Instruction: Extract chemical and disease entities from the following text.

Input: Effects of long-term pretreatment with isoproterenol on bromocriptine-induced tachycardia in conscious rats. It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 receptors.

Output: Chemical/Disease Entities: isoproterenol (Chemical), bromocriptine (Chemical), tachycardia (Disease), bromocriptine (Chemical), tachycardia (Disease), dopamine (Chemical), isoproterenol (Chemical), isoproterenol (Chemical), bromocriptine (Chemical), tachycardia (Disease), Isoproterenol (Chemical), cardiac hypertrophy (Disease), bromocriptine (Chemical), hypotension (Disease), tachycardia (Disease), Bromocriptine (Chemical), hypotension (Disease), isoproterenol (Chemical), tachycardia (Disease), bradycardia (Disease), domperidone (Chemical), isoproterenol (Chemical), isoproterenol (Chemical), isoproterenol (Chemical), isoproterenol (Chemical), isoproterenol (Chemical), bromocriptine (Chemical), tachycardia (Disease), bradycardia (Disease), tachycardia (Disease), bromocriptine (Chemical), bradycardia (Disease), dopamine (Chemical)


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Input: A developmental analysis of clonidine's effects on cardiac rate and ultrasound production in infant rats. Under controlled conditions, infant rats emit ultrasonic vocalizations during extreme cold exposure and after administration of the alpha(2) adrenoceptor agonist, clonidine. Previous investigations have determined that, in response to clonidine, ultrasound production increases through the 2nd-week postpartum and decreases thereafter. Given that sympathetic neural dominance exhibits a similar developmental pattern, and given that clonidine induces sympathetic withdrawal and bradycardia, we hypothesized that clonidine's developmental effects on cardiac rate and ultrasound production would mirror each other. Therefore, in the present experiment, the effects of clonidine administration (0.5 mg/kg) on cardiac rate and ultrasound production were examined in 2-, 8-, 15-, and 20-day-old rats. Age-related changes in ultrasound production corresponded with changes in cardiovascular variables, including baseline cardiac rate and clonidine-induced bradycardia. This experiment is discussed with regard to the hypothesis that ultrasound production is the acoustic by-product of a physiological maneuver that compensates for clonidine's detrimental effects on cardiovascular function.

Output: Chemical/Disease Entities: clonidine (Chemical), clonidine (Chemical), clonidine (Chemical), clonidine (Chemical), bradycardia (Disease), clonidine (Chemical), clonidine (Chemical), clonidine (Chemical), bradycardia (Disease), clonidine (Chemical)


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Input: Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans. We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments. Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced the area of punctate-evoked hyperalgesia significantly. It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain. The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms and have a distinct pharmacology.

Output: Chemical/Disease Entities: ketamine (Chemical), lidocaine (Chemical), hyperalgesia (Disease), capsaicin (Chemical), ketamine (Chemical), lidocaine (Chemical), pain (Disease), hyperalgesia (Disease), capsaicin (Chemical), Capsaicin (Chemical), ketamine (Chemical), lidocaine (Chemical), capsaicin (Chemical), pain (Disease), pain (Disease), hyperalgesia (Disease), Ketamine (Chemical), hyperalgesia (Disease), pain (Disease), Lidocaine (Chemical), hyperalgesia (Disease), pain (Disease), pain (Disease), ketamine (Chemical), lidocaine (Chemical), hyperalgesia (Disease), hyperalgesia (Disease)


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Input: Cyclosporine and tacrolimus-associated thrombotic microangiopathy. The development of thrombotic microangiopathy (TMA) associated with the use of cyclosporine has been well documented. Treatments have included discontinuation or reduction of cyclosporine dose with or without concurrent plasma exchange, plasma infusion, anticoagulation, and intravenous immunoglobulin G infusion. However, for recipients of organ transplantation, removing the inciting agent is not without the attendant risk of precipitating acute rejection and graft loss. The last decade has seen the emergence of tacrolimus as a potent immunosuppressive agent with mechanisms of action virtually identical to those of cyclosporine. As a result, switching to tacrolimus has been reported to be a viable therapeutic option in the setting of cyclosporine-induced TMA. With the more widespread application of tacrolimus in organ transplantation, tacrolimus-associated TMA has also been recognized. However, literature regarding the incidence of the recurrence of TMA in patients exposed sequentially to cyclosporine and tacrolimus is limited. We report a case of a living donor renal transplant recipient who developed cyclosporine-induced TMA that responded to the withdrawal of cyclosporine in conjunction with plasmapheresis and fresh frozen plasma replacement therapy. Introduction of tacrolimus as an alternative immunosuppressive agent resulted in the recurrence of TMA and the subsequent loss of the renal allograft. Patients who are switched from cyclosporine to tacrolimus or vice versa should be closely monitored for the signs and symptoms of recurrent TMA.

Output: Chemical/Disease Entities: Cyclosporine (Chemical), tacrolimus (Chemical), thrombotic microangiopathy (Disease), thrombotic microangiopathy (Disease), TMA (Disease), cyclosporine (Chemical), cyclosporine (Chemical), tacrolimus (Chemical), cyclosporine (Chemical), tacrolimus (Chemical), cyclosporine (Chemical), TMA (Disease), tacrolimus (Chemical), tacrolimus (Chemical), TMA (Disease), TMA (Disease), cyclosporine (Chemical), tacrolimus (Chemical), cyclosporine (Chemical), TMA (Disease), cyclosporine (Chemical), tacrolimus (Chemical), TMA (Disease), cyclosporine (Chemical), tacrolimus (Chemical), TMA (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Repeated transient anuria following losartan administration in a patient with a solitary kidney. We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.

Output: Chemical/Disease Entities: anuria (Disease), losartan (Chemical), hypertensive (Disease), chronic renal insufficiency (Disease), anuria (Disease), losartan (Chemical), myocardial infarction (Disease), pulmonary edema (Disease), systolic dysfunction (Disease), losartan (Chemical), losartan (Chemical), anuria (Disease), furosemide (Chemical), amine (Chemical), losartan (Chemical), anuria (Disease), hypotension (Disease), renal artery stenosis (Disease), renal artery stenosis (Disease), heart failure (Disease), angiotensin (Chemical), angiotensin II (Chemical), losartan (Chemical), angiotensin II (Chemical), losartan (Chemical), renovascular disease (Disease)


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Input: In vivo protection of dna damage associated apoptotic and necrotic cell deaths during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract. Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.

Output: Chemical/Disease Entities: necrotic (Disease), acetaminophen (Chemical), nephrotoxicity (Disease), amiodarone (Chemical), lung toxicity (Disease), doxorubicin (Chemical), cardiotoxicity (Disease), IH636 grape seed proanthocyanidin extract (Chemical), Grape seed extract (Chemical), proanthocyanidins (Chemical), IH636 grape seed proanthocyanidin extract (Chemical), GSPE (Chemical), acetaminophen (Chemical), AAP (Chemical), nephrotoxicity (Disease), amiodarone (Chemical), AMI (Chemical), lung toxicity (Disease), doxorubicin (Chemical), DOX (Chemical), cardiotoxicity (Disease), GSPE (Chemical), GSPE (Chemical), GSPE (Chemical), AAP (Chemical), AMI (Chemical), DOX (Chemical), GSPE (Chemical), AAP (Chemical), AMI (Chemical), DOX (Chemical), tissue damage (Disease), GSPE (Chemical), GSPE (Chemical), AAP (Chemical), AMI (Chemical), DOX (Chemical), necrosis (Disease), GSPE (Chemical), AAP (Chemical), AMI (Chemical), DOX (Chemical), GSPE (Chemical), AMI (Chemical), GSPE (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Palpebral twitching in a depressed adolescent on citalopram. Current estimates suggest that between 0.4% and 8.3% of children and adolescents are affected by major depression. We report a favorable response to treatment with citalopram by a 15-year-old boy with major depression who exhibited palpebral twitching during his first 2 weeks of treatment. This may have been a side effect of citalopram as it remitted with redistribution of doses.

Output: Chemical/Disease Entities: Palpebral twitching (Disease), depressed (Disease), citalopram (Chemical), major depression (Disease), citalopram (Chemical), major depression (Disease), palpebral twitching (Disease), citalopram (Chemical)


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Input: Metamizol potentiates morphine antinociception but not constipation after chronic treatment. This work evaluates the antinociceptive and constipating effects of the combination of 3.2 mg/kg s.c. morphine with 177.8 mg/kg s.c. metamizol in acutely and chronically treated (once a day for 12 days) rats. On the 13th day, antinociceptive effects were assessed using a model of inflammatory nociception, pain-induced functional impairment model, and the charcoal meal test was used to evaluate the intestinal transit. Simultaneous administration of morphine with metamizol resulted in a markedly antinociceptive potentiation and an increasing of the duration of action after a single (298+/-7 vs. 139+/-36 units area (ua); P<0.001) and repeated administration (280+/-17 vs. 131+/-22 ua; P<0.001). Antinociceptive effect of morphine was reduced in chronically treated rats (39+/-10 vs. 18+/-5 au) while the combination-induced antinociception was remained similar as an acute treatment (298+/-7 vs. 280+/-17 au). Acute antinociceptive effects of the combination were partially prevented by 3.2 mg/kg naloxone s.c. (P<0.05), suggesting the partial involvement of the opioidergic system in the synergism observed. In independent groups, morphine inhibited the intestinal transit in 48+/-4% and 38+/-4% after acute and chronic treatment, respectively, suggesting that tolerance did not develop to the constipating effects. The combination inhibited intestinal transit similar to that produced by morphine regardless of the time of treatment, suggesting that metamizol did not potentiate morphine-induced constipation. These findings show a significant interaction between morphine and metamizol in chronically treated rats, suggesting that this combination could be useful for the treatment of chronic pain.

Output: Chemical/Disease Entities: Metamizol (Chemical), morphine (Chemical), constipation (Disease), constipating (Disease), morphine (Chemical), metamizol (Chemical), pain (Disease), charcoal (Chemical), morphine (Chemical), metamizol (Chemical), morphine (Chemical), naloxone (Chemical), morphine (Chemical), constipating (Disease), morphine (Chemical), metamizol (Chemical), morphine (Chemical), constipation (Disease), morphine (Chemical), metamizol (Chemical), chronic pain (Disease)


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Input: Ifosfamide encephalopathy presenting with asterixis. CNS toxic effects of the antineoplastic agent ifosfamide (IFX) are frequent and include a variety of neurological symptoms that can limit drug use. We report a case of a 51-year-old man who developed severe, disabling negative myoclonus of the upper and lower extremities after the infusion of ifosfamide for plasmacytoma. He was awake, revealed no changes of mental status and at rest there were no further motor symptoms. Cranial magnetic resonance imaging and extensive laboratory studies failed to reveal structural lesions of the brain and metabolic abnormalities. An electroencephalogram showed continuous, generalized irregular slowing with admixed periodic triphasic waves indicating symptomatic encephalopathy. The administration of ifosfamide was discontinued and within 12 h the asterixis resolved completely. In the patient described, the presence of asterixis during infusion of ifosfamide, normal laboratory findings and imaging studies and the resolution of symptoms following the discontinuation of the drug suggest that negative myoclonus is associated with the use of IFX.

Output: Chemical/Disease Entities: Ifosfamide (Chemical), encephalopathy (Disease), asterixis (Disease), ifosfamide (Chemical), IFX (Chemical), myoclonus (Disease), ifosfamide (Chemical), plasmacytoma (Disease), structural lesions of the brain (Disease), metabolic abnormalities (Disease), encephalopathy (Disease), ifosfamide (Chemical), asterixis (Disease), asterixis (Disease), ifosfamide (Chemical), myoclonus (Disease), IFX (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Sub-chronic low dose gamma-vinyl GABA (vigabatrin) inhibits cocaine-induced increases in nucleus accumbens dopamine. RATIONALE: gamma-Vinyl GABA (GVG) irreversibly inhibits GABA-transaminase. This non-receptor mediated inhibition requires de novo synthesis for restoration of functional GABA catabolism. OBJECTIVES: Given its preclinical success for treating substance abuse and the increased risk of visual field defects (VFD) associated with cumulative lifetime exposure, we explored the effects of sub-chronic low dose GVG on cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA). METHODS: Using in vivo microdialysis, we compared acute exposure (450 mg/kg) to an identical sub-chronic exposure (150 mg/kg per day for 3 days), followed by 1- or 3-day washout. Finally, we examined the low dose of 150 mg/kg (50 mg/kg per day) using a similar washout period. RESULTS: Sub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose. CONCLUSIONS: Sub-chronic low dose GVG potentiates and extends the inhibition of cocaine-induced increases in dopamine, effectively reducing cumulative exposures and the risk for VFDS.

Output: Chemical/Disease Entities: gamma-vinyl GABA (Chemical), vigabatrin (Chemical), cocaine (Chemical), dopamine (Chemical), gamma-Vinyl GABA (Chemical), GVG (Chemical), GABA (Chemical), GABA (Chemical), substance abuse (Disease), visual field defects (Disease), VFD (Disease), GVG (Chemical), cocaine (Chemical), dopamine (Chemical), DA (Chemical), GVG (Chemical), cocaine (Chemical), GVG (Chemical), cocaine (Chemical), dopamine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Amount of bleeding and hematoma size in the collagenase-induced intracerebral hemorrhage rat model. The aggravated risk on intracerebral hemorrhage (ICH) with drugs used for stroke patients should be estimated carefully. We therefore established sensitive quantification methods and provided a rat ICH model for detection of ICH deterioration. In ICH intrastriatally induced by 0.014-unit, 0.070-unit, and 0.350-unit collagenase, the amount of bleeding was measured using a hemoglobin assay developed in the present study and was compared with the morphologically determined hematoma volume. The blood amounts and hematoma volumes were significantly correlated, and the hematoma induced by 0.014-unit collagenase was adequate to detect ICH deterioration. In ICH induction using 0.014-unit collagenase, heparin enhanced the hematoma volume 3.4-fold over that seen in control ICH animals and the bleeding 7.6-fold. Data suggest that this sensitive hemoglobin assay is useful for ICH detection, and that a model with a small ICH induced with a low-dose collagenase should be used for evaluation of drugs that may affect ICH.

Output: Chemical/Disease Entities: bleeding (Disease), hematoma (Disease), intracerebral hemorrhage (Disease), intracerebral hemorrhage (Disease), ICH (Disease), stroke (Disease), ICH (Disease), ICH (Disease), ICH (Disease), bleeding (Disease), hematoma (Disease), hematoma (Disease), hematoma (Disease), ICH (Disease), ICH (Disease), heparin (Chemical), hematoma (Disease), ICH (Disease), bleeding (Disease), ICH (Disease), ICH (Disease), ICH (Disease)


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Input: Estradiol reduces seizure-induced hippocampal injury in ovariectomized female but not in male rats. Estrogens protect ovariectomized rats from hippocampal injury induced by kainic acid-induced status epilepticus (SE). We compared the effects of 17beta-estradiol in adult male and ovariectomized female rats subjected to lithium-pilocarpine-induced SE. Rats received subcutaneous injections of 17beta-estradiol (2 microg/rat) or oil once daily for four consecutive days. SE was induced 20 h following the second injection and terminated 3 h later. The extent of silver-stained CA3 and CA1 hippocampal neurons was evaluated 2 days after SE. 17beta-Estradiol did not alter the onset of first clonus in ovariectomized rats but accelerated it in males. 17beta-Estradiol reduced the argyrophilic neurons in the CA1 and CA3-C sectors of ovariectomized rats. In males, estradiol increased the total damage score. These findings suggest that the effects of estradiol on seizure threshold and damage may be altered by sex-related differences in the hormonal environment.

Output: Chemical/Disease Entities: Estradiol (Chemical), seizure (Disease), hippocampal injury (Disease), hippocampal injury (Disease), kainic acid (Chemical), status epilepticus (Disease), SE (Disease), 17beta-estradiol (Chemical), lithium (Chemical), pilocarpine (Chemical), SE (Disease), 17beta-estradiol (Chemical), SE (Disease), silver (Chemical), SE (Disease), 17beta-Estradiol (Chemical), 17beta-Estradiol (Chemical), estradiol (Chemical), estradiol (Chemical), seizure (Disease)


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Input: Delirium during clozapine treatment: incidence and associated risk factors. BACKGROUND: Incidence and risk factors for delirium during clozapine treatment require further clarification. METHODS: We used computerized pharmacy records to identify all adult psychiatric inpatients treated with clozapine (1995-96), reviewed their medical records to score incidence and severity of delirium, and tested associations with potential risk factors. RESULTS: Subjects (n = 139) were 72 women and 67 men, aged 40.8 +/- 12.1 years, hospitalized for 24.9 +/- 23.3 days, and given clozapine, gradually increased to an average daily dose of 282 +/- 203 mg (3.45 +/- 2.45 mg/kg) for 18.9 +/- 16.4 days. Delirium was diagnosed in 14 (10.1 % incidence, or 1.48 cases/person-years of exposure); 71.4 % of cases were moderate or severe. Associated factors were co-treatment with other centrally antimuscarinic agents, poor clinical outcome, older age, and longer hospitalization (by 17.5 days, increasing cost); sex, diagnosis or medical co-morbidity, and daily clozapine dose, which fell with age, were unrelated. CONCLUSIONS: Delirium was found in 10 % of clozapine-treated inpatients, particularly in older patients exposed to other central anticholinergics. Delirium was inconsistently recognized clinically in milder cases and was associated with increased length-of-stay and higher costs, and inferior clinical outcome.

Output: Chemical/Disease Entities: Delirium (Disease), clozapine (Chemical), delirium (Disease), clozapine (Chemical), psychiatric (Disease), clozapine (Chemical), delirium (Disease), clozapine (Chemical), Delirium (Disease), clozapine (Chemical), Delirium (Disease), clozapine (Chemical), Delirium (Disease)


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Input: Ketoconazole-induced neurologic sequelae. A 77-y-old patient developed weakness of extremities, legs paralysis, dysarthria and tremor 1 h after ingestion of 200 mg ketoconazole for the first time in his life. All complaints faded away within 24 h. Few days later, the patient used another 200 mg ketoconazole tablet, and within an hour experienced a similar clinical picture, which resolved again spontaneously within hours. Laboratory evaluations, including head CT scan, were normal. This case illustrates the need for close vigilance in adverse drug reactions, particularly in the elderly.

Output: Chemical/Disease Entities: Ketoconazole (Chemical), neurologic sequelae (Disease), weakness of extremities (Disease), legs paralysis (Disease), dysarthria (Disease), tremor (Disease), ketoconazole (Chemical), ketoconazole (Chemical), adverse drug reactions (Disease)


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Input: Noxious chemical stimulation of rat facial mucosa increases intracranial blood flow through a trigemino-parasympathetic reflex--an experimental model for vascular dysfunctions in cluster headache. Cluster headache is characterized by typical autonomic dysfunctions including facial and intracranial vascular disturbances. Both the trigeminal and the cranial parasympathetic systems may be involved in mediating these dysfunctions. An experimental model was developed in the rat to measure changes in lacrimation and intracranial blood flow following noxious chemical stimulation of facial mucosa. Blood flow was monitored in arteries of the exposed cranial dura mater and the parietal cortex using laser Doppler flowmetry. Capsaicin (0.01-1 mm) applied to oral or nasal mucosa induced increases in dural and cortical blood flow and provoked lacrimation. These responses were blocked by systemic pre-administration of hexamethonium chloride (20 mg/kg). The evoked increases in dural blood flow were also abolished by topical pre-administration of atropine (1 mm) and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (0.1 mm), a vasoactive intestinal polypeptide (VIP) antagonist, onto the exposed dura mater. We conclude that noxious stimulation of facial mucosa increases intracranial blood flow and lacrimation via a trigemino-parasympathetic reflex. The blood flow responses seem to be mediated by the release of acetylcholine and VIP within the meninges. Similar mechanisms may be involved in the pathogenesis of cluster headache.

Output: Chemical/Disease Entities: vascular dysfunctions (Disease), cluster headache (Disease), Cluster headache (Disease), intracranial vascular disturbances (Disease), Capsaicin (Chemical), increases in dural and cortical blood flow (Disease), hexamethonium chloride (Chemical), increases in dural blood flow (Disease), atropine (Chemical), acetylcholine (Chemical), cluster headache (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Recurrent excitation in the dentate gyrus of a murine model of temporal lobe epilepsy. Similar to rats, systemic pilocarpine injection causes status epilepticus (SE) and the eventual development of spontaneous seizures and mossy fiber sprouting in C57BL/6 and CD1 mice, but the physiological correlates of these events have not been identified in mice. Population responses in granule cells of the dentate gyrus were examined in transverse slices of the ventral hippocampus from pilocarpine-treated and untreated mice. In Mg(2+)-free bathing medium containing bicuculline, conditions designed to increase excitability in the slices, electrical stimulation of the hilus resulted in a single population spike in granule cells from control mice and pilocarpine-treated mice that did not experience SE. In SE survivors, similar stimulation resulted in a population spike followed, at a variable latency, by negative DC shifts and repetitive afterdischarges of 3-60 s duration, which were blocked by ionotropic glutamate receptor antagonists. Focal glutamate photostimulation of the granule cell layer at sites distant from the recording pipette resulted in population responses of 1-30 s duration in slices from SE survivors but not other groups. These data support the hypothesis that SE-induced mossy fiber sprouting and synaptic reorganization are relevant characteristics of seizure development in these murine strains, resembling rat models of human temporal lobe epilepsy.

Output: Chemical/Disease Entities: temporal lobe epilepsy (Disease), pilocarpine (Chemical), status epilepticus (Disease), SE (Disease), seizures (Disease), pilocarpine (Chemical), Mg (Chemical), bicuculline (Chemical), pilocarpine (Chemical), SE (Disease), SE (Disease), glutamate (Chemical), glutamate (Chemical), SE (Disease), SE (Disease), seizure (Disease), temporal lobe epilepsy (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice. Binding of nicotine to nicotinic acetylcholine receptors (nAChRs) elicits a series of dose-dependent behaviors that go from altered exploration, sedation, and tremors, to seizures and death. nAChRs are pentameric ion channels usually composed of alpha and beta subunits. A gene cluster comprises the alpha3, alpha5 and beta4 subunits, which coassemble to form functional receptors. We examined the role of the beta4 subunits in nicotine-induced seizures and hypolocomotion in beta4 homozygous null (beta4 -/-) and alpha3 heterozygous (+/-) mice. beta4 -/- mice were less sensitive to the effects of nicotine both at low doses, measured as decreased exploration in an open field, and at high doses, measured as sensitivity to nicotine-induced seizures. Using in situ hybridization probes for the alpha3 and alpha5 subunits, we showed that alpha5 mRNA levels are unchanged, whereas alpha3 mRNA levels are selectively decreased in the mitral cell layer of the olfactory bulb, and the inferior and the superior colliculus of beta4 -/- brains. alpha3 +/- mice were partially resistant to nicotine-induced seizures when compared to wild-type littermates. mRNA levels for the alpha5 and the beta4 subunits were unchanged in alpha3 +/- brains. Together, these results suggest that the beta4 and the alpha3 subunits are mediators of nicotine-induced seizures and hypolocomotion.

Output: Chemical/Disease Entities: acetylcholine (Chemical), nicotine (Chemical), seizures (Disease), hypolocomotion (Disease), nicotine (Chemical), acetylcholine (Chemical), tremors (Disease), seizures (Disease), death (Disease), nicotine (Chemical), seizures (Disease), hypolocomotion (Disease), nicotine (Chemical), nicotine (Chemical), seizures (Disease), nicotine (Chemical), seizures (Disease), nicotine (Chemical), seizures (Disease), hypolocomotion (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Recurrent acute interstitial nephritis induced by azithromycin. A 14-year-old girl is reported with recurrent, azithromycin-induced, acute interstitial nephritis. The second episode was more severe than the first; and although both were treated with intensive corticosteroid therapy, renal function remained impaired. Although most cases of antibiotic induced acute interstitial nephritis are benign and self-limited, some patients are at risk for permanent renal injury.

Output: Chemical/Disease Entities: interstitial nephritis (Disease), azithromycin (Chemical), azithromycin (Chemical), interstitial nephritis (Disease), interstitial nephritis (Disease), renal injury (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Valproate-induced encephalopathy. Valproate-induced encephalopathy is a rare syndrome that may manifest in otherwise normal epileptic individuals. It may even present in patients who have tolerated this medicine well in the past. It is usually but not necessarily associated with hyperammonemia. The EEG shows characteristic triphasic waves in most patients with this complication. A case of valproate-induced encephalopathy is presented. The problems in diagnosing this condition are subsequently discussed.

Output: Chemical/Disease Entities: Valproate (Chemical), encephalopathy (Disease), Valproate (Chemical), encephalopathy (Disease), epileptic (Disease), hyperammonemia (Disease), valproate (Chemical), encephalopathy (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Nitro-L-arginine methyl ester: a potential protector against gentamicin ototoxicity. The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.

Output: Chemical/Disease Entities: Nitro-L-arginine methyl ester (Chemical), gentamicin (Chemical), ototoxicity (Disease), nitric oxide (Chemical), NO (Chemical), nitro-L-arginine methyl ester (Chemical), L-NAME (Chemical), high-frequency hearing loss (Disease), gentamicin (Chemical), Aminoglycoside (Chemical), ototoxicity (Disease), ototoxic (Disease), NO (Chemical), NO (Chemical), aminoglycoside (Chemical), sensorineural hearing loss (Disease), gentamicin (Chemical), L-NAME (Chemical), hearing loss (Disease), L-NAME (Chemical), gentamicin (Chemical), hearing loss (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Cerebral vasculitis following oral methylphenidate intake in an adult: a case report. Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.

Output: Chemical/Disease Entities: Cerebral vasculitis (Disease), methylphenidate (Chemical), Methylphenidate (Chemical), amphetamine (Chemical), Cerebral vasculitis (Disease), amphetamine abuse (Disease), ischaemic stroke (Disease), methylphenidate (Chemical), methylphenidate (Chemical), hyperactivity (Disease), ischaemic strokes (Disease), cerebral vasculitis (Disease), ischaemic strokes (Disease), methylphenidate (Chemical), vasculitis (Disease), methylphenidate (Chemical), methylphenidate (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Cerebral haemorrhage induced by warfarin - the influence of drug-drug interactions. PURPOSE: To evaluate the frequency, severity and preventability of warfarin-induced cerebral haemorrhages due to warfarin and warfarin-drug interactions in patients living in the county of Osterg  tland, Sweden. METHODS: All patients with a diagnosed cerebral haemorrhage at three hospitals during the period 2000-2002 were identified. Medical records were studied retrospectively to evaluate whether warfarin and warfarin-drug interactions could have caused the cerebral haemorrhage. The proportion of possibly avoidable cases due to drug interactions was estimated. RESULTS: Among 593 patients with cerebral haemorrhage, 59 (10%) were assessed as related to warfarin treatment. This imply an incidence of 1.7/100,000 treatment years. Of the 59 cases, 26 (44%) had a fatal outcome, compared to 136 (25%) among the non-warfarin patients (p < 0.01). A warfarin-drug interaction could have contributed to the haemorrhage in 24 (41%) of the warfarin patients and in 7 of these (12%) the bleeding complication was considered being possible to avoid. CONCLUSIONS: Warfarin-induced cerebral haemorrhages are a major clinical problem with a high fatality rate. Almost half of the cases was related to a warfarin-drug interaction. A significant proportion of warfarin-related cerebral haemorrhages might have been prevented if greater caution had been taken when prescribing drugs known to interact with warfarin.

Output: Chemical/Disease Entities: Cerebral haemorrhage (Disease), warfarin (Chemical), warfarin (Chemical), cerebral haemorrhages (Disease), warfarin (Chemical), warfarin (Chemical), cerebral haemorrhage (Disease), warfarin (Chemical), warfarin (Chemical), cerebral haemorrhage (Disease), cerebral haemorrhage (Disease), warfarin (Chemical), warfarin (Chemical), warfarin (Chemical), haemorrhage (Disease), warfarin (Chemical), bleeding (Disease), Warfarin (Chemical), cerebral haemorrhages (Disease), warfarin (Chemical), warfarin (Chemical), cerebral haemorrhages (Disease), warfarin (Chemical)


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Input: Side effects of postoperative administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space. PURPOSE: To assess the incidence of postoperative emetic side effects after the administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space at the end of routine cataract surgery. SETTING: St. Luke's Hospital, Gwardamangia, Malta. METHODS: A double-blind double-armed prospective study comprised 40 patients who had uneventful sutureless phacoemulsification under sub-Tenon's local infiltration of 3 mL of plain lignocaine. At the end of the procedure, Group A (n = 20) had 20 mg/0.5 mL of methylprednisolone and 10 mg/0.5 mL of gentamicin injected into the posterior sub-Tenon's space and Group B (n = 20) had the same combination injected into the anterior sub-Tenon's space. Postoperatively, all patients were assessed for symptoms of nausea, vomiting, and headache. A chi-square test was used to assess the statistical significance of results. RESULTS: Sixty percent in Group A developed postoperative emetic symptoms, headache, or both; 1 patient in Group B developed symptoms. CONCLUSIONS: The administration of methylprednisolone and gentamicin in the posterior sub-Tenon's space was related to a high incidence of side effects including nausea, vomiting, and headache. All adverse effects were self-limiting.

Output: Chemical/Disease Entities: methylprednisolone (Chemical), gentamicin (Chemical), methylprednisolone (Chemical), gentamicin (Chemical), cataract (Disease), lignocaine (Chemical), methylprednisolone (Chemical), gentamicin (Chemical), nausea, vomiting (Disease), headache (Disease), postoperative emetic symptoms (Disease), headache (Disease), methylprednisolone (Chemical), gentamicin (Chemical), nausea, vomiting (Disease), headache (Disease)


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Input: Cardiac Angiography in Renally Impaired Patients (CARE) study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease. BACKGROUND: No direct comparisons exist of the renal tolerability of the low-osmolality contrast medium iopamidol with that of the iso-osmolality contrast medium iodixanol in high-risk patients. METHODS AND RESULTS: The present study is a multicenter, randomized, double-blind comparison of iopamidol and iodixanol in patients with chronic kidney disease (estimated glomerular filtration rate, 20 to 59 mL/min) who underwent cardiac angiography or percutaneous coronary interventions. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2 to 5 days after receiving medications. The primary outcome was a postdose SCr increase > or = 0.5 mg/dL (44.2 micromol/L) over baseline. Secondary outcomes were a postdose SCr increase > or = 25%, a postdose estimated glomerular filtration rate decrease of > or = 25%, and the mean peak change in SCr. In 414 patients, contrast volume, presence of diabetes mellitus, use of N-acetylcysteine, mean baseline SCr, and estimated glomerular filtration rate were comparable in the 2 groups. SCr increases > or = 0.5 mg/dL occurred in 4.4% (9 of 204 patients) after iopamidol and 6.7% (14 of 210 patients) after iodixanol (P=0.39), whereas rates of SCr increases > or = 25% were 9.8% and 12.4%, respectively (P=0.44). In patients with diabetes, SCr increases > or = 0.5 mg/dL were 5.1% (4 of 78 patients) with iopamidol and 13.0% (12 of 92 patients) with iodixanol (P=0.11), whereas SCr increases > or = 25% were 10.3% and 15.2%, respectively (P=0.37). Mean post-SCr increases were significantly less with iopamidol (all patients: 0.07 versus 0.12 mg/dL, 6.2 versus 10.6 micromol/L, P=0.03; patients with diabetes: 0.07 versus 0.16 mg/dL, 6.2 versus 14.1 micromol/L, P=0.01). CONCLUSIONS: The rate of contrast-induced nephropathy, defined by multiple end points, is not statistically different after the intraarterial administration of iopamidol or iodixanol to high-risk patients, with or without diabetes mellitus. Any true difference between the agents is small and not likely to be clinically significant.

Output: Chemical/Disease Entities: nephropathy (Disease), chronic kidney disease (Disease), contrast medium (Chemical), iopamidol (Chemical), contrast medium (Chemical), iodixanol (Chemical), iopamidol (Chemical), iodixanol (Chemical), chronic kidney disease (Disease), creatinine (Chemical), diabetes mellitus (Disease), N-acetylcysteine (Chemical), iopamidol (Chemical), iodixanol (Chemical), diabetes (Disease), iopamidol (Chemical), iodixanol (Chemical), iopamidol (Chemical), diabetes (Disease), nephropathy (Disease), iopamidol (Chemical), iodixanol (Chemical), diabetes mellitus (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: A novel compound, maltolyl p-coumarate, attenuates cognitive deficits and shows neuroprotective effects in vitro and in vivo dementia models. To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.

Output: Chemical/Disease Entities: maltolyl p-coumarate (Chemical), cognitive deficits (Disease), dementia (Disease), maltolyl p-coumarate (Chemical), maltol (Chemical), p-coumaric acid (Chemical), maltolyl p-coumarate (Chemical), cognitive decline (Disease), scopolamine (Chemical), amyloid beta peptide(1-42) (Chemical), Maltolyl p-coumarate (Chemical), cognitive deficits (Disease), amyloid beta peptide(1-42) (Chemical), maltolyl p-coumarate (Chemical), maltolyl p-coumarate (Chemical), amyloid beta peptide(1-42) (Chemical), glutamate (Chemical), H2O2 (Chemical), maltolyl p-coumarate (Chemical), maltolyl p-coumarate (Chemical), Alzheimer's disease (Disease), neuronal death (Disease), decline of cognitive function (Disease)


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Input: Interaction between warfarin and levofloxacin: case series. Warfarin is the most widely used oral anticoagulant and is indicated for many clinical conditions. Levofloxacin, a fluoroquinolone, is one of the most commonly prescribed antibiotics in clinical practice and is effective against Gram-positive, Gram-negative, and atypical bacteria. While small prospective studies have not revealed any significant drug-drug interaction between warfarin and levofloxacin, several case reports have indicated that levofloxacin may significantly potentiate the anticoagulation effect of warfarin. We report 3 cases of serious bleeding complications that appear to be the result of the interaction between warfarin and levofloxacin. Physicians should be aware of this potential interaction and use caution when prescribing levofloxacin to patients taking warfarin.

Output: Chemical/Disease Entities: warfarin (Chemical), levofloxacin (Chemical), Warfarin (Chemical), Levofloxacin (Chemical), fluoroquinolone (Chemical), warfarin (Chemical), levofloxacin (Chemical), levofloxacin (Chemical), warfarin (Chemical), bleeding (Disease), warfarin (Chemical), levofloxacin (Chemical), levofloxacin (Chemical), warfarin (Chemical)


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Input: Mutations associated with lamivudine-resistance in therapy-na  ve hepatitis B virus (HBV) infected patients with and without HIV co-infection: implications for antiretroviral therapy in HBV and HIV co-infected South African patients. This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-na  ve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-na  ve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-na  ve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients.

Output: Chemical/Disease Entities: lamivudine (Chemical), na (Chemical), hepatitis B virus (HBV) infected (Disease), HIV co-infection (Disease), lamivudine (Chemical), hepatitis B (Disease), lamivudine (Chemical), na (Chemical), human immunodeficiency virus (HIV) co-infection (Disease), lamivudine (Chemical), na (Chemical), HBV infected (Disease), HIV co-infection (Disease), HBV mono-infected (Disease), HBsAg (Chemical), HBsAg (Chemical), HBsAg (Chemical), tyrosine (Chemical), methionine (Chemical), aspartate (Chemical), aspartate (Chemical), lamivudine (Chemical), hepatitis B (Disease), lamivudine (Chemical), na (Chemical), lamivudine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Sex differences in NMDA antagonist enhancement of morphine antihyperalgesia in a capsaicin model of persistent pain: comparisons to two models of acute pain. In acute pain models, N-methyl-D-aspartate (NMDA) antagonists enhance the antinociceptive effects of morphine to a greater extent in males than females. The purpose of this investigation was to extend these findings to a persistent pain model which could be distinguished from acute pain models on the basis of the nociceptive fibers activated, neurochemical substrates, and duration of the nociceptive stimulus. To this end, persistent hyperalgesia was induced by administration of capsaicin in the tail of gonadally intact F344 rats, following which the tail was immersed in a mildly noxious thermal stimulus, and tail-withdrawal latencies measured. For comparison, tests were conducted in two acute pain models, the hotplate and warm water tail-withdrawal procedures. In males, the non-competitive NMDA antagonist dextromethorphan enhanced the antihyperalgesic effect of low to moderate doses of morphine in a dose-and time-dependent manner. Across the doses and pretreatment times examined, enhancement was not observed in females. Enhancement of morphine antinociception by dextromethorphan was seen in both males and females in the acute pain models, with the magnitude of this effect being greater in males. These findings demonstrate a sexually-dimorphic interaction between NMDA antagonists and morphine in a persistent pain model that can be distinguished from those observed in acute pain models.

Output: Chemical/Disease Entities: NMDA (Chemical), morphine (Chemical), capsaicin (Chemical), pain (Disease), acute pain (Disease), acute pain (Disease), N-methyl-D-aspartate (Chemical), NMDA (Chemical), morphine (Chemical), pain (Disease), acute pain (Disease), hyperalgesia (Disease), capsaicin (Chemical), acute pain (Disease), NMDA (Chemical), dextromethorphan (Chemical), morphine (Chemical), morphine (Chemical), dextromethorphan (Chemical), acute pain (Disease), NMDA (Chemical), morphine (Chemical), pain (Disease), acute pain (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Development of proteinuria after switch to sirolimus-based immunosuppression in long-term cardiac transplant patients. Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.

Output: Chemical/Disease Entities: proteinuria (Disease), sirolimus (Chemical), renal dysfunction (Disease), sirolmus (Chemical), Srl (Chemical), nephrotoxic (Disease), proteinuria (Disease), Srl (Chemical), proteinuria (Disease), Srl (Chemical), cyclosporine (Chemical), Srl (Chemical), mycophenolate mofetil (Chemical), steroids (Chemical), proteinuria (Disease), ACE inhibitor (Chemical), angiotensin-releasing blocker (Chemical), ARB (Chemical), proteinuria (Disease), proteinuria (Disease), proteinuria (Disease), proteinuria (Disease), Srl (Chemical), Srl (Chemical), ACEi (Chemical), ARB (Chemical), proteinuria (Disease), renal dysfunction (Disease)


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Input: Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonists. A series of N-pyrimidinyl-2-phenoxyacetamide adenosine A(2A) antagonists is described. SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM), selectivity (A(1)/A(2A) > 100), and efficacy (MED 10 mg/kg p.o.) in the rat haloperidol-induced catalepsy model for Parkinson's disease.

Output: Chemical/Disease Entities: N-pyrimidinyl-2-phenoxyacetamides (Chemical), adenosine (Chemical), N-pyrimidinyl-2-phenoxyacetamide (Chemical), adenosine (Chemical), haloperidol (Chemical), catalepsy (Disease), Parkinson's disease (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Methamphetamine-induced neurotoxicity and microglial activation are not mediated by fractalkine receptor signaling. Methamphetamine (METH) damages dopamine (DA) nerve endings by a process that has been linked to microglial activation but the signaling pathways that mediate this response have not yet been delineated. Cardona et al. [Nat. Neurosci. 9 (2006), 917] recently identified the microglial-specific fractalkine receptor (CX3CR1) as an important mediator of MPTP-induced neurodegeneration of DA neurons. Because the CNS damage caused by METH and MPTP is highly selective for the DA neuronal system in mouse models of neurotoxicity, we hypothesized that the CX3CR1 plays a role in METH-induced neurotoxicity and microglial activation. Mice in which the CX3CR1 gene has been deleted and replaced with a cDNA encoding enhanced green fluorescent protein (eGFP) were treated with METH and examined for striatal neurotoxicity. METH depleted DA, caused microglial activation, and increased body temperature in CX3CR1 knockout mice to the same extent and over the same time course seen in wild-type controls. The effects of METH in CX3CR1 knockout mice were not gender-dependent and did not extend beyond the striatum. Striatal microglia expressing eGFP constitutively show morphological changes after METH that are characteristic of activation. This response was restricted to the striatum and contrasted sharply with unresponsive eGFP-microglia in surrounding brain areas that are not damaged by METH. We conclude from these studies that CX3CR1 signaling does not modulate METH neurotoxicity or microglial activation. Furthermore, it appears that striatal-resident microglia respond to METH with an activation cascade and then return to a surveying state without undergoing apoptosis or migration.

Output: Chemical/Disease Entities: Methamphetamine (Chemical), neurotoxicity (Disease), Methamphetamine (Chemical), METH (Chemical), dopamine (Chemical), DA (Chemical), MPTP (Chemical), neurodegeneration (Disease), DA (Chemical), CNS damage (Disease), METH (Chemical), MPTP (Chemical), DA (Chemical), neurotoxicity (Disease), METH (Chemical), neurotoxicity (Disease), METH (Chemical), neurotoxicity (Disease), METH (Chemical), DA (Chemical), METH (Chemical), METH (Chemical), METH (Chemical), METH (Chemical), neurotoxicity (Disease), METH (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Recovery of tacrolimus-associated brachial neuritis after conversion to everolimus in a pediatric renal transplant recipient--case report and review of the literature. TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.

Output: Chemical/Disease Entities: tacrolimus (Chemical), brachial neuritis (Disease), everolimus (Chemical), TAC (Chemical), Neurotoxicity (Disease), encephalopathy (Disease), headaches (Disease), seizures (Disease), neurological deficits (Disease), myelitis (Disease), brachial plexitis (Disease), TAC (Chemical), methylprednisolone (Chemical), TAC (Chemical), everolimus (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Valvular heart disease in patients with Parkinson's disease treated with pergolide. Course following treatment modifications. Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.

Output: Chemical/Disease Entities: Valvular heart disease (Disease), Parkinson's disease (Disease), pergolide (Chemical), Valvular heart abnormalities (Disease), Parkinson's disease (Disease), PD (Disease), pergolide (Chemical), valvular heart abnormality (Disease), PD (Disease), pergolide (Chemical), PD (Disease), pergolide (Chemical), PD (Disease), aortic regurgitation (Disease), mitral regurgitation (Disease), PD (Disease), pergolide (Chemical), pergolide (Chemical), valvular regurgitation (Disease), pergolide (Chemical), heart failure (Disease), Pergolide (Chemical), valvular heart disease (Disease), heart failure (Disease), valve regurgitation (Disease), PD (Disease), pergolide (Chemical), dopamine (Chemical)


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Input: Adverse effects of topical papaverine on auditory nerve function. BACKGROUND: Papaverine hydrochloride is a direct-acting vasodilator used to manage vasospasm during various neurosurgical operations. Transient cranial nerve dysfunction has been described in a few cases with topical papaverine. This study supports previous reports and provides neurophysiological evidence of an adverse effect on the auditory nerve. METHODS: We conducted a retrospective review of 70 consecutive microvascular decompression operations and studied those patients who received topical papaverine for vasospasm. Topical papaverine was used as a direct therapeutic action to manage vasospasm in a total of 11 patients. The timing of papaverine application and ongoing operative events was reviewed relative to changes in neurophysiological recordings. Brainstem auditory evoked potentials (BAEPs) were routinely used to monitor cochlear nerve function during these operations. FINDINGS: A temporal relationship was found between topical papaverine and BAEP changes leading to complete waveform loss. The average temporal delay between papaverine and the onset of an adverse BAEP change was 5 min. In 10 of 11 patients, BAEP waves II/III-V completely disappeared within 2 to 25 min after papaverine. Eight of these 10 patients had complete loss of BAEP waveforms within 10 min. One patient showed no recovery of later waves and a delayed profound sensorineural hearing loss. The average recovery time of BAEP waveforms to pre-papaverine baseline values was 39 min. CONCLUSIONS: Topical papaverine for the treatment of vasospasm was associated with the onset of a transient disturbance in neurophysiological function of the ascending auditory brainstem pathway. The complete disappearance of BAEP waveforms with a consistent temporal delay suggests a possible adverse effect on the proximal eighth nerve. Recommendations to avoid potential cranial nerve deficits from papaverine are provided.

Output: Chemical/Disease Entities: papaverine (Chemical), Papaverine hydrochloride (Chemical), vasospasm (Disease), cranial nerve dysfunction (Disease), papaverine (Chemical), papaverine (Chemical), vasospasm (Disease), papaverine (Chemical), vasospasm (Disease), papaverine (Chemical), papaverine (Chemical), papaverine (Chemical), papaverine (Chemical), sensorineural hearing loss (Disease), papaverine (Chemical), papaverine (Chemical), vasospasm (Disease), adverse effect on the proximal eighth nerve (Disease), cranial nerve deficits (Disease), papaverine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Massive proteinuria and acute renal failure after oral bisphosphonate (alendronate) administration in a patient with focal segmental glomerulosclerosis. A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure.

Output: Chemical/Disease Entities: proteinuria (Disease), acute renal failure (Disease), bisphosphonate (Chemical), alendronate (Chemical), focal segmental glomerulosclerosis (Disease), nephrotic syndrome (Disease), focal segmental glomerulosclerosis (Disease), steroid (Chemical), bisphosphonate (Chemical), alendronate sodium (Chemical), acute renal failure (Disease), alendronate (Chemical), creatinine (Chemical), bisphosphonates (Chemical), proteinuria (Disease), acute renal failure (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Serum- and glucocorticoid-inducible kinase 1 in doxorubicin-induced nephrotic syndrome. Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.

Output: Chemical/Disease Entities: doxorubicin (Chemical), nephrotic syndrome (Disease), Doxorubicin (Chemical), nephropathy (Disease), sodium (Chemical), volume retention (Disease), fibrosis (Disease), aldosterone (Chemical), fibrosis (Disease), volume retention (Disease), fibrosis (Disease), nephrotic syndrome (Disease), doxorubicin (Chemical), Doxorubicin (Chemical), proteinuria (Disease), nephrotic syndrome (Disease), ascites (Disease), lipidemia (Disease), hypoalbuminemia (Disease), aldosterone (Chemical), nephrotic (Disease), sodium (Chemical), weight gain (Disease), nephrotic syndrome (Disease), urea (Chemical), uremia (Disease), volume retention (Disease), fibrosis (Disease), nephrotic syndrome (Disease)


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Input: Severe and long lasting cholestasis after high-dose co-trimoxazole treatment for Pneumocystis pneumonia in HIV-infected patients--a report of two cases. Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early.

Output: Chemical/Disease Entities: cholestasis (Disease), co-trimoxazole (Chemical), Pneumocystis pneumonia (Disease), HIV-infected (Disease), Pneumocystis pneumonia (Disease), PCP (Disease), opportunistic infection (Disease), HIV-infected (Disease), co-trimoxazole (Chemical), HIV-infected (Disease), intrahepatic cholestasis (Disease), liver abscess (Disease), co-trimoxazole (Chemical), PCP (Disease), co-trimoxazole (Chemical)


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Input: Clinically significant proteinuria following the administration of sirolimus to renal transplant recipients. BACKGROUND: Sirolimus is the latest immunosuppressive agent used to prevent rejection, and may have less nephrotoxicity than calcineurin inhibitor (CNI)-based regimens. To date there has been little documentation of clinically significant proteinuria linked with the use of sirolimus. We have encountered several patients who developed substantial proteinuria associated with sirolimus use. In each patient, the close temporal association between the commencement of sirolimus therapy and proteinuria implicated sirolimus as the most likely etiology of the proteinuria. METHODS: We analyzed the clinical and laboratory information available for all 119 patients transplanted at the Washington Hospital Center between 1999-2003 for whom sirolimus was a component of their immunosuppressant regimen. In these patients, the magnitude of proteinuria was assessed on morning urine samples by turbidometric measurement or random urine protein:creatinine ratios, an estimate of grams of proteinuria/day. Laboratory results were compared between prior, during and following sirolimus use. RESULTS: Twenty-eight patients (24%) developed increased proteinuria from baseline during their post-transplantation course. In 21 patients an alternative cause of proteinuria was either obvious or insufficient data was available to be conclusive. In 7 of the 28 patients there was a striking temporal association between the initiation of sirolimus and the development of nephrotic-range proteinuria. Proteinuria correlated most strongly with sirolimus therapy when compared to other demographic and clinical variables. In most patients, discontinuation of sirolimus resulted in a decrease, but not resolution, of proteinuria. CONCLUSIONS: Sirolimus induces or aggravates pre-existing proteinuria in an unpredictable subset of renal allograft recipients. Proteinuria may improve, but does not resolve, when sirolimus is withdrawn.

Output: Chemical/Disease Entities: proteinuria (Disease), sirolimus (Chemical), Sirolimus (Chemical), nephrotoxicity (Disease), proteinuria (Disease), sirolimus (Chemical), proteinuria (Disease), sirolimus (Chemical), sirolimus (Chemical), proteinuria (Disease), sirolimus (Chemical), proteinuria (Disease), sirolimus (Chemical), proteinuria (Disease), creatinine (Chemical), proteinuria (Disease), sirolimus (Chemical), proteinuria (Disease), proteinuria (Disease), sirolimus (Chemical), nephrotic (Disease), proteinuria (Disease), Proteinuria (Disease), sirolimus (Chemical), sirolimus (Chemical), proteinuria (Disease), Sirolimus (Chemical), proteinuria (Disease), Proteinuria (Disease), sirolimus (Chemical)


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Input: Comparative cognitive and subjective side effects of immediate-release oxycodone in healthy middle-aged and older adults. This study measured the objective and subjective neurocognitive effects of a single 10-mg dose of immediate-release oxycodone in healthy, older (> 65 years), and middle-aged (35 to 55 years) adults who were not suffering from chronic or significant daily pain. Seventy-one participants completed 2 separate study days and were blind to medication condition (placebo, 10-mg oxycodone). Plasma oxycodone concentration peaked between 60 and 90 minutes postdose (P < .01) and pupil size, an indication of physiological effects of the medication, peaked at approximately 90 to 120 minutes postdose (P < .01). Significant declines in simple and sustained attention, working memory, and verbal memory were observed at 1 hour postdose compared to baseline for both age groups with a trend toward return to baseline by 5 hours postdose. For almost all cognitive measures, there were no medication by age-interaction effects, which indicates that the 2 age groups exhibited similar responses to the medication challenge. This study suggests that for healthy older adults who are not suffering from chronic pain, neurocognitive and pharmacodynamic changes in response to a 10-mg dose of immediate-release oxycodone are similar to those observed for middle-aged adults. PERSPECTIVE: Study findings indicate that the metabolism, neurocognitive effects, and physical side effects of oral oxycodone are similar for healthy middle-aged and older adults. Therefore, clinicians should not avoid prescribing oral opioids to older adults based on the belief that older adults are at higher risk for side effects than younger adults.

Output: Chemical/Disease Entities: oxycodone (Chemical), oxycodone (Chemical), pain (Disease), oxycodone (Chemical), oxycodone (Chemical), chronic pain (Disease), oxycodone (Chemical), oxycodone (Chemical)


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Input: Normalizing effects of modafinil on sleep in chronic cocaine users. OBJECTIVE: The purpose of the present study was to determine the effect of morning-dosed modafinil on sleep and daytime sleepiness in chronic cocaine users. METHOD: Twenty cocaine-dependent participants were randomly assigned to receive modafinil, 400 mg (N=10), or placebo (N=10) every morning at 7:30 a.m. for 16 days in an inpatient, double-blind randomized trial. Participants underwent polysomnographic sleep recordings on days 1 to 3, 7 to 9, and 14 to 16 (first, second, and third weeks of abstinence). The Multiple Sleep Latency Test was performed at 11:30 a.m., 2:00 p.m., and 4:30 p.m. on days 2, 8, and 15. For comparison of sleep architecture variables, 12 healthy comparison participants underwent a single night of experimental polysomnography that followed 1 night of accommodation polysomnography. RESULTS: Progressive abstinence from cocaine was associated with worsening of all measured polysomnographic sleep outcomes. Compared with placebo, modafinil decreased nighttime sleep latency and increased slow-wave sleep time in cocaine-dependent participants. The effect of modafinil interacted with the abstinence week and was associated with longer total sleep time and shorter REM sleep latency in the third week of abstinence. Comparison of slow-wave sleep time, total sleep time, and sleep latency in cocaine-dependent and healthy participants revealed a normalizing effect of modafinil in cocaine-dependent participants. Modafinil was associated with increased daytime sleep latency, as measured by the Multiple Sleep Latency Test, and a nearly significant decrease in subjective daytime sleepiness. CONCLUSIONS: Morning-dosed modafinil promotes nocturnal sleep, normalizes sleep architecture, and decreases daytime sleepiness in abstinent cocaine users. These effects may be relevant in the treatment of cocaine dependence.

Output: Chemical/Disease Entities: modafinil (Chemical), cocaine (Chemical), modafinil (Chemical), daytime sleepiness (Disease), cocaine (Chemical), cocaine (Chemical), modafinil (Chemical), cocaine (Chemical), modafinil (Chemical), cocaine (Chemical), modafinil (Chemical), cocaine (Chemical), modafinil (Chemical), cocaine (Chemical), Modafinil (Chemical), daytime sleepiness (Disease), modafinil (Chemical), daytime sleepiness (Disease), cocaine (Chemical), cocaine (Chemical)


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Input: Efficacy and safety of asenapine in a placebo- and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia. Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. In a double-blind 6-week trial, 458 patients with acute schizophrenia were randomly assigned to fixed-dose treatment with asenapine at 5 mg twice daily (BID), asenapine at 10 mg BID, placebo, or haloperidol at 4 mg BID (to verify assay sensitivity). With last observations carried forward (LOCF), mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID (-16.2) and haloperidol (-15.4) than placebo (-10.7; both P < 0.05); using mixed model for repeated measures (MMRM), changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID (-21.3 and -19.4, respectively) and haloperidol (-20.0) than placebo (-14.6; all P < 0.05). On the Positive and Negative Syndrome Scale positive subscale, all treatments were superior to placebo with LOCF and MMRM; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM. Treatment-related adverse events (AEs) occurred in 44% and 52%, 57%, and 41% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Extrapyramidal symptoms reported as AEs occurred in 15% and 18%, 34%, and 10% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Across all groups, no more than 5% of patients had clinically significant weight change. Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol; greater contrasts were seen in AEs, especially extrapyramidal symptoms.

Output: Chemical/Disease Entities: asenapine (Chemical), haloperidol (Chemical), schizophrenia (Disease), Asenapine (Chemical), schizophrenia (Disease), manic (Disease), bipolar I disorder (Disease), psychotic (Disease), schizophrenia (Disease), asenapine (Chemical), asenapine (Chemical), haloperidol (Chemical), asenapine (Chemical), haloperidol (Chemical), asenapine (Chemical), haloperidol (Chemical), asenapine (Chemical), asenapine (Chemical), haloperidol (Chemical), Extrapyramidal symptoms (Disease), asenapine (Chemical), haloperidol (Chemical), asenapine (Chemical), haloperidol (Chemical), extrapyramidal symptoms (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Permeability, ultrastructural changes, and distribution of novel proteins in the glomerular barrier in early puromycin aminonucleoside nephrosis. BACKGROUND/AIMS: It is still unclear what happens in the glomerulus when proteinuria starts. Using puromycin aminonucleoside nephrosis (PAN) rats, we studied early ultrastructural and permeability changes in relation to the expression of the podocyte-associated molecules nephrin, a-actinin, dendrin, and plekhh2, the last two of which were only recently discovered in podocytes. METHODS: Using immune stainings, semiquantitative measurement was performed under the electron microscope. Permeability was assessed using isolated kidney perfusion with tracers. Possible effects of ACE inhibition were tested. RESULTS: By day 2, some patchy foot process effacement, but no proteinuria, appeared. The amount of nephrin was reduced in both diseased and normal areas. The other proteins showed few changes, which were limited to diseased areas. By day 4, foot process effacement was complete and proteinuria appeared in parallel with signs of size barrier damage. Nephrin decreased further, while dendrin and plekhh2 also decreased but a-actinin remained unchanged. ACE inhibition had no significant protective effect. CONCLUSIONS: PAN glomeruli already showed significant pathology by day 4, despite relatively mild proteinuria. This was preceded by altered nephrin expression, supporting its pivotal role in podocyte morphology. The novel proteins dendrin and plekhh2 were both reduced, suggesting roles in PAN, whereas a-actinin was unchanged.

Output: Chemical/Disease Entities: puromycin aminonucleoside (Chemical), nephrosis (Disease), proteinuria (Disease), puromycin aminonucleoside (Chemical), nephrosis (Disease), proteinuria (Disease), proteinuria (Disease), proteinuria (Disease)


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Input: Twin preterm neonates with cardiac toxicity related to lopinavir/ritonavir therapy. We report twin neonates who were born prematurely at 32 weeks of gestation to a mother with human immunodeficiency virus infection. One of the twins developed complete heart block and dilated cardiomyopathy related to lopinavir/ritonavir therapy, a boosted protease-inhibitor agent, while the other twin developed mild bradycardia. We recommend caution in the use of lopinavir/ritonavir in the immediate neonatal period.

Output: Chemical/Disease Entities: cardiac toxicity (Disease), lopinavir/ritonavir (Chemical), human immunodeficiency virus infection (Disease), heart block (Disease), dilated cardiomyopathy (Disease), lopinavir/ritonavir (Chemical), bradycardia (Disease), lopinavir/ritonavir (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Learning of rats under amnesia caused by pentobarbital. Dissociated learning of rats in the normal state and the state of amnesia produced by pentobarbital (15 mg/kg, ip) was carried out. Rats were trained to approach a shelf where they received food reinforcement. In Group 1 the rats were trained under the influence of pentobarbital to run to the same shelf as in the normal state. In Group 2 the rats were trained to approach different shelves in different drug states. It was shown that memory dissociation occurred in both groups. Differences in the parameters of training under the influence of pentobarbital between Groups 1 and 2 were revealed. These findings show that the brain-dissociated state induced by pentobarbital is formed with the participation of the mechanisms of information perception.

Output: Chemical/Disease Entities: amnesia (Disease), pentobarbital (Chemical), amnesia (Disease), pentobarbital (Chemical), pentobarbital (Chemical), memory dissociation (Disease), pentobarbital (Chemical), pentobarbital (Chemical)


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Input: Angiosarcoma of the liver associated with diethylstilbestrol. Angiosarcoma of the liver occurred in a 76-year-old man who had been treated for a well-differentiated adenocarcinoma of the liver with diethylstilbestrol for 13 years. Angiosarcoma was also present within pulmonary and renal arteries. The possibility that the intraarterial lesions might represent independent primary tumors is considered.

Output: Chemical/Disease Entities: diethylstilbestrol (Chemical), diethylstilbestrol (Chemical), Angiosarcoma (Disease), intraarterial lesions (Disease), tumors (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Role of xanthine oxidase in dexamethasone-induced hypertension in rats. 1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.

Output: Chemical/Disease Entities: xanthine (Chemical), dexamethasone (Chemical), hypertension (Disease), hypertension (Disease), HT (Disease), nitric oxide (Chemical), xanthine (Chemical), dexamethasone (Chemical), hypertension (Disease), dex (Chemical), HT (Disease), dexamethasone (Chemical), dex (Chemical), allopurinol (Chemical), allopurinol (Chemical), dex (Chemical), urate (Chemical), Dex (Chemical), increased SBP (Disease), decreased thymus (P < 0.001) and bodyweights (Disease), Allopurinol (Chemical), urate (Chemical), dex (Chemical), Allopurinol (Chemical), dex (Chemical), HT (Disease), allopurinol (Chemical), hypertension (Disease), HT (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels. Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5-HT2 receptors. Previous clinical studies have proposed that risperidone's pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so-called 'atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [123I]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug-induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects.

Output: Chemical/Disease Entities: risperidone (Chemical), haloperidol (Chemical), Risperidone (Chemical), dopamine (Chemical), serotonin 5-HT2 (Chemical), risperidone (Chemical), psychotic symptoms (Disease), risperidone (Chemical), risperidone (Chemical), haloperidol (Chemical), risperidone (Chemical), haloperidol (Chemical), haloperidol (Chemical), risperidone (Chemical), Drug-induced parkinsonism (Disease), risperidone (Chemical), haloperidol (Chemical), risperidone (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Simvastatin-ezetimibe-induced hepatic failure necessitating liver transplantation. Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.

Output: Chemical/Disease Entities: Simvastatin-ezetimibe (Chemical), hepatic failure (Disease), statin (Chemical), hepatotoxic (Disease), ezetimibe (Chemical), simvastatin-ezetimibe (Chemical), fulminant hepatic failure (Disease), simvastatin (Chemical), simvastatin 10 mg-ezetimibe 40 mg (Chemical), simvastatin (Chemical), hepatotoxicity (Disease), Simvastatinezetimibe (Chemical), escitalopram (Chemical), depression (Disease), hepatotoxicity (Disease), drug toxicity (Disease), Ezetimibe (Chemical), uridine diphosphate (Chemical), simvastatin hydroxy acid (Chemical), simvastatin (Chemical), hepatotoxicity (Disease), simvastatin-ezetimibe (Chemical), liver failure (Disease), simvastatinezetimibe (Chemical), hepatotoxicity (Disease), simvastatin (Chemical), ezetimibe (Chemical), hepatotoxicity (Disease), simvastatin-ezetimibe (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Oral manifestations of "meth mouth": a case report. AIM: The aim of the documentation of this clinical case is to make clinicians aware of "meth mouth" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries ("meth mouth"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of "meth mouth." Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.

Output: Chemical/Disease Entities: meth mouth (Disease), meth mouth (Disease), Methamphetamine (Chemical), cardiac dysrhythmias (Disease), hypertension (Disease), hallucinations (Disease), violent behavior (Disease), methamphetamine (Chemical), xerostomia (Disease), caries (Disease), meth mouth (Disease), tooth wear (Disease), methamphetamine (Chemical), pain (Disease), bad breath (Disease), carious lesions (Disease), methamphetamine (Chemical), carious episodes (Disease), meth mouth (Disease), meth mouth (Disease), methamphetamines (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Thyroxine abuse: an unusual case of thyrotoxicosis in pregnancy. Eating disorders and the associated behavioural problems and drug abuse are uncommon in pregnancy. When they do occur they are often unrecognized because of denial but when significant may pose a risk to both the mother and her fetus. This case illustrates a number of problems that may be encountered in women with eating disorders in pregnancy, including prolonged and recurrent metabolic disturbances and diuretic abuse. In particular it illustrates the derangements of thyroid function seen in pregnant women with eating disorders and reminds us that when a cause for thyrotoxicosis remains obscure, thyroxine abuse should be considered and explored.

Output: Chemical/Disease Entities: Thyroxine (Chemical), thyrotoxicosis (Disease), Eating disorders (Disease), drug abuse (Disease), eating disorders (Disease), eating disorders (Disease), thyrotoxicosis (Disease), thyroxine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Attenuation of methamphetamine-induced nigrostriatal dopaminergic neurotoxicity in mice by lipopolysaccharide pretreatment. Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity.

Output: Chemical/Disease Entities: methamphetamine (Chemical), neurotoxicity (Disease), lipopolysaccharide (Chemical), methamphetamine (Chemical), dopaminergic terminal damage (Disease), lipopolysaccharide (Chemical), methamphetamine (Chemical), dopamine (Chemical), neurotoxicity (Disease), Lipopolysaccharide (Chemical), methamphetamine (Chemical), hyperthermia (Disease), lipopolysaccharide (Chemical), methamphetamine (Chemical), dopamine (Chemical), 3,4-dihydroxyphenylacetic acid (Chemical), lipopolysaccharide (Chemical), methamphetamine (Chemical), methamphetamine (Chemical), dopamine (Chemical), 3,4-dihydroxyphenylacetic acid (Chemical), lipopolysaccharide (Chemical), methamphetamine (Chemical), dopamine (Chemical), 3,4-dihydroxyphenylacetic acid (Chemical), lipopolysaccharide (Chemical), methamphetamine (Chemical), lipopolysaccharide (Chemical), methamphetamine (Chemical), dopamine (Chemical), neurotoxicity (Disease)