Acute pancreatitis in the course of meprobamate poisoning.

CONTEXT: We report a case of massive poisoning with meprobamate leading to acute pancreatitis. CASE REPORT: A 43-year-old patient with a history of schizophrenia and multiple suicide attempts was admitted to the intensive care unit for severe poisoning with meprobamate (voluntary ingestion of 60 g). On admission, the patient was deeply comatose with low blood pressure and hypothermia. Laboratory analysis revealed leukocytosis and high lipase and amylase serum levels. There was no eosinophilia. Abdominal computed tomography showed pancreatitis grade A. The patient was intubated and ventilated, and intravenous dopamine was infused. The patient regained consciousness and was extubated five days later. Improvement in pancreatic tests was noted several days later. The outcome was favorable. DISCUSSION: According to the Naranjo probability scale, meprobamate-induced acute pancreatitis was probable. Acute pancreatitis in meprobamate poisoning is exceptional. The pathogenesis of pancreatitis-induced meprobamate poisoning may be explained by two mechanisms: stimulation of pancreatic secretion secondary to cholinergic activation and pancreatic ductal hypertension. CONCLUSIONS: The signs of severe meprobamate toxicity are numerous including cardiovascular and central nervous symptoms. Acute pancreatitis should also be added as a possible manifestation of meprobamate poisoning.

Azathioprine-induced severe cholestatic hepatitis in patient carrying TPMT*3C polymorphism.

CASE DESCRIPTION: A 40-year-old man with pemphigus foliaceus developed a jaundice and pruritus three weeks after starting azathioprine 100 mg daily. Laboratory investigations revealed a severe cholestatic hepatitis. Azathioprine-induced hepatitis was suspected. The dosage of thiopurine methyltransferase activity showed a low activity of the enzyme and the genotype of this enzyme found a TPMT*3C heterozygous mutant allele. Azathioprine was withdrawn. The icterus regressed progressively and the hepatic tests normalised slowly. The patient had no further episodes of hepatitis over a follow-up period of 6 months. CONCLUSION: Although, hematotoxicity seems to be associated with homozygous TPMT variants, a possible association between azathioprine hepatotoxicity and a TPMT*3C genotype should be investigated further.

Fatal allopurinol-induced hypersensitivity syndrome associated with pancreatic abnormalities.

Allopurinol hypersensitivity syndrome is a severe adverse reaction characterized by rash, fever, and internal organ involvement. We report a case of fatal allopurinol-induced hypersensitivity syndrome associated with acute pancreatitis.A 46-year-old man was treated by allopurinol for asymptomatic hyperuricemia. The patient developed a diffuse erythrodermic maculopapular eruption and fever. Laboratory analysis revealed cytolysis and cholestasis, amylases and lipases were highly elevated. Computed tomography scans revealed pancreatitis Grade C. The treatment of asymptomatic hyperuricemia should only be initiated when there is a clear indication to reduce the incidence and the severe consequences of allopurinol hypersensitivity syndrome.

Captopril-induced lichen planus pemphigoides.

PURPOSE: To report a rare case of lichen planus pemphigoides (LPP) possibly induced by captopril. CASE SUMMARY: A 74-year-old woman developed pruriginous and bullous lichenoid eruption after starting captopril for hypertension. Histopathological and immunological features were consistent with the diagnosis of LPP that was managed by discontinuing captopril and corticosteroid therapy. Eight months after the cessation of oral steroid therapy, no relapse had occurred. DISCUSSION: LPP, a rare skin disorder, has been generally considered to represent a mixture of clinical, histopathological and immunological patterns of lichen planus and bullous pemphigoid. It is predominantly idiopathic. However, in rare cases it has been associated with the administration of drugs. Here we present a typical LPP related to the use of captopril. CONCLUSIONS: Clinicians should be aware of the ability of captopril to induce LPP.

Rare case of metformin-induced leukocytoclastic vasculitis.

OBJECTIVE: To report a case of leukocytoclastic vasculitis (LV) related to metformin. CASE SUMMARY: A 33-year-old woman developed palpable purpura on her lower limbs after starting self-medication with metformin 850 mg/day for weight loss. Drug-induced vasculitis was suspected, metformin was stopped, and the rash improved significantly. One month later, the woman again took metformin. Similar cutaneous lesions recurred, and skin biopsy showed LV, which was managed by discontinuing metformin and applying topical antiseptics. The patient had no further episodes of skin rash over a follow-up period of 3 months. DISCUSSION: Metformin has widespread use throughout the world. It has a variety of metabolic and vascular effects. Our patient developed a rash within a few days of metformin administration. Resolution of skin manifestations within several days after withdrawal of the drug and their recurrence when the drug was reintroduced were consistent with a pathogenic role of metformin. Other known causes of vasculitis were excluded in a reasonable way. According to the Naranjo probability scale, the vasculitis experienced by our patient was probably due to metformin. CONCLUSIONS: Clinicians should be aware of the ability of metformin to induce cutaneous LV.

[Current aspects and future perspectives of pharmacotherapy or type II diabetes]. / Actualités et perspectives des prescriptions dans le diabète de type II.

Type II diabetes mellitus is a group of metabolic disorders of fat, carbohydrate and protein metabolism that results from defects in insulin action. It is associated with microvascular and macrovascular disease complications. Goals of therapy in management of type II diabetes mellitus are directed at reducing symptoms of hyperglycemia, reducing the onset and progression of retinopathy, nephropathy and neuropathy complications, intensive therapy of associated cardiovascular risk factors and improving quality and quantity of life. Multidisciplinary teams of health care professions are needed to optimize outcomes in persons with diabetes mellitus. This article will focus on the pharmacotherapeutic agents used in type II diabetes mellitus with or without microvascular and macrovascular disease risk. We will describe also the agents used in prevention of this disense.

In silico screening and study of novel ERK2 inhibitors using 3D QSAR, docking and molecular dynamics.

ERK2 is a dual specificity protein kinase, part of the Ras/Raf/MEK/ERK signal transduction cascade. It forms an interesting target for inhibition based on its relationship with cell proliferation and oncogenesis. A 3D QSAR pharmacophore model (Hypo1) with high correlation (r=0.938) was developed for ERK2 ATP site on the basis of experimentally known inhibitors. The model included three hydrogen bonds, and one hydrophobic site. Assessment of Hypo1 through Fisher randomization, cost analysis, leave one out method and decoy test suggested that the model can reliably detect ERK2 inhibitors. Hypo1 has been used for virtual screening of potential inhibitors from ZINC, Drug Bank, NCI, Maybridge and Chembank databases. Using Hypo1 as a query, databases have been interrogated for compounds who meet the pharmacophore features. The resulting hit compounds were subject to docking and analysis. Docking and molecular dynamics analysis showed that in order to achieve a higher potency compounds have to interact with catalytic site, glycine rich loop, Hinge region, Gatekeeper region and ATP site entrance residues. We also identified catalytic site and Glycine rich loop as important regions to bind by molecules for better potency and selectivity.

Insight into TPMT(∗)23 mutation mis-folding using molecular dynamics simulation and protein structure analysis.

Thiopurine S-methyltransferase (TPMT) is an important enzyme that metabolizes thiopurine drugs. This enzyme exhibits a large number of interindividual polymorphism. TPMT(∗)23 polymorphism has been reported in a few cases in the world in co-dominance with TPMT(∗)3A. The phenotype has been reported to affect enzyme activity in vivo and in vitro. Its underlying structural basis is not clarified yet. In our study, the wild type (WT) protein structure was analyzed and the amino acids bordering water channels in thiopurine sites were identified. Molecular dynamics of both the WT and TPMT(∗)23 mutation was carried out. In addition, the effects of this mutation, especially on the thiopurine site which is closed with a pincer like mechanism, were investigated. We focused on explaining how a locally occurred A167G substitution propagated through hydrogen bonds alteration to induce structural modification which affects both thiopurine and S-adenosylmethionine receptors. Finally, a genetic prediction of mutation functional consequences has been conducted confirming altered activity. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:20.