Species- and sex-specific variations in binding of ochratoxin A by renal proteins in vitro

The mycotoxin ochratoxin A (OTA) is a potent renal carcinogen in rodents and induces renal fibrosis in pigs. Furthermore, OTA has been associated with the development of renal tumors and nephropathies in humans. Large species- and sex-differences are observed in sensitivity toward OTA-mediated toxicity and carcinogenicity, yet neither the mechanism(s) resulting in OTA toxicity nor the reasons for the observed species- and sex-specificities are known. This paper investigated variations in OTA handling viz binding to renal proteins which could possibly explain the observed differences in OTA susceptibility in vivo and in vitro. The results obtained via a modification of a standard receptor-binding assay demonstrated the presence of at least one homogeneous binding component in renal cortical homogenates from pig, mouse, rat and humans. This component was shown to bind OTA in a specific and saturable manner. A range of compounds selected for their affinity for steroid receptors and/or for various known organic anion transporters were employed in a competition assay to answer the question whether this homogenous OTA binding component represents a steroid-like receptor component or one of the known organic anion transporters of the kidney. Although many of the compounds were able to compete with OTA for protein-binding, the competition patterns displayed a distinct species specificity and did not correspond to the competition patterns associated with presently known organic anion transporters of the kidney in the mouse, rat or human. The data thus suggests the presence of a new organic anion transporter or more likely, a cytosolic binding component of unknown function with high affinity and capacity for OTA binding in humans, rats, mice and possibly pigs.     

The combination oral and nutritional treatment of late-onset diabetes mellitus (CONTROL DM) trial results.

OBJECTIVE: To examine the effect of short-term improvements in glycaemic control on brachial artery endothelial function as a marker of cardiovascular health. METHODS: Persons with Type 2 diabetes who were poorly controlled on oral therapy were randomly assigned to monotherapy with repaglinide or combination therapy with repaglinide plus metformin. Brachial artery flow-mediated vasodilation was assessed by ultrasonography at randomization and following 16 weeks of therapy. The primary outcome was change in brachial artery endothelial function from baseline. Comparison of randomized groups was a secondary aim. RESULTS: Eighty-six participants were randomized, and 83 were followed to study completion. Post occlusion brachial artery vasodilation was 3.74% at baseline and 3.82% following 16 weeks of therapy (P = 0.77). The treatment effect was 0.08% (95% CI: -0.48%, 0.64%). No difference was seen between treatment groups (P = 0.69). Overall, A1C was reduced from 8.3% to 7.0%, with a greater reduction in the combination therapy group (from 8.4% to 6.7%) than in the monotherapy group (from 8.3% to 7.3%, p for difference between groups = 0.01). Statistically significant reductions were observed in fasting glucose, and plasminogen activator inhibitor-1. Statistically significant increases were observed for fasting insulin, uric acid, weight and BMI. CONCLUSIONS: Brachial artery endothelial function was not influenced by short-term improvements in glycaemic control. The CONTROL DM group was successful in lowering A1C. Future research should explore more intensive and longer-lasting improvements in glycaemic control on endothelial function. Some data previously published in abstract form (Diabetes 2001; 50 (Suppl. 2): A217).     

太极通天液治疗血管性痴呆的疗效评价

目的：评价太极通天液治疗血管性痴呆的临床疗效。方法：随机将148例血管性痴呆分为太极通天液治疗组和丹参口服液对照组，另接应用韦氏成人智力量表评分，将血管性痴呆组分为3个亚组：即80－89分组，70－79分组和70分以下组，观察期为3个月。结果：太极通天液治疗前后WAIS－RC评分与对照组比较，80－89分组和70－79分组均有统计学差异（P＜0．05），而70分以下组无统计学差异（P＞0．05），结论：太极通天液对血管性痴呆有较好的治疗效果，且与痴呆病情程度有关。     

Comparison of the diagnostic criteria for diabetes mellitus, WHO-1985, ADA-1997 and WHO-1999 in the adult population of Asturias (Spain).

AIMS: To estimate the prevalence of diabetes mellitus with three diagnostic criteria (WHO-1985 and 1999 and ADA-1997), evaluate their concordance and analyse the sensitivity and specificity of the different screening strategies for diabetes. METHODS: A cross-sectional population study with two-step sampling. One thousand and 34 people were selected randomly. A 75-g oral glucose tolerance test (OGTT) was performed and venous blood samples were obtained fasting and at 2 h. RESULTS: The prevalence of known Type 2 diabetes mellitus (DM-2) is 4%[95% confidence interval (CI) 2.8, 5.1]. By WHO-1985 criteria the prevalence of unknown DM-2 is 5.9% (4.5, 7.4); by ADA-1997 criteria 3.5% (2.5, 4.6) and by WHO-1999 criteria 7.3% (5.8, 8.8). Diagnostic overlap and statistical concordance (coefficient K) are WHO-1985/ADA-1997 29.3%, K=0.42; WHO-1985/WHO-1999 80%, K=0.88; ADA-1997/WHO-1999 48%, K=0.63. If only fasting glucose was used (following ADA-1997), 36.3% of those with diabetes (2-h glucose > or =11.1 mmol/l) would be diagnosed. If OGTT was performed (i) in those with a fasting glucose between 6.1 mmol/l and 6.9 mmol/l (9.8% of the population) we would diagnose 66.6%, and (ii) in all those between 5.7 mmol/l and 6.9 mmol/l (18.9% of the population) 81.8% would be diagnosed. CONCLUSIONS: The ADA criteria decrease the prevalence of DM in the adult population of Asturias by 2.4% and concordance with the classical criteria (WHO-1985) was only 29.3%. Using fasting glucose only (ADA-1997) diagnoses 36.3% of those with diabetes. The recent recommendations of the WHO-1999 increases this to 66.6%. To improve the diagnostic strategy for diabetes and detect up to 81.8% of patients, we propose the use of OGTT for all those with a fasting glucose between 5.7 mmol/l and 6.9 mmol/l.     

Effects of Carbamazepine on Murine Humoral and Cellular Immune Responses

Summary: Oral administration of carbamazepine (CBZ)(15, 10, or 5 mg/kg) to mice significantly decreased both humoral and cellular immune responses evaluated by enumeration of direct and indirect plaque-forming spleen cells (PFC) and delayed–type hypersensitivity reaction (DTH) against sheep red blood cells (SRBC) as compared with those observed in normal control animals. Moreover, spleen T cells obtained from CBZ–treated donor mice were capable of decreasing both PFC and DTH responses of normal spleen cells transferred into lethally irradiated recipient animals. The immunodepressor effect of CBZ was observed even though administration of CBZ induced augmentation of spleen cellularity.     

Photoleukomelanodermatitis (Kobori) Induced by Afloqualone

We reported a case of photoleukomelanodermatitis (Kobori) type drug eruption due to afloqualone (Arofuto®). The patient was given afloqualone and imipramine hydrochloride (Chrytemin®) for cervical spondylosis from November of 1990. Edematous erythema with slight itching appeared on the sun-exposed areas in December of 1990. As drug eruption was suspected, drugs were ceased, and the cutaneous lesions almost disappeared but pigmentations and depigmentations developed in spots in sun-exposed areas in March of 1991. Photopatch and oral challenge tests were positive.     

Nodular hyperplasia surrounding fibrolamellar carcinoma

We report a case of acetaminophen-induced liver necrosis in a 14-year-old girl. At autopsy, a 9 cm subcapsular nodule was present in the right lobe of the liver which showed distinct zonation: a central greyish white area of fibrolamellar carcinoma with a peripheral fleshy, tan-coloured rim ranging from 1 to 2 cm in thickness. This peripheral zone consisted of nodular, hyperplastic parenchyma resembling the changes seen in focal nodular hyperplasia, and stood out from the adjacent necrotic parenchyma. The sparing of this zone from the deleterious effects of acetaminophen provides indirect evidence of a predominantly arterial rather than portal blood supply to this region. The arterial supply was most probably derived from the tumour vasculature and may explain the parenchymal hyperplasia sometimes reported adjacent to a fibrolamellar carcinoma. Awareness of this phenomenon is essential when evaluating a needle biopsy, as sampling of this region may lead to a false negative diagnosis.     

Pollen extracts reduce the hepatotoxicity of paracetamol in mice

Cernitins are preparations obtained from plant pollen which contain numerous compounds of potential biological significance. This work deals with the influence of cernitins upon acute paracetamol toxicity in mice. The survival rate and indices of hepatic injury: aminotransferase and alkaline phosphatase activities, bilirubin level in serum, glutathione and cytochrome P-450 content in liver, liver weight, histopathologic picture of the liver and presence of glycogen and lipids in stained liver sections, under different experimental protocols, were determined. It was found that cernitins are able to increase the survival rate of mice and reduce liver injury in acute paracetamol poisoning. Cernitins are more effective when administered after, rather than before, a dose of paracetamol. The possible mechanism through which cernitins may act is discussed.     

Acute heart failure and acute renal failure in Kawasaki disease

Acute renal failure and acute heart failure are rare in Kawasaki disease. We experienced two patients with Kawasaki disease who presented acute renal failure and acute heart failure. These two patients gave us an important insight into the understanding of water balance and fluid therapy in Kawasaki disease. One patient showed acute prerenal failure due to fluid exudation from the intravascular to the extravascular space, and subsequent acute heart failure. The other patient showed acute heart failure caused by fluid infusion for the treatment of dehydration. It is suggested that acute renal failure could be caused by a fluid shift from the intravascular to the extravascular space in Kawasaki disease. It is also demonstrated that the reserve of cardiac function could be decreased in patients with Kawasaki disease due to myocarditis even with normal echocardiography and chest X-rays.