Ultrafiltration coefficient and glomerular capillary resistance in a model of immune complex glomerulonephritis

Ultrafiltration coefficient and glomerular capillary resistance in a model of immune complex glomerulonephritis. Decreased ultrafiltration coefficient, LpA or Kf, was documented previously in micropuncture studies of glomerulonephritis in rats. Observations were made immediately following an injection of antiglomerular basement membrane (anti-GBM) antibody, later in the course of glomerulonephritis, and during the chronic phase of Heymann nephritis. To gain further insight into the basis of reduced glomerular filtration rate in immune-complex glomerulonephritis, we studied the anatomic, physiologic, and rheologic properties of isolated glomeruli from female Buffalo rats with nephritis which developed during infection withTrypanosoma rhodesiense. Immune-complex mediated glomerulonephritis was present 2 weeks after inoculation and progressed throughout the 4 weeks of study. Renal insufficiency occurred, with serum creatinine concentrations rising to 5 to 10 times control values by week 4. Mesangial hypercellularity, mesangial electron dense deposits, and endothelial cell swelling were observed. Increased numbers of mononuclear cells were present within the glomerulus. Total glomerular water volume was greater in nephritic than in normal animals. Increased cell volume accounted for most of the volume increment. When filtration into the capillaries was induced in vitro by imposing an oncotic gradient of 6.5mm Hg or greater across the capillary wall, rapid and uniform erythrocyte movement occurred within the capillaries of control glomeruli and erythrocytes were ejected into the medium. In contrast, a transcapillary gradient of 30 to 40mm Hg was required to produce erythrocyte movement in glomeruli from nephritic animals studied 4 weeks after inoculation. The ultrafiltration coefficient of nephritic glomeruli was estimated in vitro and was not different from that of control glomeruli (5.81 ± 0.35 vs. 6.21 ± 0.49 nl/minmm Hg). An impairment of capillary perfusion may be responsible for the decreased rate of glomerular filtration observed in this model of glomerulonephritis.Evaluation in vitro du coefficient d'ultrafiltration et de la résistance capillaire glomérulaire dans un modèle de glomérulonéphrite des comples immuns. La diminution du coefficient d'ultrafiltration, LpA ou Kf, a été établie précédement au cours de travaux utilisant les microponctions chez des rats atteints de glomérulonéphrite, immédiatement après l'injection d'anti-corps anti-membrane basale glomérulaire (anti-GBM) et, ultérieurement, au cours de l'évolution de glomérulonéphrite et durant la phase chronique de la néphrite de Heymann. Afin d'obtenir plus d'informations sur les fondements de la diminution du débit de filtration glomérulaire au cours de la néphrite des complexes immuns, nous avons étudié les propriétés anatomiques, physiologiques, et biologiques des glomérules isolés de rats femelles de la souche Buffalo atteints de néphrite développée au cours de l'infection parTrypanosoma rhodesiense. Une glomérulonéphrite des complexes immuns existait deux semaines après l'inoculation et évoluait pendant les 4 semaines de l'étude. Il existait une insuffisance rénale et la créatinine sérique atteignait des valeurs 5 à 10 fois plus grandes que les contrôles à la 4 semaine. L'hypercellularité mésangiale, sous la forme de dépôts denses mésangiaux en microscopie électronique, et le gonflement des cellules endothéliales ont été observés. Le nombre des cellules mononucléés du glomérule était augmenté. Le volume total d'eau du glomérule était plus grand chez les animaux atteints de néphrite que chez les contrôles. L'augmentation du volume cellulaire rendait compte de la plus grande partie de l'augmentation de volume. Quand la filtration dans les capillaires a été declenchée par l'imposition d'un gradient oncotique de 6,5mm Hg ou plus à travers la paroi capillaire, un mouvement rapide et uniforme des érythrocytes est apparu et les érythrocytes ont été éjectés dans le milieu. Par contre, pour les glomérules provenant d'animaux néphritiques, étudiés quatre semaines après l'inoculation, un gradient de 30 à 40mm Hg était nécessaire pour produire un mouvement des érythrocytes. Le coefficient d'ultrafiltration des glomérules d'animaux néphritiques a été évalué in vitro et n'est pas différent de celui des animaux contrôles (5,81 ± 0,35 vs. 6,21 ± 0,49 nl/minmm Hg). L'altération de la perfusion capillaire est responsable de la diminution du débit de filtration glomérulaire observée dans ce modèle de glomérulonéphrite

New Alloying Systems for Sintered Steels: Critical Aspects of Sintering Behavior

Oxygen-sensitive alloying elements such as Mn, Si, and Cr have a high potential for improving the properties of low alloyed sintered steels while reducing the alloying cost. However, it is necessary to find a way for avoiding, or at least minimizing, the oxidation of these elements especially during the early stages of the sintering cycle. In this study Mn, Si, and Cr were introduced in the form of a master alloy powder designed to be mixed with the iron base powder and provide the final composition of the steel during the sintering process. The reduction/oxidation phenomena taking place during the heating stage were studied by thermogravimetry, dilatometry, and mass spectroscopy, using either reducing (H2) or inert (Ar) atmospheres. The results show how the difference in chemical activity between base iron powder and master alloy causes the so called "internal-getter" effect, by which the reduction of less stable iron oxides leads to oxidation of the elements with higher affinity for oxygen. This effect can be somehow minimized when sintering in H2, since the iron oxides are reduced at lower temperatures at which the reactivity of the elements in the master alloy is lower. However, H2 concentration in the processing atmosphere needs to be carefully adapted to the specific composition of the materials being processed in order to minimize decarburization by methane formation during sintering.Höganäs AB Sweden, financial support provided through the Höganäs Chair IVPublicad

Combination leflunomide and methotrexate (MTX) therapy for patients with active rheumatoid arthritis failing MTX monotherapy: open-label extension of a randomized, double-blind, placebo controlled trial

P e r s o n a l n o n -c o m m e r c i a l u s e o n l y . T h e J o u r n a l o f R h e u m a t o l o g y . C o p y r i g h t © 2 0 0 4 . A l l r i g h t s r e s e r v e d Conclusion. Response to therapy was maintained to 48 weeks of treatment in patients who continued to receive LEF and MTX during the extension. Importantly, ACR20 response rates after 24 weeks of LEF therapy were similar between patients switched from PLA to LEF without loading dose, and those who received a loading does of LEF (100 mg/day × 2 days) at randomization. Fewer adverse events were reported in patients switched to LEF without a loading dose. (J Rheumatol 2004;31:1521-31

Early lineage restriction in temporally distinct populations of Mesp1 progenitors during mammalian heart development.

Cardiac development arises from two sources of mesoderm progenitors, the first heart field (FHF) and the second (SHF). Mesp1 has been proposed to mark the most primitive multipotent cardiac progenitors common for both heart fields. Here, using clonal analysis of the earliest prospective cardiovascular progenitors in a temporally controlled manner during early gastrulation, we found that Mesp1 progenitors consist of two temporally distinct pools of progenitors restricted to either the FHF or the SHF. FHF progenitors were unipotent, whereas SHF progenitors were either unipotent or bipotent. Microarray and single-cell PCR with reverse transcription analysis of Mesp1 progenitors revealed the existence of molecularly distinct populations of Mesp1 progenitors, consistent with their lineage and regional contribution. Together, these results provide evidence that heart development arises from distinct populations of unipotent and bipotent cardiac progenitors that independently express Mesp1 at different time points during their specification, revealing that the regional segregation and lineage restriction of cardiac progenitors occur very early during gastrulation.This is the author's accepted manuscript and will be under embargo until the 24th of February 2015. The final version is published by NPG in Nature Cell Biology here: http://www.nature.com/ncb/journal/v16/n9/full/ncb3024.html