Studies on post-transplant dyslipidemia in kidney transplant patients

This study was performed to retrospectively compare changes in the levels of total cholesterol, non-HDL cholesterol, triglycerides, and immunosuppressive drugs, cyclosporine A and steroids in patients with living-relation renal transplants with those from non-heart-beating donors. We experienced 11 cases of kidney transplants from non-heart-beating donors during the period from April 1995 to May 2003. We evaluated 13 cases of kidney transplants from living-relation donors during the same period. The immunosuppressants used included mainly cyclosporine A as well as mycophenolate mofetil or azathioprine, steroid and ALG, or basiliximab. Over-night fasting lipids (total cholesterol, triglycerides and HDL cholesterol) were studied before renal transplantation and repeated after renal transplantation at 1, 3, 6 and 12 months. The levels of total cholesterol and triglycerides remained in the normal range before transplantation. However, the levels of total cholesterol increased siginificantly 1 and 3 months after transplantation from non-heart-beating donors and remained at higher levels up to 12 months after transplantation. A similar pattern in the levels of triglycerides was observed. The levels of HDL cholesterol remained unchanged and stayed in the normal range before and 1, 3, 6, and 12 months after transplantation from non-heart-beating donors. On the other hand, significant increases in non-HDL cholesterol were observed 3 and 6 months after transplantation from non-heart-beating donors. After transplantation from living-relation donors, levels of total cholesterol, triglycerides, and non-HDL cholesterol remained unchanged and remained in the normal range up to 12 months after transplantation. Although there were no significant differences in the total dosage of cyclosporine A between the patients with living-relation donors and those with non-heart-beating donors, a significant increase in the total dosage of methylprednisolone was observed in patients with non-heart-beating donors compared with those in the patients with living-relation donors. Renal function recovery in patients with living-relation donors was better than in those with non-heart-beating donors. These results may suggest that significant increases in total cholesterol, especially non-HDL cholesterol and triglycerides, were probably partly due to an increased use of immunosuppressants, steroids. It is necessary to aggressively control post-transplant hyperlipidemia and important to reduce or withdraw steroids in the selected, low-risk recipients as early as possible from the viewpoint of preventing post-transplant hyperlipidemia.     

Factors relating to the conditions and characteristics of mental health among the inhabitants in a methylmercury polluted area

OBJECTIVES: Little attention has been paid to mental health of inhabitants of methylmercury-polluted areas. The objective of this study was to examine the factors relating to the conditions and characteristics of mental health of inhabitants residing in a methylmercury-polluted area. METHODS: The eligible subjects of the study were inhabitants over the age of 40 years (n=301) living in two fishing village districts that were polluted by high concentrations of methylmercury. The study was conducted in two phases. In the first phase, a structured questionnaire was used to gather information on the current health condition and experience with Minamata disease of each subject through interviews. In the second phase, the General Health Questionnaire (GHQ)-30 was distributed to measure the psychological distress of the respondents. RESULTS: There were 133 (44.2%) study subjects. Factor analysis of the data collected using the GHQ was carried out and five factors that accounted for 57.9% of the total variance were selected. The first factor was labeled "depression and anxiety". Depression and anxiety were significantly associated with self-rated health status, the number of subjective symptoms, monthly outpatient visits and the receipt of compensation. Covariance structure analysis using the Amos 4.0 program demonstrated that depression and anxiety were significantly associated with the subjects' health condition, which in turn was influenced by experience with Minamata disease. CONCLUSION: Depression and anxiety of the inhabitants may be directly caused by the health condition. Further investigations with more precise and detailed measurements are needed to corroborate the causal relationship.     

Acute onset and worsening of diabetes concurrent with administration of statins

We report a patient in whom the administration of HMG CoA reductase inhibitors (statins) might have triggered the onset and worsening of diabetes. The patient was a 48-year-old Japanese man who underwent annual medical examination but had never been told of hyperglycemia. Four months after the commencement of atorvastatin (10 mg/day) treatment, a diagnosis of diabetes mellitus was made from his typical symptoms of hyperglycemia, postprandial plasma glucose level of 29.8 mmol/l and HbA1c of 11.5%. After 2 months of insulin therapy and 3 months after the cessation of atorvastatin, almost complete resolution of diabetes was observed. During the subsequent 3 months, diet therapy alone was sufficient to control blood glucose level. Then, we prescribed pravastatin (20 mg/day). During the subsequent 3 months, HbA1c was gradually increased. However, after discontinuation of pravastatin, HbA1c was gradually decreased. In the general population, statin does not seem to have critical adverse effects on glucose tolerance, but it may uncommonly modify the natural course of the development of diabetes in certain patients.     

Immunohistological study for estrogenic activities of nitrophenols in diesel exhaust particles

We recently isolated 3-methyl-4-nitrophenol (4-nitro-m-cresol; PNMC) and 4-nitro-3-phenylphenol (PNMPP) from diesel exhaust particles (DEP) and identified them as vasodilators and xenoestrogens. The estrogenic activity of PNMC and PNMPP was further examined by using immunohistochemical staining of proliferating cell nuclear antigen (PCNA) in uterine luminal epithelium of ovariectomized 25-d-old immature female rats injected with PNMC and PNMPP subcutaneously for 2 d. Significant increases were observed in uterine luminal epithelium in PCNA positive cells of animals receiving 10 and 100 mg/kg PNMC and 0.1 mg/kg PNMPP compared with controls. These results clearly show the estrogenic activity of PNMC and PNMPP by cell proliferation on the uterine luminal epithelium.     

Genetic diversity of sapovirus in fecal specimens from infants and children with acute gastroenteritis in Pakistan

Summary. A total of 517 fecal specimens collected from infants and children with acute gastroenteritis in Karachi city, Pakistan during 1990–1994 were examined for the presence of sapovirus by RT-PCR and sequence analysis methods. Sapovirus was identified in 17 of 517 (3.2%) specimens. Sapovirus was further clustered into three distinct genogroups (I, II and IV) and these presented 70.6%, 23.5% and 5.9%, respectively. Our results clearly indicated that sapovirus could be classified into 7 GI and 4 GII genotypes. It was noteworthy to point out that sapovirus detected among Pakistani infants and children with acute gastroenteritis demonstrated the great genetic diversity and presented novel sapovirus genotypes.     

Neutralization Test by New Isolates of Human Rotavirus

Thre newly isolated human rotaviruses in MA104 cells were used as antigens in the neutralization test of paired sera of infants and young children with acute gastroenteritis during three epidemic seasons. Twenty-three of 41 paired sera (56%) from outpatients with acute gastroenteritis responded with development of NT antibody to one, two, or three antigens. Of 23 paired sera which showed significant rises of antibody to any strain, 20 paired sera (87%) responded to strain Hochi, 15 cases (65%) to strain Ito, and 16 cases (70%) to strain Nemoto. Ten of 14 cases that were seronegative to any isolated strain at onset of illness showed significant rises of antibodies to three strains. Three strains were determined to be subgroup 2 by RNA pattern and were recently found to be similar if not identical to serotype 3 and 4 by Wyatt et al. The neutralization test showed extensive immunologic cross-reativity among these strains. The rate of acquisition of serum antibody by age was similar with the three antigens.     

Elimination of CD4(+)CD25(+) T cell accelerates the development of glomerulonephritis during the preactive phase in autoimmune-prone female NZB x NZW F mice

The role of CD4(+)CD25+ T cell in glomerulonephritis (GN) development during the preactive phase was investigated in autoimmune-prone female NZB x NZW F1 (B/WF1) mice. The administration of anti-mouse CD25+ T-cell monoclonal antibody (PC61.5) 3 days after birth induced the development of GN with an increase in IgG2a antinuclear antibody, productions of IL-6 and IFN-gamma, whereas TGF-beta1 production decreased, compared to untreated control mice. The present study results suggest that CD4(+)CD25+ T cells may, at least in part, downregulate the development of GN during the preactive phase in B/WF1 mice.     

Regeneration of granule neurons after lesioning of hippocampal dentate gyrus: evaluation using adult mice treated with trimethyltin chloride as a model

The hippocampal dentate gyrus in adult animals is known to contain neural progenitors that proliferate and differentiate into neurons in response to brain injury. Little has been observed, however, on regeneration of the granule cell layer of the dentate gyrus that has been directly injured. Using trimethyltin (TMT)-treated mice as an in vivo model, we evaluated the ability of this layer to regenerate after injury. The administration of TMT induced neuronal death in the dentate gyrus selectively 2 days later, with recovery of granule neurons on day 14 and thereafter. At an early stage (days 2-5) after the damage by TMT treatment, 5-bromo-2'-deoxyuridine (BrdU) incorporation into at least two different types of cells was facilitated in the dentate gyrus: BrdU-positive/neuronal nuclear antigen (NeuN)-negative cells were found predominantly in the subgranular zone and granule cell layer, whereas BrdU-positive/NeuN-positive cells were numerous in the dentate molecular layer and hilus. In addition, expression of proliferating cell nuclear antigen, nestin, NeuroD3, and doublecortin, which are markers for proliferating cells and neural progenitors/neuronal precursors, was extremely enhanced in the dentate gyrus at the early stage after treatment. Double staining revealed that BrdU was colocalized with nestin and doublecortin in the subgranular zone. Behavioral analysis revealed that TMT-induced cognition impairment was ameliorated by day 14 after the treatment. Taken together, our data indicate that the hippocampal dentate gyrus itself is capable of regenerating the neuronal cell layer through rapid enhancement of neurogenesis after injury.