Serum IgA/C3 ratio may predict diagnosis and prognostic grading in patients with IgA nephropathy

Recently, the authors reported that the ratio of serum IgA to C3 (serum IgA/C3 ratio) is a good marker to distinguish patients with IgA nephropathy from non-IgA nephropathy patients together with serum IgA levels using an international reference preparation (IFCC/CRM470). In this study, the authors investigated whether the serum IgA/C3 ratio might be an indicator of prognostic grading in patients with IgA nephropathy. Two hundred and thirteen patients with IgA nephropathy and 96 other glomerular diseases including diffuse or focal mesangial proliferative glomerulonephritis without mesangial IgA deposition (non-IgA PGN), membranous nephropathy and thin basement membrane syndrome were examined. The levels of serum IgA and C3 in these patients were adjusted by the specified formula to those using international standard serum (IFCC/CRM470) in this study. The results of this study showed the highest levels of IgA/C3 ratio in patients with IgA nephropathy. The serum IgA/C3 ratio appears to gradually increase according to the prognostic grading of this disease. Therefore, measurement of the serum IgA/C3 ratio may be useful for prediction of diagnosis and prognostic grading in patients with IgA nephropathy.     

Role of hypomagnesemia in chronic cyclosporine nephropathy

BACKGROUND: Hypomagnesemia is a common finding of cyclosporine (CsA)-treated patients and has been proposed as both a cause and a consequence of CsA-induced nephrotoxicity. This experiment was conducted to elucidate the role of hypomagnesemia in the pathogenesis of chronic CsA nephropathy. METHODS: CsA (15 mg/kg/day subcutaneously) was administered to rats maintained on a low-sodium diet for 1, 2, and 4 weeks, and the effects of magnesium (Mg) supplementation on renal function, renal histology, and renal gene expression profile of fibrogenic molecules and vasoconstrictors was examined. RESULTS: CsA elicited hypomagnesemia and induced a progressive decline in glomerular filtration. At 28 day, renal tubular atrophy and cortical striped interstitial fibrosis were evident with CsA treatment. Dietary supplementation of Mg ameliorated CsA-induced hypomagnesemia and almost completely abolished CsA-induced chronic fibrotic lesions. Neither CsA nor Mg supplementation affected blood pressure. Renal cortical mRNA of transforming growth factor beta, plasminogen activator inhibitor (PAI)-1, and extracellular matrix started to increase at 14 days and elevated further at 28 days. In contrast, the increase in mRNA of tissue inhibitor of matrix metalloproteinase-1 and renin was evident early at 7 days and reached peak at 14 days. These mRNA increases, except that of renin, were almost abolished when hypomagnesemia was corrected. Magnesium supplementation also improved glomerular dysfunction, at least in part, through inhibition of up-regulated mRNA of endothelin-1. CONCLUSION: CsA-induced hypomagnesemia contributes to chronic renal fibrotic lesions seen during CsA treatment through up-regulation of fibrogenic molecules, most notably early activation of tissue inhibitor of matrix metalloproteinase-1 expression.     

Habitual intake of lactic acid bacteria and risk reduction of bladder cancer

INTRODUCTION: A kind of lactic acid bacteria, Lactobacillus casei strain Shirota, shows antitumor activity in experimental animals. One clinical trial using L. casei showed a significant decrease in the recurrence of superficial bladder cancer. So, to assess the preventive effect of the intake of L. casei, widely taken as fermented milk products in Japan, against bladder cancer, we conducted a case-control study. METHODS: A total of 180 cases (mean age: 67 years, SD 10) were selected from 7 hospitals, and 445 population-based controls matched by gender and age were also selected. Interviewers asked them 81 items. The conditional logistic regression was used to estimate adjusted odds ratios (OR). RESULTS: The OR of smoking was 1.61 (95% confidence interval: 1.10-2.36). Those of previous (10-15 years ago) intake of fermented milk products were 0.46 (0.27-0.79) for 1-2 times/week and 0.61 (0.38-0.99) for 3-4 or more times/week, respectively. CONCLUSION: It was strongly suggested that the habitual intake of lactic acid bacteria reduces the risk of bladder cancer.     

Bupivacaine attenuates contractility by decreasing sensitivity of myofilaments to Ca2+ in rat ventricular muscle

BACKGROUND: Bupivacaine exhibits a cardiodepressant effect, the molecular mechanism(s) of which have yet to be fully understood. Bupivacaine may directly act on contractile proteins and thereby decrease myofibrillar Ca2+ sensitivity. METHODS: Rat ventricular muscle was used. First, the effect of bupivacaine was examined on tetanic contractions in isolated intact myocytes. Next, Triton X-100-treated ventricular trabeculae were used to investigate the effect of bupivacaine on the pCa (= -log [Ca2+ ])-tension relation as well as on maximal Ca2+ -activated tension. Furthermore, to test whether bupivacaine inhibits the pathway downstream from Ca2+ binding to troponin C, tension was elicited in the skinned preparations by lowering the Mg-adenosine triphosphate (MgATP) concentration in the absence of Ca2+. The effect of bupivacaine on the pMgATP (= -log [MgATP])-tension relation was examined. RESULTS: In myocytes, 3 microm bupivacaine significantly (P < 0.01) increased intracellular Ca2+ concentration required for 5% cell shortening from the resting cell length. In skinned preparations, bupivacaine shifted the pCa-tension relation to the lower pCa side; the midpoint of the pCa curve (pCa50) was significantly (P < 0.05) changed by 10 and 100 microm bupivacaine. A highly correlated linear relation (R = 0.81; P< 0.0005) was present between pCa50 and maximal Ca2+ -activated tension. Bupivacaine (10 and 100 microm) significantly (P < 0.05) shifted the midpoint of the pMgATP-tension relation to the higher pMgATP side. CONCLUSIONS: Bupivacaine decreases myofibrillar Ca2+ sensitivity in ventricular muscle, and this is coupled with the compound's inhibitory effect on the pathway beyond Ca2+ binding to troponin C, possibly on the actomyosin interaction. The current results may partly explain the overall cardiodepressant effect of bupivacaine in vivo.     

Diagnosis of visceral pleural invasion by lung cancer using intraoperative touch cytology

BACKGROUND: Invasion to the visceral pleura is an important component of lung cancer staging and an independent prognostic factor. However, the accuracy of pathologic examination depends on how the sections are made, and the pathologist may miss the most invaded part of the pleura. Therefore, we have designed "touch" cytology in an effort to more accurately diagnose the pleural invasion by lung cancer. METHODS: Immediately after thoracotomy, the surface of the visceral pleura just above the tumor was gently touched by a glass slide without scrubbing in 100 patients who simultaneously underwent pleural lavage cytology or cytology of the subclinical pleural effusion. RESULTS: Seventeen percent of the tumors were diagnosed as invading the visceral pleura by touch cytology. Lavage cytology was found to be positive in 7%. In reference to the pathologic examination of the tumor specimen, touch cytology was found to be positive in all of p3, 5 out of 6 of p2, 5 out of 30 of p1, and 5 out of 62 of p0 cases. Touch cytology correctly diagnosed all the positive cases detected by lavage or effusion cytology. CONCLUSIONS: This study suggests that our method is useful in detecting the visceral pleural invasion and raises a possibility that pathologic p0 and p1 lung cancers include a subset of patients with tumor cells exposed on the pleural surface.     

Seminal lactate dehydrogenase C4 (LDH-C4) isozyme activity in infertile men

Lactate dehydrogenase C4 (LDH-C4) is the specific isozyme of LDH produced by germ cells. We measured LDH-C4 activity in seminal plasma from infertile men with oligozoospermia or azoospermia using gel electrophoresis. Total LDH activity in seminal plasma from infertile patients (n = 99) was 2,487 +/- 1,384 IU/l (mean +/- SD). LDH-C4 isozyme activity was detected in 63 out of 75 seminal plasma samples from infertile patients with a mean of 383 +/- 356 IU/l (13.8 +/- 8.6% of total LDH). Sperm count was positively correlated with LDH-C4 (r = 0.298; P < 0.05), but not with any other LDH isozymes or with total LDH. Seminal LDH-C4 was significantly lower in patients with varicoceles (253 +/- 223 IU/l) than without varicoceles (474 +/- 262 IU/l). Six azoospermia patients were treated with hCG and hMG. Three out of four patients whose seminal plasma revealed LDH-C4 activity responded to the treatment, whereas none of the other two patients without seminal LDH-C4 activity did. These results indicate the clinical usefulness of seminal LDH-C4 as a potential marker for seminal epithelium activity in the diagnosis and treatment of male infertility.     

Region-specific reduction of A beta-degrading endopeptidase,neprilysin, in mouse hippocampus upon aging

Metabolism of amyloid-beta peptide (A beta) is closely associated with the pathology and etiology of Alzheimer's disease (AD). Neprilysin is the only rate-limiting catabolic peptidase proven by means of reverse genetics to participate in A beta metabolism in vivo. The aim of the present study is to assess whether possible spatial changes in neprilysin level in the brain with aging correlate to AD-vulnerable regions. When neprilysin levels in various brain regions of 10-, 80- and 132-week-old mice were evaluated by neprilysin-dependent endopeptidase activity assay and Western blot-based quantitative analysis, a clear change in neprilysin level with aging was observed in the hippocampal formation, in which the level was reduced by 20% at 132 weeks, compared to the 10-week group. Quantitative immunohistochemical analysis confirmed a marked local reduction of neprilysin levels with aging at the outer molecular layer and polymorphic layer of the dentate gyrus, and the stratum lucidum of the hippocampus, where the densities were reduced by 56%, 82% and 83%, respectively, at 132 weeks compared to the 10-week group. Thus, neprilysin was decreased selectively at the terminal zones and on axons of the lateral perforant path and the mossy fibers. These are the sites that show A beta pathology in mutant amyloid precursor protein (APP) transgenic mice, and that show synaptic loss in AD. The immunoreactivities to synaptic vesicle protein-2 and synaptophysin in the stratum lucidum and the dentate gyrus were unchanged, suggesting that a loss or decrease of synapses was not responsible for the decrease in the neprilysin levels. These observations suggest that downregulation of neprilysin is likely to be related to AD pathology and to the A beta deposition associated with normal aging in humans.