Renal C3 synthesis in idiopathic membranous nephropathy: correlation to urinary C5b-9 excretion

Renal C3 synthesis in idiopathic membranous nephropathy: Correlation to urinary C5b-9 excretion. BACKGROUND: Complement activation plays a central pathogenetic role in idiopathic membranous nephropathy (IMN). Urinary excretion of C5b-9 correlates to the immunologic activity of this disease. Recently, renal cortical C3 gene expression has been described in several nephropathies. METHODS: The aim of this study was to investigate the renal C3 gene expression by in situ hybridization in IMN and to correlate it with histopathologic, pathophysiologic, and immunologic (urinary C5b-9) indices of disease activity. RESULTS: C3 was expressed in 77% of 22 renal biopsies of IMN patients, mainly at the cortical tubular and glomerular parietal epithelial cell levels. C3 protein synthesis by tubular cells was demonstrated by immunofluorescence. The intensity of C3 gene expression by both glomerular and tubulointerstitial compartments correlated with the glomerular stage of disease (P = 0. 0023 and P = 0.0214, respectively). Although no correlation was found with proteinuria, serum creatinine at renal biopsy time was strongly associated with renal C3 expression. IMN patients showed a trend of increased urinary C5b-9 levels, which correlated to C3 at the tubulointerstitial level (P = 0.0143). CONCLUSION: Renal C3 production, mainly at the tubular level, may be induced by urinary excretion of C5b-9 in IMN and may have a pathogenetic role in the tubulointerstitial damage that can be associated with this disease.     

GABAB receptor activation exacerbates spontaneous spike-and-wave discharges in DBA/2J mice

Rich evidence has highlighted that stimulation of γ-amino-butyric acid (GABA)_B receptors increases the occurrence of spike-and-wave discharges (SWDs), the electroencephalographic (EEG) landmark of absence epilepsy (AE). Recent findings suggest that the outcomes of GABA_B activation in vivo are contingent on the chemical characteristics of the agonist. In particular, the endogenous ligand γ-hydroxybutyrate (GHB) and its precursor γ-butyro-lactone (GBL) have been shown to elicit different effects than the prototypical GABA_B agonist baclofen. In view of these premises, the present study was aimed at the characterization of the effects of baclofen (0.5–10 mg/kg, i.p.) and GBL (5–100 mg/kg, i.p.) on the spontaneous SWDs and locomotor activity of DBA/2J mice.While both baclofen and GBL dose-dependently increased SWDs episodes, high doses of the latter (100 mg/kg, i.p.) reduced the occurrence of these phenomena and increased the number of isolated spikes. Interestingly, both compounds elicited a dose-dependent reduction of locomotor activity, in comparison with their vehicle-treated controls. The GABA_B selective antagonist, SCH50911 (50 mg/kg, i.p.), reversed the changes in SWD occurrence and locomotion induced by baclofen and GBL, but failed to elicit intrinsic effects on either paradigm. These results indicate that GABA_B receptor signaling might exert differential effects on SWDs in DBA/2J mice.     

Multiple sclerosis in children under 10 years of age

Neurological Sciences - Despite the consistent amount of information accumulated in recent years on multiple sclerosis (MS) in childhood, many clinicians still view this condition as an exclusively...     

Angiotropic large-cell lymphoma with predominant kidney involvement. A case report

The authors report a case of non Hodgkin lymphoma which, given its particular course and histomorphological features, can be classified as angiotropic large-cell lymphoma (i.e. proliferating angioendotheliomatosis). The most important characteristic is that the kidney was the target organ in this case, an observation rarely reported in the literature.     

Differences in H-reflex between athletes trained for explosive contractions and non-trained subjects

Summary The efficacy of type la synapse on alpha-motoneurons of soleus and lateral gastrocnemius muscles has been investigated, using the H-reflex technique, in athletes engaged in sports requiring very rapid and intense contractions (sprinters and volley-ball players) as well as in non-trained subjects. It has been observed, in both muscles, that the ratio between the mean value of the maximal reflex response (H_max) and the mean value of the maximal direct response (M_max) elicited upon electrical stimulation of the tibial nerve is significantly smaller in athletes trained for explosive-type movements than in non-trained subjects. This difference in the H_max:M_max ratio was dependent on a smaller amplitude of H_max and not on a greater amplitude of M_max. No significant differences were observed between sprinters and volley-ball players. In both trained and non-trained subjects, soleus and lateral gastrocnemius muscles displayed significant differences in H_max: M_max ratio and M_max amplitude but not in H_max amplitude. Since the H-response is considered to be due mainly to activation of the smallest motoneurons in the motoneuronal pools, the difference in H_max amplitude and H_max:M_max ratio between athletes and non-trained subjects could have been dependent on a lower incidence of these motoneurons in the athletes. This is in accord with the mechanical needs of muscles during explosive-type power training. Although this difference ,ay have been wholly determined genetically, the possibility is discussed as to whether the lower incidence in sprinters and volley-ball players of small motoneurons could have been related to a training-induced transformation of small and slow motoneurons into large and fast ones.     

General Health,Systemic Diseases and Oral Status in Adult Patients with Coeliac Disease

The prevalence of coeliac disease in the general population is 0.5–1%; however, most patients remain undiagnosed until adult age. In some cases, the onset is represented by sub-clinical signs, some of which can be found in the mouth. The aim of this research was to identify any associations between the clinical characteristics of coeliac disease and oral manifestations. A structured questionnaire was administered to a group of 237 individuals with coeliac disease. 100% of the subjects fully completed the questionnaire. Among them, 182 (76.7%) were female, 64 patients (27%) were aged 15 to 24 years, 159 (67%) were aged 25 to 55 and 14 (6%) were aged 56 and over. Significant associations were observed in caries prevalence and dentin sensitivity; in addition, an inappropriate diet was related to oral manifestations; following a gluten-free diet could be important to control the gingival bleeding levels and to manage oral symptoms associated to coeliac disease. In general, the presence of inflammatory symptoms in the mouth seems to be associated with general symptoms of inflammation related to coeliac disease.     

Note on the Use of Diametrical Compression to Determine Tablet Tensile Strength

The diametrical compression (DC) test, as defined in United States Pharmacopeia <1217> and in American Society for Testing and Materials testing standard D 3967, has been used extensively to derive the tensile strength (TS) of pharmaceutical tablets from the measured breaking force. DC-derived TSs provide a good approach to measuring the consistency of tablet mechanical properties from one batch to the next. For these quality control type applications, method precision is required, but accuracy is not. In addition, DC has been used to calibrate parameters of the Druker Prager Cap model, a yield criterion expressing the failure of a powder compact under arbitrary 3D loading conditions. For this application, the DC method must not only provide suitable precision but also provide accuracy. In this work, we explore the accuracy of the DC method by comparing TS results to those of the 3-point bend test method (also defined in United States Pharmacopeia <1217>). We conclude that the true TS of a powder compact is approximately double the DC-derived value. Although historical literature assumes that tablets fracture under tension along the centerline of the tablet, analysis of the stress state suggests that tablets are likely to fracture under shear. The impact of this ～50% error should be considered when accuracy of the TS result is required.