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Notizen: Orexins are endogenous neuropeptides that potently facilitate appetite and food consumption. In the present study, we examined orexin immunoreactivity and prepro-orexin mRNA expression in the lateral hypothalamus by immunohistochemistry and competitive reverse transcription-polymerase chain reaction (RT-PCR) methods in different models of hyperphagia in rats. Hyperphagia was induced by lesions of either the ventromedial hypothalamus (VMHL) or the paraventricular nucleus (PVNL), and we also compared lactating rats to nonlactating controls. Both VMHL and PVNL increased food intake and body weight compared to shams. On day 7 post lesion, serum leptin and insulin concentrations exhibited 3.2- and 2.8-fold increases in VMHL rats, and nonsignificant 1.8- and 1.8-fold increases in PVNL rats; there were significant decreases (48% and 33%) in lactating rats on day 12 postpartum compared to controls, respectively. Serum glucose concentrations were not significantly changed compared to controls in these rats. Quantification by image analysis suggests that VMHL significantly decreased the number and mean staining intensity of orexin-A immunoreactive neurones compared to those in the sham-lesioned group; while PVNL did not change orexin-A immunoreactivity. Competitive RT-PCR analysis showed that VMHL significantly decreased the prepro-orexin mRNA expression compared to those in the sham-lesioned group, and PVNL did not change it. Lactating rats on days 11–12 of lactation had significantly greater number and mean staining intensity of orexin-A immunoreactive neurones, prepro-orexin mRNA expression food intake and body weight than nonlactating postpartum rats. Thus, changes in orexin-A immunoreactivity and prepro-orexin mRNA expression were not consistent between the hyperphagia models. These results suggest that the hyperphagia from VMHL or PVNL and lactating rats differ in their involvement of orexin-A, and the change in circulating leptin and insulin concentrations may be involved in the change of orexin-A immunoreactivity in these rats.

Notizen: Melanin-concentrating hormone (MCH) is believed to be an important orexigenic peptide mainly localized in the lateral hypothalamic area. Its involvement in the hyperphagia induced by hypothalamic lesions and lactation remains unclear. In this study, we investigated MCH immunoreactivity in the hypothalamus using immunohistochemistry and MCH concentration in the peripheral circulation using an enzyme immunoassay in rats with a lesion in the ventromedial hypothalamus or the paraventricular nucleus, and in lactating rats. Bilateral lesions of the ventromedial or paraventricular nuclei were performed using an electrolytic method. Quantification of immunoreactivity by image analysis revealed that the number and mean staining intensity of MCH-immunoreactive neurones in the lateral hypothalamic area and the zona incerta were significantly decreased by both types of lesions compared to sham controls, whereas circulating MCH concentration was not significantly different on day 7 postlesion. By contrast, in lactating rats on days 11–12 postpartum, the expression of MCH in the lateral hypothalamic area and the zona incerta was significantly increased compared to nonlactating controls. Circulating MCH concentration was not changed in lactating rats. These results suggest that hyperphagia induced by lactation, but not hypothalamic lesion, might be induced by excessive expression of MCH in the lateral hypothalamic area and the zona incerta.

Notizen: Background: Incidental IgA deposition in glomerular mesangium exists in 10–20% of autopsy kidneys1,2 or renal allograft donors.3 In the present study, we examined the clinicopathological features of incidental mesangial IgA deposition in renal biopsy from patients with minimal change nephrotic syndrome (MCNS) to understand the significance of mesangial IgA deposition in MCNS and pathogenesis of IgA nephropathy.Patients and Methods: From January 1994 to September 2000, 63 patients were diagnosed with MCNS by renal biopsy at Kidney Center, Tokyo Women’s Medical University. Mesangial IgA and C3 deposition was examined by immunofluorescence staining using frozen sections. The frequency of IgA and C3 deposition in MCNS and clinicopathological features of IgA-positive patients with MCNS were investigated.Results: The mesangial IgA deposition was present in 15 out of 63 patients (23.8%). Among these 15 patients, codeposition of C3 was present in 10 patients (66.7%) (〈link href="#f1"〉Fig. 1). The serum IgA concentration was significantly higher in the IgA-positive patients than in the IgA-negative patients (309 ± 75 mg/dL versus 245 ± 106 mg/dL, P = 0.043) (〈link href="#f2"〉Fig. 2). The urinary red blood cell count was higher in IgA-positive patients than in IgA-negative patients, although not significantly different (11.7 ± 12.7 counts/HPF versus 5.3 ± 4.0 counts/HPF, P = 0.067) (〈link href="#f3"〉Fig. 3). Other clinical parameters (age, sex, amount of proteinuria, serum creatinine and creatinine clearance) were not significantly different. Histologically, no significant differences were observed between IgA-positive and IgA-negative patients in following parameters: grade of mesangial cell proliferation and mesangial matrix increase, extents of tubular atrophy and interstitial fibrosis and grade of vascular sclerosis. After steroid treatment, all 15 patients with mesangial IgA deposition had become complete remission, although three patients once relapsed proteinuria. The haematuria also disappeared after steroid treatment in these patients.〈figure xml:id="f1"〉1〈mediaResource alt="image" href="urn:x-wiley:13205358:NEP14:NEP_14_f1"/〉The frequency of mesangial IgA and C3 deposition in MCNS patients (n = 63). The mesangial IgA deposition was present in 15 out of 63 patients (23.8%). Among these 15 patients, codeposition of C3 was present in 10 patients (66.7%).〈figure xml:id="f2"〉2〈mediaResource alt="image" href="urn:x-wiley:13205358:NEP14:NEP_14_f2"/〉The serum IgA concentration of the MCNS patients with and without mesangial IgA deposition. The serum IgA concentration was significantly higher in IgA-positive patients (n = 15) than in IgA-negative patients (n = 48) (309 ± 75 mg/dL vs 245 ± 106 mg/dL, P = 0.043).〈figure xml:id="f3"〉3〈mediaResource alt="image" href="urn:x-wiley:13205358:NEP14:NEP_14_f3"/〉The urinary red blood cell counts of the MCNS patients with and without mesangial IgA deposition. The urinary red blood cell count was higher in IgA-positive patients (n = 15) than in IgA-negative patients (n = 48), although not significantly different (11.7 ± 12.7 counts/HPF vs 5.3 ± 4.0 counts/HPF, P = 0.067).Conclusion: The incidental mesangial IgA deposition was frequently observed in MCNS patients (15/60 patients, 23.8%). The phenomenon of mesangial IgA deposition in MCNS patients was related to higher serum IgA concentration and might cause slight haematuria. However, no influence of mesangial IgA deposition was found on the renal function and the clinical outcome of MCNS after treatment.

Notizen: The aim of the present study was to examine the role of CD28-B7 signalling in the development of glomerulonephritis in ddY mice, an animal model for IgA nephropathy. To achieve this aim, we investigated whether the CTLA-4 (CD152) fusion protein, which binds to B7.1 (CD80) and B7.2 (CD86), affects glomerular pathological changes (including IgA deposition), or functional parameters (such as serum creatinine and proteinuria). Each group (n = 4) was given either human CTLA-4 fused with human IgG (CTLA4Ig) or control human IgG1. All treated groups of mice were injected intraperitoneally at a dose of 0.1 mg twice a week for the duration of the study. Mice given control human IgG1 progressively developed typical mesangioproliferative glomerulonephritis, with remarkable glomerular IgA deposits. In contrast, mice treated with CTLA4Ig showed a significant reduction in proteinuria and mesangioproliferative change, with an expansion of the mesangial matrix at 40 weeks of age. The serum IgA levels of these mice were considerably lower than those in mice given the control human IgG1. A direct immunofluorescence study showed the reduction of glomerular IgA deposits in CTLA4Ig-treated mice. We have demonstrated for the first time that the development of spontaneously occurring IgA nephropathy can be prevented in ddY mice by blocking the CD28-B7 interaction using a soluble form of CTLA4Ig. These results suggest that a costimulatory signal via CD28-B7 may play a crucial role in the development and progression of IgA nephropathy.

Notizen: Background:  Pyridinoline (Pyr) and deoxypyridinoline (Dpyr) collagen cross-links are known markers of bone and cartilage turnover that are found in urine in various diseases. The present study was designed to quantify Pyr and Dpyr levels in urine of patients with osteoarthritis (OA) of the temporomandibular joint (TMJ), and to evaluate whether their concentrations are related to specific pathologic findings in the TMJ.Methods:  Urine samples were obtained from 12 patients with OA of the TMJ and 16 asymptomatic controls, and following appropriate preparation, analyzed by high-performance liquid chromatography (HPLC) and fluorescence spectroscopy for Pyr and Dpyr.Results:  The urinary concentration of Pyr and the Pyr to Dpyr (Pyr/Dpyr) ratio were significantly higher (P 〈 0.05) in OA patients than in the controls (182.2 ± 86.5 pmol/ml vs. 115.6 ± 27.9 pmol/ml and 4.00 ± 1.53 pmol/ml vs. 2.86 ± 0.97 pmol/ml, respectively). However, the Pyr/Dpyr ratio was not associated with any specific clinical or radiographic findings.Conclusion:  These findings suggest that the level of Pyr and the Pyr/Dpyr ratio in urine may be a useful diagnostic indicator for intra-articular pathologic changes during TMJ OA.

Notizen: Zusammenfassung Die Anisotropie der Magnetisierbarkeit des ferromagnetischen Einkristalls wird auf Grund eines neuen und übersichtlichen Modells des ferromagnetischen Stoffes diskutiert. Die nach dieser Theorie berechneten Konstanten der magnetischen Anisotropie stimmen beim Eisen und Nickel mit dem Experiment befriedigenderweise überein. Beim Kobalt bleibt zwischen Theorie und Experiment eine kleine Diskrepanz, die durch Berücksichtigung der Hysteresis bei den Magnetisierungs- und Entmagnetisierungsvorgängen verkleinert werden kann.