Toxicological evaluation of oral exposure to isoniazid: behavioral, biochemical, and histopathological assessments in rats.

Isoniazid (INH), being the first-line drug used as an anti-tuberculosis drug, is known to be associated with physiological deteriorations including hepatic and neurologic disturbances. This study was aimed at biochemical and behavioral characterization of toxic manifestations of isoniazid treatment in Wistar rats. Experimental animals were divided into four groups. Each group consists of six animals including the control group (saline solution), I25 group (25 mg/kg of INH), I50 group (50 mg/kg of INH), and I100 group (100 mg/kg of INH). Animals received daily INH for 30 days. Isoniazid is known to be associated with hepatotoxicity; it's among the most common causes of drug-induced toxicities. For this reason assays for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were performed to assess liver toxicity. Moreover, behavioral study, renal, and lipid parameters were also assessed in addition to histological features of the liver and brain. Significant differences in all studied parameters were seen especially in the I100 group and a marked increase in liver enzymes activities, such as AST and ALT was observed. In another hand, there were no major clinical signs in treated animals, except fatigue and anxiety in the I100 group. On the other hand, the histological findings showed potential liver and brain injury which was evidenced by degenerative changes, infiltration, and hepatocyte necrosis, in addition to the appearance of many pyramidales cells in the gyrus. The current study findings suggest that INH interacts with multiple biochemical pathways in the body what comes up by behavioral changes and liver disturbances in animals caused by INH toxicity.

[Bone metabolism, biochemical markers of bone resorption and formation processes and interleukine 6 cytokin level during coeliac disease]. / Anomalies du métabolisme osseux et résultats des marqueurs biochimiques du remodelage osseux et de l'interleukine 6 au cours de la maladie coeliaque.

BACKGROUND: Celiac disease (CD) is characterized by a malabsorption syndrom. The bone anomalies are one of the principal complications of this disease. The osteoporosis frequency is high: 3.4% among patients having with CD versus 0.2% in the general population. AIM: To study the bone mineral density during the CD, to compare it to a control group and to determine the anomalies of biochemical markers of bone turn over and level of interleukin 6 cytokin (IL6) in these patients. METHODS: All patients with CD have a measurement of bone mineral density by dual-energy x-ray absorptiometry (DXA), a biological exam with dosing calcemia, vitamin D, parathormone (PTH), the osteoblastic bone formation markers (serum osteocalcin, ALP phosphates alkaline), bone osteoclastic activity (C Télopeptide: CTX) and of the IL6. RESULTS: 42 patients were included, with a median age of 33.6 years. 52. 8% of the patients had a low level of D vitamine associated to a high level of PTH. An osteoporosis was noted in 21.5% of patients. No case of osteoporosis was detected in the control group. The mean level of the CTX, ostéocalcine and the IL6 was higher among patients having an osteoporosis or ostéopenia compared to patients with normal bone (p = 0,017). The factors associated with an bone loss (osteopenia or osteoporosis) were: an age > 30 years, a weight <50 kg, a level of ALP phosphates alkaline > 90 UI/ml, an hypo albuminemia < 40 g/l and a level of CTX higher than 1.2. CONCLUSION: Our study confirms the impact of the CD on the bone mineral statute. The relative risk to have an osteopenia or an osteoporosis was 5 in our series. The measurement of the osseous mineral density would be indicated among patients having a CD.

HLA class II alleles susceptibility markers of type 1 diabetes fail to specify phenotypes of ketosis-prone diabetes in adult Tunisian patients.

We aimed to characterize the different subgroups of ketosis-prone diabetes (KPD) in a sample of Tunisian patients using the Aß scheme based on the presence or absence of ß-cell autoantibodies (A+ or A-) and ß-cell functional reserve (ß+ or ß-) and we investigated whether HLA class II alleles could contribute to distinct KPD phenotypes. We enrolled 43 adult patients with a first episode of ketosis. For all patients we evaluated clinical parameters, ß-cell autoimmunity, ß-cell function and HLA class II alleles. Frequency distribution of the 4 subgroups was 23.3% A+ß-, 23.3% A-ß-, 11.6% A+ß+ and 41.9% A-ß+. Patients from the group A+ß- were significantly younger than those from the group A-ß- (P = .002). HLA susceptibility markers were significantly more frequent in patients with autoantibodies (P = .003). These patients also had resistance alleles but they were more frequent in A+ß+ than A+ß- patients (P = .04). Insulin requirement was not associated to the presence or the absence of HLA susceptibility markers. HLA class II alleles associated with susceptibility to autoimmune diabetes have not allowed us to further define Tunisian KPD groups. However, high prevalence of HLA resistance alleles in our patients may reflect a particular genetic background of Tunisian KPD population.

Congenital hyperinsulinism: review of 12 Tunisian cases.

BACKGROUND: Congenital hyperinsulinism in infancy (CHI) is a heterogeneous disorder with respect to genetics and response to therapy. Data on CHI are sporadic in North African population. AIM: To characterize the clinical features and outcome of 12 Tunisian patients with CHI. METHODS: data of patients diagnosed with CHI during the period 1989-2007 were retrospectively analyzed. Diagnosis was considered whenever hyperinsulinemia ≥ 10µ UI/ml was concomitant to hypoglycemia < 3mmol/l and/or high insulin to glucose ratio > 0.3 and/or positif glucagon test. Transient causes of hypoglycemia, adrenal and growth hormone deficiency were excluded. RESULTS: There were nine infants diagnosed at a median age of 17 months and three newborns. Permanent hyperammoniemia, found in one patient, guided to leucine-sensitive hyperinsulinism. Seven patients presented with seizures, two with psychomotor delay and one with recurrent malaises. Among 42 assays of plasmatic insulin, when in hypoglycemia, 40% only were ≥ 10µU/ml. Three patients resisted to diazoxide and underwent subtotal pancreatectomy complicated by diabetes mellitus in two cases and persistent hypoglycemia in one patient. Histological examination concluded to diffuse hyperplasia of pancreatic cells. Diazoxide was discontinued in four out the eight responders' patients. Four patients died, seven patients developed variable degrees of mental retardation and five suffered from epilepsy. CONCLUSION: Early onset forms were, as reported in the literature, mostly resistant to medical therapy. The high proportion of neurological sequelae is related to diagnosis delay or to a late surgery. We focus on the importance of a precocious diagnosis and aggressive treatment of hypoglycemia.

Identification of patients with abetalipoproteinemia and homozygous familial hypobetalipoproteinemia in Tunisia.

BACKGROUND: Abetalipoproteinemia (ABL) and Homozygous Familial Hypobetalipoproteinemia (Ho-FHBL) are rare monogenic diseases characterised by very low plasma levels of cholesterol and triglyceride and the absence or a great reduction of apolipoprotein B (apoB)-containing lipoproteins. ABL results from mutations in the MTP gene; Ho-FHBL may be due to mutations in the APOB gene. METHODS: We sequenced MTP and APOB genes in three Tunisian children, born from consanguineous marriage, with very low levels of plasma apoB-containing lipoproteins associated with severe intestinal fat malabsorption. RESULTS: Two of them were found to be homozygous for two novel mutations in intron 5 (c.619-3T>G) and in exon 8 (c.923 G>A) of the MTP gene, respectively. The c.619-3T>G substitution caused the formation of an abnormal mRNA devoid of exon 6, predicted to encode a truncated MTP of 233 amino acids. The c.923 G>A is a nonsense mutation resulting in a truncated MTP protein (p.W308X). The third patient was homozygous for a novel nucleotide deletion (c.2172delT) in exon 15 of APOB gene resulting in the formation of a truncated apoB of 706 amino acids (apoB-15.56). CONCLUSIONS: These mutations are expected to abolish the apoB lipidation and the assembly of apoB-containing lipoproteins in both liver and intestine.