Input: Pre - treatment of bupivacaine - induced cardiovascular depression using different lipid formulations of propofol. BACKGROUND: Pre - treatment with lipid emulsions has been shown to increase lethal doses of bupivacaine, and the lipid content of propofol may alleviate bupivacaine - induced cardiotoxicity. The aim of this study is to investigate the effects of propofol in intralipid or medialipid emulsions on bupivacaine - induced cardiotoxicity. METHODS: Rats were anaesthetised with ketamine and were given 0. 5 mg / kg / min propofol in intralipid (Group P), propofol in medialipid (Group L), or saline (Group C) over 20 min. Thereafter, 2 mg / kg / min bupivacaine 0. 5% was infused. We recorded time to first dysrhythmia occurrence, respective times to 25% and 50% reduction of the heart rate (HR) and mean arterial pressure, and time to asystole and total amount of bupivacaine consumption. Blood and tissue samples were collected following asystole. RESULTS: The time to first dysrhythmia occurrence, time to 25% and 50% reductions in HR, and time to asystole were longer in Group P than the other groups. The cumulative bupivacaine dose given at those time points was higher in Group P. Plasma bupivacaine levels were significantly lower in Group P than in Group C. Bupivacaine levels in the brain and heart were significantly lower in Group P and Group L than in Group C. CONCLUSION: We conclude that pre - treatment with propofol in intralipid, compared with propofol in medialipid or saline, delayed the onset of bupivacaine - induced cardiotoxic effects as well as reduced plasma bupivacaine levels. Further studies are needed to explore tissue bupivacaine levels of propofol in medialipid and adapt these results to clinical practice.

bupivacaine

propofol

bupivacaine

propofol

bupivacaine

propofol

bupivacaine

ketamine

propofol

propofol

bupivacaine

bupivacaine

bupivacaine

bupivacaine

Bupivacaine

propofol

propofol

bupivacaine

bupivacaine

bupivacaine

propofol

cardiovascular depression

cardiotoxicity

cardiotoxicity

dysrhythmia

asystole

asystole

dysrhythmia

asystole

cardiotoxic

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

Bupivacaine

asystole

Bupivacaine

asystole

Bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

asystole

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxic

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxic

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxic

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxic

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxic

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxic

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxic

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxic

Bupivacaine

cardiotoxicity

Bupivacaine

cardiotoxicity

Bupivacaine

cardiotoxic

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxic

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxic

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxicity

bupivacaine

cardiotoxic


Input: Drug - Induced Acute Liver Injury Within 12 Hours After Fluvastatin Therapy. Although statins are generally well - tolerated drugs, recent cases of drug - induced liver injury associated with their use have been reported. A 52 - year - old Chinese man reported with liver damage, which appeared 12 hours after beginning treatment with fluvastatin. Patient presented with complaints of increasing nausea, anorexia, and upper abdominal pain. His laboratory values showed elevated creatine kinase and transaminases. Testing for autoantibodies was also negative. The liver biochemistries eventually normalized within 3 weeks of stopping the fluvastatin. Therefore, when prescribing statins, the possibility of hepatic damage should be taken into account.

Drug - Induced Acute Liver Injury

drug - induced liver injury

liver damage

nausea

anorexia

abdominal pain

hepatic damage

Fluvastatin

statins

fluvastatin

creatine

fluvastatin

Fluvastatin

abdominal pain

fluvastatin

abdominal pain

fluvastatin

abdominal pain

Fluvastatin

Drug - Induced Acute Liver Injury

Fluvastatin

drug - induced liver injury

Fluvastatin

liver damage

Fluvastatin

hepatic damage

fluvastatin

Drug - Induced Acute Liver Injury

fluvastatin

drug - induced liver injury

fluvastatin

liver damage

fluvastatin

hepatic damage

fluvastatin

Drug - Induced Acute Liver Injury

fluvastatin

drug - induced liver injury

fluvastatin

liver damage

fluvastatin

hepatic damage

Fluvastatin

anorexia

fluvastatin

anorexia

fluvastatin

anorexia

Fluvastatin

nausea

fluvastatin

nausea

fluvastatin

nausea


Input: Fluconazole associated agranulocytosis and thrombocytopenia. CASE: We describe a second case of fluconazole associated agranulocytosis with thrombocytopenia and recovery upon discontinuation of therapy. The patient began to have changes in white blood cells and platelets within 48 h of administration of fluconazole and began to recover with 48 h of discontinuation. This case highlights that drug - induced blood dyscrasias can occur unexpectedly as a result of treatment with a commonly used drug thought to be " safe ". CONCLUSION: According to Naranjo' s algorithm the likelihood that our patient' s agranulocytosis and thrombocytopenia occurred as a result of therapy with fluconazole is probable, with a total of six points. We feel that the weight of the overall evidence of this evidence is strong. In particular the temporal relationship of bone marrow suppression to the initiation of fluconazole and the abatement of symptoms that rapidly reversed immediately following discontinuation.

Fluconazole

fluconazole

fluconazole

fluconazole

fluconazole

agranulocytosis

thrombocytopenia

agranulocytosis

thrombocytopenia

blood dyscrasias

agranulocytosis

thrombocytopenia

bone marrow suppression

Fluconazole

agranulocytosis

Fluconazole

agranulocytosis

Fluconazole

agranulocytosis

fluconazole

agranulocytosis

fluconazole

agranulocytosis

fluconazole

agranulocytosis

fluconazole

agranulocytosis

fluconazole

agranulocytosis

fluconazole

agranulocytosis

fluconazole

agranulocytosis

fluconazole

agranulocytosis

fluconazole

agranulocytosis

fluconazole

agranulocytosis

fluconazole

agranulocytosis

fluconazole

agranulocytosis

Fluconazole

thrombocytopenia

Fluconazole

thrombocytopenia

Fluconazole

thrombocytopenia

fluconazole

thrombocytopenia

fluconazole

thrombocytopenia

fluconazole

thrombocytopenia

fluconazole

thrombocytopenia

fluconazole

thrombocytopenia

fluconazole

thrombocytopenia

fluconazole

thrombocytopenia

fluconazole

thrombocytopenia

fluconazole

thrombocytopenia

fluconazole

thrombocytopenia

fluconazole

thrombocytopenia

fluconazole

thrombocytopenia


Input: Two - dimensional speckle tracking echocardiography combined with high - sensitive cardiac troponin T in early detection and prediction of cardiotoxicity during epirubicine - based chemotherapy. AIMS: To investigate whether alterations of myocardial strain and high - sensitive cardiac troponin T (cTnT) could predict future cardiac dysfunction in patients after epirubicin exposure. METHODS: Seventy - five patients with non - Hodgkin lymphoma treated with epirubicin were studied. Blood collection and echocardiography were performed at baseline, 1 day after the third cycle, and 1 day after completion of chemotherapy. Patients were studied using echocardiography during follow - up. Global longitudinal (GLS), circumferential (GCS), and radial strain (GRS) were calculated using speckle tracking echocardiography. Left ventricular ejection fraction was analysed by real - time 3D echocardiography. Cardiotoxicity was defined as a reduction of the LVEF of > 5% to < 55% with symptoms of heart failure or an asymptomatic reduction of the LVEF of > 10% to < 55%. RESULTS: Fourteen patients (18. 67%) developed cardiotoxicity after treatment. GLS (- 18. 48 + 1. 72% vs. - 15. 96 + 1. 6%), GCS (- 20. 93 + 2. 86% vs. - 19. 20 + 3. 21%), and GRS (39. 23 + 6. 44% vs. 34. 98 + 6. 2%) were markedly reduced and cTnT was elevated from 0. 0010 + 0. 0020 to 0. 0073 + 0. 0038 ng / mL (P all < 0. 01) at the completion of chemotherapy compared with baseline values. A > 15. 9% decrease in GLS [sensitivity, 86%; specificity, 75%; area under the curve (AUC) = 0. 815; P = 0. 001] and a > 0. 004 ng / mL elevation in cTnT (sensitivity, 79%; specificity, 64%; AUC = 0. 757; P = 0. 005) from baseline to the third cycle of chemotherapy predicted later cardiotoxicity. The decrease in GLS remained the only independent predictor of cardiotoxicity (P = 0. 000). CONCLUSIONS: GLS combined with cTnT may provide a reliable and non - invasive method to predict cardiac dysfunction in patients receiving anthracycline - based chemotherapy.

cardiotoxicity

myocardial strain

cardiac dysfunction

non - Hodgkin lymphoma

Cardiotoxicity

heart failure

cardiotoxicity

cardiotoxicity

cardiotoxicity

cardiac dysfunction

epirubicine

epirubicin

epirubicin

anthracycline

epirubicine

cardiotoxicity

epirubicine

Cardiotoxicity

epirubicine

cardiotoxicity

epirubicine

cardiotoxicity

epirubicine

cardiotoxicity

epirubicin

cardiotoxicity

epirubicin

Cardiotoxicity

epirubicin

cardiotoxicity

epirubicin

cardiotoxicity

epirubicin

cardiotoxicity

epirubicin

cardiotoxicity

epirubicin

Cardiotoxicity

epirubicin

cardiotoxicity

epirubicin

cardiotoxicity

epirubicin

cardiotoxicity

epirubicine

heart failure

epirubicin

heart failure

epirubicin

heart failure


Input: Prevention of etomidate - induced myoclonus: which is superior: Fentanyl, midazolam, or a combination? A Retrospective comparative study. BACKGROUND: In this retrospective comparative study, we aimed to compare the effectiveness of fentanyl, midazolam, and a combination of fentanyl and midazolam to prevent etomidate - induced myoclonus. MATERIAL AND METHODS: This study was performed based on anesthesia records. Depending on the drugs that would be given before the induction of anesthesia with etomidate, the patients were separated into 4 groups: no pretreatment (Group NP), fentanyl 1 ug. kg - 1 (Group F), midazolam 0. 03 mg. kg - 1 (Group M), and midazolam 0. 015 mg. kg - 1 + fentanyl 0. 5 ug. kg - 1 (Group FM). Patients who received the same anesthetic procedure were selected: 2 minutes after intravenous injections of the pretreatment drugs, anesthesia is induced with 0. 3 mg. kg - 1 etomidate injected intravenously over a period of 20 - 30 seconds. Myoclonic movements are evaluated, which were observed and graded according to clinical severity during the 2 minutes after etomidate injection. The severity of pain due to etomidate injection, mean arterial pressure, heart rate, and adverse effects were also evaluated. RESULTS: Study results showed that myoclonus incidence was 85%, 40%, 70%, and 25% in Group NP, Group F, Group M, and Group FM, respectively, and were significantly lower in Group F and Group FM. CONCLUSIONS: We conclude that pretreatment with fentanyl or combination of fentanyl and midazolam was effective in preventing etomidate - induced myoclonus.

etomidate

Fentanyl

midazolam

fentanyl

midazolam

fentanyl

midazolam

etomidate

etomidate

fentanyl

midazolam

midazolam

fentanyl

etomidate

etomidate

etomidate

fentanyl

fentanyl

midazolam

etomidate

myoclonus

myoclonus

Myoclonic movements

pain

myoclonus

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus


Input: Cholestatic presentation of yellow phosphorus poisoning. Yellow phosphorus, a component of certain pesticide pastes and fireworks, is well known to cause hepatotoxicity. Poisoning with yellow phosphorus classically manifests with acute hepatitis leading to acute liver failure which may need liver transplantation. We present a case of yellow phosphorus poisoning in which a patient presented with florid clinical features of cholestasis highlighting the fact that cholestasis can rarely be a presenting feature of yellow phosphorus hepatotoxicity.

Cholestatic

poisoning

hepatotoxicity

Poisoning

acute hepatitis

acute liver failure

poisoning

cholestasis

cholestasis

hepatotoxicity

phosphorus

phosphorus

phosphorus

phosphorus

phosphorus

phosphorus

acute hepatitis

phosphorus

acute hepatitis

phosphorus

acute hepatitis

phosphorus

acute hepatitis

phosphorus

acute hepatitis

phosphorus

Cholestatic

phosphorus

cholestasis

phosphorus

cholestasis

phosphorus

Cholestatic

phosphorus

cholestasis

phosphorus

cholestasis

phosphorus

Cholestatic

phosphorus

cholestasis

phosphorus

cholestasis

phosphorus

Cholestatic

phosphorus

cholestasis

phosphorus

cholestasis

phosphorus

Cholestatic

phosphorus

cholestasis

phosphorus

cholestasis

phosphorus

acute liver failure

phosphorus

acute liver failure

phosphorus

acute liver failure

phosphorus

acute liver failure

phosphorus

acute liver failure


Input: Vasovagal syncope and severe bradycardia following intranasal dexmedetomidine for pediatric procedural sedation. We report syncope and bradycardia in an 11 - year - old girl following administration of intranasal dexmedetomidine for sedation for a voiding cystourethrogram. Following successful completion of VCUG and a 60 - min recovery period, the patient' s level of consciousness and vital signs returned to presedation levels. Upon leaving the sedation area, the patient collapsed, with no apparent inciting event. The patient quickly regained consciousness and no injury occurred. The primary abnormality found was persistent bradycardia, and she was admitted to the hospital for telemetric observation. The bradycardia lasted ~ 2 h, and further cardiac workup revealed no underlying abnormality. Unanticipated and previously unreported outcomes may be witnessed as we expand the use of certain sedatives to alternative routes of administration.

Vasovagal syncope

bradycardia

syncope

bradycardia

bradycardia

bradycardia

dexmedetomidine

dexmedetomidine

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

Vasovagal syncope

dexmedetomidine

Vasovagal syncope


Input: Paradoxical severe agitation induced by add - on high - doses quetiapine in schizo - affective disorder. We report the case of a 35 - year - old patient suffering from schizo - affective disorder since the age of 19 years, treated by a combination of first - generation antipsychotics, zuclopenthixol (100 mg / day) and lithium (1200 mg / day) (serum lithium = 0. 85 mEq / l). This patient had no associated personality disorder (particularly no antisocial disorder) and no substance abuse disorder. Within the 48 h following the gradual introduction of quetiapine (up to 600 mg / day), the patient presented severe agitation without an environmental explanation, contrasting with the absence of a history of aggressiveness or personality disorder. The diagnoses of manic shift and akathisia were dismissed. The withdrawal and the gradual reintroduction of quetiapine 2 weeks later, which led to another severe agitation, enabled us to attribute the agitation specifically to quetiapine.

agitation

schizo - affective disorder

schizo - affective disorder

personality disorder

antisocial disorder

substance abuse disorder

agitation

aggressiveness

personality disorder

manic

akathisia

agitation

agitation

quetiapine

zuclopenthixol

lithium

lithium

quetiapine

quetiapine

quetiapine

quetiapine

agitation

quetiapine

agitation

quetiapine

agitation

quetiapine

agitation

quetiapine

agitation

quetiapine

agitation

quetiapine

agitation

quetiapine

agitation

quetiapine

agitation

quetiapine

agitation

quetiapine

agitation

quetiapine

agitation

quetiapine

agitation

quetiapine

agitation

quetiapine

agitation

quetiapine

agitation


Input: Antioxidant effects of bovine lactoferrin on dexamethasone - induced hypertension in rat. Dexamethasone - (Dex -) induced hypertension is associated with enhanced oxidative stress. Lactoferrin (LF) is an iron - binding glycoprotein with antihypertensive properties. In this study, we investigated the effect of chronic administration of LF on oxidative stress and hypertension upon Dex administration. Male Wistar rats were treated by Dex (30 u g / kg / day subcutaneously) or saline for 14 days. Oral bovine LF (30, 100, 300 mg / kg) was given from day 8 to 14 in a reversal study. In a prevention study, rats received 4 days of LF treatment followed by Dex and continued during the test period. Systolic blood pressure (SBP) was measured using tail - cuff method. Thymus weight was used as a marker of glucocorticoid activity. Plasma hydrogen peroxide (H2O2) concentration and ferric reducing antioxidant power (FRAP) value were determined. Dexamethasone significantly increased SBP and plasma H2O2 level and decreased thymus and body weights. LF lowered (P < 0. 01) and dose dependently prevented (P < 0. 001) Dex - induced hypertension. LF prevented body weight loss and significantly reduced the elevated plasma H2O2 and increased FRAP values. Chronic administration of LF strongly reduced the blood pressure and production of ROS and improved antioxidant capacity in Dex - induced hypertension, suggesting the role of inhibition of oxidative stress as another mechanism of antihypertensive action of LF.

dexamethasone

Dexamethasone

Dex

iron

Dex

Dex

Dex

hydrogen peroxide

Dexamethasone

Dex

Dex

hypertension

hypertension

hypertension

hypertension

weight loss

hypertension

dexamethasone

hypertension

dexamethasone

hypertension

dexamethasone

hypertension

dexamethasone

hypertension

dexamethasone

hypertension

Dexamethasone

hypertension

Dexamethasone

hypertension

Dexamethasone

hypertension

Dexamethasone

hypertension

Dexamethasone

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dexamethasone

hypertension

Dexamethasone

hypertension

Dexamethasone

hypertension

Dexamethasone

hypertension

Dexamethasone

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

dexamethasone

weight loss

Dexamethasone

weight loss

Dex

weight loss

Dex

weight loss

Dex

weight loss

Dex

weight loss

Dexamethasone

weight loss

Dex

weight loss

Dex

weight loss


Input: The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients. Because of a lack of contemporary data regarding seizures after cardiac surgery, we undertook a retrospective analysis of prospectively collected data from 11 529 patients in whom cardiopulmonary bypass was used from January 2004 to December 2010. A convulsive seizure was defined as a transient episode of disturbed brain function characterised by abnormal involuntary motor movements. Multivariate regression analysis was performed to identify independent predictors of postoperative seizures. A total of 100 (0. 9%) patients developed postoperative convulsive seizures. Generalised and focal seizures were identified in 68 and 32 patients, respectively. The median (IQR [range]) time after surgery when the seizure occurred was 7 (6 - 12 [1 - 216]) h and 8 (6 - 11 [4 - 18]) h, respectively. Epileptiform findings on electroencephalography were seen in 19 patients. Independent predictors of postoperative seizures included age, female sex, redo cardiac surgery, calcification of ascending aorta, congestive heart failure, deep hypothermic circulatory arrest, duration of aortic cross - clamp and tranexamic acid. When tested in a multivariate regression analysis, tranexamic acid was a strong independent predictor of seizures (OR 14. 3, 95% CI 5. 5 - 36. 7; p < 0. 001). Patients with convulsive seizures had 2. 5 times higher in - hospital mortality rates and twice the length of hospital stay compared with patients without convulsive seizures. Mean (IQR [range]) length of stay in the intensive care unit was 115 (49 - 228 [32 - 481]) h in patients with convulsive seizures compared with 26 (22 - 69 [14 - 1080]) h in patients without seizures (p < 0. 001). Convulsive seizures are a serious postoperative complication after cardiac surgery. As tranexamic acid is the only modifiable factor, its administration, particularly in doses exceeding 80 mg. kg (- 1), should be weighed against the risk of postoperative seizures.

tranexamic acid

tranexamic acid

tranexamic acid

tranexamic acid

convulsive

seizures

seizures

convulsive

seizure

abnormal involuntary motor movements

seizures

convulsive

seizures

Generalised and focal seizures

seizure

seizures

congestive heart failure

hypothermic

seizures

convulsive

seizures

convulsive

seizures

convulsive

seizures

seizures

Convulsive

seizures

postoperative complication

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizure

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

Generalised and focal seizures

tranexamic acid

seizure

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

Convulsive

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizure

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

Generalised and focal seizures

tranexamic acid

seizure

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

Convulsive

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizure

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

Generalised and focal seizures

tranexamic acid

seizure

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

Convulsive

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizure

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

Generalised and focal seizures

tranexamic acid

seizure

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

Convulsive

tranexamic acid

seizures

tranexamic acid

seizures


Input: Dysfunctional overnight memory consolidation in ecstasy users. Sleep plays an important role in the consolidation and integration of memory in a process called overnight memory consolidation. Previous studies indicate that ecstasy users have marked and persistent neurocognitive and sleep - related impairments. We extend past research by examining overnight memory consolidation among regular ecstasy users (n = 12) and drug naive healthy controls (n = 26). Memory recall of word pairs was evaluated before and after a period of sleep, with and without interference prior to testing. In addition, we assessed neurocognitive performances across tasks of learning, memory and executive functioning. Ecstasy users demonstrated impaired overnight memory consolidation, a finding that was more pronounced following associative interference. Additionally, ecstasy users demonstrated impairments on tasks recruiting frontostriatal and hippocampal neural circuitry, in the domains of proactive interference memory, long - term memory, encoding, working memory and complex planning. We suggest that ecstasy - associated dysfunction in fronto - temporal circuitry may underlie overnight consolidation memory impairments in regular ecstasy users.

Dysfunctional overnight memory

sleep - related impairments

impaired overnight memory

memory impairments

ecstasy

ecstasy

ecstasy

Ecstasy

ecstasy

ecstasy

ecstasy

ecstasy

sleep - related impairments

ecstasy

sleep - related impairments

ecstasy

sleep - related impairments

Ecstasy

sleep - related impairments

ecstasy

sleep - related impairments

ecstasy

sleep - related impairments

ecstasy

sleep - related impairments

ecstasy

Dysfunctional overnight memory

ecstasy

impaired overnight memory

ecstasy

memory impairments

ecstasy

Dysfunctional overnight memory

ecstasy

impaired overnight memory

ecstasy

memory impairments

ecstasy

Dysfunctional overnight memory

ecstasy

impaired overnight memory

ecstasy

memory impairments

Ecstasy

Dysfunctional overnight memory

Ecstasy

impaired overnight memory

Ecstasy

memory impairments

ecstasy

Dysfunctional overnight memory

ecstasy

impaired overnight memory

ecstasy

memory impairments

ecstasy

Dysfunctional overnight memory

ecstasy

impaired overnight memory

ecstasy

memory impairments

ecstasy

Dysfunctional overnight memory

ecstasy

impaired overnight memory

ecstasy

memory impairments


Input: Normoammonemic encephalopathy: solely valproate induced or multiple mechanisms? A 77 - year - old woman presented with subacute onset progressive confusion, aggression, auditory hallucinations and delusions. In the preceding months, the patient had a number of admissions with transient unilateral hemiparesis with facial droop, and had been started on valproate for presumed hemiplegic migraine. Valproate was withdrawn soon after admission and her cognitive abilities have gradually improved over 3 months of follow - up. Valproate levels taken prior to withdrawal were subtherapeutic and the patient was normoammonaemic. EEG undertaken during inpatient stay showed changes consistent with encephalopathy, and low titre N - methyl - D - aspartate (NMDA) receptor antibodies were present in this patient. The possible aetiologies of valproate - induced encephalopathy and NMDA receptor - associated encephalitis present a diagnostic dilemma. We present a putative combinatorial hypothesis to explain this patient' s symptoms.

encephalopathy

confusion

aggression

auditory hallucinations

delusions

hemiparesis

hemiplegic migraine

encephalopathy

encephalopathy

encephalitis

valproate

valproate

Valproate

Valproate

N - methyl - D - aspartate

NMDA

valproate

NMDA

valproate

delusions

valproate

delusions

Valproate

delusions

Valproate

delusions

valproate

delusions

valproate

confusion

valproate

confusion

Valproate

confusion

Valproate

confusion

valproate

confusion

valproate

auditory hallucinations

valproate

auditory hallucinations

Valproate

auditory hallucinations

Valproate

auditory hallucinations

valproate

auditory hallucinations


Input: Cerebellar and oculomotor dysfunction induced by rapid infusion of pethidine. Pethidine is an opioid that gains its popularity for the effective pain control through acting on the opioid - receptors. However, rapid pain relief sometimes brings about unfavourable side effects that largely limit its clinical utility. Common side effects include nausea, vomiting and hypotension. In patients with impaired renal and liver function, and those who need long - term pain control, pethidine may cause excitatory central nervous system (CNS) effects through its neurotoxic metabolite, norpethidine, resulting in irritability and seizure attack. On the contrary, though not clinically apparent, pethidine potentially causes inhibitory impacts on the CNS and impairs normal cerebellar and oculomotor function in the short term. In this case report, we highlight opioid' s inhibitory side effects on the cerebellar structure that causes dysmetria, dysarthria, reduced smooth pursuit gain and decreased saccadic velocity.

Cerebellar and oculomotor dysfunction

Cerebellar and oculomotor dysfunction

oculomotor dysfunction

pain

pain

nausea

vomiting

hypotension

impaired renal and liver function

impaired renal and liver function

impaired renal and liver function

pain

neurotoxic

irritability

seizure

dysmetria

dysarthria

pethidine

Pethidine

pethidine

norpethidine

pethidine

pethidine

dysmetria

Pethidine

dysmetria

pethidine

dysmetria

pethidine

dysmetria

pethidine

nausea

Pethidine

nausea

pethidine

nausea

pethidine

nausea

norpethidine

seizure

pethidine

dysarthria

Pethidine

dysarthria

pethidine

dysarthria

pethidine

dysarthria

pethidine

vomiting

Pethidine

vomiting

pethidine

vomiting

pethidine

vomiting

pethidine

hypotension

Pethidine

hypotension

pethidine

hypotension

pethidine

hypotension


Input: Baboon syndrome induced by ketoconazole. A 27 - year - old male patient presented with a maculopapular eruption on the flexural areas and buttocks after using oral ketoconazole. The patient was diagnosed with drug - induced baboon syndrome based on his history, which included prior sensitivity to topical ketoconazole, a physical examination, and histopathological findings. Baboon syndrome is a drug - or contact allergen - related maculopapular eruption that typically involves the flexural and gluteal areas. To the best of our knowledge, this is the first reported case of ketoconazole - induced baboon syndrome in the English literature.

Baboon syndrome

maculopapular eruption

baboon syndrome

Baboon syndrome

maculopapular eruption

baboon syndrome

ketoconazole

ketoconazole

ketoconazole

ketoconazole

ketoconazole

maculopapular eruption

ketoconazole

maculopapular eruption

ketoconazole

maculopapular eruption

ketoconazole

maculopapular eruption

ketoconazole

maculopapular eruption

ketoconazole

maculopapular eruption

ketoconazole

maculopapular eruption

ketoconazole

maculopapular eruption


Input: A Case of Sudden Cardiac Death due to Pilsicainide - Induced Torsades de Pointes. An 84 - year - old male received oral pilsicainide, a pure sodium channel blocker with slow recovery kinetics, to convert his paroxysmal atrial fibrillation to a sinus rhythm; the patient developed sudden cardiac death two days later. The Holter electrocardiogram, which was worn by chance, revealed torsade de pointes with gradually prolonged QT intervals. This drug is rapidly absorbed from the gastrointestinal tract, and most of it is excreted from the kidney. Although the patient' s renal function was not highly impaired and the dose of pilsicainide was low, the plasma concentration of pilsicainide may have been high, which can produce torsades de pointes in the octogenarian. Although the oral administration of class IC drugs, including pilsicainide, is effective to terminate atrial fibrillation, careful consideration must be taken before giving these drugs to octogenarians.

Sudden Cardiac Death

Torsades de Pointes

atrial fibrillation

sudden cardiac death

torsade de pointes

torsades de pointes

atrial fibrillation

Pilsicainide

pilsicainide

sodium

pilsicainide

pilsicainide

pilsicainide

Pilsicainide

Torsades de Pointes

Pilsicainide

torsade de pointes

Pilsicainide

torsades de pointes

pilsicainide

Torsades de Pointes

pilsicainide

torsade de pointes

pilsicainide

torsades de pointes

pilsicainide

Torsades de Pointes

pilsicainide

torsade de pointes

pilsicainide

torsades de pointes

pilsicainide

Torsades de Pointes

pilsicainide

torsade de pointes

pilsicainide

torsades de pointes

pilsicainide

Torsades de Pointes

pilsicainide

torsade de pointes

pilsicainide

torsades de pointes

Pilsicainide

Sudden Cardiac Death

Pilsicainide

sudden cardiac death

pilsicainide

Sudden Cardiac Death

pilsicainide

sudden cardiac death

pilsicainide

Sudden Cardiac Death

pilsicainide

sudden cardiac death

pilsicainide

Sudden Cardiac Death

pilsicainide

sudden cardiac death

pilsicainide

Sudden Cardiac Death

pilsicainide

sudden cardiac death


Input: All - trans retinoic acid - induced inflammatory myositis in a patient with acute promyelocytic leukemia. All - trans retinoic acid (ATRA), a component of standard therapy for acute promyelocytic leukemia (APL), is associated with potentially serious but treatable adverse effects involving numerous organ systems, including rare skeletal muscle involvement. Only a handful of cases of ATRA - induced myositis in children have been reported, and none in the radiology literature. We present such a case in a 15 - year - old boy with APL, where recognition of imaging findings played a crucial role in making the diagnosis and facilitated prompt, effective treatment.

All - trans retinoic acid

All - trans retinoic acid

ATRA

ATRA

myositis

acute promyelocytic leukemia

acute promyelocytic leukemia

APL

myositis

APL

All - trans retinoic acid

myositis

All - trans retinoic acid

myositis

All - trans retinoic acid

myositis

All - trans retinoic acid

myositis

ATRA

myositis

ATRA

myositis

ATRA

myositis

ATRA

myositis


Input: Tolerability of lomustine in combination with cyclophosphamide in dogs with lymphoma. This retrospective study describes toxicity associated with a protocol of lomustine (CCNU) and cyclophosphamide (CTX) in dogs with lymphoma. CCNU was administered per os (PO) at a targeted dosage of 60 mg / m (2) body surface area on day 0, CTX was administered PO at a targeted dosage of 250 mg / m (2) divided over days 0 through 4, and all dogs received prophylactic antibiotics. Ninety treatments were given to the 57 dogs included in the study. Neutropenia was the principal toxic effect, and the overall frequency of grade 4 neutropenia after the first treatment of CCNU / CTX was 30% (95% confidence interval, 19 - 43%). The mean body weight of dogs with grade 4 neutropenia (19. 7 kg + 13. 4 kg) was significantly less than the mean body weight of dogs that did not develop grade 4 neutropenia (31. 7 kg + 12. 4 kg; P =. 005). One dog (3%) developed hematologic changes suggestive of hepatotoxicity. No dogs had evidence of either renal toxicity or hemorrhagic cystitis. Adverse gastrointestinal effects were uncommon. On the basis of the findings reported herein, a dose of 60 mg / m (2) of CCNU combined with 250 mg / m (2) of CTX (divided over 5 days) q 4 wk is tolerable in tumor - bearing dogs.

lomustine

cyclophosphamide

lomustine

CCNU

cyclophosphamide

CTX

CCNU

CTX

CCNU

CTX

CCNU

CTX

lymphoma

toxicity

lymphoma

Neutropenia

neutropenia

neutropenia

neutropenia

hepatotoxicity

renal toxicity

hemorrhagic cystitis

hemorrhagic

cystitis

tumor

cyclophosphamide

Neutropenia

cyclophosphamide

neutropenia

cyclophosphamide

neutropenia

cyclophosphamide

neutropenia

cyclophosphamide

Neutropenia

cyclophosphamide

neutropenia

cyclophosphamide

neutropenia

cyclophosphamide

neutropenia

CTX

Neutropenia

CTX

neutropenia

CTX

neutropenia

CTX

neutropenia

CTX

Neutropenia

CTX

neutropenia

CTX

neutropenia

CTX

neutropenia

CTX

Neutropenia

CTX

neutropenia

CTX

neutropenia

CTX

neutropenia

CTX

Neutropenia

CTX

neutropenia

CTX

neutropenia

CTX

neutropenia

lomustine

Neutropenia

lomustine

neutropenia

lomustine

neutropenia

lomustine

neutropenia

lomustine

Neutropenia

lomustine

neutropenia

lomustine

neutropenia

lomustine

neutropenia

CCNU

Neutropenia

CCNU

neutropenia

CCNU

neutropenia

CCNU

neutropenia

CCNU

Neutropenia

CCNU

neutropenia

CCNU

neutropenia

CCNU

neutropenia

CCNU

Neutropenia

CCNU

neutropenia

CCNU

neutropenia

CCNU

neutropenia

CCNU

Neutropenia

CCNU

neutropenia

CCNU

neutropenia

CCNU

neutropenia


Input: Nelarabine neurotoxicity with concurrent intrathecal chemotherapy: Case report and review of literature. Severe nelarabine neurotoxicity in a patient who received concurrent intrathecal (IT) chemotherapy is reported. A 37 - year - old Caucasian woman with a history of T - cell lymphoblastic lymphoma was admitted for relapsed disease. She was originally treated with induction chemotherapy followed by an autologous transplant. She developed relapsed disease 10 months later with leukemic involvement. She was re - induced with nelarabine 1500 mg / m (2) on days 1, 3, and 5 with 1 dose of IT cytarabine 100 mg on day 2 as central nervous system (CNS) prophylaxis. At the time of treatment, she was on continuous renal replacement therapy due to sequelae of tumor lysis syndrome (TLS). She tolerated therapy well, entered a complete remission, and recovered her renal function. She received a second cycle of nelarabine without additional IT prophylaxis one month later. A week after this second cycle, she noted numbness in her lower extremities. Predominantly sensory, though also motor and autonomic, peripheral neuropathy started in her feet, ascended proximally to the mid - thoracic region, and eventually included her distal upper extremities. A magnetic resonance imaging (MRI) of her spine demonstrated changes from C2 to C6 consistent with subacute combined degeneration. Nelarabine was felt to be the cause of her symptoms. Her neuropathy stabilized and showed slight improvement and ultimately received an unrelated, reduced - intensity allogeneic transplant while in complete remission, but relapsed disease 10 weeks later. She is currently being treated with best supportive care. To our knowledge, this is the first published case report of severe neurotoxicity caused by nelarabine in a patient who received concurrent IT chemotherapy.

Nelarabine

nelarabine

nelarabine

cytarabine

nelarabine

Nelarabine

nelarabine

neurotoxicity

neurotoxicity

T - cell lymphoblastic lymphoma

leukemic

tumor lysis syndrome

TLS

peripheral neuropathy

neuropathy

neurotoxicity

Nelarabine

peripheral neuropathy

nelarabine

peripheral neuropathy

nelarabine

peripheral neuropathy

nelarabine

peripheral neuropathy

Nelarabine

peripheral neuropathy

nelarabine

peripheral neuropathy


Input: Valproate - induced hyperammonemic encephalopathy in a renal transplanted patient. Neurological complications after renal transplantation constitute an important cause of morbidity and mortality. Their differential diagnosis is difficult and essential for subsequent patient' s management. Valproate - induced hyperammonemic encephalopathy is an uncommon but serious effect of valproate treatment. Here, we describe the case of a 15 - year - old girl who was on a long - term therapy with valproate due to epilepsy and revealed impaired consciousness with hyperammonemia 12 days after renal transplantation. After withdraw of valproate, patients' symptoms resolved within 24 h. Clinicians should increase their awareness for potential complication of valproate, especially in transplanted patients.

Valproate

Valproate

valproate

valproate

valproate

valproate

hyperammonemic

encephalopathy

Neurological complications

hyperammonemic

encephalopathy

epilepsy

impaired consciousness

hyperammonemia

Valproate

impaired consciousness

Valproate

impaired consciousness

valproate

impaired consciousness

valproate

impaired consciousness

valproate

impaired consciousness

valproate

impaired consciousness

Valproate

hyperammonemic

Valproate

hyperammonemic

Valproate

hyperammonemia

Valproate

hyperammonemic

Valproate

hyperammonemic

Valproate

hyperammonemia

valproate

hyperammonemic

valproate

hyperammonemic

valproate

hyperammonemia

valproate

hyperammonemic

valproate

hyperammonemic

valproate

hyperammonemia

valproate

hyperammonemic

valproate

hyperammonemic

valproate

hyperammonemia

valproate

hyperammonemic

valproate

hyperammonemic

valproate

hyperammonemia


Input: Necrotising fasciitis after bortezomib and dexamethasone - containing regimen in an elderly patient of Waldenstrom macroglobulinaemia. Bortezomib and high - dose dexamethasone - containing regimens are considered to be generally tolerable with few severe bacterial infections in patients with B - cell malignancies. However, information is limited concerning the safety of the regimen in elderly patients. We report a case of a 76 - year - old man with Waldenstrom macroglobulinaemia who suffered necrotising fasciitis without neutropenia after the combination treatment with bortezomib, high - dose dexamethasone and rituximab. Despite immediate intravenous antimicrobial therapy, he succumbed 23 h after the onset. Physicians should recognise the possibility of fatal bacterial infections related to bortezomib plus high - dose dexamethasone in elderly patients, and we believe this case warrants further investigation.

Necrotising fasciitis

Waldenstrom macroglobulinaemia

bacterial infections

malignancies

Waldenstrom macroglobulinaemia

necrotising fasciitis

neutropenia

bacterial infections

bortezomib

dexamethasone

Bortezomib

dexamethasone

bortezomib

dexamethasone

bortezomib

dexamethasone

dexamethasone

Necrotising fasciitis

dexamethasone

necrotising fasciitis

dexamethasone

Necrotising fasciitis

dexamethasone

necrotising fasciitis

dexamethasone

Necrotising fasciitis

dexamethasone

necrotising fasciitis

dexamethasone

Necrotising fasciitis

dexamethasone

necrotising fasciitis

bortezomib

Necrotising fasciitis

bortezomib

necrotising fasciitis

Bortezomib

Necrotising fasciitis

Bortezomib

necrotising fasciitis

bortezomib

Necrotising fasciitis

bortezomib

necrotising fasciitis

bortezomib

Necrotising fasciitis

bortezomib

necrotising fasciitis


Input: An integrated characterization of serological, pathological, and functional events in doxorubicin - induced cardiotoxicity. Many efficacious cancer treatments cause significant cardiac morbidity, yet biomarkers or functional indices of early damage, which would allow monitoring and intervention, are lacking. In this study, we have utilized a rat model of progressive doxorubicin (DOX) - induced cardiomyopathy, applying multiple approaches, including cardiac magnetic resonance imaging (MRI), to provide the most comprehensive characterization to date of the timecourse of serological, pathological, and functional events underlying this toxicity. Hannover Wistar rats were dosed with 1. 25 mg / kg DOX weekly for 8 weeks followed by a 4 week off - dosing " recovery " period. Electron microscopy of the myocardium revealed subcellular degeneration and marked mitochondrial changes after a single dose. Histopathological analysis revealed progressive cardiomyocyte degeneration, hypertrophy / cytomegaly, and extensive vacuolation after two doses. Extensive replacement fibrosis (quantified by Sirius red staining) developed during the off - dosing period. Functional indices assessed by cardiac MRI (including left ventricular ejection fraction (LVEF), cardiac output, and E / A ratio) declined progressively, reaching statistical significance after two doses and culminating in " clinical " LV dysfunction by 12 weeks. Significant increases in peak myocardial contrast enhancement and serological cardiac troponin I (cTnI) emerged after eight doses, importantly preceding the LVEF decline to < 50%. Troponin I levels positively correlated with delayed and peak gadolinium contrast enhancement, histopathological grading, and diastolic dysfunction. In summary, subcellular cardiomyocyte degeneration was the earliest marker, followed by progressive functional decline and histopathological manifestations. Myocardial contrast enhancement and elevations in cTnI occurred later. However, all indices predated " clinical " LV dysfunction and thus warrant further evaluation as predictive biomarkers.

doxorubicin

doxorubicin

DOX

DOX

gadolinium

cardiotoxicity

cancer

cardiomyopathy

toxicity

subcellular degeneration

cardiomyocyte degeneration

hypertrophy

fibrosis

LV dysfunction

diastolic dysfunction

cardiomyocyte degeneration

LV dysfunction

doxorubicin

fibrosis

doxorubicin

fibrosis

DOX

fibrosis

DOX

fibrosis

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

DOX

cardiomyopathy

DOX

cardiomyopathy

doxorubicin

LV dysfunction

doxorubicin

LV dysfunction

doxorubicin

LV dysfunction

doxorubicin

LV dysfunction

DOX

LV dysfunction

DOX

LV dysfunction

DOX

LV dysfunction

DOX

LV dysfunction


Input: Intradermal glutamate and capsaicin injections: intra - and interindividual variability of provoked hyperalgesia and allodynia. Intradermal injections of glutamate and capsaicin are attractive to use in human experimental pain models because hyperalgesia and allodynia mimic isolated aspects of clinical pain disorders. The aim of the present study was to investigate the reproducibility of these models. Twenty healthy male volunteers (mean age 24 years; range 18 - 38 years) received intradermal injections of glutamate and capsaicin in the volar forearm. Magnitudes of secondary pinprick hyperalgesia and brush - evoked allodynia were investigated using von Frey filaments (gauges 10, 15, 60 and 100 g) and brush strokes. Areas of secondary hyperalgesia and allodynia were quantified immediately after injection and after 15, 30 and 60 min. Two identical experiments separated by at least 7 days were performed. Reproducibility across and within volunteers (inter - and intra - individual variation, respectively) was assessed using intraclass correlation coefficient (ICC) and coefficient of variation (CV). Secondary pinprick hyperalgesia was observed as a marked increase in the visual analogue scale (VAS) response to von Frey gauges 60 and 100 g (P < 0. 001) after glutamate injection. For capsaicin, secondary pinprick hyperalgesia was detected with all von Frey gauges (P < 0. 001). Glutamate evoked reproducible VAS response to all von Frey gauges (ICC > 0. 60) and brush strokes (ICC > 0. 83). Capsaicin injection was reproducible for secondary hyperalgesia (ICC > 0. 70) and allodynia (ICC > 0. 71). Intra - individual variability was generally lower for the VAS response to von Frey and brush compared with areas of secondary hyperalgesia and allodynia. In conclusion, glutamate and capsaicin yield reproducible hyperalgesic and allodynic responses, and the present model is well suited for basic research, as well as for assessing the modulation of central phenomena.

glutamate

capsaicin

glutamate

capsaicin

glutamate

capsaicin

glutamate

capsaicin

Glutamate

Capsaicin

glutamate

capsaicin

hyperalgesia

allodynia

pain

hyperalgesia

allodynia

pain disorders

hyperalgesia

allodynia

secondary hyperalgesia

allodynia

hyperalgesia

hyperalgesia

secondary hyperalgesia

allodynia

secondary hyperalgesia

allodynia

hyperalgesic

allodynic

capsaicin

hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesia

capsaicin

allodynia

capsaicin

secondary hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

secondary hyperalgesia

capsaicin

allodynia

capsaicin

secondary hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesic

capsaicin

allodynic

capsaicin

hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesia

capsaicin

allodynia

capsaicin

secondary hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

secondary hyperalgesia

capsaicin

allodynia

capsaicin

secondary hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesic

capsaicin

allodynic

capsaicin

hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesia

capsaicin

allodynia

capsaicin

secondary hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

secondary hyperalgesia

capsaicin

allodynia

capsaicin

secondary hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesic

capsaicin

allodynic

capsaicin

hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesia

capsaicin

allodynia

capsaicin

secondary hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

secondary hyperalgesia

capsaicin

allodynia

capsaicin

secondary hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesic

capsaicin

allodynic

Capsaicin

hyperalgesia

Capsaicin

allodynia

Capsaicin

hyperalgesia

Capsaicin

allodynia

Capsaicin

hyperalgesia

Capsaicin

allodynia

Capsaicin

secondary hyperalgesia

Capsaicin

allodynia

Capsaicin

hyperalgesia

Capsaicin

hyperalgesia

Capsaicin

secondary hyperalgesia

Capsaicin

allodynia

Capsaicin

secondary hyperalgesia

Capsaicin

allodynia

Capsaicin

hyperalgesic

Capsaicin

allodynic

capsaicin

hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesia

capsaicin

allodynia

capsaicin

secondary hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

secondary hyperalgesia

capsaicin

allodynia

capsaicin

secondary hyperalgesia

capsaicin

allodynia

capsaicin

hyperalgesic

capsaicin

allodynic


Input: Ocular - specific ER stress reduction rescues glaucoma in murine glucocorticoid - induced glaucoma. Administration of glucocorticoids induces ocular hypertension in some patients. If untreated, these patients can develop a secondary glaucoma that resembles primary open - angle glaucoma (POAG). The underlying pathology of glucocorticoid - induced glaucoma is not fully understood, due in part to lack of an appropriate animal model. Here, we developed a murine model of glucocorticoid - induced glaucoma that exhibits glaucoma features that are observed in patients. Treatment of WT mice with topical ocular 0. 1% dexamethasone led to elevation of intraocular pressure (IOP), functional and structural loss of retinal ganglion cells, and axonal degeneration, resembling glucocorticoid - induced glaucoma in human patients. Furthermore, dexamethasone - induced ocular hypertension was associated with chronic ER stress of the trabecular meshwork (TM). Similar to patients, withdrawal of dexamethasone treatment reduced elevated IOP and ER stress in this animal model. Dexamethasone induced the transcriptional factor CHOP, a marker for chronic ER stress, in the anterior segment tissues, and Chop deletion reduced ER stress in these tissues and prevented dexamethasone - induced ocular hypertension. Furthermore, reduction of ER stress in the TM with sodium 4 - phenylbutyrate prevented dexamethasone - induced ocular hypertension in WT mice. Our data indicate that ER stress contributes to glucocorticoid - induced ocular hypertension and suggest that reducing ER stress has potential as a therapeutic strategy for treating glucocorticoid - induced glaucoma.

glaucoma

glaucoma

ocular hypertension

glaucoma

primary open - angle glaucoma

POAG

glaucoma

glaucoma

glaucoma

retinal ganglion

axonal degeneration

glaucoma

ocular hypertension

ocular hypertension

ocular hypertension

ocular hypertension

glaucoma

dexamethasone

dexamethasone

dexamethasone

Dexamethasone

dexamethasone

sodium 4 - phenylbutyrate

dexamethasone

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

Dexamethasone

glaucoma

Dexamethasone

glaucoma

Dexamethasone

glaucoma

Dexamethasone

glaucoma

Dexamethasone

glaucoma

Dexamethasone

glaucoma

Dexamethasone

glaucoma

Dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

glaucoma

dexamethasone

axonal degeneration

dexamethasone

axonal degeneration

dexamethasone

axonal degeneration

Dexamethasone

axonal degeneration

dexamethasone

axonal degeneration

dexamethasone

axonal degeneration

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

Dexamethasone

ocular hypertension

Dexamethasone

ocular hypertension

Dexamethasone

ocular hypertension

Dexamethasone

ocular hypertension

Dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension

dexamethasone

ocular hypertension


Input: Effects of ginsenosides on opioid - induced hyperalgesia in mice. Opioid - induced hyperalgesia (OIH) is characterized by nociceptive sensitization caused by the cessation of chronic opioid use. OIH can limit the clinical use of opioid analgesics and complicate withdrawal from opioid addiction. In this study, we investigated the effects of Re, Rg1, and Rb1 ginsenosides, the bioactive components of ginseng, on OIH. OIH was achieved in mice after subcutaneous administration of morphine for 7 consecutive days three times per day. During withdrawal (days 8 and 9), these mice were administered Re, Rg1, or Rb1 intragastrically two times per day. On the test day (day 10), mice were subjected to the thermal sensitivity test and the acetic acid - induced writhing test. Re (300 mg / kg) inhibited OIH in both the thermal sensitivity test and the acetic acid - induced writhing test. However, the Rg1 and Rb1 ginsenosides failed to prevent OIH in either test. Furthermore, Rg1 showed a tendency to aggravate OIH in the acetic acid - induced writhing test. Our data suggested that the ginsenoside Re, but not Rg1 or Rb1, may contribute toward reversal of OIH.

ginsenosides

Re, Rg1, and Rb1 ginsenosides

Re, Rg1, and Rb1 ginsenosides

Rg1, and Rb1 ginsenosides

Rb1 ginsenosides

morphine

Re

acetic acid

Re

acetic acid

Rg1 and Rb1 ginsenosides

Rg1 and Rb1 ginsenosides

Rb1 ginsenosides

acetic acid

ginsenoside Re

hyperalgesia

hyperalgesia

OIH

OIH

opioid addiction

OIH

OIH

OIH

OIH

OIH

OIH

morphine

hyperalgesia

morphine

hyperalgesia

morphine

OIH

morphine

OIH

morphine

OIH

morphine

OIH

morphine

OIH

morphine

OIH

morphine

OIH

morphine

OIH


Input: A comparison of severe hemodynamic disturbances between dexmedetomidine and propofol for sedation in neurocritical care patients. OBJECTIVE: Dexmedetomidine and propofol are commonly used sedatives in neurocritical care as they allow for frequent neurologic examinations. However, both agents are associated with significant hemodynamic side effects. The primary objective of this study is to compare the prevalence of severe hemodynamic effects in neurocritical care patients receiving dexmedetomidine and propofol. DESIGN: Multicenter, retrospective, propensity - matched cohort study. SETTING: Neurocritical care units at two academic medical centers with dedicated neurocritical care teams and board - certified neurointensivists. PATIENTS: Neurocritical care patients admitted between July 2009 and September 2012 were evaluated and then matched 1: 1 based on propensity scoring of baseline characteristics. INTERVENTIONS: Continuous sedation with dexmedetomidine or propofol. MEASUREMENTS AND MAIN RESULTS: A total of 342 patients (105 dexmedetomidine and 237 propofol) were included in the analysis, with 190 matched (95 in each group) by propensity score. The primary outcome of this study was a composite of severe hypotension (mean arterial pressure < 60 mm Hg) and bradycardia (heart rate < 50 beats / min) during sedative infusion. No difference in the primary composite outcome in both the unmatched (30% vs 30%, p = 0. 94) or matched cohorts (28% vs 34%, p = 0. 35) could be found. When analyzed separately, no differences could be found in the prevalence of severe hypotension or bradycardia in either the unmatched or matched cohorts. CONCLUSIONS: Severe hypotension and bradycardia occur at similar prevalence in neurocritical care patients who receive dexmedetomidine or propofol. Providers should similarly consider the likelihood of hypotension or bradycardia before starting either sedative.

dexmedetomidine

propofol

Dexmedetomidine

propofol

dexmedetomidine

propofol

dexmedetomidine

propofol

dexmedetomidine

propofol

dexmedetomidine

propofol

hypotension

bradycardia

hypotension

bradycardia

hypotension

bradycardia

hypotension

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

propofol

bradycardia

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

Dexmedetomidine

hypotension

Dexmedetomidine

hypotension

Dexmedetomidine

hypotension

Dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

hypotension

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

Dexmedetomidine

bradycardia

Dexmedetomidine

bradycardia

Dexmedetomidine

bradycardia

Dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

dexmedetomidine

bradycardia

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

hypotension


Input: Hydroxytyrosol ameliorates oxidative stress and mitochondrial dysfunction in doxorubicin - induced cardiotoxicity in rats with breast cancer. Oxidative stress is involved in several processes including cancer, aging and cardiovascular disease, and has been shown to potentiate the therapeutic effect of drugs such as doxorubicin. Doxorubicin causes significant cardiotoxicity characterized by marked increases in oxidative stress and mitochondrial dysfunction. Herein, we investigate whether doxorubicin - associated chronic cardiac toxicity can be ameliorated with the antioxidant hydroxytyrosol in rats with breast cancer. Thirty - six rats bearing breast tumors induced chemically were divided into 4 groups: control, hydroxytyrosol (0. 5mg / kg, 5days / week), doxorubicin (1mg / kg / week), and doxorubicin plus hydroxytyrosol. Cardiac disturbances at the cellular and mitochondrial level, mitochondrial electron transport chain complexes I - IV and apoptosis - inducing factor, and oxidative stress markers have been analyzed. Hydroxytyrosol improved the cardiac disturbances enhanced by doxorubicin by significantly reducing the percentage of altered mitochondria and oxidative damage. These results suggest that hydroxytyrosol improve the mitochondrial electron transport chain. This study demonstrates that hydroxytyrosol protect rat heart damage provoked by doxorubicin decreasing oxidative damage and mitochondrial alterations.

Hydroxytyrosol

doxorubicin

doxorubicin

Doxorubicin

doxorubicin

hydroxytyrosol

hydroxytyrosol

doxorubicin

doxorubicin

hydroxytyrosol

Hydroxytyrosol

doxorubicin

hydroxytyrosol

hydroxytyrosol

doxorubicin

mitochondrial dysfunction

cardiotoxicity

breast cancer

cancer

cardiovascular disease

cardiotoxicity

mitochondrial dysfunction

cardiac toxicity

breast cancer

breast tumors

Cardiac disturbances

cardiac disturbances

heart damage

doxorubicin

Cardiac disturbances

doxorubicin

cardiac disturbances

doxorubicin

heart damage

doxorubicin

Cardiac disturbances

doxorubicin

cardiac disturbances

doxorubicin

heart damage

Doxorubicin

Cardiac disturbances

Doxorubicin

cardiac disturbances

Doxorubicin

heart damage

doxorubicin

Cardiac disturbances

doxorubicin

cardiac disturbances

doxorubicin

heart damage

doxorubicin

Cardiac disturbances

doxorubicin

cardiac disturbances

doxorubicin

heart damage

doxorubicin

Cardiac disturbances

doxorubicin

cardiac disturbances

doxorubicin

heart damage

doxorubicin

Cardiac disturbances

doxorubicin

cardiac disturbances

doxorubicin

heart damage

doxorubicin

Cardiac disturbances

doxorubicin

cardiac disturbances

doxorubicin

heart damage


Input: Amiodarone - induced myxoedema coma. A 62 - year - old man was found to have bradycardia, hypothermia and respiratory failure 3 weeks after initiation of amiodarone therapy for atrial fibrillation. Thyroid - stimulating hormone was found to be 168 uIU / mL (nl. 0. 3 - 5 uIU / mL) and free thyroxine (FT4) was < 0. 2 ng / dL (nl. 0. 8 - 1. 8 ng / dL). He received intravenous fluids, vasopressor therapy and stress dose steroids; he was intubated and admitted to the intensive care unit. He received 500 ug of intravenous levothyroxine in the first 18 h of therapy, and 150 ug intravenous daily thereafter. Haemodynamic improvement, along with complete recovery of mental status, occurred after 48 h. Twelve hours after the initiation of therapy, FT4 was 0. 96 ng / dL. The patient was maintained on levothyroxine 175 (g POorally daily. A thyroid ultrasound showed diffuse heterogeneity. The 24 hour excretion of iodine was 3657 (mcg (25 - 756 (mcg). The only two cases of amiodarone - induced myxoedema coma in the literature report patient death despite supportive therapy and thyroid hormone replacement. This case represents the most thoroughly investigated case of amiodarone - induced myxoedema coma with a history significant for subclinical thyroid disease.

Amiodarone

amiodarone

thyroxine

steroids

levothyroxine

levothyroxine

iodine

amiodarone

amiodarone

myxoedema coma

myxoedema

coma

bradycardia

hypothermia

respiratory failure

atrial fibrillation

myxoedema coma

myxoedema

coma

myxoedema coma

myxoedema

coma

thyroid disease

Amiodarone

myxoedema coma

Amiodarone

myxoedema

Amiodarone

myxoedema coma

Amiodarone

myxoedema

Amiodarone

myxoedema coma

Amiodarone

myxoedema

amiodarone

myxoedema coma

amiodarone

myxoedema

amiodarone

myxoedema coma

amiodarone

myxoedema

amiodarone

myxoedema coma

amiodarone

myxoedema

amiodarone

myxoedema coma

amiodarone

myxoedema

amiodarone

myxoedema coma

amiodarone

myxoedema

amiodarone

myxoedema coma

amiodarone

myxoedema

amiodarone

myxoedema coma

amiodarone

myxoedema

amiodarone

myxoedema coma

amiodarone

myxoedema

amiodarone

myxoedema coma

amiodarone

myxoedema

Amiodarone

bradycardia

amiodarone

bradycardia

amiodarone

bradycardia

amiodarone

bradycardia

Amiodarone

hypothermia

amiodarone

hypothermia

amiodarone

hypothermia

amiodarone

hypothermia

Amiodarone

respiratory failure

amiodarone

respiratory failure

amiodarone

respiratory failure

amiodarone

respiratory failure

Amiodarone

coma

Amiodarone

coma

Amiodarone

coma

amiodarone

coma

amiodarone

coma

amiodarone

coma

amiodarone

coma

amiodarone

coma

amiodarone

coma

amiodarone

coma

amiodarone

coma

amiodarone

coma


Input: Use of argatroban and catheter - directed thrombolysis with alteplase in an oncology patient with heparin - induced thrombocytopenia with thrombosis. PURPOSE: The case of an oncology patient who developed heparin - induced thrombocytopenia with thrombosis (HITT) and was treated with argatroban plus catheter - directed thrombolysis (CDT) with alteplase is presented. SUMMARY: A 63 - year - old Caucasian man with renal amyloidosis undergoing peripheral blood stem cell collection for an autologous stem cell transplant developed extensive bilateral upper - extremity deep venous thrombosis (DVT) and pulmonary embolism secondary to heparin - induced thrombocytopenia. A continuous i. v. infusion of argatroban was initiated, and the patient was managed on the general medical floor. After one week of therapy, he was transferred to the intensive care unit with cardiopulmonary compromise related to superior vena cava (SVC) syndrome. A percutaneous mechanical thrombectomy and CDT with alteplase were attempted, but the procedure was aborted due to epistaxis. The epistaxis resolved the next day, and the patient was restarted on argatroban. A second percutaneous mechanical thrombectomy was performed six days later and resulted in partial revascularization of the SVC and central veins. Postthrombectomy continuous CDT with alteplase was commenced while argatroban was withheld, and complete patency of the SVC and central veins was achieved after three days of therapy. Alteplase was discontinued, and the patient was reinitiated on argatroban; ultimately, he was transitioned to warfarin for long - term anticoagulation. Although the patient recovered, he experienced permanent vision and hearing loss, as well as end - stage renal disease. CONCLUSION: A 63 - year - old man with renal amyloidosis and SVC syndrome secondary to HITT was successfully treated with argatroban and CDT with alteplase.

argatroban

heparin

heparin

argatroban

heparin

argatroban

argatroban

argatroban

argatroban

warfarin

argatroban

thrombolysis

thrombocytopenia

thrombosis

thrombocytopenia

thrombosis

HITT

thrombolysis

amyloidosis

upper - extremity deep venous thrombosis

DVT

pulmonary embolism

thrombocytopenia

superior vena cava (SVC) syndrome

epistaxis

epistaxis

vision and hearing loss

vision and hearing loss

hearing loss

end - stage renal disease

amyloidosis

SVC syndrome

HITT

heparin

thrombocytopenia

heparin

thrombocytopenia

heparin

HITT

heparin

thrombocytopenia

heparin

HITT

heparin

thrombocytopenia

heparin

thrombocytopenia

heparin

HITT

heparin

thrombocytopenia

heparin

HITT

heparin

thrombocytopenia

heparin

thrombocytopenia

heparin

HITT

heparin

thrombocytopenia

heparin

HITT

heparin

pulmonary embolism

heparin

pulmonary embolism

heparin

pulmonary embolism

heparin

DVT

heparin

DVT

heparin

DVT


Input: Effects of dehydroepiandrosterone in amphetamine - induced schizophrenia models in mice. OBJECTIVE: To examine the effects of dehydroepiandrosterone (DHEA) on animal models of schizophrenia. METHODS: Seventy Swiss albino female mice (25 - 35 g) were divided into 4 groups: amphetamine - free (control), amphetamine, 50, and 100 mg / kg DHEA. The DHEA was administered intraperitoneally (ip) for 5 days. Amphetamine (3 mg / kg ip) induced hyper locomotion, apomorphine (1. 5 mg / kg subcutaneously [sc]) induced climbing, and haloperidol (1. 5 mg / kg sc) induced catalepsy tests were used as animal models of schizophrenia. The study was conducted at the Animal Experiment Laboratories, Department of Pharmacology, Medical School, Eskisehir Osmangazi University, Eskisehir, Turkey between March and May 2012. Statistical analysis was carried out using Kruskal - Wallis test for hyper locomotion, and one - way ANOVA for climbing and catalepsy tests. RESULTS: In the amphetamine - induced locomotion test, there were significant increases in all movements compared with the amphetamine - free group. Both DHEA 50 mg / kg (p < 0. 05), and 100 mg / kg (p < 0. 01) significantly decreased all movements compared with the amphetamine - induced locomotion group. There was a significant difference between groups in the haloperidol - induced catalepsy test (p < 0. 05). There was no significant difference between groups in terms of total climbing time in the apomorphine - induced climbing test (p > 0. 05). CONCLUSION: We observed that DHEA reduced locomotor activity and increased catalepsy at both doses, while it had no effect on climbing behavior. We suggest that DHEA displays typical neuroleptic - like effects, and may be used in the treatment of schizophrenia.

dehydroepiandrosterone

amphetamine

dehydroepiandrosterone

DHEA

amphetamine

amphetamine

DHEA

DHEA

Amphetamine

apomorphine

haloperidol

amphetamine

amphetamine

DHEA

amphetamine

haloperidol

apomorphine

DHEA

DHEA

schizophrenia

schizophrenia

hyper

catalepsy

schizophrenia

hyper

catalepsy

catalepsy

catalepsy

schizophrenia

apomorphine

schizophrenia

apomorphine

schizophrenia

apomorphine

schizophrenia

apomorphine

schizophrenia

apomorphine

schizophrenia

apomorphine

schizophrenia

apomorphine

schizophrenia

apomorphine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

Amphetamine

schizophrenia

Amphetamine

schizophrenia

Amphetamine

schizophrenia

Amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

amphetamine

schizophrenia

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

schizophrenia

haloperidol

schizophrenia

haloperidol

schizophrenia

haloperidol

schizophrenia

haloperidol

schizophrenia

haloperidol

schizophrenia

haloperidol

schizophrenia

haloperidol

schizophrenia


Input: Availability of human induced pluripotent stem cell - derived cardiomyocytes in assessment of drug potential for QT prolongation. Field potential duration (FPD) in human - induced pluripotent stem cell - derived cardiomyocytes (hiPS - CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K (+) channel and Ca (2 +) channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS - CMs can detect QT prolongation induced by multichannel blockers. hiPS - CMs were seeded onto MEA and FPD was measured for 2min every 10min for 30min after drug exposure for the vehicle and each drug concentration. IKr and IKs blockers concentration - dependently prolonged corrected FPD (FPDc), whereas Ca (2 +) channel blockers concentration - dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the IKr blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS - CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential.

QT prolongation

QT prolongation

QT prolongation

Torsade de Pointes

TdP

TdP

K

Ca

Ca

Amiodarone

Paroxetine

Terfenadine

Citalopram

Terfenadine

Citalopram

Citalopram

Torsade de Pointes

Citalopram

TdP

Citalopram

TdP

Citalopram

Torsade de Pointes

Citalopram

TdP

Citalopram

TdP

Terfenadine

Torsade de Pointes

Terfenadine

TdP

Terfenadine

TdP

Terfenadine

Torsade de Pointes

Terfenadine

TdP

Terfenadine

TdP


Input: Dermal developmental toxicity of N - phenylimide herbicides in rats. BACKGROUND: S - 53482 and S - 23121 are N - phenylimide herbicides and produced embryolethality, teratogenicity (mainly ventricular septal defects and wavy ribs), and growth retardation in rats in conventional oral developmental toxicity studies. Our objective in this study was to investigate whether the compounds induce developmental toxicity via the dermal route, which is more relevant to occupational exposure, hence better addressing human health risks. METHODS: S - 53482 was administered dermally to rats at 30, 100, and 300 mg / kg during organogenesis, and S - 23121 was administered at 200, 400, and 800 mg / kg (the maximum applicable dose level). Fetuses were obtained by a Cesarean section and examined for external, visceral, and skeletal alterations. RESULTS: Dermal exposure of rats to S - 53482 at 300 mg / kg produced patterns of developmental toxicity similar to those resulting from oral exposure. Toxicity included embryolethality, teratogenicity, and growth retardation. Dermal administration of S - 23121 at 800 mg / kg resulted in an increased incidence of embryonic death and ventricular septal defect, but retarded fetal growth was not observed as it was following oral exposure to S - 23121. CONCLUSIONS: Based on the results, S - 53482 and S - 23121 were teratogenic when administered dermally to pregnant rats as were the compounds administered orally. Thus, investigation of the mechanism and its human relevancy become more important.

toxicity

embryolethality

teratogenicity

ventricular septal defects

growth retardation

toxicity

toxicity

toxicity

Toxicity

embryolethality

teratogenicity

growth retardation

embryonic death

ventricular septal defect

teratogenic

S - 53482

S - 23121

S - 53482

S - 23121

S - 53482

S - 23121

S - 23121

S - 53482

S - 23121

S - 53482

growth retardation

S - 53482

growth retardation

S - 53482

growth retardation

S - 53482

growth retardation

S - 53482

growth retardation

S - 53482

growth retardation

S - 53482

growth retardation

S - 53482

growth retardation

S - 23121

growth retardation

S - 23121

growth retardation

S - 23121

growth retardation

S - 23121

growth retardation

S - 23121

growth retardation

S - 23121

growth retardation

S - 23121

growth retardation

S - 23121

growth retardation

S - 23121

growth retardation

S - 23121

growth retardation

S - 23121

teratogenicity

S - 23121

teratogenicity

S - 23121

teratogenic

S - 23121

teratogenicity

S - 23121

teratogenicity

S - 23121

teratogenic

S - 23121

teratogenicity

S - 23121

teratogenicity

S - 23121

teratogenic

S - 23121

teratogenicity

S - 23121

teratogenicity

S - 23121

teratogenic

S - 23121

teratogenicity

S - 23121

teratogenicity

S - 23121

teratogenic

S - 23121

embryolethality

S - 23121

embryolethality

S - 23121

embryonic death

S - 23121

embryolethality

S - 23121

embryolethality

S - 23121

embryonic death

S - 23121

embryolethality

S - 23121

embryolethality

S - 23121

embryonic death

S - 23121

embryolethality

S - 23121

embryolethality

S - 23121

embryonic death

S - 23121

embryolethality

S - 23121

embryolethality

S - 23121

embryonic death

S - 53482

embryolethality

S - 53482

embryolethality

S - 53482

embryonic death

S - 53482

embryolethality

S - 53482

embryolethality

S - 53482

embryonic death

S - 53482

embryolethality

S - 53482

embryolethality

S - 53482

embryonic death

S - 53482

embryolethality

S - 53482

embryolethality

S - 53482

embryonic death

S - 53482

teratogenicity

S - 53482

teratogenicity

S - 53482

teratogenic

S - 53482

teratogenicity

S - 53482

teratogenicity

S - 53482

teratogenic

S - 53482

teratogenicity

S - 53482

teratogenicity

S - 53482

teratogenic

S - 53482

teratogenicity

S - 53482

teratogenicity

S - 53482

teratogenic

S - 23121

ventricular septal defects

S - 23121

ventricular septal defect

S - 23121

ventricular septal defects

S - 23121

ventricular septal defect

S - 23121

ventricular septal defects

S - 23121

ventricular septal defect

S - 23121

ventricular septal defects

S - 23121

ventricular septal defect

S - 23121

ventricular septal defects

S - 23121

ventricular septal defect

S - 53482

ventricular septal defects

S - 53482

ventricular septal defect

S - 53482

ventricular septal defects

S - 53482

ventricular septal defect

S - 53482

ventricular septal defects

S - 53482

ventricular septal defect

S - 53482

ventricular septal defects

S - 53482

ventricular septal defect


Input: Rates of Renal Toxicity in Cancer Patients Receiving Cisplatin With and Without Mannitol. BACKGROUND: Cisplatin is a widely used antineoplastic. One of the major complications of cisplatin use is dose - limiting nephrotoxicity. There are many strategies to prevent this toxicity, including the use of mannitol as a nephroprotectant in combination with hydration. OBJECTIVE: We aimed to evaluate the rates of cisplatin - induced nephrotoxicity in cancer patients receiving single - agent cisplatin with and without mannitol. METHODS: This single - center retrospective analysis was a quasi experiment created by the national mannitol shortage. Data were collected on adult cancer patients receiving single - agent cisplatin as an outpatient from January 2011 to September 2012. The primary outcome was acute kidney injury (AKI). RESULTS: We evaluated 143 patients who received single - agent cisplatin; 97. 2% of patients had head and neck cancer as their primary malignancy. Patients who did not receive mannitol were more likely to develop nephrotoxicity: odds ratio [OR] = 2. 646 (95% CI = 1. 008, 6. 944; P = 0. 048). Patients who received the 100 mg / m (2) dosing and patients who had a history of hypertension also had a higher likelihood of developing nephrotoxicity: OR = 11. 494 (95% CI = 4. 149, 32. 258; P < 0. 0001) and OR = 3. 219 (95% CI = 1. 228, 8. 439; P = 0. 017), respectively. CONCLUSIONS: When limited quantities of mannitol are available, it should preferentially be given to patients at particularly high risk of nephrotoxicity. Our analysis suggests that those patients receiving the dosing schedule of 100 mg / m (2) cisplatin every 3 weeks and those with hypertension are at the greatest risk of nephrotoxicity and would benefit from the addition of mannitol.

Renal Toxicity

Cancer

nephrotoxicity

toxicity

nephrotoxicity

cancer

cancer

acute kidney injury

AKI

head and neck cancer

malignancy

nephrotoxicity

hypertension

nephrotoxicity

nephrotoxicity

hypertension

nephrotoxicity

Cisplatin

Mannitol

Cisplatin

cisplatin

mannitol

cisplatin

cisplatin

mannitol

mannitol

cisplatin

cisplatin

mannitol

mannitol

cisplatin

mannitol

Cisplatin

acute kidney injury

Cisplatin

AKI

Cisplatin

acute kidney injury

Cisplatin

AKI

cisplatin

acute kidney injury

cisplatin

AKI

cisplatin

acute kidney injury

cisplatin

AKI

cisplatin

acute kidney injury

cisplatin

AKI

cisplatin

acute kidney injury

cisplatin

AKI

cisplatin

acute kidney injury

cisplatin

AKI

cisplatin

acute kidney injury

cisplatin

AKI


Input: Metformin protects against seizures, learning and memory impairments and oxidative damage induced by pentylenetetrazole - induced kindling in mice. Cognitive impairment, the most common and severe comorbidity of epilepsy, greatly diminishes the quality of life. However, current therapeutic interventions for epilepsy can also cause untoward cognitive effects. Thus, there is an urgent need for new kinds of agents targeting both seizures and cognition deficits. Oxidative stress is considered to play an important role in epileptogenesis and cognitive deficits, and antioxidants have a putative antiepileptic potential. Metformin, the most commonly prescribed antidiabetic oral drug, has antioxidant properties. This study was designed to evaluate the ameliorative effects of metformin on seizures, cognitive impairment and brain oxidative stress markers observed in pentylenetetrazole - induced kindling animals. Male C57BL / 6 mice were administered with subconvulsive dose of pentylenetetrazole (37 mg / kg, i. p.) every other day for 14 injections. Metformin was injected intraperitoneally in dose of 200mg / kg along with alternate - day PTZ. We found that metformin suppressed the progression of kindling, ameliorated the cognitive impairment and decreased brain oxidative stress. Thus the present study concluded that metformin may be a potential agent for the treatment of epilepsy as well as a protective medicine against cognitive impairment induced by seizures.

Metformin

pentylenetetrazole

Metformin

metformin

pentylenetetrazole

pentylenetetrazole

Metformin

PTZ

metformin

metformin

seizures

learning and memory impairments

learning and memory impairments

memory impairments

Cognitive impairment

epilepsy

epilepsy

seizures

cognition deficits

cognitive deficits

seizures

cognitive impairment

cognitive impairment

epilepsy

cognitive impairment

seizures

pentylenetetrazole

learning and memory impairments

pentylenetetrazole

memory impairments

pentylenetetrazole

learning and memory impairments

pentylenetetrazole

memory impairments

pentylenetetrazole

learning and memory impairments

pentylenetetrazole

memory impairments

PTZ

learning and memory impairments

PTZ

memory impairments

pentylenetetrazole

learning and memory impairments

pentylenetetrazole

learning and memory impairments

pentylenetetrazole

learning and memory impairments

PTZ

learning and memory impairments

pentylenetetrazole

Cognitive impairment

pentylenetetrazole

cognition deficits

pentylenetetrazole

cognitive deficits

pentylenetetrazole

cognitive impairment

pentylenetetrazole

cognitive impairment

pentylenetetrazole

cognitive impairment

pentylenetetrazole

Cognitive impairment

pentylenetetrazole

cognition deficits

pentylenetetrazole

cognitive deficits

pentylenetetrazole

cognitive impairment

pentylenetetrazole

cognitive impairment

pentylenetetrazole

cognitive impairment

pentylenetetrazole

Cognitive impairment

pentylenetetrazole

cognition deficits

pentylenetetrazole

cognitive deficits

pentylenetetrazole

cognitive impairment

pentylenetetrazole

cognitive impairment

pentylenetetrazole

cognitive impairment

PTZ

Cognitive impairment

PTZ

cognition deficits

PTZ

cognitive deficits

PTZ

cognitive impairment

PTZ

cognitive impairment

PTZ

cognitive impairment

pentylenetetrazole

seizures

pentylenetetrazole

seizures

pentylenetetrazole

seizures

pentylenetetrazole

seizures

pentylenetetrazole

seizures

pentylenetetrazole

seizures

pentylenetetrazole

seizures

pentylenetetrazole

seizures

pentylenetetrazole

seizures

pentylenetetrazole

seizures

pentylenetetrazole

seizures

pentylenetetrazole

seizures

PTZ

seizures

PTZ

seizures

PTZ

seizures

PTZ

seizures


Input: P53 inhibition exacerbates late - stage anthracycline cardiotoxicity. AIMS: Doxorubicin (DOX) is an effective anti - cancer therapeutic, but is associated with both acute and late - stage cardiotoxicity. Children are particularly sensitive to DOX - induced heart failure. Here, the impact of p53 inhibition on acute vs. late - stage DOX cardiotoxicity was examined in a juvenile model. METHODS AND RESULTS: Two - week - old MHC - CB7 mice (which express dominant - interfering p53 in cardiomyocytes) and their non - transgenic (NON - TXG) littermates received weekly DOX injections for 5 weeks (25 mg / kg cumulative dose). One week after the last DOX treatment (acute stage), MHC - CB7 mice exhibited improved cardiac function and lower levels of cardiomyocyte apoptosis when compared with the NON - TXG mice. Surprisingly, by 13 weeks following the last DOX treatment (late stage), MHC - CB7 exhibited a progressive decrease in cardiac function and higher rates of cardiomyocyte apoptosis when compared with NON - TXG mice. p53 inhibition blocked transient DOX - induced STAT3 activation in MHC - CB7 mice, which was associated with enhanced induction of the DNA repair proteins Ku70 and Ku80. Mice with cardiomyocyte - restricted deletion of STAT3 exhibited worse cardiac function, higher levels of cardiomyocyte apoptosis, and a greater induction of Ku70 and Ku80 in response to DOX treatment during the acute stage when compared with control animals. CONCLUSION: These data support a model wherein a p53 - dependent cardioprotective pathway, mediated via STAT3 activation, mitigates DOX - induced myocardial stress during drug delivery. Furthermore, these data suggest an explanation as to how p53 inhibition can result in cardioprotection during drug treatment and, paradoxically, enhanced cardiotoxicity long after the cessation of drug treatment.

anthracycline

Doxorubicin

DOX

DOX

DOX

DOX

DOX

DOX

DOX

DOX

DOX

cardiotoxicity

cancer

cardiotoxicity

heart failure

cardiotoxicity

cardiotoxicity

Doxorubicin

heart failure

DOX

heart failure

DOX

heart failure

DOX

heart failure

DOX

heart failure

DOX

heart failure

DOX

heart failure

DOX

heart failure

DOX

heart failure

DOX

heart failure


Input: Metronidazole - induced encephalopathy: an uncommon scenario. Metronidazole can produce neurological complications although it is not a common scenario. We present a case where a patient developed features of encephalopathy following prolonged metronidazole intake. Magnetic resonance imaging (MRI) brain showed abnormal signal intensity involving both dentate nuclei of cerebellum and splenium of corpus callosum. The diagnosis of metronidazole toxicity was made by the MRI findings and supported clinically.

Metronidazole

Metronidazole

metronidazole

metronidazole

encephalopathy

encephalopathy

toxicity

Metronidazole

encephalopathy

Metronidazole

encephalopathy

Metronidazole

encephalopathy

Metronidazole

encephalopathy

metronidazole

encephalopathy

metronidazole

encephalopathy

metronidazole

encephalopathy

metronidazole

encephalopathy


Input: Aconitine - induced Ca2 + overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats. Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage - dependent Na (+) channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca (2 +) in aconitine poisoning. In this study, we explored the importance of pathological Ca (2 +) signaling in aconitine poisoning in vitro and in vivo. We found that Ca (2 +) overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats. To investigate effects of aconitine on myocardial injury, we performed cytotoxicity assay in neonatal rat ventricular myocytes (NRVMs), as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in rats. The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose - dependently. To confirm the pro - apoptotic effects, we performed flow cytometric detection, cardiac histology, transmission electron microscopy and terminal deoxynucleotidyl transferase - mediated dUTP - biotin nick end labeling assay. The results showed that aconitine stimulated apoptosis time - dependently. The expression analysis of Ca (2 +) handling proteins demonstrated that aconitine promoted Ca (2 +) overload through the expression regulation of Ca (2 +) handling proteins. The expression analysis of apoptosis - related proteins revealed that pro - apoptotic protein expression was upregulated, and anti - apoptotic protein BCL - 2 expression was downregulated. Furthermore, increased phosphorylation of MAPK family members, especially the P - P38 / P38 ratio was found in cardiac tissues. Hence, our results suggest that aconitine significantly aggravates Ca (2 +) overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen - activated protein kinase.

Aconitine

Aconitine

aconitine

Ca

aconitine

Ca

aconitine

Ca

aconitine

lactate

aconitine

dUTP

biotin

aconitine

Ca

aconitine

Ca

Ca

aconitine

Ca

arrhythmia

cardiotoxicity

poisoning

poisoning

arrhythmia

myocardial injury

cytotoxicity

myocardial injury

arrhythmia

Aconitine

poisoning

Aconitine

poisoning

Aconitine

poisoning

Aconitine

poisoning

aconitine

poisoning

aconitine

poisoning

aconitine

poisoning

aconitine

poisoning

aconitine

poisoning

aconitine

poisoning

aconitine

poisoning

aconitine

poisoning

aconitine

poisoning

aconitine

poisoning

aconitine

poisoning

aconitine

poisoning

aconitine

poisoning

aconitine

poisoning

aconitine

poisoning

aconitine

poisoning

Aconitine

cardiotoxicity

Aconitine

cardiotoxicity

aconitine

cardiotoxicity

aconitine

cardiotoxicity

aconitine

cardiotoxicity

aconitine

cardiotoxicity

aconitine

cardiotoxicity

aconitine

cardiotoxicity

aconitine

cardiotoxicity

aconitine

cardiotoxicity

Aconitine

arrhythmia

Aconitine

arrhythmia

Aconitine

arrhythmia

Aconitine

arrhythmia

Aconitine

arrhythmia

Aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia

aconitine

arrhythmia


Input: Chronic treatment with metformin suppresses toll - like receptor 4 signaling and attenuates left ventricular dysfunction following myocardial infarction. Acute treatment with metformin has a protective effect in myocardial infarction by suppression of inflammatory responses due to activation of AMP - activated protein kinase (AMPK). In the present study, the effect of chronic pre - treatment with metformin on cardiac dysfunction and toll - like receptor 4 (TLR4) activities following myocardial infarction and their relation with AMPK were assessed. Male Wistar rats were randomly assigned to one of 5 groups (n = 6): normal control and groups were injected isoproterenol after chronic pre - treatment with 0, 25, 50, or 100mg / kg of metformin twice daily for 14 days. Isoproterenol (100mg / kg) was injected subcutaneously on the 13th and 14th days to induce acute myocardial infarction. Isoproterenol alone decreased left ventricular systolic pressure and myocardial contractility indexed as LVdp / dtmax and LVdp / dtmin. The left ventricular dysfunction was significantly lower in the groups treated with 25 and 50mg / kg of metformin. Metfromin markedly lowered isoproterenol - induced elevation in the levels of TLR4 mRNA, myeloid differentiation protein 88 (MyD88), tumor necrosis factor - alpha (TNF - a), and interleukin 6 (IL - 6) in the heart tissues. Similar changes were also seen in the serum levels of TNF - a and IL - 6. However, the lower doses of 25 and 50mg / kg were more effective than 100mg / kg. Phosphorylated AMPKa (p - AMPK) in the myocardium was significantly elevated by 25mg / kg of metformin, slightly by 50mg / kg, but not by 100mg / kg. Chronic pre - treatment with metformin reduces post - myocardial infarction cardiac dysfunction and suppresses inflammatory responses, possibly through inhibition of TLR4 activities. This mechanism can be considered as a target to protect infarcted myocardium.

metformin

metformin

AMP

metformin

isoproterenol

metformin

Isoproterenol

Isoproterenol

metformin

isoproterenol

metformin

metformin

left ventricular dysfunction

myocardial infarction

myocardial infarction

cardiac dysfunction

myocardial infarction

acute myocardial infarction

left ventricular dysfunction

tumor

necrosis

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

acute myocardial infarction

isoproterenol

myocardial infarction

Isoproterenol

myocardial infarction

Isoproterenol

myocardial infarction

Isoproterenol

myocardial infarction

Isoproterenol

acute myocardial infarction

Isoproterenol

myocardial infarction

Isoproterenol

myocardial infarction

Isoproterenol

myocardial infarction

Isoproterenol

myocardial infarction

Isoproterenol

acute myocardial infarction

Isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

acute myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

left ventricular dysfunction

isoproterenol

left ventricular dysfunction

Isoproterenol

left ventricular dysfunction

Isoproterenol

left ventricular dysfunction

Isoproterenol

left ventricular dysfunction

Isoproterenol

left ventricular dysfunction

isoproterenol

left ventricular dysfunction

isoproterenol

left ventricular dysfunction