THE EFFECIENCY OF ENTERIC LACTOBACILLUS IN PREVENTING HEMORRHAGIC COLITIS AND BLOCKING SHIGA TOXINS PRODUCTIONS IN RATS MODELS INFECTED WITH ENTEROHEMORRHAGIC ESCHERICHIA COLI (EHEC)

The objective of this study was to investigate the prophylactic roles of human enteric derived Lactobacillus plantarum L1 (Ll) and Lactobacillus paracasei L2 (L2), on EHEC O157:H7 infection in rodent models (In vivo). The Lactobacillus suspensions (L1 and L2) were individually and orally administered to experimental rats at a daily two consecutives of 100 μl (108 CFU/ ml/rat) for up to two weeks. Thereafter, on the 8th day of experiment rats were orally challenged with one dose infection of EHEC (105 CFU/ml/rat). Animals mortality and illness symptoms have been monitored. There was no fatal EHEC infection in rats that had been pre‑colonized with the Lactobacillus strains, while most of EHEC infected rats were died (90%). The Stx1 and Stx2 levels were significantly lower (14 and 12 folds) in the L1and L2 pre-inoculated rates respectively, compared with those in the EHEC colonized group. Histological sections were proven the prophylactic roles of L1 and L2, whereas, no effective histological upsets were detected in Lactobacillus + EHEC- colonized rats. The cytopathic symptoms were predominant in kidney and intestinal sections of EHEC infected rats. The kidney sections cytopathy manifested to lining membrane ulceration, infiltration of mononuclear cells and glomerular and tubular epithelium necrosis. The striking attaching and effacing (A/E) lesions were prominent in intestinal sections of EHEC infected animal models.

Morphological Characteristics Of The Kidney In Chronic Alcoholism

This research aimed to study the nature of pathomorphological changes in the kidney in chronic alcoholism in rats. In the present study, we have studied experimentally the nature of pathomorphological changes in the kidneys in chronic alcoholism in rats. The longer the intoxication is, the more the kidneys are damaged and homeostatic shifts are more pronounced in young animals. In an experiment on rats, it was found that taking ethanol orally has a short-term effect on kidney tissue and affects water-salt metabolism. Histologically, there are foci of acute inflammation of nephrocytes, spasm of small arterioles, and on the 15th day, atrophic changes in the renal parenchyma. Long-term alcohol intoxication (AIM) leads to persistent morphological disorders of the nephron, which are manifested in changes in the shape and size of the glomerulus, partial sclerosis of loops, vacuolar dystrophy of endothelial cells and partial vacuolar dystrophy of the tubular epithelium, especially the distal part.

The Effect of Pseudoephedrine (Sudafed) on Kinetic activity and histology of Livers and Kidneys in Albino Mice

Pseudoephedrine (PSE) or (Sudafed) is one of the sympathomimetic group of drugs (ephedrine, PSE and amphetamines) which effects cardiovascular system, respiratory system, and gastrointestinal tract. However, only little researches had supported its effect on solid abdominal organs. This study aims to investigate the effects of different doses of Sudafed in the liver and kidney of albino mice. The current study included 18 albino mice grouped into 2 groups: control (3 mice), and acute group (15 mice). The acute group was further subdivided into 5 subgroups, each subgroup of 3mice wasgiven a lonely intaperitonial injection of 0.3ml of the following conc. (500mg/kg, 250mg/kg, 125mg/kg, 62.52mg/kg, and 31.24mg/kg) for 24hrs. After the mentioned period, the mice of all subgroups were sacrificed and the livers and kidneys were removed, processed, sectioned and stained for histological analysis. Results of liver analysis using 500mg/Kg Sudafed intraperitoneallyshowed mild ballooning degeneration of hepatocytes and central vein congestion, while lower doses (250mg/Kg – 31.42mg/Kg) revealed less prominent effect or no significant pathological changes.Moreover, sections from the kidney with the 500mg/Kg Sudafed intraperitoneally showed mild hydropic swelling of tubular epithelium with congestion of intertubular blood vessels and relatively healthy glomeruli. Lower doses revealed no significant pathological changes. Conclusion: The present study demonstrated various pathological effects of PSE on kinetic activity, and histology of Livers and Kidneys of albino mice.

From Proteinuria to Fibrosis: An Update on Pathophysiology and Treatment Options

<b><i>Background:</i></b> Proteinuria is a key biomarker in nephrology. It is central to diagnosis and risk assessment and the primary target of many important therapies. Etiologies resulting in pathological proteinuria include congenital and acquired disorders, as well as both glomerular (immune/non-immune mediated) and tubular defects. <b><i>Summary:</i></b> Untreated proteinuria is strongly linked to progressive loss of kidney function and kidney failure. Excess protein reaching the renal tubules is ordinarily resorbed by the tubular epithelium. However, when these mechanisms are overwhelmed, a variety of inflammatory and fibrotic pathways are activated, causing both interstitial fibrosis and glomerulosclerosis. Nevertheless, the specific mechanisms underlying this are complex and remain incompletely understood. Recently, a number of treatments, in addition to angiotensin system blockade, have been shown to effectively slow the progression of proteinuric chronic kidney disease. However, additional therapies are clearly needed. <b><i>Key message:</i></b> This review provides an update on the pathophysiology of proteinuria, the pathways leading to fibrosis, and an overview of current and emerging therapies.

Tubular and interstitial disease

Tubulointerstitial diseases refer to a group of disorders in which inflammatory cell infiltrates within the kidney interstitium and/or tubular epithelium are seen on kidney biopsy. These disorders constitute an important group of kidney diseases with varying prevalences and presentations due to a number of causes. It is difficult to estimate the worldwide incidence of tubular and interstitial disease as it is a histological diagnosis and biopsy rates vary substantially around the world. Increasing incidence of tubulointerstitial nephritis has been related to polypharmacy, particularly in the older population. Tubulointerstitial nephritis may present acutely as an immunologically mediated hypersensitivity reaction to an inciting agent—typically a drug or infection—or chronically as a part of a disease process leading to chronic interstitial fibrosis and tubular atrophy. Allergic interstitial nephritis, analgesic nephropathy, nephrotoxic metals, hyperuricemia, Balkan nephropathy, Mesoamerican nephropathy, aristolochic acid nephropathy, and other rare causes of tubulointerstitial nephritis are covered in this section. Isolated defects of tubular function, tubular disorder-related nephropathies, and electrolyte derangements also constitute important aspects of tubulointerstitial diseases.

Yellow Fever as Cause of Death of Titi Monkeys (Callicebus Spp.)

From 2016 to 2018, an epidemic wave of yellow fever (YF) occurred in Brazil, affecting a large number of Platyrrhini monkeys. Titi monkeys ( Callicebus spp.) were severely affected yet pathological characterizations are lacking. This study characterized epizootic YF in 43 titi monkeys ( Callicebus spp.) with respect to the microscopic lesions in liver, kidney, spleen, heart, brain, and lung, as well as the distribution of immunolabeling for YF virus antigen, and the flaviviral load in the liver. Of 43 titi monkeys examined, 18 (42%) were positive for yellow fever virus (YFV) by immunohistochemistry or reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Affected livers had consistent marked panlobular necrotizing hepatitis, lipidosis, and mild inflammation, with intense immunolabeling for YFV mainly in centrilobular hepatocytes (zone 1; P = .05). In the spleen, consistent findings were variable lymphoid depletion (10/11), lymphoid necrosis (lymphocytolysis; 4/11), and immunolabeling for YFV in histiocytic cells (3/16). The main finding in the kidney was multifocal acute necrosis of tubular epithelium (5/7) that was occasionally associated with intracytoplasmic immunolabeling for YFV (6/15). These data indicate that titi monkeys are susceptible to YFV infection, developing severe hepatic lesions and high viral loads, comparable to humans and Alouatta spp. Thus, Callicebus spp. may be reliable sentinels for YF surveillance.

Store-operated calcium entry: Pivotal roles in renal physiology and pathophysiology

Research conducted over the last two decades has dramatically advanced the understanding of store-operated calcium channels (SOCC) and their impact on renal function. Kidneys contain many types of cells, including those specialized for glomerular filtration (fenestrated capillary endothelium, podocytes), water and solute transport (tubular epithelium), and regulation of glomerular filtration and renal blood flow (vascular smooth muscle cells, mesangial cells). The highly integrated function of these myriad cells effects renal control of blood pressure, extracellular fluid volume and osmolality, electrolyte balance, and acid–base homeostasis. Many of these cells are regulated by Ca2+ signaling. Recent evidence demonstrates that SOCCs are major Ca2+ entry portals in several renal cell types. SOCC is activated by depletion of Ca2+ stores in the sarco/endoplasmic reticulum, which communicates with plasma membrane SOCC via the Ca2+ sensor Stromal Interaction Molecule 1 (STIM1). Orai1 is recognized as the main pore-forming subunit of SOCC in the plasma membrane. Orai proteins alone can form highly Ca2+ selective SOCC channels. Also, members of the Transient Receptor Potential Canonical (TRPC) channel family are proposed to form heteromeric complexes with Orai1 subunits, forming SOCC with low Ca2+ selectivity. Recently, Ca2+ entry through SOCC, known as store-operated Ca2+ entry (SOCE), was identified in glomerular mesangial cells, tubular epithelium, and renovascular smooth muscle cells. The physiological and pathological relevance and the characterization of SOCC complexes in those cells are still unclear. In this review, we summarize the current knowledge of SOCC and their roles in renal glomerular, tubular and vascular cells, including studies from our laboratory, emphasizing SOCE regulation of fibrotic protein deposition. Understanding the diverse roles of SOCE in different renal cell types is essential, as SOCC and its signaling pathways are emerging targets for treatment of SOCE-related diseases.

Protective effect of Nannochloropsis Oculata against mercuric-induced histopathological alterations in the kidney of Nile tilapia

Objective: The present study was designed to evaluate the toxic effect of sublethal concentration of mercuric chloride (0.3 mg/L HgCl2) on histopathological lesions in the kidney of Nile tilapia (O. niloticus) and the protective effect of microalgae, Nannochloropsis oculata (N. oculata) against the induced tissue alterations for 3 weeks. Design: Randomized controlled study Animals: Nile tilapia Procedures: Fish were randomly assigned to 4 groups, group1: control (basal diet), group 2 (Hg/ exposed to HgCl2 at a dose of 0.3 mg/L (1/4 of LC50), and fed basal diet), group 3: (Hg+N5, similar to group2, but fed diet supplemented with N. oculata 5% and group 4 (Hg+N10, similar to group2, but fed diet supplemented with N. oculata 10 %. Two fish from each aquarium tank (6 fish/group) were sampled at weeks 1, 2, and 3 of the experiment. The posterior kidney was dried out in a graded ethanol series and then embedded in paraffin. Each block of tissue was cut into serial sections (5 μm thick) and stained with hematoxylin and eosin (H&E). Results: Histopathological alterations were induced following mercuric exposure in a time-dependent manner. The kidney showed congestion, hemosiderosis, and hemorrhage with vacuolated tubular epithelium, hyaline droplet degeneration, and necrosis of the tubular epithelium. Supplementation with N. oculata, particularly at 10 %, succeeded in alleviating the histopathological induced lesions in the kidney. Conclusion and clinical relevance: Our findings demonstrate that HgCl2 has nephrotoxic properties that led to severe histopathological alterations in the kidney of Nile tilapia, while dietary supplementation with N. oculata was able to alleviate the induced kidney alterations.

CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by Chloroquine

Inflammation is a major contributor to tubular epithelium injury in kidney disorders, and the involvement of blood platelets in driving inflammation is increasingly stressed. CD154, the ligand of CD40, is one of the mediators supporting platelet proinflammatory properties. Although hypoxia is an essential constituent of the inflammatory reaction, if and how platelets and CD154 regulate inflammation in hypoxic conditions remain unclear. Here, we studied the control by CD154 of the proinflammatory cytokine interleukin- (IL-) 6 secretion in short-term oxygen (O2) deprivation conditions, using the HK-2 cell line as a kidney tubular epithelial cell (TEC) model. IL-6 secretion was markedly stimulated by CD154 after 1 to 3 hours of hypoxic stress. Both intracellular IL-6 expression and secretion were stimulated by CD154 and associated with a strong upregulation of IL-6 mRNA and increased transcription. Searching for inhibitors of CD154-mediated IL-6 production by HK-2 cells in hypoxic conditions, we observed that chloroquine, a drug that has been repurposed as an anti-inflammatory agent, alleviated this induction. Therefore, CD154 is a potent early stimulus for IL-6 secretion by TECs in O2 deprivation conditions, a mechanism likely to take part in the deleterious inflammatory consequences of platelet activation in kidney tubular injury. The inhibition of CD154-induced IL-6 production by chloroquine suggests the potential usefulness of this drug as a therapeutic adjunct in conditions associated with acute kidney injury.