

lomustine

renal, hepatic and gastrointestinal toxicities

1 - (2 - chloroethyl) - 3 - cyclohexyl - 1 - nitrosourea

renal, hepatic and gastrointestinal toxicities

CCNU

renal, hepatic and gastrointestinal toxicities

CCNU

renal, hepatic and gastrointestinal toxicities

CCNU

renal, hepatic and gastrointestinal toxicities

CCNU

renal, hepatic and gastrointestinal toxicities

CCNU

renal, hepatic and gastrointestinal toxicities

CCNU

anaemia

lomustine

anaemia

1 - (2 - chloroethyl) - 3 - cyclohexyl - 1 - nitrosourea

anaemia

CCNU

anaemia

CCNU

anaemia

CCNU

anaemia

CCNU

anaemia

CCNU

anaemia

CCNU

neutropenia

lomustine

neutropenia

1 - (2 - chloroethyl) - 3 - cyclohexyl - 1 - nitrosourea

neutropenia

CCNU

neutropenia

CCNU

neutropenia

CCNU

neutropenia

CCNU

neutropenia

CCNU

neutropenia

CCNU

vomiting

lomustine

vomiting

1 - (2 - chloroethyl) - 3 - cyclohexyl - 1 - nitrosourea

vomiting

CCNU

vomiting

CCNU

vomiting

CCNU

vomiting

CCNU

vomiting

CCNU

vomiting


Input: Neuroactive steroids protect against pilocarpine - and kainic acid - induced limbic seizures and status epilepticus in mice. Several structurally related metabolites of progesterone (3 alpha - hydroxy pregnane - 20 - ones) and deoxycorticosterone (3 alpha - hydroxy pregnane - 21 - diol - 20 - ones) and their 3 beta - epimers were evaluated for protective activity against pilocarpine -, kainic acid - and N - methyl - D - aspartate (NMDA) - induced seizures in mice. Steroids with the 3 - hydroxy group in the alpha - position and 5 - H in the alpha - or beta - configurations were highly effective in protecting against pilocarpine (416 mg / kg, s. c.) - induced limbic motor seizures and status epilepticus (ED50 values, 7. 0 - 18. 7 mg / kg, i. p.). The corresponding epimers with the 3 - hydroxy group in the beta - position were also effective but less potent (ED50 values, 33. 8 - 63. 5, i. p.). Although the neuroactive steroids were considerably less potent than the benzodiazepine clonazepam in protecting against pilocarpine seizures, steroids with the 5 alpha, 3 alpha - configuration had comparable or higher protective index values (TD50 for motor impairment divided by ED50 for seizure protection) than clonazepam, indicating that some neuroactive steroids may have lower relative toxicity. Steroids with the 5 alpha, 3 alpha - or 5 beta, 3 alpha - configurations also produced a dose - dependent delay in the onset of limbic seizures induced by kainic acid (32 mg / kg, s. c.), but did not completely protect against the seizures. However, when a second dose of the steroid was administered 1 hr after the first dose, complete protection from the kainic acid - induced limbic seizures and status epilepticus was obtained. The steroids also caused a dose - dependent delay in NMDA (257 mg / kg, s. c.) - induced lethality, but did not completely protect against NMDA seizures or lethality. We conclude that neuroactive steroids are highly effective in protecting against pilocarpine - and kainic acid - induced seizures and status epilepticus in mice, and may be of utility in the treatment of some forms of status epilepticus in humans.

steroids

pilocarpine

kainic acid

progesterone

3 alpha - hydroxy pregnane - 20 - ones

deoxycorticosterone

3 alpha - hydroxy pregnane - 21 - diol - 20 - ones

pilocarpine

kainic acid

N - methyl - D - aspartate

NMDA

Steroids

pilocarpine

steroids

benzodiazepine

clonazepam

pilocarpine

steroids

clonazepam

steroids

Steroids

kainic acid

steroid

kainic acid

steroids

NMDA

NMDA

steroids

pilocarpine

kainic acid

seizures

status epilepticus

seizures

seizures

status epilepticus

seizures

seizure

toxicity

seizures

seizures

seizures

status epilepticus

seizures

seizures

status epilepticus

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

kainic acid

status epilepticus

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizure

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizure

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizure

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizure

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizure

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures

kainic acid

seizures


Input: The safety and efficacy of combination N - butyl - deoxynojirimycin (SC - 48334) and zidovudine in patients with HIV - 1 infection and 200 - 500 CD4 cells / mm3. We conducted a double - blind, randomized phase II study to evaluate the safety and activity of combination therapy with N - butyl - deoxynojirimycin (SC - 48334) (an alpha - glucosidase I inhibitor) and zidovudine versus zidovudine alone. Patients with 200 to 500 CD4 cells / mm3 who tolerated < or = 12 weeks of prior zidovudine therapy received SC - 48334 (1000 mg every 8 h) and zidovudine (100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58, zidovudine and placebo. Twenty - three patients (38%) and 15 (26%), in the combination and zidovudine groups, respectively, discontinued therapy (p = 0. 15). The mean SC - 48334 steady - state trough level (4. 04 + / - 0. 99 micrograms / ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73. 8 cells / mm3 and 52. 4 cells / mm3 for the combination and zidovudine groups, respectively (p > 0. 36). For patients with prior zidovudine therapy, the mean change in CD4 cells in the combination and zidovudine groups was 63. 7 cells / mm3 and 4. 9 cells / mm3 at week 8 and 6. 8 cells / mm3 and - 45. 1 cells / mm3 at week 16, respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40%) and two (11%) at week 4 (p = 0. 10) and five (45%) and two (14%) at week 24 (p = 0. 08), respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients. (ABSTRACT TRUNCATED AT 250 WORDS)

N - butyl - deoxynojirimycin

SC - 48334

zidovudine

N - butyl - deoxynojirimycin

SC - 48334

zidovudine

zidovudine

zidovudine

SC - 48334

zidovudine

zidovudine

zidovudine

zidovudine

SC - 48334

zidovudine

zidovudine

zidovudine

zidovudine

HIV - 1 infection

immunodeficiency

Diarrhea

flatulence

abdominal pain

weight loss

N - butyl - deoxynojirimycin

flatulence

SC - 48334

flatulence

N - butyl - deoxynojirimycin

flatulence

SC - 48334

flatulence

SC - 48334

flatulence

SC - 48334

flatulence

zidovudine

weight loss

zidovudine

weight loss

zidovudine

weight loss

zidovudine

weight loss

zidovudine

weight loss

zidovudine

weight loss

zidovudine

weight loss

zidovudine

weight loss

zidovudine

weight loss

zidovudine

weight loss

zidovudine

weight loss

zidovudine

weight loss

zidovudine

flatulence

zidovudine

flatulence

zidovudine

flatulence

zidovudine

flatulence

zidovudine

flatulence

zidovudine

flatulence

zidovudine

flatulence

zidovudine

flatulence

zidovudine

flatulence

zidovudine

flatulence

zidovudine

flatulence

zidovudine

flatulence

N - butyl - deoxynojirimycin

abdominal pain

SC - 48334

abdominal pain

N - butyl - deoxynojirimycin

abdominal pain

SC - 48334

abdominal pain

SC - 48334

abdominal pain

SC - 48334

abdominal pain

N - butyl - deoxynojirimycin

Diarrhea

SC - 48334

Diarrhea

N - butyl - deoxynojirimycin

Diarrhea

SC - 48334

Diarrhea

SC - 48334

Diarrhea

SC - 48334

Diarrhea

zidovudine

abdominal pain

zidovudine

abdominal pain

zidovudine

abdominal pain

zidovudine

abdominal pain

zidovudine

abdominal pain

zidovudine

abdominal pain

zidovudine

abdominal pain

zidovudine

abdominal pain

zidovudine

abdominal pain

zidovudine

abdominal pain

zidovudine

abdominal pain

zidovudine

abdominal pain

zidovudine

Diarrhea

zidovudine

Diarrhea

zidovudine

Diarrhea

zidovudine

Diarrhea

zidovudine

Diarrhea

zidovudine

Diarrhea

zidovudine

Diarrhea

zidovudine

Diarrhea

zidovudine

Diarrhea

zidovudine

Diarrhea

zidovudine

Diarrhea

zidovudine

Diarrhea

N - butyl - deoxynojirimycin

weight loss

SC - 48334

weight loss

N - butyl - deoxynojirimycin

weight loss

SC - 48334

weight loss

SC - 48334

weight loss

SC - 48334

weight loss


Input: Recent preclinical and clinical studies with the thymidylate synthase inhibitor N10 - propargyl - 5, 8 - dideazafolic acid (CB 3717). CB 3717, N10 - propargyl - 5, 8 - dideazafolic acid, is a tight - binding inhibitor of thymidylate synthase (TS) whose cytotoxicity is mediated solely through the inhibition of this enzyme. Recent preclinical studies have focused on the intracellular formation of CB 3717 polyglutamates. Following a 12 - hour exposure of L1210 cells to 50 microM [3H] CB 3717, 30% of the extractable radioactivity could be accounted for as CB 3717 tetra - and pentaglutamate, as determined by high - pressure liquid chromatography (HPLC) analyses. As inhibitors of isolated L1210 TS, CB 3717 di -, tri -, tetra - and pentaglutamate are 26 -, 87 -, 119 - and 114 - fold more potent than CB 3717, respectively, and their formation may, therefore, be an important determinant of CB 3717 cytotoxicity. In early clinical studies with CB 3717, activity has been seen in breast cancer, ovarian cancer, hepatoma, and mesothelioma. Toxicities included hepatotoxicity, malaise, and dose - limiting nephrotoxicity. This latter effect is thought to be due to drug precipitation within the renal tubule as a result of the poor solubility of CB 3717 under acidic conditions. In an attempt to overcome this problem, a clinical trial of CB 3717 administered with alkaline diuresis is under way. Preliminary results at 400 and 500 mg / m2 suggest that a reduction in nephrotoxicity may have been achieved with only 1 instance of renal toxicity in 10 patients. Hepatotoxicity and malaise are again the most frequent side effects. Evidence of antitumor activity has been seen in 3 patients. Pharmacokinetic investigations have shown that alkaline diuresis does not alter CB 3717 plasma levels or urinary excretion and that satisfactory urinary alkalinization can be readily achieved.

N10 - propargyl - 5, 8 - dideazafolic acid

CB 3717

CB 3717

N10 - propargyl - 5, 8 - dideazafolic acid

CB 3717

CB 3717

CB 3717

CB 3717

CB 3717

CB 3717

CB 3717

CB 3717

CB 3717

cytotoxicity

cytotoxicity

breast cancer

ovarian cancer

hepatoma

mesothelioma

Toxicities

hepatotoxicity

malaise

nephrotoxicity

nephrotoxicity

renal toxicity

Hepatotoxicity

malaise

N10 - propargyl - 5, 8 - dideazafolic acid

hepatotoxicity

N10 - propargyl - 5, 8 - dideazafolic acid

Hepatotoxicity

CB 3717

hepatotoxicity

CB 3717

Hepatotoxicity

CB 3717

hepatotoxicity

CB 3717

Hepatotoxicity

N10 - propargyl - 5, 8 - dideazafolic acid

hepatotoxicity

N10 - propargyl - 5, 8 - dideazafolic acid

Hepatotoxicity

CB 3717

hepatotoxicity

CB 3717

Hepatotoxicity

CB 3717

hepatotoxicity

CB 3717

Hepatotoxicity

CB 3717

hepatotoxicity

CB 3717

Hepatotoxicity

CB 3717

hepatotoxicity

CB 3717

Hepatotoxicity

CB 3717

hepatotoxicity

CB 3717

Hepatotoxicity

CB 3717

hepatotoxicity

CB 3717

Hepatotoxicity

CB 3717

hepatotoxicity

CB 3717

Hepatotoxicity

CB 3717

hepatotoxicity

CB 3717

Hepatotoxicity

CB 3717

hepatotoxicity

CB 3717

Hepatotoxicity

N10 - propargyl - 5, 8 - dideazafolic acid

nephrotoxicity

N10 - propargyl - 5, 8 - dideazafolic acid

nephrotoxicity

N10 - propargyl - 5, 8 - dideazafolic acid

renal toxicity

CB 3717

nephrotoxicity

CB 3717

nephrotoxicity

CB 3717

renal toxicity

CB 3717

nephrotoxicity

CB 3717

nephrotoxicity

CB 3717

renal toxicity

N10 - propargyl - 5, 8 - dideazafolic acid

nephrotoxicity

N10 - propargyl - 5, 8 - dideazafolic acid

nephrotoxicity

N10 - propargyl - 5, 8 - dideazafolic acid

renal toxicity

CB 3717

nephrotoxicity

CB 3717

nephrotoxicity

CB 3717

renal toxicity

CB 3717

nephrotoxicity

CB 3717

nephrotoxicity

CB 3717

renal toxicity

CB 3717

nephrotoxicity

CB 3717

nephrotoxicity

CB 3717

renal toxicity

CB 3717

nephrotoxicity

CB 3717

nephrotoxicity

CB 3717

renal toxicity

CB 3717

nephrotoxicity

CB 3717

nephrotoxicity

CB 3717

renal toxicity

CB 3717

nephrotoxicity

CB 3717

nephrotoxicity

CB 3717

renal toxicity

CB 3717

nephrotoxicity

CB 3717

nephrotoxicity

CB 3717

renal toxicity

CB 3717

nephrotoxicity

CB 3717

nephrotoxicity

CB 3717

renal toxicity

CB 3717

nephrotoxicity

CB 3717

nephrotoxicity

CB 3717

renal toxicity

N10 - propargyl - 5, 8 - dideazafolic acid

malaise

N10 - propargyl - 5, 8 - dideazafolic acid

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

N10 - propargyl - 5, 8 - dideazafolic acid

malaise

N10 - propargyl - 5, 8 - dideazafolic acid

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise

CB 3717

malaise


Input: Ethopropazine and benztropine in neuroleptic - induced parkinsonism. In a 12 - week controlled study ethopropazine was compared to benztropine in the treatment of parkinsonism induced by fluphenazine enanthate in 60 schizophrenic outpatients. Ethopropazine and benztropine were found to be equally effective in controlling parkinsonian symptoms and were as efficacious as procyclidine, their previous antiparkinsonian drug. However, benztropine treated patients had a significant increase in tardive dyskinesia compared to their condition during procyclindine treatment, and significantly more anxiety and depression than ethopropazine treated patients. This suggests that benztropine is not the anticholinergic drug of choice in the treatment of neuroleptic - induced parkinsonian symptoms, because of its more toxic central and peripheral atropinic effect.

Ethopropazine

benztropine

ethopropazine

benztropine

fluphenazine enanthate

Ethopropazine

benztropine

procyclidine

benztropine

procyclindine

ethopropazine

benztropine

parkinsonism

parkinsonism

schizophrenic

parkinsonian symptoms

tardive dyskinesia

anxiety

depression

parkinsonian symptoms

benztropine

anxiety

benztropine

anxiety

benztropine

anxiety

benztropine

anxiety

benztropine

anxiety

benztropine

depression

benztropine

depression

benztropine

depression

benztropine

depression

benztropine

depression

benztropine

tardive dyskinesia

benztropine

tardive dyskinesia

benztropine

tardive dyskinesia

benztropine

tardive dyskinesia

benztropine

tardive dyskinesia

fluphenazine enanthate

parkinsonism

fluphenazine enanthate

parkinsonism

fluphenazine enanthate

parkinsonian symptoms

fluphenazine enanthate

parkinsonian symptoms


Input: Effect of alpha - tocopherol and deferoxamine on methamphetamine - induced neurotoxicity. Methamphetamine (MA) - induced dopaminergic neurotoxicity is believed to be associated with the increased formation of free radicals. This study examined the effect of alpha - tocopherol (alpha - TC), a scavenger of reactive oxygen species, and deferoxamine (DFO), an iron chelator, on the MA - induced neurotoxicity. Male rats were treated with MA (10 mg / kg, every 2 h for four injections). The rat received either alpha - TC (20 mg / kg) intraperitoneally for 3 days and 30 min prior to MA administration or DFO (50 mg / kg) subcutaneously 30 min before MA administration. The concentrations of dopamine (DA), serotonin and their metabolites decreased significantly after MA administration, which was inhibited by the alpha - TC and DFO pretreatment. alpha - TC and DFO attenuated the MA - induced hyperthermia as well as the alterations in the locomotor activity. The level of lipid peroxidation was higher and the reduced glutathione concentration was lower in the MA - treated rats. These changes were significantly attenuated by alpha - TC and DFO. This suggests that alpha - TC and DFO ameliorate the MA - induced neuronal damage by decreasing the level of oxidative stress.

alpha - tocopherol

deferoxamine

methamphetamine

Methamphetamine

MA

alpha - tocopherol

alpha - TC

oxygen

deferoxamine

DFO

iron

MA

MA

alpha - TC

MA

DFO

MA

dopamine

DA

serotonin

MA

alpha - TC

DFO

alpha - TC

DFO

MA

glutathione

MA

alpha - TC

DFO

alpha - TC

DFO

MA

neurotoxicity

neurotoxicity

neurotoxicity

hyperthermia

neuronal damage

methamphetamine

neuronal damage

Methamphetamine

neuronal damage

MA

neuronal damage

MA

neuronal damage

MA

neuronal damage

MA

neuronal damage

MA

neuronal damage

MA

neuronal damage

MA

neuronal damage

MA

neuronal damage

MA

neuronal damage

methamphetamine

hyperthermia

Methamphetamine

hyperthermia

MA

hyperthermia

MA

hyperthermia

MA

hyperthermia

MA

hyperthermia

MA

hyperthermia

MA

hyperthermia

MA

hyperthermia

MA

hyperthermia

MA

hyperthermia


Input: Use of dexamethasone with mesna for the prevention of ifosfamide - induced hemorrhagic cystitis. AIM: Hemorrhagic cystitis (HC) is a limiting side - effect of chemotherapy with ifosfamide (IFS). In the study presented here, we investigated the use of dexamethasone in combination with mesna for the prevention of IFS - induced HC. METHODS: Male Wistar rats (150 - 200 g; 6 rats per group) were treated with saline or mesna 5 min (i. p.) before and 2 and 6 h after (v. o.) administration of IFS. One, two or three doses of mesna were replaced with dexamethasone alone or with dexamethasone plus mesna. Cystitis was evaluated 24 h after its induction by the changes in bladder wet weight and by macroscopic and microscopic analysis. RESULTS: The replacement of the last dose or the last two doses of mesna with dexamethasone reduced the increase in bladder wet weight induced by IFS by 84. 79% and 89. 13%, respectively. In addition, it almost abolished the macroscopic and microscopic alterations induced by IFS. Moreover, the addition of dexamethasone to the last two doses of mesna was more efficient than three doses of mesna alone when evaluated microscopically. CONCLUSION: Dexamethasone in combination with mesna was efficient in blocking IFS - induced HC. However, the replacement of last two doses of mesna with saline or all of the mesna doses with dexamethasone did not prevent HC.

dexamethasone

mesna

ifosfamide

ifosfamide

IFS

dexamethasone

mesna

IFS

mesna

IFS

mesna

dexamethasone

dexamethasone

mesna

mesna

dexamethasone

IFS

IFS

dexamethasone

mesna

mesna

Dexamethasone

mesna

IFS

mesna

mesna

dexamethasone

hemorrhagic cystitis

hemorrhagic

cystitis

Hemorrhagic cystitis

Hemorrhagic

cystitis

HC

HC

Cystitis

HC

HC

ifosfamide

hemorrhagic cystitis

ifosfamide

hemorrhagic

ifosfamide

Hemorrhagic cystitis

ifosfamide

Hemorrhagic

ifosfamide

HC

ifosfamide

HC

ifosfamide

HC

ifosfamide

HC

ifosfamide

hemorrhagic cystitis

ifosfamide

hemorrhagic

ifosfamide

Hemorrhagic cystitis

ifosfamide

Hemorrhagic

ifosfamide

HC

ifosfamide

HC

ifosfamide

HC

ifosfamide

HC

IFS

hemorrhagic cystitis

IFS

hemorrhagic

IFS

Hemorrhagic cystitis

IFS

Hemorrhagic

IFS

HC

IFS

HC

IFS

HC

IFS

HC

IFS

hemorrhagic cystitis

IFS

hemorrhagic

IFS

Hemorrhagic cystitis

IFS

Hemorrhagic

IFS

HC

IFS

HC

IFS

HC

IFS

HC

IFS

hemorrhagic cystitis

IFS

hemorrhagic

IFS

Hemorrhagic cystitis

IFS

Hemorrhagic

IFS

HC

IFS

HC

IFS

HC

IFS

HC

IFS

hemorrhagic cystitis

IFS

hemorrhagic

IFS

Hemorrhagic cystitis

IFS

Hemorrhagic

IFS

HC

IFS

HC

IFS

HC

IFS

HC

IFS

hemorrhagic cystitis

IFS

hemorrhagic

IFS

Hemorrhagic cystitis

IFS

Hemorrhagic

IFS

HC

IFS

HC

IFS

HC

IFS

HC

IFS

hemorrhagic cystitis

IFS

hemorrhagic

IFS

Hemorrhagic cystitis

IFS

Hemorrhagic

IFS

HC

IFS

HC

IFS

HC

IFS

HC

ifosfamide

cystitis

ifosfamide

cystitis

ifosfamide

Cystitis

ifosfamide

cystitis

ifosfamide

cystitis

ifosfamide

Cystitis

IFS

cystitis

IFS

cystitis

IFS

Cystitis

IFS

cystitis

IFS

cystitis

IFS

Cystitis

IFS

cystitis

IFS

cystitis

IFS

Cystitis

IFS

cystitis

IFS

cystitis

IFS

Cystitis

IFS

cystitis

IFS

cystitis

IFS

Cystitis

IFS

cystitis

IFS

cystitis

IFS

Cystitis


Input: Behavioral effects of MK - 801 on reserpine - treated mice. The effects of dizocilpine (MK - 801), a noncompetitive N - methyl - D - aspartate (NMDA) receptor antagonist, were studied on dopamine - related behaviors induced by reserpine treatments. This study focuses on behavioral syndromes that may used as models for Parkinson' s disease, or tardive dyskinesia, and its response after glutamatergic blockage. Reserpine (1 mg / kg), administered once every other day for 4 days, produced increases in orofacial dyskinesia, tongue protrusion and vacuous chewing in mice, which are signs indicative of tardive dyskinesia. Reserpine also produced tremor and catalepsy, which are signs suggestive of Parkinson' s disease. MK - 801 (0. 1 mg / kg), administered 30 min before the observation test, prevented the vacuous chewing movements, tongue protrusions and catalepsy induced by reserpine. However, MK - 801 injection produced a significant increase of tremor in reserpine - treated mice. Reserpine (1 mg / kg), administered 90 min before the test and followed by apomophine injection (0. 1 mg / kg) 5 min before the test, did not produce oral dyskinesia in mice. On the other hand, reserpine induced increases in tremor and catalepsy compared to control mice. MK - 801 (0. 1 mg / kg) administration attenuated the catalepsy and tremor induced by reserpine. Pretreatment with reserpine (1 mg / kg) 24 h before the observation test produced increases in vacuous chewing movements and tongue protrusion, as well as increases in tremor and catalepsy, whereas MK - 801 (0. 1 mg / kg) injection 90 min before the test reversed the effects of reserpine. These results show that reserpine produces different and abnormal movements, which are related to dose and schedule employed and can be considered as parkinsonian - like and tardive dsykinesia signs. The glutamatergic blockage produced by NMDA can restore these signs, such as vacuous chewing movements, tongue protrusions, catalepsy and tremor according to the employed model.

MK - 801

reserpine

dizocilpine

MK - 801

N - methyl - D - aspartate

NMDA

dopamine

reserpine

Reserpine

Reserpine

MK - 801

reserpine

MK - 801

reserpine

Reserpine

apomophine

reserpine

MK - 801

reserpine

reserpine

MK - 801

reserpine

reserpine

NMDA

Parkinson' s disease

tardive dyskinesia

orofacial dyskinesia

tardive dyskinesia

tremor

catalepsy

Parkinson' s disease

catalepsy

tremor

oral dyskinesia

tremor

catalepsy

catalepsy

tremor

tremor

catalepsy

abnormal movements

parkinsonian

tardive dsykinesia

catalepsy

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

Reserpine

tremor

Reserpine

tremor

Reserpine

tremor

Reserpine

tremor

Reserpine

tremor

Reserpine

tremor

Reserpine

tremor

Reserpine

tremor

Reserpine

tremor

Reserpine

tremor

Reserpine

tremor

Reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

Reserpine

tremor

Reserpine

tremor

Reserpine

tremor

Reserpine

tremor

Reserpine

tremor

Reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tremor

reserpine

tardive dyskinesia

reserpine

tardive dyskinesia

reserpine

abnormal movements

reserpine

tardive dsykinesia

reserpine

tardive dyskinesia

reserpine

tardive dyskinesia

reserpine

abnormal movements

reserpine

tardive dsykinesia

Reserpine

tardive dyskinesia

Reserpine

tardive dyskinesia

Reserpine

abnormal movements

Reserpine

tardive dsykinesia

Reserpine

tardive dyskinesia

Reserpine

tardive dyskinesia

Reserpine

abnormal movements

Reserpine

tardive dsykinesia

reserpine

tardive dyskinesia

reserpine

tardive dyskinesia

reserpine

abnormal movements

reserpine

tardive dsykinesia

reserpine

tardive dyskinesia

reserpine

tardive dyskinesia

reserpine

abnormal movements

reserpine

tardive dsykinesia

Reserpine

tardive dyskinesia

Reserpine

tardive dyskinesia

Reserpine

abnormal movements

Reserpine

tardive dsykinesia

reserpine

tardive dyskinesia

reserpine

tardive dyskinesia

reserpine

abnormal movements

reserpine

tardive dsykinesia

reserpine

tardive dyskinesia

reserpine

tardive dyskinesia

reserpine

abnormal movements

reserpine

tardive dsykinesia

reserpine

tardive dyskinesia

reserpine

tardive dyskinesia

reserpine

abnormal movements

reserpine

tardive dsykinesia

reserpine

tardive dyskinesia

reserpine

tardive dyskinesia

reserpine

abnormal movements

reserpine

tardive dsykinesia

reserpine

tardive dyskinesia

reserpine

tardive dyskinesia

reserpine

abnormal movements

reserpine

tardive dsykinesia

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

Reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy

reserpine

catalepsy


Input: Effect of glyceryl trinitrate on the sphincter of Oddi spasm evoked by prostigmine - morphine administration. OBJECTIVE: In this study the effect of glyceryl trinitrate on the prostigmine - morphine - induced sphincter of Oddi spasm was evaluated in nine female patients with sphincter of Oddi dyskinesia. METHOD: Sphincter of Oddi spasm was induced by prostigmine - morphine administration (0. 5 mg prostigmine intramuscularly and 10 mg morphine subcutaneously) and visualized by quantitative hepatobiliary scintigraphy. The entire procedure was repeated during glyceryl trinitrate infusion (Nitrolingual 1 microg / kg / min for 120 min). RESULTS: Prostigmine - morphine provocation caused significant increases in the time to peak activity (Tmax) over the hepatic hilum (HH: 34. 33 + / - 5. 05 vs. 22. 77 + / - 3. 26) and the common bile duct (CBD: 60. 44 + / - 5. 99 vs. 40. 0 + / - 2. 88) and in the half - time of excretion (T1 / 2) over the liver parenchyma (LP: 120. 04 + / - 16. 01 vs. 27. 37 + / - 2. 19), HH (117. 61 + / - 14. 71 vs. 31. 85 + / - 3. 99) and CBD (158. 11 + / - 9. 18 vs. 40. 1 + / - 6. 24), indicating a complete spasm at the level of the sphincter of Oddi. Glyceryl trinitrate infusion completely normalized the prostigmine - morphine - induced alterations in these quantitative parameters (TmaX over the LP: 11. 33 + / - 1. 13; over the HH: 18. 88 + / - 1. 48; and over the CBD: 36. 22 + / - 1. 92; and T1 / 2 over the LP: 28. 21 + / - 1. 83; over the HH: 33. 42 + / - 3. 10; and over the CBD: 41. 66 + / - 6. 33), suggesting an effective sphincter - relaxing effect of glyceryl trinitrate. CONCLUSION: These results provide the first evidence of the effectiveness of glyceryl trinitrate on the morphine - induced sphincter of Oddi spasm in humans. Since glyceryl trinitrate is able to overcome even the drastic effect of morphine, it might be of relevance in the treatment of sphincter of Oddi dyskinesia.

glyceryl trinitrate

prostigmine

morphine

glyceryl trinitrate

prostigmine

morphine

prostigmine

morphine

prostigmine

morphine

glyceryl trinitrate

Nitrolingual

Prostigmine

morphine

Glyceryl trinitrate

prostigmine

morphine

glyceryl trinitrate

glyceryl trinitrate

morphine

glyceryl trinitrate

morphine

sphincter of Oddi spasm

sphincter of Oddi spasm

spasm

sphincter of Oddi spasm

sphincter of Oddi spasm

spasm

sphincter of Oddi dyskinesia

Sphincter of Oddi spasm

Sphincter of Oddi spasm

spasm

spasm

sphincter of Oddi spasm

sphincter of Oddi spasm

spasm

sphincter of Oddi dyskinesia

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

morphine

Sphincter of Oddi spasm

morphine

Sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

morphine

Sphincter of Oddi spasm

morphine

Sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

morphine

Sphincter of Oddi spasm

morphine

Sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

morphine

Sphincter of Oddi spasm

morphine

Sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

morphine

Sphincter of Oddi spasm

morphine

Sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

morphine

Sphincter of Oddi spasm

morphine

Sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

morphine

Sphincter of Oddi spasm

morphine

Sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

morphine

Sphincter of Oddi spasm

morphine

Sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi spasm

morphine

sphincter of Oddi dyskinesia

prostigmine

sphincter of Oddi spasm

prostigmine

spasm

prostigmine

sphincter of Oddi spasm

prostigmine

spasm

prostigmine

Sphincter of Oddi spasm

prostigmine

spasm

prostigmine

spasm

prostigmine

sphincter of Oddi spasm

prostigmine

spasm

prostigmine

sphincter of Oddi spasm

prostigmine

spasm

prostigmine

sphincter of Oddi spasm

prostigmine

spasm

prostigmine

Sphincter of Oddi spasm

prostigmine

spasm

prostigmine

spasm

prostigmine

sphincter of Oddi spasm

prostigmine

spasm

prostigmine

sphincter of Oddi spasm

prostigmine

spasm

prostigmine

sphincter of Oddi spasm

prostigmine

spasm

prostigmine

Sphincter of Oddi spasm

prostigmine

spasm

prostigmine

spasm

prostigmine

sphincter of Oddi spasm

prostigmine

spasm

prostigmine

sphincter of Oddi spasm

prostigmine

spasm

prostigmine

sphincter of Oddi spasm

prostigmine

spasm

prostigmine

Sphincter of Oddi spasm

prostigmine

spasm

prostigmine

spasm

prostigmine

sphincter of Oddi spasm

prostigmine

spasm

Prostigmine

sphincter of Oddi spasm

Prostigmine

spasm

Prostigmine

sphincter of Oddi spasm

Prostigmine

spasm

Prostigmine

Sphincter of Oddi spasm

Prostigmine

spasm

Prostigmine

spasm

Prostigmine

sphincter of Oddi spasm

Prostigmine

spasm

prostigmine

sphincter of Oddi spasm

prostigmine

spasm

prostigmine

sphincter of Oddi spasm

prostigmine

spasm

prostigmine

Sphincter of Oddi spasm

prostigmine

spasm

prostigmine

spasm

prostigmine

sphincter of Oddi spasm

prostigmine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

morphine

spasm

prostigmine

sphincter of Oddi spasm

prostigmine

sphincter of Oddi spasm

prostigmine

sphincter of Oddi dyskinesia

prostigmine

Sphincter of Oddi spasm

prostigmine

sphincter of Oddi spasm

prostigmine

sphincter of Oddi dyskinesia

prostigmine

sphincter of Oddi spasm

prostigmine

sphincter of Oddi spasm

prostigmine

sphincter of Oddi dyskinesia

prostigmine

Sphincter of Oddi spasm

prostigmine

sphincter of Oddi spasm

prostigmine

sphincter of Oddi dyskinesia

prostigmine

sphincter of Oddi spasm

prostigmine

sphincter of Oddi spasm

prostigmine

sphincter of Oddi dyskinesia

prostigmine

Sphincter of Oddi spasm

prostigmine

sphincter of Oddi spasm

prostigmine

sphincter of Oddi dyskinesia

prostigmine

sphincter of Oddi spasm

prostigmine

sphincter of Oddi spasm

prostigmine

sphincter of Oddi dyskinesia

prostigmine

Sphincter of Oddi spasm

prostigmine

sphincter of Oddi spasm

prostigmine

sphincter of Oddi dyskinesia

Prostigmine

sphincter of Oddi spasm

Prostigmine

sphincter of Oddi spasm

Prostigmine

sphincter of Oddi dyskinesia

Prostigmine

Sphincter of Oddi spasm

Prostigmine

sphincter of Oddi spasm

Prostigmine

sphincter of Oddi dyskinesia

prostigmine

sphincter of Oddi spasm

prostigmine

sphincter of Oddi spasm

prostigmine

sphincter of Oddi dyskinesia

prostigmine

Sphincter of Oddi spasm

prostigmine

sphincter of Oddi spasm

prostigmine

sphincter of Oddi dyskinesia


Input: Effects of acute steroid administration on ventilatory and peripheral muscles in rats. Occasional case reports have shown that acute myopathy may occur in patients treated with massive doses of corticosteroids. The mechanism of this myopathy is poorly understood. Therefore, 60 male rats were randomly assigned to receive daily injection of saline (C), methylprednisolone (M), or triamcinolone (T) 80 mg / kg / d for 5 d. Nutritional intake, measured daily in 15 animals, showed a significant reduction of food intake in the steroid - treated groups (- 50 and - 79% in M and T, respectively). This was associated with a similar loss in body weight. In the 45 remaining animals, diaphragm contractility and histopathologic features of several muscles were studied. Weights of respiratory and peripheral muscles were similarly decreased after steroid treatment. Maximal twitches of the diaphragm were lower in the C group (653 + / - 174 g / cm (2)) than in the M group (837 + / - 171 g / cm (2); p < 0. 05) and the T group (765 + / - 145 g / cm (2), NS). Half - relaxation time was prolonged in both steroid groups, and time to peak tension was longer with M, whereas tetanic tensions were similar. Steroid treatment also induced a leftward shift of the force - frequency curve at 25 and 50 Hz when compared with saline treatment (p < 0. 05). ATPase staining of the diaphragm, scalenus medius, and gastrocnemius showed type IIb fiber atrophy in the steroid groups and also diaphragmatic type IIa atrophy with T, whereas histologic examinations revealed a normal muscular pattern with absence of necrosis. Finally, a pair - fed (PF) study, performed in 18 rats (C, T, and PF), showed that muscle atrophy was considerably less pronounced in PF animals than in T - treated animals. We conclude that (1) short - term treatment with massive doses of steroids induced severe respiratory and limb muscle wasting; (2) both types of steroids induced predominantly type IIb atrophy, resulting in the expected alterations in diaphragm contractile properties; (3) neither steroid caused muscle necrosis; (4) type IIb atrophy was not caused by acute nutritional deprivation alone.

steroid

corticosteroids

methylprednisolone

M

triamcinolone

T

steroid

M

T

steroid

M

T

steroid

M

Steroid

steroid

T

T

T

steroids

steroids

steroid

myopathy

myopathy

reduction of food intake

loss in body weight

tetanic

atrophy

atrophy

necrosis

muscle atrophy

atrophy

necrosis

atrophy

triamcinolone

loss in body weight

T

loss in body weight

T

loss in body weight

T

loss in body weight

T

loss in body weight

T

loss in body weight

T

loss in body weight

methylprednisolone

loss in body weight

M

loss in body weight

M

loss in body weight

M

loss in body weight

M

loss in body weight

triamcinolone

atrophy

triamcinolone

atrophy

triamcinolone

muscle atrophy

triamcinolone

atrophy

T

atrophy

T

atrophy

T

muscle atrophy

T

atrophy

T

atrophy

T

atrophy

T

muscle atrophy

T

atrophy

T

atrophy

T

atrophy

T

muscle atrophy

T

atrophy

T

atrophy

T

atrophy

T

muscle atrophy

T

atrophy

T

atrophy

T

atrophy

T

muscle atrophy

T

atrophy

T

atrophy

T

atrophy

T

muscle atrophy

T

atrophy

methylprednisolone

atrophy

methylprednisolone

atrophy

methylprednisolone

muscle atrophy

methylprednisolone

atrophy

M

atrophy

M

atrophy

M

muscle atrophy

M

atrophy

M

atrophy

M

atrophy

M

muscle atrophy

M

atrophy

M

atrophy

M

atrophy

M

muscle atrophy

M

atrophy

M

atrophy

M

atrophy

M

muscle atrophy

M

atrophy

methylprednisolone

reduction of food intake

M

reduction of food intake

M

reduction of food intake

M

reduction of food intake

M

reduction of food intake

triamcinolone

reduction of food intake

T

reduction of food intake

T

reduction of food intake

T

reduction of food intake

T

reduction of food intake

T

reduction of food intake

T

reduction of food intake


Input: Refractory cardiogenic shock and complete heart block after verapamil SR and metoprolol treatment. A case report. A seventy - eight - year - old woman presented with complete heart block and refractory hypotension two days after a therapeutic dose of sustained - release verapamil with concomitant use of metoprolol. The patient continued to remain hypotensive with complete heart block, even with multiple uses of intravenous atropine as well as high doses of pressor agents such as dopamine and dobutamine. However, shortly after the use of intravenous calcium chloride, the refractory hypotension and complete heart block resolved.

cardiogenic shock

heart block

heart block

hypotension

hypotensive

heart block

hypotension

heart block

verapamil

metoprolol

verapamil

metoprolol

atropine

dopamine

dobutamine

calcium chloride

metoprolol

hypotension

metoprolol

hypotensive

metoprolol

hypotension

metoprolol

hypotension

metoprolol

hypotensive

metoprolol

hypotension

verapamil

heart block

verapamil

heart block

verapamil

heart block

verapamil

heart block

verapamil

heart block

verapamil

heart block

verapamil

heart block

verapamil

heart block

verapamil

hypotension

verapamil

hypotensive

verapamil

hypotension

verapamil

hypotension

verapamil

hypotensive

verapamil

hypotension

metoprolol

heart block

metoprolol

heart block

metoprolol

heart block

metoprolol

heart block

metoprolol

heart block

metoprolol

heart block

metoprolol

heart block

metoprolol

heart block


Input: A phase I clinical study of the antipurine antifolate lometrexol (DDATHF) given with oral folic acid. Lometrexol is an antifolate which inhibits glycinamide ribonucleotide formyltransferase (GARFT), an enzyme essential for de novo purine synthesis. Extensive experimental and limited clinical data have shown that lometrexol has activity against tumours which are refractory to other drugs, notably methotrexate. However, the initial clinical development of lometrexol was curtailed because of severe and cumulative antiproliferative toxicities. Preclinical murine studies demonstrated that the toxicity of lometrexol can be prevented by low dose folic acid administration, i. e. for 7 days prior to and 7 days following a single bolus dose. This observation prompted a Phase I clinical study of lometrexol given with folic acid supplementation which has confirmed that the toxicity of lometrexol can be markedly reduced by folic acid supplementation. Thrombocytopenia and mucositis were the major toxicities. There was no clear relationship between clinical toxicity and the extent of plasma folate elevation. Associated studies demonstrated that lometrexol plasma pharmacokinetics were not altered by folic acid administration indicating that supplementation is unlikely to reduce toxicity by enhancing lometrexol plasma clearance. The work described in this report has identified for the first time a clinically acceptable schedule for the administration of a GARFT inhibitor. This information will facilitate the future evaluation of this class of compounds in cancer therapy.

antipurine

lometrexol

DDATHF

folic acid

Lometrexol

glycinamide ribonucleotide

purine

lometrexol

methotrexate

lometrexol

lometrexol

folic acid

lometrexol

folic acid

lometrexol

folic acid

folate

lometrexol

folic acid

lometrexol

tumours

toxicities

toxicity

toxicity

Thrombocytopenia

mucositis

toxicities

toxicity

toxicity

cancer

lometrexol

mucositis

DDATHF

mucositis

Lometrexol

mucositis

lometrexol

mucositis

lometrexol

mucositis

lometrexol

mucositis

lometrexol

mucositis

lometrexol

mucositis

lometrexol

mucositis

lometrexol

mucositis

lometrexol

Thrombocytopenia

DDATHF

Thrombocytopenia

Lometrexol

Thrombocytopenia

lometrexol

Thrombocytopenia

lometrexol

Thrombocytopenia

lometrexol

Thrombocytopenia

lometrexol

Thrombocytopenia

lometrexol

Thrombocytopenia

lometrexol

Thrombocytopenia

lometrexol

Thrombocytopenia


Input: Involvement of the mu - opiate receptor in peripheral analgesia. The intradermal injection of mu (morphine, Tyr - D - Ala - Gly - NMe - Phe - Gly - ol and morphiceptin), kappa (trans - 3, 4 - dichloro - N - methyl - N [2 - (1 - pyrrolidinyl) cyclohexyl] benzeneactemide) and delta ([D - Pen2. 5] - enkephalin and [D - Ser2] - [Leu] enkephalin - Thr) selective opioid - agonists, by themselves, did not significantly affect the mechanical nociceptive threshold in the hindpaw of the rat. Intradermal injection of mu, but not delta or kappa opioid - agonists, however, produced dose - dependent inhibition of prostaglandin E2 - induced hyperalgesia. The analgesic effect of the mu - agonist morphine was dose - dependently antagonized by naloxone and prevented by co - injection of pertussis toxin. Morphine did not, however, alter the hyperalgesia induced by 8 - bromo cyclic adenosine monophosphate. We conclude that the analgesic action of opioids on the peripheral terminals of primary afferents is via a binding site with characteristics of the mu - opioid receptor and that this action is mediated by inhibition of the cyclic adenosine monophosphate second messenger system.

analgesia

hyperalgesia

hyperalgesia

morphine

Tyr - D - Ala - Gly - NMe - Phe - Gly - ol

morphiceptin

trans - 3, 4 - dichloro - N - methyl - N [2 - (1 - pyrrolidinyl) cyclohexyl] benzeneactemide

[D - Pen2. 5] - enkephalin

[D - Ser2] - [Leu] enkephalin - Thr

prostaglandin E2

morphine

naloxone

Morphine

8 - bromo cyclic adenosine monophosphate

cyclic adenosine monophosphate

8 - bromo cyclic adenosine monophosphate

hyperalgesia

8 - bromo cyclic adenosine monophosphate

hyperalgesia

prostaglandin E2

hyperalgesia

prostaglandin E2

hyperalgesia


Input: Adequate timing of ribavirin reduction in patients with hemolysis during combination therapy of interferon and ribavirin for chronic hepatitis C. BACKGROUND: Hemolytic anemia is one of the major adverse events of the combination therapy of interferon and ribavirin. Because of ribavirin - related hemolytic anemia, dose reduction is a common event in this therapy. In this clinical retrospective cohort study we have examined the suitable timing of ribavirin reduction in patients with hemolysis during combination therapy. METHODS: Thirty - seven of 160 patients who had HCV - genotype 1b, had high virus load, and received 24 - week combination therapy developed anemia with hemoglobin level < 10 g / dl or anemia - related signs during therapy. After that, these 37 patients were reduced one tablet of ribavirin (200 mg) per day. After reduction of ribavirin, 27 of 37 patients could continue combination therapy for a total of 24 weeks (group A). However, 10 of 37 patients with reduction of ribavirin could not continue combination therapy because their < 8. 5 g / dl hemoglobin values decreased to or anemia - related severe side effects occurred (group B). We assessed the final efficacy and safety after reduction of ribavirin in groups A and B. RESULTS: A sustained virological response (SVR) was 29. 6% (8 / 27) in group A and 10% (1 / 10) in group B, respectively. A 34. 4% (12 / 27) of SVR + biological response in group A was higher than 10% (1 / 10) in group B (P = 0. 051), with slight significance. With respect to hemoglobin level at the time of ribavirin reduction, a rate of continuation of therapy in patients with > or = 10 g / dl hemoglobin was higher than that in patients with < 10 g / dl (P = 0. 036). CONCLUSIONS: Reduction of ribavirin at hemoglobin level > or = 10 g / dl is suitable in terms of efficacy and side effects.

ribavirin

interferon

ribavirin

interferon

ribavirin

ribavirin

ribavirin

ribavirin

ribavirin

ribavirin

ribavirin

ribavirin

ribavirin

hemolysis

chronic hepatitis C

Hemolytic anemia

hemolytic anemia

hemolysis

anemia

anemia

anemia

interferon

Hemolytic anemia

interferon

hemolytic anemia

interferon

Hemolytic anemia

interferon

hemolytic anemia

ribavirin

Hemolytic anemia

ribavirin

hemolytic anemia

ribavirin

Hemolytic anemia

ribavirin

hemolytic anemia

ribavirin

Hemolytic anemia

ribavirin

hemolytic anemia

ribavirin

Hemolytic anemia

ribavirin

hemolytic anemia

ribavirin

Hemolytic anemia

ribavirin

hemolytic anemia

ribavirin

Hemolytic anemia

ribavirin

hemolytic anemia

ribavirin

Hemolytic anemia

ribavirin

hemolytic anemia

ribavirin

Hemolytic anemia

ribavirin

hemolytic anemia

ribavirin

Hemolytic anemia

ribavirin

hemolytic anemia

ribavirin

Hemolytic anemia

ribavirin

hemolytic anemia

ribavirin

Hemolytic anemia

ribavirin

hemolytic anemia


Input: Increased expression and apical targeting of renal ENaC subunits in puromycin aminonucleoside - induced nephrotic syndrome in rats. Nephrotic syndrome is often accompanied by sodium retention and generalized edema. However, the molecular basis for the decreased renal sodium excretion remains undefined. We hypothesized that epithelial Na channel (ENaC) subunit dysregulation may be responsible for the increased sodium retention. An experimental group of rats was treated with puromycin aminonucleoside (PAN; 180 mg / kg iv), whereas the control group received only vehicle. After 7 days, PAN treatment induced significant proteinuria, hypoalbuminemia, decreased urinary sodium excretion, and extensive ascites. The protein abundance of alpha - ENaC and beta - ENaC was increased in the inner stripe of the outer medulla (ISOM) and in the inner medulla (IM) but was not altered in the cortex. gamma - ENaC abundance was increased in the cortex, ISOM, and IM. Immunoperoxidase brightfield - and laser - scanning confocal fluorescence microscopy demonstrated increased targeting of alpha - ENaC, beta - ENaC, and gamma - ENaC subunits to the apical plasma membrane in the distal convoluted tubule (DCT2), connecting tubule, and cortical and medullary collecting duct segments. Immunoelectron microscopy further revealed an increased labeling of alpha - ENaC in the apical plasma membrane of cortical collecting duct principal cells of PAN - treated rats, indicating enhanced apical targeting of alpha - ENaC subunits. In contrast, the protein abundances of Na (+) / H (+) exchanger type 3 (NHE3), Na (+) - K (+) - 2Cl (-) cotransporter (BSC - 1), and thiazide - sensitive Na (+) - Cl (-) cotransporter (TSC) were decreased. Moreover, the abundance of the alpha (1) - subunit of the Na - K - ATPase was decreased in the cortex and ISOM, but it remained unchanged in the IM. In conclusion, the increased or sustained expression of ENaC subunits combined with increased apical targeting in the DCT2, connecting tubule, and collecting duct are likely to play a role in the sodium retention associated with PAN - induced nephrotic syndrome. The decreased abundance of NHE3, BSC - 1, TSC, and Na - K - ATPase may play a compensatory role to promote sodium excretion.

puromycin aminonucleoside

sodium

sodium

sodium

puromycin aminonucleoside

PAN

PAN

sodium

PAN

H

K

thiazide

Cl

K

sodium

PAN

K

sodium

nephrotic syndrome

Nephrotic syndrome

edema

proteinuria

hypoalbuminemia

ascites

nephrotic syndrome

puromycin aminonucleoside

ascites

puromycin aminonucleoside

ascites

PAN

ascites

PAN

ascites

PAN

ascites

PAN

ascites

puromycin aminonucleoside

nephrotic syndrome

puromycin aminonucleoside

Nephrotic syndrome

puromycin aminonucleoside

nephrotic syndrome

puromycin aminonucleoside

nephrotic syndrome

puromycin aminonucleoside

Nephrotic syndrome

puromycin aminonucleoside

nephrotic syndrome

PAN

nephrotic syndrome

PAN

Nephrotic syndrome

PAN

nephrotic syndrome

PAN

nephrotic syndrome

PAN

Nephrotic syndrome

PAN

nephrotic syndrome

PAN

nephrotic syndrome

PAN

Nephrotic syndrome

PAN

nephrotic syndrome

PAN

nephrotic syndrome

PAN

Nephrotic syndrome

PAN

nephrotic syndrome

puromycin aminonucleoside

proteinuria

puromycin aminonucleoside

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

puromycin aminonucleoside

hypoalbuminemia

puromycin aminonucleoside

hypoalbuminemia

PAN

hypoalbuminemia

PAN

hypoalbuminemia

PAN

hypoalbuminemia

PAN

hypoalbuminemia


Input: Does hormone therapy for the treatment of breast cancer have a detrimental effect on memory and cognition? A pilot study. This pilot study examines whether hormone therapy for breast cancer affects cognition. Patients participating in a randomised trial of anastrozole, tamoxifen alone or combined (ATAC) (n = 94) and a group of women without breast cancer (n = 35) completed a battery of neuropsychological measures. Compared with the control group, the patients were impaired on a processing speed task (p = 0. 032) and on a measure of immediate verbal memory (p = 0. 026) after controlling for the use of hormone replacement therapy in both groups. Patient group performance was not significantly related to length of treatment or measures of psychological morbidity. The results showed specific impairments in processing speed and verbal memory in women receiving hormonal therapy for the treatment of breast cancer. Verbal memory may be especially sensitive to changes in oestrogen levels, a finding commonly reported in studies of hormone replacement therapy in healthy women. In view of the increased use of hormone therapies in an adjuvant and preventative setting their impact on cognitive functioning should be investigated more thoroughly.

breast cancer

detrimental effect on memory and cognition

detrimental effect on memory

detrimental effect on memory and cognition

breast cancer

breast cancer

breast cancer

anastrozole

tamoxifen

oestrogen

tamoxifen

detrimental effect on memory and cognition

tamoxifen

detrimental effect on memory

anastrozole

detrimental effect on memory and cognition

anastrozole

detrimental effect on memory

anastrozole

detrimental effect on memory and cognition

tamoxifen

detrimental effect on memory and cognition


Input: Association of nitric oxide production and apoptosis in a model of experimental nephropathy. BACKGROUND: In recent studies increased amounts of nitric oxide (NO) and apoptosis have been implicated in various pathological conditions in the kidney. We have studied the role of NO and its association with apoptosis in an experimental model of nephrotic syndrome induced by a single injection of adriamycin (ADR). METHODS: The alteration in the NO pathway was assessed by measuring nitrite levels in serum / urine and by evaluating the changes in vascular reactivity of the isolated perfused rat kidney (IPRK) system. Rats were stratified into control groups and ADR - induced nephropathy groups. These two groups were then divided into: group 1, animals receiving saline; and group 2, animals receiving aminoguanidine (AG) which is a specific inhibitor of inducible - NO synthase. On day 21, rats were sacrificed after obtaining material for biochemical analysis. RESULTS: Histopathological examination of the kidneys of rats treated with ADR revealed focal areas of mesangial proliferation and mild tubulointerstitial inflammation. They also had significantly higher levels of proteinuria compared with control and treatment groups (P < 0. 05). Urine nitrite levels were significantly increased in the ADR - nephropathy group (P < 0. 05). In the IPRK phenylephrine and acetylcholine related responses were significantly impaired in the ADR - nephropathy group. Apoptosis was not detected in controls. However, in the ADR - nephropathy group, numerous apoptotic cells were identified in the tubulointerstitial areas. Double staining revealed numerous interstitial apoptotic cells to stain for ED1, a marker for monocytes / macrophages. Treatment with AG prevented the impairment of renal vascular bed responses and reduced both urine nitrite levels and apoptosis to control levels. CONCLUSION: We suggest that interactions between NO and apoptosis are important in the pathogenesis of the ADR - induced nephrosis.

nitric oxide

nitric oxide

NO

NO

adriamycin

ADR

NO

nitrite

ADR

aminoguanidine

AG

NO

ADR

nitrite

ADR

phenylephrine

acetylcholine

ADR

ADR

AG

nitrite

NO

ADR

nephropathy

nephrotic syndrome

nephropathy

mesangial proliferation

tubulointerstitial inflammation

proteinuria

nephropathy

nephropathy

nephropathy

nephrosis

adriamycin

proteinuria

ADR

proteinuria

ADR

proteinuria

ADR

proteinuria

ADR

proteinuria

ADR

proteinuria

ADR

proteinuria

ADR

proteinuria

adriamycin

nephrotic syndrome

ADR

nephrotic syndrome

ADR

nephrotic syndrome

ADR

nephrotic syndrome

ADR

nephrotic syndrome

ADR

nephrotic syndrome

ADR

nephrotic syndrome

ADR

nephrotic syndrome


Input: The attenuating effect of carteolol hydrochloride, a beta - adrenoceptor antagonist, on neuroleptic - induced catalepsy in rats. It is known that beta - adrenoceptor antagonists are effective in the treatment of akathisia, one of the extrapyramidal side effects that occur during neuroleptic treatment. Neuroleptic - induced catalepsy, a model of neuroleptic - induced extrapyramidal side effects, was considered suitable as a model for predicting neuroleptic - induced akathisia in humans, although neuroleptic - induced catalepsy was not considered a specific test for neuroleptic - induced akathisia. Therefore, the effects of carteolol, a beta - adrenoceptor antagonist, on haloperidol - induced catalepsy in rats were behaviorally studied and compared with those of propranolol and biperiden, a muscarinic receptor antagonist. Carteolol, as well as propranolol and biperiden, inhibited the haloperidol - induced catalepsy. The inhibitory effect of carteolol was almost comparable to that of propranolol, but was weaker than that of biperiden. Carteolol did not evoke postsynaptic dopamine receptor - stimulating behavioral signs such as stereotypy and hyperlocomotion in rats. Carteolol did not antagonize the inhibitory effects of haloperidol on apomorphine - induced stereotypy and locomotor activity in rats. In addition, carteolol did not evoke 5 - HT1A receptor - stimulating behavioral signs such as flat body posture and forepaw treading and did not inhibit 5 - hydroxytryptophan - induced head twitch in rats. Finally, carteolol did not inhibit physostigmine - induced lethality in rats. These results strongly suggest that carteolol improves haloperidol - induced catalepsy via its beta - adrenoceptor antagonistic activity and is expected to be effective in the treatment of akathisia without attenuating neuroleptic - induced antipsychotic effects due to its postsynaptic dopamine receptor antagonistic activity.

carteolol hydrochloride

carteolol

haloperidol

propranolol

biperiden

Carteolol

propranolol

biperiden

haloperidol

carteolol

propranolol

biperiden

Carteolol

dopamine

Carteolol

haloperidol

apomorphine

carteolol

5 - hydroxytryptophan

carteolol

physostigmine

carteolol

haloperidol

dopamine

catalepsy

akathisia

catalepsy

akathisia

catalepsy

akathisia

catalepsy

catalepsy

hyperlocomotion

catalepsy

akathisia

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy


Input: Penicillamine - induced rapidly progressive glomerulonephritis in a patient with rheumatoid arthritis. A 67 - year - old woman with rheumatoid arthritis presented rapidly progressive glomerulonephritis (RPGN) after 5 months of D - penicillamine (250 mg / day) treatment. Light microscopy study showed severe glomerulonephritis with crescent formation in 60% of the glomeruli and infiltration of inflammatory cells in the wall of an arteriole. Immunofluorescence revealed scanty granular IgG, IgA and C3 deposits along the capillary walls and mesangium. The patient was treated with steroid pulse, plasmapheresis, cyclophosphamide and antiplatelet agents. A complete recovery of renal function was achieved in a few weeks. This new case of RPGN in the course of D - penicillamine treatment emphasizes the need for frequent monitoring of renal function and evaluation of urinary sediment and proteinuria in these patients. The prompt discontinuation of D - penicillamine and vigorous treatment measures could allow for a good prognosis as in this case.

Penicillamine

D - penicillamine

steroid

cyclophosphamide

antiplatelet agents

D - penicillamine

D - penicillamine

glomerulonephritis

rheumatoid arthritis

rheumatoid arthritis

glomerulonephritis

RPGN

glomerulonephritis

RPGN

proteinuria

Penicillamine

glomerulonephritis

Penicillamine

glomerulonephritis

Penicillamine

RPGN

Penicillamine

glomerulonephritis

Penicillamine

RPGN

D - penicillamine

glomerulonephritis

D - penicillamine

glomerulonephritis

D - penicillamine

RPGN

D - penicillamine

glomerulonephritis

D - penicillamine

RPGN

D - penicillamine

glomerulonephritis

D - penicillamine

glomerulonephritis

D - penicillamine

RPGN

D - penicillamine

glomerulonephritis

D - penicillamine

RPGN

D - penicillamine

glomerulonephritis

D - penicillamine

glomerulonephritis

D - penicillamine

RPGN

D - penicillamine

glomerulonephritis

D - penicillamine

RPGN


Input: Nature, time course and dose dependence of zidovudine - related side effects: results from the Multicenter Canadian Azidothymidine Trial. To characterize the nature, time course and dose dependency of zidovudine - related side effects, we undertook a multicenter, prospective, dose - range finding study. Our study group consisted of 74 HIV - positive homosexual men belonging to groups II B, III and IV C2 from the Centers for Disease Control (CDC) classification of HIV disease. Following a 3 - week observation period, volunteers were treated with zidovudine 600 mg / day for 18 weeks, 900 mg / day for 9 weeks and 1200 mg / day for 9 weeks, followed by a washout period of 6 weeks after which they were re - started on 1200 mg / day or the highest tolerated dose at 8 - hourly intervals. Subjects were randomly assigned to 4 - hourly or 8 - hourly regimens within CDC groups while taking 600 and 1200 mg / day. Clinical and laboratory evaluations were performed at 3 - week intervals. Symptomatic adverse effects were present in 96% of subjects, most commonly nausea (64%), fatigue (55%) and headache (49%). These were generally self - limited, reappearing briefly at each dose increment. A decrease in hemoglobin occurred shortly after initiation of therapy. This was not dose dependent and reversed rapidly upon discontinuation of treatment. A red blood cell count decrease, a mean cell volume increase and a granulocyte count decrease developed early in a dose - independent fashion, reverting at least partially during the washout phase. The decrease in reticulocyte count was dose related between 600 and 900 mg / day with no further change when the dose was escalated to 1200 mg / day. Bone marrow changes occurred rapidly as demonstrated by megaloblastosis in 95% of 65 specimens at week 18. (ABSTRACT TRUNCATED AT 250 WORDS)

zidovudine

Azidothymidine

zidovudine

zidovudine

HIV disease

nausea

fatigue

headache

megaloblastosis

zidovudine

nausea

Azidothymidine

nausea

zidovudine

nausea

zidovudine

nausea

zidovudine

fatigue

Azidothymidine

fatigue

zidovudine

fatigue

zidovudine

fatigue

zidovudine

headache

Azidothymidine

headache

zidovudine

headache

zidovudine

headache


Input: Bilateral optic neuropathy due to combined ethambutol and isoniazid treatment. The case of a 40 - year - old patient who underwent an unsuccessful cadaver kidney transplantation and was treated with ethambutol and isoniazid is reported. A bilateral retrobulbar neuropathy with an unusual central bitemporal hemianopic scotoma was found. Ethambutol was stopped and only small improvement of the visual acuity followed. Isoniazid was discontinued later, followed by a dramatic improvement in the visual acuity. The hazards of optic nerve toxicity due to ethambutol are known. We emphasize the potential danger in the use of ethambutol and isoniazid.

Bilateral optic neuropathy

bilateral retrobulbar neuropathy

scotoma

toxicity

ethambutol

isoniazid

ethambutol

isoniazid

Ethambutol

Isoniazid

ethambutol

ethambutol

isoniazid

isoniazid

scotoma

isoniazid

scotoma

Isoniazid

scotoma

isoniazid

scotoma

ethambutol

Bilateral optic neuropathy

ethambutol

bilateral retrobulbar neuropathy

ethambutol

Bilateral optic neuropathy

ethambutol

bilateral retrobulbar neuropathy

Ethambutol

Bilateral optic neuropathy

Ethambutol

bilateral retrobulbar neuropathy

ethambutol

Bilateral optic neuropathy

ethambutol

bilateral retrobulbar neuropathy

ethambutol

Bilateral optic neuropathy

ethambutol

bilateral retrobulbar neuropathy

isoniazid

Bilateral optic neuropathy

isoniazid

bilateral retrobulbar neuropathy

isoniazid

Bilateral optic neuropathy

isoniazid

bilateral retrobulbar neuropathy

Isoniazid

Bilateral optic neuropathy

Isoniazid

bilateral retrobulbar neuropathy

isoniazid

Bilateral optic neuropathy

isoniazid

bilateral retrobulbar neuropathy

ethambutol

scotoma

ethambutol

scotoma

Ethambutol

scotoma

ethambutol

scotoma

ethambutol

scotoma


Input: Progestational agents and blood coagulation. VII. Thromboembolic and other complications of oral contraceptive therapy in relationship to pretreatment levels of blood coagulation factors: summary report of a ten - year study. During a ten - year period, 348 women were studied for a total of 5, 877 patient months in four separate studies relating oral contraceptives to changes in hematologic parameters. Significant increases in certain factors of the blood coagulation and fibrinolysin systems (factors I, II, VII, VIII, IX, and X and plasminogen) were observed in the treated groups. Severe complications developed in four patients. All four had an abnormal blood coagulation profile, suggesting " hypercoagulability " before initiation of therapy. Some of these findings represented the most extreme abnormalities seen in the entire group of patients; some increased further during therapy. One of these patients developed a myocardial infarction before receiving any medication, shortly after the base - line values were obtained. One patient developed retinopathy 19 months after she began therapy, and another developed thrombophlebitis after 27 months of therapy. The fourth patient developed thrombophlebitis 14 days after initiation of contraceptive therapy. All four patients were of the A or AB blood group. Previous studies suggested the possiblility of increased propensity for thromboembolic episodes in patients possessing the A antigen. It appears from these data that hematologic work - ups may be useful in women who are about to start long - term oral contraceptive therapy.

blood coagulation

Thromboembolic

blood coagulation

blood coagulation

blood coagulation

hypercoagulability

myocardial infarction

retinopathy

thrombophlebitis

thrombophlebitis

thromboembolic episodes

oral contraceptive

oral contraceptives

oral contraceptive

oral contraceptive

blood coagulation

oral contraceptive

blood coagulation

oral contraceptive

blood coagulation

oral contraceptive

blood coagulation

oral contraceptives

blood coagulation

oral contraceptives

blood coagulation

oral contraceptives

blood coagulation

oral contraceptives

blood coagulation

oral contraceptive

blood coagulation

oral contraceptive

blood coagulation

oral contraceptive

blood coagulation

oral contraceptive

blood coagulation

oral contraceptive

retinopathy

oral contraceptives

retinopathy

oral contraceptive

retinopathy

oral contraceptive

thrombophlebitis

oral contraceptive

thrombophlebitis

oral contraceptives

thrombophlebitis

oral contraceptives

thrombophlebitis

oral contraceptive

thrombophlebitis

oral contraceptive

thrombophlebitis

oral contraceptive

myocardial infarction

oral contraceptives

myocardial infarction

oral contraceptive

myocardial infarction


Input: Cardiac arrest in a child with cerebral palsy undergoing sevoflurane induction of anesthesia after preoperative clonidine. Clonidine is a frequently administered alpha2 - adrenergic agonist which can decrease heart rate and blood pressure. We present a case of a 5 - year - old child with cerebral palsy and seizure disorder, receiving clonidine for restlessness, who presented for placement of a baclofen pump. Without the knowledge of the medical personnel, the patient' s mother administered three doses of clonidine during the evening before and morning of surgery to reduce anxiety. During induction of anesthesia, the patient developed bradycardia and hypotension requiring cardiac resuscitation. There are no previous reports of clonidine - associated cardiac arrest in a child undergoing induction of anesthesia.

Cardiac arrest

cerebral palsy

cerebral palsy

seizure disorder

restlessness

anxiety

bradycardia

hypotension

cardiac arrest

sevoflurane

clonidine

Clonidine

clonidine

baclofen

clonidine

clonidine

clonidine

hypotension

Clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

bradycardia

Clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

Cardiac arrest

clonidine

cardiac arrest

Clonidine

Cardiac arrest

Clonidine

cardiac arrest

clonidine

Cardiac arrest

clonidine

cardiac arrest

clonidine

Cardiac arrest

clonidine

cardiac arrest

clonidine

Cardiac arrest

clonidine

cardiac arrest


Input: Effects of UMB24 and (+ / -) - SM 21, putative sigma2 - preferring antagonists, on behavioral toxic and stimulant effects of cocaine in mice. Earlier studies have demonstrated that antagonism of sigma1 receptors attenuates the convulsive, lethal, locomotor stimulatory and rewarding actions of cocaine in mice. In contrast, the contribution of sigma2 receptors is unclear because experimental tools to selectively target this subtype are unavailable. To begin addressing this need, we characterized UMB24 (1 - (2 - phenethyl) - 4 - (2 - pyridyl) - piperazine) and (+ / -) - SM 21 (3alpha - tropanyl - 2 - (4 - chorophenoxy) butyrate) in receptor binding and behavioral studies. Receptor binding studies confirmed that UMB24 and (+ / -) - SM 21 display preferential affinity for sigma2 over sigma1 receptors. In behavioral studies, pretreatment of Swiss Webster mice with UMB24 or (+ / -) - SM 21 significantly attenuated cocaine - induced convulsions and locomotor activity, but not lethality. When administered alone, (+ / -) - SM 21 produced no significant effects compared to control injections of saline, but UMB24 had locomotor depressant actions. Together, the data suggest that sigma2 receptor antagonists have the potential to attenuate some of the behavioral effects of cocaine, and further development of more selective, high affinity ligands are warranted.

SM 21

cocaine

cocaine

1 - (2 - phenethyl) - 4 - (2 - pyridyl) - piperazine

SM 21

3alpha - tropanyl - 2 - (4 - chorophenoxy) butyrate

SM 21

SM 21

cocaine

SM 21

cocaine

convulsive

convulsions

cocaine

convulsive

cocaine

convulsions

cocaine

convulsive

cocaine

convulsions

cocaine

convulsive

cocaine

convulsions

cocaine

convulsive

cocaine

convulsions


Input: Methimazole - induced cholestatic jaundice. Methimazole is a widely used and generally well - tolerated antithyroid agent. A 43 - year - old woman had severe jaundice and itching 1 month after receiving methimazole (10 mg tid) and propranolol (20 mg tid) for treatment of hyperthyroidism. The patient continued treatment for another 4 days after the appearance of jaundice until she finished both medications. When seen at the emergency department 2 weeks later, she still had severe icterus, pruritus, and hyperbilirubinemia, formed mainly of the conjugated fraction. Methimazole - induced cholestasis was diagnosed, and propranolol therapy was resumed. Over the following 9 days, the symptoms improved and plasma bilirubin levels were normal after 12 weeks without methimazole. In rare cases within the first few weeks of therapy, this drug can cause severe and reversible cholestatic jaundice. Physicians and patients should be aware of this adverse effect so that, upon occurrence, they can discontinue methimazole therapy and avoid unnecessary invasive procedures.

Methimazole

Methimazole

methimazole

propranolol

Methimazole

propranolol

bilirubin

methimazole

methimazole

cholestatic jaundice

jaundice

itching

hyperthyroidism

jaundice

icterus

pruritus

hyperbilirubinemia

cholestasis

cholestatic jaundice

Methimazole

hyperbilirubinemia

Methimazole

hyperbilirubinemia

methimazole

hyperbilirubinemia

Methimazole

hyperbilirubinemia

methimazole

hyperbilirubinemia

methimazole

hyperbilirubinemia

Methimazole

cholestatic jaundice

Methimazole

cholestatic jaundice

Methimazole

cholestatic jaundice

Methimazole

cholestatic jaundice

methimazole

cholestatic jaundice

methimazole

cholestatic jaundice

Methimazole

cholestatic jaundice

Methimazole

cholestatic jaundice

methimazole

cholestatic jaundice

methimazole

cholestatic jaundice

methimazole

cholestatic jaundice

methimazole

cholestatic jaundice

Methimazole

itching

Methimazole

pruritus

Methimazole

itching

Methimazole

pruritus

methimazole

itching

methimazole

pruritus

Methimazole

itching

Methimazole

pruritus

methimazole

itching

methimazole

pruritus

methimazole

itching

methimazole

pruritus


Input: Ciprofloxacin - induced acute interstitial nephritis and autoimmune hemolytic anemia. Ciprofloxacin has been associated with several side effects including interstitial nephritis and hemolytic anemia. The combination of both side effects is extremely rare. In this report, we describe a case of ciprofloxacin - induced interstitial nephritis and autoimmune hemolytic anemia. Hemolytic anemia improved after stopping the drug and initiation of steroid therapy. Unfortunately, acute interstitial nephritis was irreversible and the patient developed end - stage renal disease.

Ciprofloxacin

Ciprofloxacin

ciprofloxacin

steroid

interstitial nephritis

autoimmune hemolytic anemia

interstitial nephritis

hemolytic anemia

interstitial nephritis

autoimmune hemolytic anemia

Hemolytic anemia

interstitial nephritis

end - stage renal disease

Ciprofloxacin

hemolytic anemia

Ciprofloxacin

Hemolytic anemia

Ciprofloxacin

hemolytic anemia

Ciprofloxacin

Hemolytic anemia

ciprofloxacin

hemolytic anemia

ciprofloxacin

Hemolytic anemia

Ciprofloxacin

end - stage renal disease

Ciprofloxacin

end - stage renal disease

ciprofloxacin

end - stage renal disease

Ciprofloxacin

interstitial nephritis

Ciprofloxacin

interstitial nephritis

Ciprofloxacin

interstitial nephritis

Ciprofloxacin

interstitial nephritis

Ciprofloxacin

interstitial nephritis

Ciprofloxacin

interstitial nephritis

Ciprofloxacin

interstitial nephritis

Ciprofloxacin

interstitial nephritis

ciprofloxacin

interstitial nephritis

ciprofloxacin

interstitial nephritis

ciprofloxacin

interstitial nephritis

ciprofloxacin

interstitial nephritis


Input: Contribution of sodium valproate to the syndrome of inappropriate secretion of antidiuretic hormone. We report the case of a 62 - year - old man who was administered sodium valproate (VPA) and who subsequently developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). He had been taking VPA for treatment of idiopathic generalized tonic - clonic convulsions since he was 56 years old. After substituting VPA with zonisamide, the serum sodium level returned to normal. We consider this episode of SIADH to be the result of a combination of factors including a weakness of the central nervous system and the long - term administration of VPA.

sodium valproate

sodium valproate

VPA

VPA

VPA

zonisamide

sodium

VPA

syndrome of inappropriate secretion of antidiuretic hormone

syndrome of inappropriate secretion of antidiuretic hormone

SIADH

tonic - clonic convulsions

SIADH

weakness of the central nervous system

sodium valproate

syndrome of inappropriate secretion of antidiuretic hormone

sodium valproate

syndrome of inappropriate secretion of antidiuretic hormone

sodium valproate

SIADH

sodium valproate

SIADH

sodium valproate

syndrome of inappropriate secretion of antidiuretic hormone

sodium valproate

syndrome of inappropriate secretion of antidiuretic hormone

sodium valproate

SIADH

sodium valproate

SIADH

VPA

syndrome of inappropriate secretion of antidiuretic hormone

VPA

syndrome of inappropriate secretion of antidiuretic hormone

VPA

SIADH

VPA

SIADH

VPA

syndrome of inappropriate secretion of antidiuretic hormone

VPA

syndrome of inappropriate secretion of antidiuretic hormone

VPA

SIADH

VPA

SIADH

VPA

syndrome of inappropriate secretion of antidiuretic hormone

VPA

syndrome of inappropriate secretion of antidiuretic hormone

VPA

SIADH

VPA

SIADH

VPA

syndrome of inappropriate secretion of antidiuretic hormone

VPA

syndrome of inappropriate secretion of antidiuretic hormone

VPA

SIADH

VPA

SIADH


Input: Vasopressin in the treatment of milrinone - induced hypotension in severe heart failure. The use of phosphodiesterase inhibitors such as milrinone in the treatment of severe heart failure is frequently restricted because they cause vasodilation and hypotension. In patients with decompensated heart failure with hypotension after treatment with milrinone, low doses of vasopressin restored blood pressure without inhibiting the inotropic effect of milrinone.

Vasopressin

milrinone

milrinone

milrinone

vasopressin

milrinone

hypotension

heart failure

heart failure

hypotension

heart failure

hypotension

Vasopressin

hypotension

Vasopressin

hypotension

Vasopressin

hypotension

vasopressin

hypotension

vasopressin

hypotension

vasopressin

hypotension

milrinone

hypotension

milrinone

hypotension

milrinone

hypotension

milrinone

hypotension

milrinone

hypotension

milrinone

hypotension

milrinone

hypotension

milrinone

hypotension

milrinone

hypotension

milrinone

hypotension

milrinone

hypotension

milrinone

hypotension


Input: Halogenated anesthetics form liver adducts and antigens that cross - react with halothane - induced antibodies. Two halogenated anesthetics, enflurane and isoflurane, have been associated with an allergic - type hepatic injury both alone and following previous exposure to halothane. Halothane hepatitis appears to involve an aberrant immune response. An antibody response to a protein - bound biotransformation product (trifluoroacetyl adduct) has been detected on halothane hepatitis patients. This study was performed to determine cross - reactivity between enflurane and isoflurane with the hypersensitivity induced by halothane. The subcellular and lobular production of hepatic neoantigens recognized by halothane - induced antibodies following enflurane and isoflurane, and the biochemical nature of these neoantigens was investigated in two animal models. Enflurane administration resulted in neoantigens detected in both the microsomal and cytosolic fraction of liver homogenates and in the centrilobular region of the liver. In the same liver, biochemical analysis detected fluorinated liver adducts that were up to 20 - fold greater in guinea pigs than in rats. This supports and extends previous evidence for a mechanism by which enflurane and / or isoflurane could produce a hypersensitivity condition similar to that of halothane hepatitis either alone or subsequent to halothane administration. The guinea pig would appear to be a useful model for further investigations of the immunological response to these antigens.

halothane

enflurane

isoflurane

halothane

Halothane

trifluoroacetyl

halothane

enflurane

isoflurane

halothane

halothane

enflurane

isoflurane

Enflurane

enflurane

isoflurane

halothane

halothane

hepatic injury

hepatitis

hepatitis

hypersensitivity

hypersensitivity

hepatitis

isoflurane

hepatic injury

isoflurane

hepatitis

isoflurane

hepatitis

isoflurane

hepatitis

isoflurane

hepatic injury

isoflurane

hepatitis

isoflurane

hepatitis

isoflurane

hepatitis

isoflurane

hepatic injury

isoflurane

hepatitis

isoflurane

hepatitis

isoflurane

hepatitis

isoflurane

hepatic injury

isoflurane

hepatitis

isoflurane

hepatitis

isoflurane

hepatitis

enflurane

hepatic injury

enflurane

hepatitis

enflurane

hepatitis

enflurane

hepatitis

enflurane

hepatic injury

enflurane

hepatitis

enflurane

hepatitis

enflurane

hepatitis

enflurane

hepatic injury

enflurane

hepatitis

enflurane

hepatitis

enflurane

hepatitis

Enflurane

hepatic injury

Enflurane

hepatitis

Enflurane

hepatitis

Enflurane

hepatitis

enflurane

hepatic injury

enflurane

hepatitis

enflurane

hepatitis

enflurane

hepatitis

halothane

hepatic injury

halothane

hepatitis

halothane

hepatitis

halothane

hepatitis

halothane

hepatic injury

halothane

hepatitis

halothane

hepatitis

halothane

hepatitis

Halothane

hepatic injury

Halothane

hepatitis

Halothane

hepatitis

Halothane

hepatitis

halothane

hepatic injury

halothane

hepatitis

halothane

hepatitis

halothane

hepatitis

halothane

hepatic injury

halothane

hepatitis

halothane

hepatitis

halothane

hepatitis

halothane

hepatic injury

halothane

hepatitis

halothane

hepatitis

halothane

hepatitis

halothane

hepatic injury

halothane

hepatitis

halothane

hepatitis

halothane

hepatitis

halothane

hepatic injury

halothane

hepatitis

halothane

hepatitis

halothane

hepatitis


Input: Induction by paracetamol of bladder and liver tumours in the rat. Effects on hepatocyte fine structure. Groups of male and female inbred Leeds strain rats were fed diets containing either 0. 5% or 1. 0% paracetamol by weight for up to 18 months. At the 1. 0% dosage level, 20% of rats of both sexes developed neoplastic nodules of the liver, a statistically significant incidence. These rats also showed gross enlargement of their livers and an increase in foci of cellular alteration, the latter also being observed in the low dosage male rats. Papillomas of the transitional epithelium of the bladder developed in all paracetamol - treated groups, and three rats bore bladder carcinomas. However, significant yields of bladder tumours were only obtained from low dosage females and high dosage males. Additionally, 20 to 25% of paracetamol - treated rats developed hyperplasia of the bladder epithelium, which was not coincident with the presence of bladder calculi. A low yield of tumours at various other sites also arose following paracetamol feeding. An electron microscope study of the livers of paracetamol - treated rats revealed ultrastructural changes in the hepatocytes that resemble those that result from exposure to a variety of known hepatocarcinogens.

paracetamol

paracetamol

paracetamol

paracetamol

paracetamol

paracetamol

bladder and liver tumours

bladder and liver tumours

liver tumours

Papillomas

bladder carcinomas

bladder tumours

hyperplasia

bladder calculi

tumours

hepatocarcinogens

paracetamol

hyperplasia

paracetamol

hyperplasia

paracetamol

hyperplasia

paracetamol

hyperplasia

paracetamol

hyperplasia

paracetamol

hyperplasia

paracetamol

bladder and liver tumours

paracetamol

bladder and liver tumours

paracetamol

bladder carcinomas

paracetamol

bladder tumours

paracetamol

bladder and liver tumours

paracetamol

bladder and liver tumours

paracetamol

bladder carcinomas

paracetamol

bladder tumours

paracetamol

bladder and liver tumours

paracetamol

bladder and liver tumours

paracetamol

bladder carcinomas

paracetamol

bladder tumours

paracetamol

bladder and liver tumours

paracetamol

bladder and liver tumours

paracetamol

bladder carcinomas

paracetamol

bladder tumours

paracetamol

bladder and liver tumours

paracetamol

bladder and liver tumours

paracetamol

bladder carcinomas

paracetamol

bladder tumours

paracetamol

bladder and liver tumours

paracetamol

bladder and liver tumours

paracetamol

bladder carcinomas

paracetamol

bladder tumours

paracetamol

liver tumours

paracetamol

hepatocarcinogens

paracetamol

liver tumours

paracetamol

hepatocarcinogens

paracetamol

liver tumours

paracetamol

hepatocarcinogens

paracetamol

liver tumours

paracetamol

hepatocarcinogens

paracetamol

liver tumours

paracetamol

hepatocarcinogens

paracetamol

liver tumours

paracetamol

hepatocarcinogens


Input: Rat extraocular muscle regeneration. Repair of local anesthetic - induced damage. Local anesthetics that are commonly used in ophthalmic surgery (0. 75% bupivacaine hydrochloride, 2. 0% mepivacaine hydrochloride, and 2. 0% lidocaine hydrochloride plus 1: 100, 000 epinephrine) were injected into the retrobulbar area of rat eyes. Controls were injected with physiological saline. All three anesthetics produced massive degeneration of the extraocular muscles. Muscle degeneration is followed by regeneration of the damaged muscle fibers. In addition to muscle damage, severe damage was also seen in harderian glands, especially after exposure to mepivacaine and lidocaine plus epinephrine. With these findings in rats, it is hypothesized that the temporary diplopia sometimes seen in patients after ophthalmic surgery might be due to anesthetic - induced damage to the extraocular muscles.

bupivacaine hydrochloride

mepivacaine hydrochloride

lidocaine hydrochloride

epinephrine

mepivacaine

lidocaine

epinephrine

Muscle degeneration

muscle damage

diplopia

lidocaine hydrochloride

Muscle degeneration

lidocaine hydrochloride

muscle damage

lidocaine

Muscle degeneration

lidocaine

muscle damage

mepivacaine hydrochloride

Muscle degeneration

mepivacaine hydrochloride

muscle damage

mepivacaine

Muscle degeneration

mepivacaine

muscle damage

bupivacaine hydrochloride

Muscle degeneration

bupivacaine hydrochloride

muscle damage


Input: Reversal of neuroleptic - induced catalepsy by novel aryl - piperazine anxiolytic drugs. The novel anxiolytic drug, buspirone, reverses catalepsy induced by haloperidol. A series of aryl - piperazine analogues of buspirone and other 5 - hydroxytryptaminergic agonists were tested for their ability to reverse haloperidol induced catalepsy. Those drugs with strong affinity for 5 - hydroxytryptamine1a receptors were able to reverse catalepsy. Drugs with affinity for other 5 - HT receptors or weak affinity were ineffective. However, inhibition of postsynaptic 5 - HT receptors neither inhibited nor potentiated reversal of catalepsy and leaves open the question as to the site or mechanism for this effect.

catalepsy

catalepsy

catalepsy

catalepsy

catalepsy

aryl - piperazine

buspirone

haloperidol

aryl - piperazine

buspirone

5 - hydroxytryptaminergic agonists

haloperidol

5 - hydroxytryptamine1a

5 - HT

5 - HT

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy


Input: Diazepam facilitates reflex bradycardia in conscious rats. The effects of diazepam on cardiovascular function were assessed in conscious rats. Intravenous administration of diazepam (1 - 30 mg kg - 1) produced a dose - dependent decrease in both the mean arterial pressure and the heart rate. Also, reflex bradycardia was produced in rats by intravenous infusion of adrenaline (1. 25 - 2. 5 micrograms kg - 1). Intravenous pretreatment of the rats with diazepam, although causing no change in the adrenaline - induced pressor effect, did enhance the adrenaline - induced reflex bradycardia. However, the diazepam enhancement of adrenaline - induced reflex bradycardia was antagonized by pretreatment of rats with an intravenous dose of picrotoxin (an agent blocks chloride channels by binding to sites associated with the benzodiazepine - GABA - chloride channel macromolecular complex). The data indicate that diazepam acts through the benzodiazepine - GABA - chloride channel macromolecular complex within the central nervous system to facilitate reflex bradycardia mediated through baroreceptor reflexes in response to an acute increase in arterial pressure.

Diazepam

diazepam

diazepam

adrenaline

diazepam

adrenaline

adrenaline

diazepam

adrenaline

picrotoxin

chloride

benzodiazepine

GABA

chloride

diazepam

benzodiazepine

GABA

chloride

bradycardia

bradycardia

bradycardia

bradycardia

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

adrenaline

bradycardia

Diazepam

bradycardia

Diazepam

bradycardia

Diazepam

bradycardia

Diazepam

bradycardia

Diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia

diazepam

bradycardia