Severe Histological Changes Research Articles

Molecular, biochemical and histopathological studies on the ameliorative effect of vitamin C on the renal and muscle tissues of Nile tilapia fish ( Oreochromis niloticus ) affected by the usage of engine oil

The present study was performed to evaluate the effect of vitamin C on the performance of Nile tilapia (Oreochromis niloticus) affected by the usage of engine oil. A total of 120 tilapia fish were randomly divided into four equal groups according to dietary treatments applied for 3 weeks: group I (control); group II was exposed to engine oil; group III was exposed to engine oil and supplemented with vitamin C: and group IV was fed only a diet supplemented with vitamin C. According to our results, the group exposed to engine oil (II) showed an induced elevation of kidney function parameters, an upregulation of CYP1A1 mRNA expression level, a reduction in antioxidant status (SOD, GSH) and severe abnormal histological and ultra-structural changes in the head kidney, trunk kidney and muscle tissue. Supplementation of group III with vitamin C ameliorated the toxic effect induced by engine oil through improvement of kidney function parameters, elevation of the antioxidant status of tissue and improvement of the histological images of renal and muscle tissues. In conclusion, vitamin C has the ability to ameliorate engine oil oxidative stress toxicity in Nile tilapia.

Pinocembrin Protects Against Dextran Sulfate Sodium-Induced Rats Colitis by Ameliorating Inflammation, Improving Barrier Function and Modulating Gut Microbiota.

Pinocembrin (PIN) is a natural flavonoid widely found in bee propolis with potent gastrointestinal protective effects. In consequence, PIN has great potential in preventing inflammatory bowel diseases (IBDs) while scant information is available. In this study, a dextran sulfate sodium (DSS)-induced rats ulcerative colitis model (3.5% DSS in drinking water for 7 days) was applied to explore the protective effects of PIN on macroscopic colitis symptoms, inflammation, intestinal epithelial barrier function, and gut microbiota homeostasis. While DSS-treated rats showed severe colitis clinical symptoms and histological changes (colonic pathological damages and intestinal goblet cells loss), pre-administration of PIN (5 and 10 mg/kg, p.o.) for a week alleviated these symptoms. Pre-administration of PIN also suppressed the pro-inflammatory gene expressions and improved tight junction functions of colonic epithelial cells. Additionally, PIN administration reversed DSS-induced short chain fatty acid loss, and improved the gut microbial diversity assessed by 16S rRNA phylogenetic sequencing. Overall, our results suggest a wide spectrum of protective effects of PIN in preventing IBDs.

Immunopathology of Fatal Human Variegated Squirrel Bornavirus 1 Encephalitis, Germany, 2011-2013.

Variegated squirrel bornavirus 1 (VSBV-1) is a zoonotic virus that causes fatal encephalitis in humans who are infected after contact with exotic squirrels. We analyzed the brain lesions and the immune responses in all 4 known human cases that showed panencephalitis. Inflammatory infiltrates in areas positive for VSBV-1 RNA and antigen consisted of CD4+ and CD8+ T cells, with perivascular B-cell accumulation. Strong microglial response and bizarre astroglial expansion were present. Areas of malacia contained neutrophils and foamy microglia and macrophages. Immunopathologic examination during infection showed cleavage of caspase 3 in brain cells adjacent to CD8+ cells and widespread p53 expression, hallmarks of apoptosis. Cerebrospinal fluid analyses over time demonstrated increasing protein concentrations and cell counts, paralleled by pathologic lactate elevations in all patients. The most severe cerebrospinal fluid and histologic changes occurred in the patient with the highest viral load, shortest duration of disease, and most medical preconditions.

Neurotoxicity and inflammation induced by individual and combined exposure to iron oxide nanoparticles and silver nanoparticles

The present study aimed to investigate the neurotoxicity of iron oxide and silver NPs solely or combined. At the molecular level, the exposure to both NPs induced marked DNA fragmentation, downregulation of mtTFA, and upregulation of PGC-1α expression. Both NPs caused decline in acetylcholine esterase, norepinephrine, serotonin, dopamine, and antioxidants enzymes, while causing an increase in lipid peroxidation, nitric oxide, tumour suppressor gene p53, tumour necrosis factor-α, interleukin-6, acetylcholine, and norepinephrine. NPs exposure was associated with severe histologic changes in brain architecture. The effect of the combined exposure to both NPs was more pronounced than each one alone. This study showed that the mechanism of neurotoxicity may involve different pathways including changes in gene expression of mTFA and PGC-1α, induced DNA fragmentation, deregulated neurotransmitters, oxidative stress and disturbed cytokine production and tumour suppressor protein p53.

Toxoplasma Hypervirulence in the Rat Model Parallels Human Infection and Is Modulated by the Toxo1 Locus.

Toxoplasmosis is considered as an opportunistic parasitic disease. If post-natally acquired in children or adults, it may pass unnoticed, at least with strains of European origin. However, in the wild biotopes especially in South America, Toxoplasma gondii strains display a greater genetic diversity, which correlates to higher virulence for humans, particularly along the Amazon River and its tributaries. In French Guiana, several atypical strains have been associated with severe clinical forms: ocular toxoplasmosis and acute respiratory distress syndrome both of which can result in death. Among these, the GUY008-ABE strain was responsible for an epidemic of severe disseminated toxoplasmosis in Suriname, which led to the death of one immunocompetent individual. To better understand the mechanism underlying the hypervirulence of the GUY008-ABE strain, we have tested the rat model which compared to the mouse, better reflects the immune resistance of humans to Toxoplasma infection. Here we compare the outcome of toxoplasmosis in F344 rats infected either by the GUY008-ABE strain or the type II Prugniaud strain. We show that the GUY008-ABE strain displays a higher virulence phenotype leading to the death of all infected rats observed in this study. GUY008-ABE infection was characterized by an increase of the parasite load in several organs, especially the heart and lung, and was mainly associated with severe histological changes in lungs. Moreover, correlating with its hypervirulence trait, the GUY008-ABE strain was able to form cysts in the LEW rat model otherwise known to be refractory to infection by other Toxoplasma strains. Together, these results show that the rat is a discriminating experimental model to study Toxoplasma virulence factors relevant to the pathogenesis of human infection and that the degree of virulence is linked to the Toxo1 locus.

Feline calicivirus infection in cats with virulent systemic disease, Italy

Feline calicivirus (FCV) is a contagious viral pathogen that usually causes a mild, self-limiting respiratory disease. More recently, highly virulent FCV strains have emerged and have been associated with severe systemic infection, referred to as virulent systemic disease (VSD).The objective of this study is to report VSD cases in Italian cats along with the molecular characterization of two detected FCV strains. Three client-owned cats showed clinical signs resembling to those described for VSD cases. The cats were subjected to molecular investigations for detection of FCV and other feline pathogens. Histopathology and immunohistochemistry were performed on internal organs of one cat; molecular characterization of two detected FCV strains was obtained through sequence and phylogenetic analyses.Putative VS-FCV strains were detected in all three cats, which were co-infected with feline panleukopenia virus. The cat submitted to histopathology and immunohistochemistry displayed severe histological changes and FCV antigens in internal organs. Two Italian FCV strains, for which amplification of ORF2 was successful, were strictly related and formed a unique phylogenetic cluster. These viruses did not show consistent changes in the amino acid sequences with respect to reference VS-FCVs.The results of our study confirm that VS-FCV strains are circulating in Italy and that VSD diagnosis is complicated since both genetic and clinical markers have not been identified so far.

Some Pharmacodynamics Effects of Rafoxanide and Its Interaction With Fenbendazole

This study was carried-out to study the pharmacodynamics characters of rafoxanide with fenbendazole and the interaction between them through study its effects on, fertility (reproductive organs weights, progressive motility, epididmal sperm count and sperm and abnormalities), Moreover, its effect on some hematological parameters including (WBCs count, differential leucocytic count, RBCs count, and Hb %, platelets count and PCV %), also, the effects on some biochemical parameters including (ALT, AST, and Albumin, total protein, globulin, urea and creatinine) were determined. Sixty mature Albino rats weighing from 140 – 180 gm each of 4 – 5 month old were used in this study. The animals were divided into 4 equal groups each of 15 rats, the first group: not gave any treatment and kept as a control group, the second group : Given orally Fenbendazole orally at dose level (37.5 mg/Kg), third group: Given orally Rafoxanide at a dose (7.5 mg/Kg) orally) and fourth fourth group: Fenbendazole (37.5 mg/Kg) + Rafoxanide (7.5 mg/Kg) orally). Our results concluded that, The using of Fenbendazole for treatment of helminthes parasites improved the index weight of accessary sex glands, tests index weight and epidedymis index weight. Also, the level of the higher WBCs, Hb, PCV, serum protein, albumin globulin, serum urea, serum creatinine level and serum observed in Fenbendazole treated group than the rafoxanide treated group or its combination. But it decreased the level of sperm motility, sperm count decreased in Fenbendazole and the higher sperm abnormalities level observed in the group treated with Fenbendazole. While, the rafoxanide improved the level of sperm motality, count and abnormalities than fenbendazole or its combination The histopathological results cleared that, there is a severe histological changes in the group treated with fenbendazole and rafoxanide than the control group and their combination.

Microemulsion based nasal spray: A systemic approach for non-CNS drug, its optimization, characterization and statistical modelling using QbD principles

The present study was investigated to design and characterize Domperidone (DM) loaded mucoadhesive microemulsion for enhanced systemic absorption through nasal delivery. Domperidone is a dopamine antagonist non-CNS drug, possessing high log P and extensive hepatic metabolism. The different microemulsion compositions were prepared by water titration method and optimized by D-Optimal mixture design. The screening criteria for optimization of formulation were drug loading, globule size, spray angle, spray pattern, mucoadhesion time, in-vitro permeation and in-vivo pharmacokinetic profile. A microemulsion formulation comprising of oleic acid (8%), labrasol (32.5%), propylene glycol (32.5%) and water (27%) was found optimum. The spray droplets were rendered mucoadhesive by optimum quantity of PEO P7 (0.5% w/w). The globule size, mucoadhesion time and cumulative amount of drug permeated (after 240 min) of optimized formulation were 25 nm, 17 ± 2.0 min, and 80.14 ± 13.47 μg cm−2, respectively. Pharmacokinetic study of developed formulation revealed significant difference (p < 0.05) in Cmax (48.34 ng/mL) and AUC0→∞ (6204 ng*h*mL−1) compared to DM solution and Domstal®, indicating enhanced bioavailability through nasal route. Safe and non-irritant nature of the formulation was proven by no severe histological changes reported in nasal irritation study. Biodistribution study exhibited least amount (2.12 ± 0.4%) of brain uptake confirming systemic absorption of drug.

Higher serum galactose-deficient immunoglobulin A1 concentration is associated with stronger mesangial cellular inflammatory response and more severe histologic findings in immunoglobulin A nephropathy.

BackgroundGalactose-deficient immunoglobulin A1 (Gd-IgA1) is known to play a key role in the pathogenesis of IgA nephropathy (IgAN). We aimed to evaluate whether serum Gd-IgA1 is associated with in vitro activation of mesangial cells in individual patients and how this affects the clinical and histologic parameters.MethodsSerum samples and clinical and histologic data were collected in the University Hospital Basel and Hammersmith Hospital, London. Serum levels of IgA1 and Gd-IgA1 were measured by enzyme-linked immunosorbent assay (ELISA) and lectin-binding assay using lectin Helix aspersa (HA). Primary human mesangial cells were stimulated with IgA1 isolated from serum from individual patients and the concentrations of monocyte chemoattractant protein-1 and interleukin-6 were measured in cell culture supernatant by ELISA.ResultsThirty-three patients were enrolled. A significant correlation was observed between serum Gd-IgA1 levels and the concentration of MCP-1 in the culture supernatant in individual patients (Spearman r = 0.5969, P = 0.0002). There was no significant correlation between serum Gd-IgA1 levels and proteinuria or estimated glomerular filtration rate at diagnosis. However, the serum Gd-IgA1 level was significantly higher in patients with segmental glomerulosclerosis (S0 versus S1, P = 0.0245) and tubular atrophy/interstitial fibrosis (T0 versus T1 and T2, P = 0.0336; T0 versus T2, P = 0.0225).ConclusionsHigher serum Gd-IgA1 concentration is associated with stronger mesangial cell inflammatory response with production of a greater amount of MCP-1 in vitro. This in turn is associated with severe histologic changes. The disease progression with worse renal outcome in patients with higher serum Gd-IgA1 may be therefore mediated by more pronounced mesangial cell inflammatory response leading to more severe histologic changes.

Low Levels of Chito-Oligosaccharides Are Not Effective in Reducing Deoxynivalenol Toxicity in Swine Jejunal Explants.

Deoxynivalenol (DON) is a mycotoxin that affects the intestinal morphology of animals, impairing nutrient intake and growth. On the other hand, dietary supplementation with functional oligosaccharides as chito-oligosaccharides (COS) has shown positive effects on the intestinal health of piglets. Therefore, the objective of the present study was to evaluate the effect of low doses of COS in preventing DON-induced intestinal histological changes, using a swine jejunal explant technique. The intestinal explants were incubated at 37 °C in culture medium for 4 h and exposed to the following treatments: (a) control (only culture medium), (b) DON (10 µM), (c) 25COS (0.025 mg·mL−1 of COS); (d) 50COS (0.05 mg·mL−1 of COS); (e) 25COS plus DON (25COS + DON); (f) 50COS plus DON (50COS + DON). Explants exposed to COS presented intestinal morphology similar to control samples. DON induced a significant decrease in the histological score as a consequence of moderate to severe histological changes (apical necrosis, villi atrophy, and fusion) and a significant decrease in morphometric parameters (villi height, crypt depth, villi height:crypt depth ratio, and goblet cells density). The intestinal morphology of samples exposed to COS + DON remained similar to DON treatment. In conclusion, low levels of COS did not counteract DON-induced intestinal lesions.

Recombinant human hepatocyte growth factor provides protective effects in cerulein-induced acute pancreatitis in mice.

Acute pancreatitis is a multifactorial disease associated with profound changes of the pancreas induced by release of digestive enzymes that lead to increase in proinflammatory cytokine production, excessive tissue necrosis, edema, and bleeding. Elevated levels of hepatocyte growth factor (HGF) and its receptor c-Met have been observed in different chronic and acute pancreatic diseases including experimental models of acute pancreatitis. In the present study, we investigated the protective effects induced by the recombinant human HGF in a mouse model of cerulein-induced acute pancreatitis. Pancreatitis was induced by 8 hourly administrations of supramaximal cerulein injections (50 µg/kg, ip). HGF treatment (20 µg/kg, iv), significantly attenuated lipase content and amylase activity in serum as well as the degree inflammation and edema overall leading to less severe histologic changes such as necrosis, induced by cerulein. Protective effects of HGF were associated with activation of pro-survival pathways such as Akt, Erk1/2, and Nrf2 and increase in executor survival-related proteins and decrease in pro-apoptotic proteins. In addition, ROS content and lipid peroxidation were diminished, and glutathione synthesis increased in pancreas. Systemic protection was observed by lung histology. In conclusion, our data indicate that HGF exerts an Nrf2 and glutathione-mediated protective effect on acute pancreatitis reflected by a reduction in inflammation, edema, and oxidative stress.

Contributions of HLA haplotypes, IL8 level and Toxoplasma gondii infection in defining celiac disease's phenotypes

BackgroundIt is not clear why some patients with coeliac disease (CD) present with severe symptoms and small intestinal mucosal damages while others present with milder symptoms and no frank enteropathy. There is no study to assess the associated factors with mild/severe symptoms and enteropathy. The terminologies like latent, silent and potential are difficult to use and are unrepresentative. In the present study we describe coeliac disease’s phenotypes based on HLA haplotypes, IL8 production and past infection with Toxoplasma gondii (T. gondii) infection.MethodsIn this case-control study, sera originating from 150 healthy subjects and 150 patients diagnosed with CD during the years 2013–14 were analyzed for the presence of antibodies specific T. gondii of the IgG and IgM subclasses. The level of IL8 were measured and HLA-DQ2 and HLA-DQ8 alleles were genotyped. The correlation between these parameters and the damages in intestinal mucosal were assessed using an accepted histopathological classification.ResultsHigh levels of IgG antibodies against T. gondii were found in the sera of control group compared to the CD group (52.6% vs. 39.4%, P = 0.02). Mean serum levels of IL8 was significantly higher in CD patients compared with control (P ≤ 0.05). By comparing the level of anti- T. gondii IgG and mucosal damage in celiac disease, we found a significant relationship between the severity of mucosal damages and anti- T. gondii IgG level (P = 0.02). No correlation was detected between Toxoplasma gondii infection and types of HLA (P > 0.05). However, patients with severely abnormal histology carried HLA-DQ2 risk alleles (92 patients (61%)) more often than the controls and those with mild histological abnormalities.ConclusionsCD patients with severe histological changes had more often Toxoplasma gondii infection than those affected with mild histological features. This suggests that CD’s phenotypes are correlated to additional factors like infections and to particular HLA DQ2 alleles that may need additional investigations and potentially will require additional treatment.

Depletion of Gprc5a Promotes Development of Diabetic Nephropathy.

Background Renal glomeruli are the primary target of injury in diabetic nephropathy (DN), and the glomerular podocyte has a key role in disease progression.Methods To identify potential novel therapeutic targets for DN, we performed high-throughput molecular profiling of G protein-coupled receptors (GPCRs) using human glomeruli.Results We identified an orphan GPCR, Gprc5a, as a highly podocyte-specific gene, the expression of which was significantly downregulated in glomeruli of patients with DN compared with those without DN. Inactivation of Gprc5a in mice resulted in thickening of the glomerular basement membrane and activation of mesangial cells, which are two hallmark features of DN in humans. Compared with wild-type mice, Gprc5a-deficient animals demonstrated increased albuminuria and more severe histologic changes after induction of diabetes with streptozotocin. Mechanistically, Gprc5a modulated TGF-β signaling and activation of the EGF receptor in cultured podocytes.Conclusions Gprc5a has an important role in the pathogenesis of DN, and further study of the podocyte-specific signaling activity of this protein is warranted.

An In Vivo Study on Intoxicating Effects of Nerium oleander Water Based Extract on Multiorgans of Wistar Rat.

This study was aimed to find histological changes in the extrahepatic organs, hepatic iron deposition, and gene expression of some iron regulatory proteins in rats after sterile muscle abscess during the acute intoxication of Nerium oleander leaves decoction. 10 ml/kg of the leaves extract was injected intramuscularly in Wistar rats (200–225 g, n = 4). Control animals received saline injection of matched volume. Animals were anesthetized and sacrificed after 3, 6, 12, and 24 h after administration of decoction. Lungs, kidney, spleen, and liver were extracted and processed for histopathological examination while portion of liver tissue was proceeded for iron regulatory gene expression quantification. Sections of all studied organs were found with signs of cellular dysfunction with infiltration of variety of leucocytes. In the lungs section at 3 h time point mononuclear cell infiltrates were observed while in alveolar tissue at 24 h time point dilation and even collapse in some of the alveoli were evident. In kidney sections distortion of renal tubules and epithelial cells with shrinkage of glomeruli was noted at all studied time points. In the splenic section of 12 h time point, degeneration, depopulation, and shrinkage of white pulp have been noted. Distension of the red pulp along with activation of splenic follicles was evident after 24 h onset of APR. Significant changes in the expression of acute phase cytokine and iron regulatory genes were noted. IL-6 and Hepc gene expression were strongly upregulated up to 12 h whereby Tf gene expression showed an early upregulation at 3 h time point followed by downregulation on later points while Hjv gene expression showed an overall downregulation at all study time points compared to control. It is concluded that inherent toxins present in the N. oleander can induce acute phase response and cause severe histological changes in the organs and marked changes in the regulation of iron regulatory proteins thus cannot be practiced routinely.

Pathologic analysis of non-neoplastic parenchyma in renal cell carcinoma: a comprehensive observation in radical nephrectomy specimens

BackgroundThis study provides a comprehensive examination of the histological features of non-neoplastic parenchyma in renal cell carcinoma (RCC). We prospectively collected radical nephrectomy (RN) specimens, to analyze the histological changes within peritumoral and distant parenchyma.MethodsData of patients who underwent RN and had no known history of diabetes, hypertension, hyperlipidemia, or chronic kidney disease etc., were prospectively collected. Tumor pseudo-capsule (PC), and parenchyma within 2 cm from tumor margin, were pathologically assessed. The parenchyma beyond PC or tumor margin was divided into 20 subsections of 1 mm in width. Histological changes, including chronic inflammation, glomerulosclerosis, arteriosclerosis and nephrosclerosis, were given scores of 0, 1, 2 or 3 for each subsection of each specimen, according to their severity. The 20 subsections of each specimen were further divided into four groups according to the distance from the tumor edge (group 1: 0–2 mm; group 2: 2–5 mm; group 3: 5–10 mm; group 4: 10–20 mm), to better compare the peritumoral parenchyma with the distant parenchyma.ResultsIn total, 53 patients were involved in this study. All tumors were confirmed RCCs (clear cell vs. papillary vs. chromophobe were 83% vs. 5.7% vs. 11.3%, respectively), with a mean size of 5.6 cm. Histological changes were more severe in peritumoral parenchyma close to PC or tumor edge (0–5 mm), and less common within parenchyma more distant from the tumor (5–20 mm) (p < 0.001). chronic inflammation and nephrosclerosis were the most common changes especially in peritumoral parenchyma (0-2 mm). PC was present in 49 tumors (92.5%), and PC invasion occurred in 5 cases (10.2%). Mean PC thickness was 0.7 mm. PCs were more likely to be present in clear cell RCC or papillary RCC than in chromophobe RCC (100% vs. 100% vs. 33.3%, respectively; p < 0.001).ConclusionsMost RCCs have a well-developed PC, especially clear cell RCC. Histological changes mainly occur in peritumoral parenchyma, being rather uncommon in distant parenchyma. A compression band filled with severe histological changes was typically observed in renal parenchyma close to the tumor. Its preservation while performing an enucleation margin may not be entirely necessary.

Pulmonary toxicity and global gene expression changes in response to sub-chronic inhalation exposure to crystalline silica in rats

ABSTRACT Exposure to crystalline silica results in serious adverse health effects, most notably, silicosis. An understanding of the mechanism(s) underlying silica-induced pulmonary toxicity is critical for the intervention and/or prevention of its adverse health effects. Rats were exposed by inhalation to crystalline silica at a concentration of 15 mg/m3, 6 hr/day, 5 days/week for 3, 6 or 12 weeks. Pulmonary toxicity and global gene expression profiles were determined in lungs at the end of each exposure period. Crystalline silica was visible in lungs of rats especially in the 12-week group. Pulmonary toxicity, as evidenced by an increase in lactate dehydrogenase (LDH) activity and albumin content and accumulation of macrophages and neutrophils in the bronchoalveolar lavage (BAL), was seen in animals depending upon silica exposure duration. The most severe histological changes, noted in the 12-week exposure group, consisted of chronic active inflammation, type II pneumocyte hyperplasia, and fibrosis. Microarray analysis of lung gene expression profiles detected significant differential expression of 38, 77, and 99 genes in rats exposed to silica for 3-, 6-, or 12-weeks, respectively, compared to time-matched controls. Among the significantly differentially expressed genes (SDEG), 32 genes were common in all exposure groups. Bioinformatics analysis of the SDEG identified enrichment of functions, networks and canonical pathways related to inflammation, cancer, oxidative stress, fibrosis, and tissue remodeling in response to silica exposure. Collectively, these results provided insights into the molecular mechanisms underlying pulmonary toxicity following sub-chronic inhalation exposure to crystalline silica in rats.

The protective effects of GYY4137 on ipsilateral testicular injury in experimentally varicocele-induced rats.

The aim of the present study was to evaluate whether morpholin-4-ium 4 methoxyphenyl (morpholino) phosphonodithioate (GYY4137) exhibits a protective effect on ipsilateral testicular injury in experimentally varicocele (VC)-induced rats. A total of 48 rats were randomly divided into the following 6 groups (n=8 each): Group A (control group); group B (sham group); group C (VC group); group D (VC group administered 5 mg/kg/day GYY4137); group E (VC group administered 10 mg/kg/day GYY4137) and group F (VC group administered 20 mg/kg/day GYY4137). Indicators of oxidative stress, apoptosis and inflammation were measured to evaluate the effect of GYY4137 on ipsilateral testicular injury. Compared with groups A and B, rats in group C exhibited severe histological changes and an increase in oxidative stress, apoptosis and inflammation. By contrast, amelioration of testicular damage was evident in the group D, E and F that were treated with GYY4137. These results demonstrate that GYY4137 may be a promising therapy to treat VC as it alleviates oxidative stress, apoptosis and inflammation in experimentally VC-induced rats.

Belatacept Rescue Therapy in Kidney Transplant Recipients With Vascular Lesions: A Case Control Study.

Immunosuppression in kidney transplant recipients with decreased graft function and severe histological vascular changes can be particularly challenging. Belatacept could be a valuable option, as a rescue therapy in this context. We report a retrospective case control study comparing a CNI to belatacept switch in 17 patients with vascular damage and low eGFR to a control group of 18 matched patients with CNI continuation. Belatacept switch was performed on average 51.5 months after kidney transplantation (6.2-198 months). There was no difference between the two groups regarding eGFR at inclusion, and 3 months before inclusion. In the "CNI to belatacept switch group," mean eGFR increased significantly from 23.5 ± 6.7 mL/min/1.73m2 on day 0, to 30.4 ± 9.1 mL/min/1.73 m2 on month 6 (p < 0.001) compared to the control group, in which no improvement was observed. These results were still significant on month 12. Two patients experienced biopsy-proven acute rejection. One was effectively treated without belatacept discontinuation. Two patients needed belatacept discontinuation for infection. In conclusion, the remplacement of CNI with belatacept in patients with decreased allograft function and vascular lesions is associated with an improvement in eGFR.

Full-layer mucosal histology in achalasia: Histological epithelial wave is characteristic in "pinstripe pattern"-positive achalasia.

Previously, the mucosal histology in achalasia has only been investigated using superficial biopsy or surgically resected esophageal specimens in end-stage cases. We investigated the histology of the full-layer mucosa in early and advanced achalasia. Endoscopy was performed for the pinstripe pattern (PSP) (an early achalasia indicator) and dilation and thickening of the mucosa (advanced achalasia indicators). A mucosal entry site for peroral endoscopic myotomy was created using cap-fitted endoscopic mucosal resection to access the full-layer mucosa and the submucosa. Mucosal histology was compared between 32 patients with achalasia and 15 controls. Histological esophagitis with findings of inflammatory cell infiltration and dilated intercellular spaces was observed more in patients with achalasia than in controls (87.5% vs 13.3%, P<.001; 84.4% vs 46.7%, P=.049). Muscularis mucosae (MM) atrophy and epithelial wave were only observed in achalasia (40.6% vs 0%, P=.005; 28.1% vs 0%, P=.043). Fibrosis was more common in achalasia, but without statistical significance (31.3% vs 20.0%, P=.503). In achalasia with endoscopic dilation and thickening of the mucosa, MM atrophy was observed histologically, and in cases involving endoscopic PSP, the histological epithelial wave was observed. Histological findings of esophagitis were observed endoscopically even in early achalasia. Pinstripe pattern corresponds to the epithelial wave observed histologically in achalasia, whereas endoscopic findings in advanced achalasia correspond to MM atrophy. Appropriate management is necessary during early achalasia to prevent progression to advanced achalasia with more severe histological changes.

A comparative histopathological study of the skin in male white mice that treated with resistant Escherichia coli and sensitive to the ciprofloxacin antibiotic.

The current study established that the histopathological changes in the skin of male mice injected with resistant isolate to ciprofloxacin harbouring gyrA mutant mixed with the ciprofloxacin at sub minimum inhibitory concentration (512 micrograms / ml) was less severe than what it waas noticed in the mice injected with the sensitive isolate, which confirms that the antibiotic imposed a stress on the bacterial cell to prevent the production of virulence factors. Simultaneously, it was observed that the sensitive isolate caused severe histological changes in the mice skin layers than wrought by the isolate bearing resistance genes for ciprofloxacin, which confirms that the sensitive isolate owns more virulence determinants than its counterpart; resistant one.