Comparison of the effects of carbon dioxide and helium pneumoperitoneum on renal function

Background and Purpose: Carbon dioxide pneumoperitoneum is associated with significant hypercarbia and acidosis. The aim of this study is to evaluate the effects of carbon dioxide and helium pneumoperitoneum on renal function. Materials and Methods: Thirty adult dogs were put randomly into one of three groups ( n = 10 animals each): group A - pneumoperitoneum not performed; group B - CO2 pneumoperitoneum; and group C - helium pneumoperitoneum. The groups were analyzed with consideration given to body weight, hematologic values, hemodynamic parameters ( heart rate, mean arterial pressure, central venous pressure, cardiac output, stroke volume, systemic vascular resistance, pulmonary vascular resistance, left cardiac work index, cardiac index, mean pulmonary artery pressure, and pulmonary capillary wedge pressure), and renal function ( plasma renin activity, urinary output, creatinine clearance, and sodium excretory fraction). Results: An accentuated decrease in urinary output was observed during pneumoperitoneum in groups B and C compared to the control group. In groups B and C, creatinine clearance declined significantly during pneumoperitoneum in comparison to group A, but after deflation a faster recovery of glomerular filtration was noticed for group C, and a significant increase in sodium excretory fraction was seen for group B. On the other hand, in comparison to the control group, group B had a significant increase in plasma renin activity, with late recovery of glomerular function. Conclusion: Helium ameliorates renal alterations when used for pneumoperitoneum, and it might be used for patients with compromised renal function who have to undergo laparoscopic surgery.

Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial

Creatine (CR) supplementation is commonly used by athletes. However, its effects on renal function remain controversial. The aim of this study was to evaluate the effects of creatine supplementation on renal function in healthy sedentary males (18-35 years old) submitted to exercise training. A randomized, double-blind, placebo-controlled trial was performed. Subjects (n = 18) were randomly allocated to receive treatment with either creatine (CR) (similar to 10 g day(-1) over 3 months) or placebo (PL) (dextrose). All subjects undertook moderate intensity aerobic training, in three 40-min sessions per week, during 3 months. Serum creatinine, serum and urinary sodium and potassium were determined at baseline and at the end of the study. Cystatin C was assessed prior to training (PRE), after 4 (POST 4) and 12 weeks (POST 12). Cystatin C levels (mg L-1) (PRE CR: 0.82 +/- 0.09; PL: 0.88 +/- 0.07 vs. POST 12 CR: 0.71 +/- 0.06; PL: 0.75 +/- 0.09, P = 0.0001) were decreased over time, suggesting an increase in glomerular filtration rate. Serum creatinine decreased with training in PL but was unchanged with training in CR. No significant differences were observed within or between groups in other parameters investigated. The decrease in cystatin C indicates that high-dose creatine supplementation over 3 months does not provoke any renal dysfunction in healthy males undergoing aerobic training. In addition, the results suggest that moderate aerobic training per se may improve renal function.

Kidney and cloaca function in the estuarine crocodile (Crocodylus porosus) at different salinities: Evidence for solute-linked water uptake

Kidney function and the role of the cloacal complex in osmoregulation was investigated in estuarine crocodile (Crocodylus porosus) exposed to three environmental salinities: hypo-, iso- and hyperosmotic to the plasma. Plasma homeostasis was maintained over the range of salinities. Antidiuresis occurred with increased salinity. Although urine from the kidneys retained an osmotic pressure between 77% and 82% of the plasma, over 93% and 98% of plasma chloride filtered at the glomeruli was reabsorbed during passage through the kidneys under hypo and hyperosmotic conditions, respectively, and only 64% in iso-osmotic water. The kidneys were the primary site of sodium reabsorption under hypo-and hyperosmotic conditions. Secondary processing of urine during storage in the cloaca varied with salinity. During post renal storage of urine, the difference in urine osmotic pressure increased from -26.1 +/- 15.5 to 35.66 +/- 9.29 mOsM with increased salinity, and potassium concentration of urine increased over 3-fold in C. porosus from freshwater. The almost complete reabsorption of both sodium and chloride under hyperosmotic conditions indicates the necessity for secretory activity by the lingual salt glands. The osmoregulatory response of the kidneys and cloacal complex to environmental salinity is both plastic and complementary. (C) 1998 Elsevier Science Inc.

Expression of galectin-1 in the mouse olfactory system

Primary sensory olfactory axons arise from the olfactory neuroepithelium that lines the nasal cavity and then project via the olfactory nerve into the olfactory bulb. The P-galactoside binding lectin, galectin-1,and its laminin ligand have been implicated in the growth of these axons along this pathway. In galectin-1 null mutant mice, a subpopulation of primary sensory olfactory axons fails to reach its targets in the olfactory bulb. In the present study we examined the spatiotemporal expression pattern of galectin-1 in normal mice in order to understand its role in the development of the olfactory nerve pathway. At E15.5, when olfactory axons have already contacted the olfactory bulb, galectin-1 was expressed in the cartilage and mesenchyme surrounding the nasal cavity but was absent from the olfactory neuroepithelium, nerve and bulb. Between E16.5 and birth galectin-1 began to be expressed by olfactory nerve ensheathing cells in the lamina propria of the neuroepithelium and nerve fibre layer. Galectin-1 was neither expressed by primary sensory neurons in the olfactory neuroepithelium nor by their axons in the olfactory nerve. Laminin, a galectin-1 ligand, also exhibited a similar expression pattern in the embryonic olfactory nerve pathway. Our results reveal that galectin-1 is dynamically expressed by glial elements within the nerve fibre layer during a discrete period in the developing olfactory nerve pathway. Previous studies have reported galectin-1 acts as a substrate adhesion molecule by cross-linking primary sensory olfactory neurons to laminin. Thus, the coordinate expression of galectin-1 and laminin in the embryonic nerve fibre layer suggests that these molecules support the adhesion and fasciculation of axons en route to their glomerular targets.

Errors in lamina growth of primary olfactory axons in the rat and mouse olfactory bulb

In the adult olfactory nerve pathway of rodents, each primary olfactory axon forms a terminal arbor in a single glomerulus in the olfactory bulb. During development, axons are believed to project directly to and terminate precisely within a glomerulus without any exuberant growth or mistargeting. To gain insight into mechanisms underlying this process, the trajectories of primary olfactory axons during glomerular formation were studied in the neonatal period. Histochemical staining of mouse olfactory bulb sections with the lectin Dolichos biflorus-agglutinin revealed that many olfactory axons overshoot the glomerular layer and course into the deeper laminae of the bulb in the early postnatal period. Single primary olfactory axons were anterogradely labelled either with the lipophilic carbocyanine dye, 1,1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), or with horseradish peroxidase (HRP) by localized microinjections into the nerve fiber layer of the rat olfactory bulb. Five distinct trajectories of primary olfactory axons were observed in DLI-labelled preparations at postnatal day 1.5 (P1.5). Axons either coursed directly to and terminated specifically within a glomerulus, branched before terminating in a glomerulus, bypassed glomeruli and entered the underlying external plexiform layer, passed through the glomerular layer with side branches into glomeruli, or branched into more than one glomerulus. HRP-labelled axon arbors from eight postnatal ages were reconstructed by camera lucida and were used to determine arbor length, arbor area, and arbor branch number. Whereas primary olfactory axons display errors in laminar targeting in the mammalian olfactory bulb, axon arbors typically achieve their adult morphology without exuberant growth. Many olfactory axons appear not to recognize appropriate cues to terminate within the glomerular layer during the early postnatal period. However, primary olfactory axons exhibit precise targeting in the glomerular layer after P5.5, indicating temporal differences in either the presence of guidance cues or the ability of axons to respond to these cues. (C) 1999 Wiley-Liss, Inc.

Development of P2 olfactory glomeruli in P2-internal ribosome entry site-tau-lacZ transgenic mice

Primary olfactory neurons project their axons to the olfactory bulb, where they terminate in discrete loci called glomeruli. All neurons expressing the same odorant receptor appear to terminate in a few glomeruli in each olfactory bulb. In the P2-IRES-tau-LacZ line of transgenic mice, LacZ is expressed in the perikarya and axons of primary olfactory neurons that express the P2 odorant receptor. In the present study, we examined the developmental appearance of P2 neurons, the topographical targeting of P2 axons, as well as the formation of P2 glomeruli in the olfactory bulb. P2 axons were first detected in the olfactory nerve fiber layer at embryonic day 14.5 (E14.5), and by E15.5 these axons terminated in a broad locus in the presumptive glomerular layer. During the next 5 embryonic days, the elongated cluster of axons developed into discrete glomerulus-like structures. In many cases, glomeruli appeared as pairs, which were initially connected by a fascicle of P2 axons. This connection was lost by postnatal day 7.5, and double glomeruli at the same locus were observed in 85% of adult animals. During the early postnatal period, there was considerable mistargeting of P2 axons. In some cases P2 axons entered inappropriate glomeruli or continued to grow past the glomerular layer into the deeper layers of the olfactory bulb. These aberrant axons were not observed in adult animals. These results indicate that olfactory axons exhibit errors while converging onto a specific glomerulus and suggest that guidance cues may be diffusely distributed at target sites in the olfactory bulb.

Expression of galectin-1 in the olfactory nerve pathway of rat

The olfactory neuroepithelium is characterised by the mosaic distribution of primary olfactory neurons that express different odorant receptors and cell surface glycoconjugates. Carbohydrates are believed to form a glycocode that mediates sorting out and fasciculation of primary olfactory axons through interactions with carbohydrate-binding proteins such as galectin-1. In the present study, we describe in detail the expression pattern of galectin-1 in the developing and adult rat olfactory system. We demonstrate that galectin-1 is expressed by olfactory ensheathing cells both in olfactory nerve and within the nerve fibre layer of the olfactory bulb of the embryonic and adult rat. In the adult rat, galectin-1 was preferentially expressed by olfactory ensheathing cells in the nerve fibre layer of the ventromedial and lateral surfaces of the olfactory bulb. Galectin-1 was also expressed by subsets of periglomerular cells and granule cells, particularly in the ventromedial region of the olfactory bulb. In adult rat, the galectin-1 ligand, N-acetyl-lactosamine, was expressed by primary olfactory axons that terminated in glomeruli present in the ventromedial and lateral olfactory bulb. These results suggest that expression of galectin-1 may provide a mechanism for the sorting of subpopulations of axons in the nerve fibre layer of the olfactory bulb during development as well as play a role in the postnatal maintenance of specific glomerular connections. (C) 1999 Elsevier Science B.V. All rights reserved.

Dynamic spatiotemporal expression patterns of neurocan and phosphacan indicate diverse roles in the developing and adult mouse olfactory system

The chondroitin sulfate proteoglycans neurocan and phosphacan are believed to modulate neurite outgrowth by binding to cell adhesion molecules, tenascin, and the differentiation factors heparin-binding growth-associated molecule and amphoterin. To assess the role of these chondroitin sulfate proteoglycans in the olfactory system, we describe here their expression patterns during both embryonic and postnatal development in the mouse. Immunoreactivity for neurocan was first detected in primary olfactory neurons at embryonic day 11.5 (E11.5). Neurocan was expressed by primary olfactory axons as they extended toward the rostral pole of the telencephalon as well as by their arbors in glomeruli after they contacted the olfactory bulb. The role of neurocan was examined by growing olfactory neurons on an extracellular matrix substrate containing neurocan or on extracellular matrix in the presence of soluble neurocan. In both cases, neurocan strongly promoted neurite outgrowth. These results suggest that neurocan supports the growth of primary olfactory axons through the extracellular matrix as they project to the olfactory bulb during development. Phosphacan, unlike neurocan, was present within the mesenchyme surrounding the E11.5 and E12.5 nasal cavity. This expression decreased at E13.5, concomitant with a transient appearance of phosphacan in nerve fascicles. Within the embryonic olfactory bulb, phosphacan was localised to the external and internal plexiform layers. However, during early postnatal development phosphacan was concentrated in the glomerular layer. These results suggest that phosphacan may play a role in delineating the pathway of growing olfactory axons as well as defining the laminar organization of the bulb. Together, the spatiotemporal expression patterns of neurocan and phosphacan indicate that these chondroitin sulfate proteoglycans have diverse in situ roles, which are dependent on context-specific interactions with extracellular and cell adhesion molecules within the developing olfactory nerve pathway. (C) 2000 Wiley-Liss, Inc.

Homocysteine, Alzheimer genes and proteins, and measures of cognition and depression in older men

The epsilon4 allele of apolipoprotem E (APOE), and the plasma levels of APOE, amyloid beta-protein precursor, arnyloid beta1-40 (Abeta40) and homocysteine, (Hcy) have all been correlated with the presence of dementia. Mutations in the methylnetetrahydrofolate reductase enzyme (MTHFR) have been associated with elevated levels of Hcy. This study explored the association of these factors with cognition and depression in community dwelling older men. Two hundred and ninety-nine men, mean age 78.9 years (SD 2.8), were studied in this cross-sectional survey. Mean plasma Hcy was 13.5 (SD 5.3) mumol/L. The MTHFR genotype had no obvious impact on Hey levels. Ln Hcy and Ln Abeta40 were both inversely correlated with calculated glomerular filtration rate (cGFR), r = -0.41 (p < 0.001) and r = -0.28 (p < 0.001), respectively. There was a positive correlation between Ln Hey and Ln Abeta40, r = 0.19 (p < 0.001), which remained significant after adjusting for cGFR, with a doubling of Hcy associated with a 24% increase of Abeta40. The e4 allele was associated with increased depressive symptoms as measured by the Geriatric Depression Scale-15, Odds ratio (OR) = 2.59 (95% CI 1.06-6.34) and poorer performance on the Clock Drawing Test, OR = 2.32 (95% CI: 1.25-4.29). There was a positive association between Abeta40 and Hcy, even after adjustment for cGFR in this sample of well, community dwelling older men. This association may help elucidate the link between elevated levels of Hey and Alzheimer's disease.

Early Brief Treatment with Losartan plus Mycophenolate Mofetil Provides Lasting Renoprotection in a Renal Ablation Model

Background: Inflammatory events antecede established renal injury in rats with 5/6 renal ablation (Nx), as indicated by the beneficial effects of early, uninterrupted treatment with mycophenolate mofetil (MMF). Angiotensin II also exerts a major pathogenic role at this initial phase. We investigated whether losartan (L) or L+MMF treatment, started early, and L+MMF treatment, started late, would exert lasting renoprotection in Nx even after being discontinued. Methods: Adult male Munich-Wistar rats underwent Nx and were divided into three groups: Nx (untreated), Nx(L) (given L), and Nx(LMMF) (given L and MMF). Protocol 1: treatments began on day 1, and ceased on day 30, after Nx. Protocol 2: L+MMF treatment began on day 30 and ceased on day 60. Results: Protocol 1: on day 30, hypertension, albuminuria and renal injury were strongly attenuated in Groups Nx(L) and Nx(LMMF). On day 120, these abnormalities were still attenuated in group Nx(LMMF). Protocol 2: on day 120, all parameters were similar between this late Nx(LMMF) group and untreated Nx. Conclusion: In Nx, temporary suppression of early, transitory hemodynamic/inflammatory phenomena affords relatively durable renoprotection even after treatment discontinuation. This effect is not obtained with similar temporary treatment initiated later in the course of renal disease. Copyright (C) 2010 S. Karger AG, Basel

Usefulness of Proteinuria as a Prognostic Marker of Mortality and Cardiovascular Events Among Patients Undergoing Percutaneous Coronary Intervention (Data from the Evaluation of Oral Xemilofiban in Controlling Thrombotic Events [EXCITE] Trial)

Proteinuria was associated with cardiovascular events and mortality in community-based cohorts. The association of proteinuria with mortality and cardiovascular events in patients undergoing percutaneous coronary intervention (PCI) was unknown. The association of urinary dipstick proteinuria with mortality and cardiovascular events (composite of death, myocardial infarction, or nonhemorrhagic stroke) in 5,835 subjects of the EXCITE trial was evaluated. Dipstick urinalysis was performed before PCI, and proteinuria was defined as trace or greater. Subjects were followed up for 210 days/7 months after enrollment for the occurrence of events. Multivariate Cox regression analysis evaluated the independent association of proteinuria with each outcome. Mean age was 59 years, 21% were women, 18% had diabetes mellitus, and mean estimated glomerular filtration rate was 90 ml/min/1.73 m(2). Proteinuria was present in 750 patients (13%). During follow-up, 22 subjects (2.9%) with proteinuria and 54 subjects (1.1%) without proteinuria died (adjusted hazard ratio 2.83, 95% confidence interval [CI] 1.65 to 4.84, p <0.001). The severity of proteinuria attenuated the strength of the association with mortality after PCI (low-grade proteinuria, hazard ratio 2.67, 95% CI 1.50 to 4.75; high-grade proteinuria, hazard ratio 3.76, 95% CI 1.24 to 11.37). No significant association was present for cardiovascular events during the relatively short follow-up, but high-grade proteinuria tended toward increased risk of cardiovascular events (hazard ratio 1.45, 95% CI 0.81 to 2.61). In conclusion, proteinuria was strongly and independently associated with mortality in patients undergoing PCI. These data suggest that such a relatively simple and clinically easy to use tool as urinary dipstick may be useful to identify and treat patients at high risk of mortality at the time of PCI. (C) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1151-1155)

AT(1) blockade during lactation as a model of chronic nephropathy: mechanisms of renal injury

Suppression of the renin-angiotensin system during lactation causes irreversible renal structural changes. In this study we investigated 1) the time course and the mechanisms underlying the chronic kidney disease caused by administration of the AT(1) receptor blocker losartan during lactation, and 2) whether this untoward effect can be used to engender a new model of chronic kidney disease. Male Munich-Wistar pups were divided into two groups: C, whose mothers were untreated, and L(Lact), whose mothers received oral losartan (250 mg.kg(-1).day(-1)) during the first 20 days after delivery. At 3 mo of life, both nephron number and the glomerular filtration rate were reduced in L(Lact) rats, whereas glomerular pressure was elevated. Unselective proteinuria and decreased expression of the zonula occludens-1 protein were also observed, along with modest glomerulosclerosis, significant interstitial expansion and inflammation, and wide glomerular volume variation, with a stable subpopulation of exceedingly small glomeruli. In addition, the urine osmolality was persistently lower in L(Lact) rats. At 10 mo of age, L(Lact) rats exhibited systemic hypertension, heavy albuminuria, substantial glomerulosclerosis, severe renal interstitial expansion and inflammation, and creatinine retention. Conclusions are that 1) oral losartan during lactation can be used as a simple and easily reproducible model of chronic kidney disease in adult life, associated with low mortality and no arterial hypertension until advanced stages; and 2) the mechanisms involved in the progression of renal injury in this model include glomerular hypertension, glomerular hypertrophy, podocyte injury, and interstitial inflammation.

Goodpasture`s syndrome

Goodpasture`s syndrome (GS) is an auto-immune disease that is part of the pulmonary-renal syndrome spectrum. It is characterized by the linear deposition of anti-glomerular basement membrane antibodies (anti-GBM) in glomerular and alveolar basement membrane, resulting in alveolar hemorrhage and progressive glomerulonephritis. An early diagnosis is important to decrease clinical morbidity. In the present work, we illustrate a GS case, initially diagnosed as Wegener`s granulomatosis.The patient showed favorable clinical evolution with corticosteroid therapy associated with plasmapheresis and cyclophosphamide.

Long-term administration of IgG2a anti-NK1.1 monoclonal antibody ameliorates lupus-like disease in NZB/W mice in spite of an early worsening induced by an IgG2a-dependent BAFF/BLyS production

The role of natural killer (NK) T cells in the development of lupus-like disease in mice is still controversial. We treated NZB/W mice with anti-NK1.1 monoclonal antibodies (mAbs) and our results revealed that administration of either an irrelevant immunoglobulin G2a (IgG2a) mAb or an IgG2a anti-NK1.1 mAb increased the production of anti-dsDNA antibodies in young NZB/W mice. However, the continuous administration of an anti-NK1.1 mAb protected aged NZB/W mice from glomerular injury, leading to prolonged survival and stabilization of the proteinuria. Conversely, the administration of the control IgG2a mAb led to an aggravation of the lupus-like disease. Augmented titres of anti-dsDNA in NZB/W mice, upon IgG2a administration, correlated with the production of BAFF/BLyS by dendritic, B and T cells. Treatment with an anti-NK1.1 mAb reduced the levels of interleukin-16, produced by T cells, in spleen cell culture supernatants from aged NZB/W. Adoptive transfer of NK T cells from aged to young NZB/W accelerated the production of anti-dsDNA in recipient NZB/W mice, suggesting that NK T cells from aged NZB/W are endowed with a B-cell helper activity. In vitro studies, using purified NK T cells from aged NZB/W, showed that these cells provided helper B-cell activity for the production of anti-dsDNA. We concluded that NK T cells are involved in the progression of lupus-like disease in mature NZB/W mice and that immunoglobulin of the IgG2a isotype has an enhancing effect on antibody synthesis due to the induction of BAFF/BLyS, and therefore have a deleterious effect in the NZB/W mouse physiology.

Worse renal outcome of lupus nephritis in male patients: a case-control study

Background: Progression and long-term renal outcome of lupus nephritis (LN) in male patients is a controversial subject in the literature. The aim of this study was to evaluate the influence of male gender on the renal outcome of LN. Methods: All male (M) LN patients who fulfilled American College of Rheumatology lupus criteria and who were referred for a kidney biopsy from 1999 to 2009 were enrolled in the study. Subjects with end-stage renal disease at baseline, or follow-up time below 6 months, were excluded. Cases were randomly matched to female (F) patients according to the class of LN, baseline estimated glomerular filtration rate (eGFR, Modification of Diet in Renal Disease simplified formula) and follow-up time. Treatment was decided by the clinical staff based on usual literature protocols. The primary endpoint was doubling of serum creatinine and/or end-stage renal disease. The secondary endpoint was defined as a variation of glomerular filtration rate (GFR) per year (Delta GFR/y index), calculated as the difference between final and initial eGFR adjusted by follow-up time for each patient. Results: We included 93 patients (31 M : 62 F). At baseline, M and F patients were not statistically different regarding WHO LN class (II 9.7%, IV 71%, V 19.3%), eGFR (M 62.4 +/- 36.4 ml/min/1.73 m(2) versus F 59.9 +/- 32.7 ml/min/1.73 m(2)), follow-up time (M 44.2 +/- 27.3 months versus F 39.9 +/- 27.9 months), and 24-hour proteinuria (M 5.3 +/- 4.6 g/day versus F 5.2 +/- 3.0 g/day), as well as age, albumin, C3, antinuclear antibody, anti-DNA antibody and haematuria. There was no difference in the primary outcome (M 19% versus F 13%, log-rank p = 0.62). However, male gender was significantly associated with a worse renal function progression, as measured by Delta GFR/y index (beta coefficient for male gender -12.4, 95% confidence interval -22.8 to -2.1, p = 0.02). The multivariate linear regression model showed that male gender remained statistically associated with a worse renal outcome even after adjustment for eGFR, proteinuria, albumin and C3 complement at baseline. Conclusion: In our study, male gender presented a worse evolution of LN (measured by an under GFR recovering) when compared with female patients with similar baseline features and treatment. Factors that influence the progression of LN in men and sex-specific treatment protocols should be further addressed in new studies. Lupus (2011) 20, 561-567.