Intracellular survival of virulence and low-virulence strains of Vibrio parahaemolyticus in Epinephelus awoara macrophages and peripheral leukocytes.

In this study, we examined the virulence factors and pathogenesis of Vibrio parahaemolyticus in Epinephelus awoara. The chemotactic motility of V. parahaemolyticus for phagocytosis and intracellular survival in fish macrophages was determined using virulence strains and low-virulence strains of V. parahaemolyticus. We found that the intracellular mean number of virulence strains of V. parahaemolyticus ranged from 0-180 min after co-incubation with macrophages and peripheral leukocytes, was relatively low, and decreased steadily over the observation period. Low-virulence strains of V. parahaemolyticus were unable to survive in peripheral leukocytes and macrophages. Cell viability in response to V. parahaemolyticus was assessed using the MTT assay. Low-virulence V. parahaemolyticus strains exhibited lower cytotoxicity compared to virulent strains. The average percent of live macrophages and peripheral leukocytes infected by V. parahaemolyticus ranged from 13.50-79.20%. These results indicate that V. parahaemolyticus in E. awoara is a facultative intracellular bacterium that may be involved in virulence.

Levels of urinary complement factor H in patients with IgA nephropathy are closely associated with disease activity.

Factor H plays a key inhibitory role in control of the activation of alternative pathway of complement system. The aim of the study was to investigate the predictive value of factor H as a biomarker of renal injury in IgA nephropathy (IgAN). Urine factor H concentration from 202 patients was measured and compared with that of 60 healthy volunteers. Forty-eight patients fulfilled Haas-I or II (group 1), 60 fulfilled Haas-III (group 2) and 94 fulfilled Haas-IV or V (group 3). Co-deposition of factor H and C3b in kidneys were investigated using confocal microscope. The levels of urinary factor H, when expressed as a ratio of urinary creatinine, were significantly higher in groups 3 than group 1 and 2, also significantly higher in group 2 than group 1. In addition, the levels of urinary factor H were significantly higher in those with factor H deposition in the kidney than those without deposition. The levels of urinary factor H may be a useful biomarker to evaluate kidney injury in IgAN.

Induction treatment of proliferative lupus nephritis with leflunomide combined with prednisone: a prospective multi-centre observational study.

To evaluate the efficacy and safety of leflunomide in the treatment of proliferative lupus nephritis, a prospective multi-centre observational study was conducted. Patients with biopsy proven proliferative lupus nephritis were assigned to receive either leflunomide or cyclophosphamide with concomitant prednisone. Leflunomide was given orally with a loading dose of 1 mg/kg/day for 3 days followed by 30 mg/day. Intravenous cyclophosphamide was administered monthly at a dose of 0.5 g/m2 of body-surface area. A total of 110 patients were enrolled, 70 in the leflunomide group and 40 in the cyclophosphamide group. The complete remission rate in the leflunomide group was 21% and partial remission rate 52%, as compared with 18% and 55%, respectively, in the cyclophosphamide group. Renal parameters and systemic lupus erythematosus disease activity index improved significantly and similarly in both groups. Serum creatinine decreased or stabilized in both treatment groups. No significant difference was noted with respect to clinical outcome between groups. Repeat biopsy also showed a significant reduction of active lesions in kidney pathology after 6 months of leflunomide treatment. Major adverse events, similar in both treatment groups, included infection, alopecia and hypertension. Leflunomide, compared with cyclophosphamide, in combination with prednisone was effective in the induction therapy of proliferative lupus nephritis and was generally well-tolerated.

[A study on the proliferative and sclerosing mechanism of glomerular mesangium].

The role of glomerular mesangial cells (MC) and mesangial matrix (MM) in glomerular sclerosis was studied by using rat mesangial cell culture, immunohistochemical studies for laminin, laminin receptors as well as collagen types IV and III. The effect of tumor necrosis factor (TNF) and endothelin (ET) on MC was also studied. Results show that TNF and ET have potent mitogenic effects on MC. The glomerular MC possess the special capability of secreting TNF and ET. TNF and ET can also influence and induce the secretion of each other. The MM is increased in the MC nodular colonies formed after prolonged culture. These colonies are composed of collagen IV and collagen III. Therefore, injuring factors can cause MC and MM to proliferate and produce glomerulosclerosis.

[The effect of T cells in pathogenesis of glomerular nephritis].

T lymphocytes were infused to congenital athymic nude mice to reconstitute its cellular immunological function. Success was then achieved in inducing crescentic glomerular nephritis in the nude mice. No pathological changes were observed in the control group of nude mice which did not receive T lymphocyte infusion. Results of this study suggest that T lymphocytes play an important role in the pathogenesis of crescentic glomerular nephritis.

[The ultrastructural characteristics of minor glomerular abnormalities].

Among 1168 patients in whom clinical data and light microscopic, immunofluorescence and electron microscopic findings of renal biopsies were available, 329 had minor glomerular abnormalities. These 329 cases included 38 with glomerular minimal change (MC), 32 with glomerular minor lesion, 143 with mild mesangioproliferative GN, 14 with mild mesangioproliferative IgM nephropathy, 4 with C1q nephropathy, 37 with IgA nephropathy, 12 with Henoch-Schönlein purpura GN, 17 with lupus nephritis, 16 with early stage membranous nephropathy (eMN), 4 with Alport's syndrome (ALS), 7 with thin basement membrane nephropathy (TMN) and 5 with nonglomerular haematuria. Their histologic appearances were nearly normal, and immunofluorescence was negative or mild positive. But electron microscopic appearances were diagnostic. Electron microscopy is the only diagnostic method for MC, ALS, TMN and eMN.

[The roles of T cells in experimental crescentic glomerulonephritis].

A crescentic glomerulonephritis (GN) model was induced by intravenous injection of rabbit anti-mouse glomerular basement membrane (GBM) antiserum and lipopolysaccharide (LPS) in BALB/c mice, heterozygous mice and nude mice respectively, in order to detect the T-cells effects on the development of crescentic GN. The immunofluorescence and morphological changes of glomeruli in different groups of animals were compared. Intense fluorescence (4+) of rabbit IgG could be found along the GBM in liner pattern in all the animals. Intense (3(+)-4+) mouse IgG was also found along the GBM in liner pattern in the normal and heterozygous mice, but could not be identified in the nude mice. The normal mice developed typical crescentic GN, characterized by serious degeneration and destruction of GBM, fibrin deposition and crescents formation, 3-6 weeks after the injection. The heterozygous mice only developed mild proliferation of the mesangial cells in the glomeruli but there was no glomerular lesion detected in the nude mice. It suggests that the glomerular immune damage requires the participation of functional T-cell.

The effect of calcitonin-gene-related peptide on acute ischemia-reperfusion renal injury: ultrastructural and membrane lipid peroxidation studies.

It is well accepted that postischemic reperfusion promotes functional and morphological impairment which may be related to oxygen free-radical-mediated membrane damage. A new purified bioactive compound, calcitonin-gene-related peptide (CGRP), is known to be not only a potent vasodilator but also a cytoprotective agent. This study was designed to observe whether CGRP has a protective effect on the ischemic kidney. Male Sprague-Dawley rats were subjected to a 45-min period of renal ischemia followed by 60 min of reperfusion. At the beginning of the reperfusion, 12 rats were given intravenous saline and served as controls whereas 5 rats were given CGRP, 10 micrograms/kg intravenously. After reperfusion the kidneys were removed for light- and electronmicroscopy, and the lipid peroxidation product malonaldehyde (MDA) was assayed by thiobarbituric acid (TBA) colorimetry. The results demonstrated that the serum creatinine (Scr) and renal MDA content in the CGRP group were significantly lower than those in the control group. The mean values for Scr were 0.75 +/- 0.09 vs 0.93 +/- 0.05 mg/dL or 62.8 +/- 9.7 vs 82.2 +/- 4.4 mumol/L (p less than 0.05), respectively; while the mean values for MDA were 18.71 +/- 2.13 vs 30.32 +/- 1.78 nmol/100 mg (ww) (p greater than 0.05), respectively. The same signals of free radicals in the ischemic-reperfused kidney with or without CGRP were found by electron spin resonance. Morphological studies demonstrated that the treatment with CGRP ameliorated the ischemic-reperfusion injury to both renal brush borders and mitochondria. The results showed that CGRP has a protective action on ischemia-reperfusion renal injury by decreasing lipid peroxidation of membranes and suggest that it may be a beneficial agent for therapy of acute renal failure.

Protective effect of zinc-induced metallothionein synthesis on gentamicin nephrotoxicity in rats.

Wistar rats were used to study the protective effect of zinc-induced metallothionein (MT) synthesis on gentamicin nephrotoxicity. We found that s.c. pre-injection of ZnSO4 (Zn 10 mg/kg/day) for 5 days could ameliorate proximal tubular necrosis and acute renal failure caused by an 8-day s.c. injection of gentamicin (100 mg/kg/day), while preinjection of saline instead of zinc or zinc and gentamicin together could not. In the zinc-pretreated rats (n = 6), renal cortical metallothionein level was significantly higher than that of normal (n = 8, p less than 0.001) and the saline controls (n = 6, p less than 0.001). Since MT is a scavenger of hydroxyl radical, it is proposed that hydroxyl radical plays a role in the pathogenesis of gentamicin nephrotoxicity and that preinjection of zinc could ameliorate gentamicin nephrotoxicity via the induction of renal cortical MT synthesis.

Relation between plasma atrial natriuretic peptide (ANP) and glomerular ANP receptors in 5/6 nephrectomized rats.

Chronic renal failure (CRF) was induced in male wistar rats (Group I) by 5/6 nephrectomy and the sham-operated ones served as control (Group II). The results showed that in Group I, plasma atrial natriuretic peptide (ANP) levels increased progressively as the Scr was elevated. Plasma R-A rose simultaneously compared to the normal (P less than 0.001). At the 20th week after operation, urine volume and Na decreased significantly (P less than 0.05). The number of glomerular receptors decreased markedly at the 12th week (P less than 0.05) and 20th week (P less than 0.01). Our data suggest that in 5/6 nephrectomized rats, the elevation of plasma ANP level might be partly caused by the damage of glomerular ANP receptors, and the elevated plasma ANP could not play its role in diuresis, natriuresis, blood pressure depression and R-A inhibition as a result of the damage of kidney ANP receptors.

Correlation between T cells and experimental crescentic glomerulonephritis.

A model of crescentic glomerulonephritis (GN) in mice was induced by intravenous injection of rabbit anti-mouse glomerular basement membrane (GBM) antiserum and lipopolysaccharide. The procedure was carried out in BALB/c mice, heterozygous mice and nude mice. In order to examine the role of T cells in the pathogenesis of crescentic GN, immunofluorescent and morphologic changes in the glomeruli of these animals were studied. Intense (4+) linear deposition of rabbit IgG was found along the GBM of all test animals. Intense (3(+)-4+) linear deposition of mouse IgG along the GBM was present in normal and heterozygous mice, but not in nude mice. Normal mice developed typical crescentic GN characterized by severe degeneration and destruction of GBM, fibrin deposition and crescent formation 3-6 weeks after injection. Heterozygous mice only developed mild mesangial proliferation. No glomerular lesions were seen in nude mice. These preliminary data suggest that glomerular immunologic damage requires the participation of functional T cells, and that the induction of typical crescentic GN requires integral T-cell function.

[Clinicopathologic correlation of lupus nephritis].

26 autopsies and 29 renal biopsies of lupus nephritis were done and examined with pathohistologic methods. They consisted of minor type 2 cases (3.6%), mesangioproliferative type 11 cases (20.0%), focal type 10 cases (18.2%), diffuse proliferative type 17 cases (30.9%), membranous type 13 cases (23.6%) and proliferosclerosing type 2 cases (3.6%). It was found that varied and atypical glomerular lesions, glomerular massive immune complex deposits and wire loop formation, fibrin necrosis, microthrombi formation, arteritis, interstitial inflammation and hematoxyphil bodies formation were common lesions for lupus nephritis. These lesions were indices of activity and progression of lupus nephritis.

Non-IgA mesangial proliferative glomerulonephritis. Clinical and pathological analysis of 77 cases.

Primary mesangial proliferative glomerulonephritis without IgA deposition (non-IgA MsPGN) is one of the most common types of glomerular disease in China. In an attempt to investigate its clinical and pathological features, we reviewed 77 such cases from 380 patients with primary glomerulonephritis taken renal biopsies during 1980-1987. Prodromal upper respiratory tract infection occurred in 31 cases (40%). In immunofluorescence microscopy, prominent IgG granular deposits in mesangium were observed in 45 cases (58%). These features are quite different from those in western countries, indicating it might have different pathogenetic processes. According to the severity of mesangial lesions, the 77 cases were divided into 3 groups: mild (55 cases), moderate (14) and severe (8). In the patients with mild mesangial lesion and massive proteinuria, the therapeutic response to prednisone was similar to that in adult minimal change disease. In the moderate and severe groups, there was a significantly higher incidence of superimposed tubulo-interstitial lesions associated with hypertension, persistent renal insufficiency and a poor response to prednisone. This work showed non-IgA MsPGN covered about 20% of our primary glomerulopathy, which may be related to a higher incidence of infection. It was suggested that minimal change nephrotic syndrome, inspite of the variety of immunoglobulin mesangium deposits, could be treated as a single disease entity, and light microscopy is most important in offering prognostic information.

[Prostatic carcinoid and neuroendocrine tumors--a case report].

This paper reports a rare primary prostatic adenocarcinoid tumor confirmed by electron microscopy as well as immunohistochemical method including prostate specific antigen and prostatic acid phosphatase. Electron microscopy showed the presence of neuroendocrine granules in the cytoplasm of some tumor cells and the latter method ruled out the possibility of secondary tumor from other organs. It is noted that prostatic adenocarcinoid tumor is one of the diffuse neuroendocrine system tumors. Although the histogenesis of these tumors is not entirely clear, it is believed to be of multiple origins, and may transform through metaplasia into neoplasm.

The effect of the thromboxane synthetase inhibitor Dazmegrel (UK-38,485) on wound healing, dermal ink perfusion and skin blood flow measurements in deep partial thickness burns.

A guinea-pig model was used to evaluate the effect of Dazmegrel (UK-38,485), a new highly selective inhibitor of thromboxane synthetase, on burn wound healing. Dazmegrel had a beneficial effect on wound healing when given systemically at a dosage of 3.4 mg kg-1 day-1 but higher doses had no effect. There was no change in dermal perfusion measured by India ink injection or by 133Xe injection in any of the groups receiving parenteral Dazmegrel. Neither was the number of hair follicles in the healing burn wound significantly different between the treated and control animals. When Dazmegrel was applied topically, it inhibited wound healing. These findings are consistent with previous reports from different laboratories that prostaglandin inhibitors impair healing of the burn wound when applied topically but improve wound healing when given parenterally. The present study further suggested that the improvement in wound healing in this model was not mediated by improved dermal perfusion.