Low-Dose vs Standard-Dose Valganciclovir for Cytomegalovirus Prophylaxis After Kidney Transplantation: A Single-Center Retrospective Analysis.

BACKGROUND: Prophylactic administration of valganciclovir (VG) is an accepted method for the prevention of cytomegalovirus (CMV) infection after kidney transplantation (KTx). The standard dosage of oral VG is 900 mg/day, adjusted to renal function. There is growing evidence that low-dose 450 mg/day VG might be safe and effective. We compared low-dose vs standard-dose prophylaxis after KTx in a single-center follow-up study. METHODS: Data from 603 renal transplantations at a single center were retrospectively analyzed (2011-2014, 12-month follow-up). Recipients with donor IgG positive-recipient IgG positive (D+/R+), (D+/R-), and (D-/R+) CMV serostatus were routinely treated with 450 mg/day VG for 3 months. Based on the same prophylactic dose, patients could be categorized into two groups according to their postoperative renal function: those receiving standard-dose VG due to a lower estimated glomerular filtration rate (eGFR) (average eGFR<60 mL/min/1.73 m2) and those receiving low-dose VG due to higher eGFR (average eGFR>60 mL/min/1.73 m2). RESULTS: Estimated glomerular filtration rate-based VG serum alterations significantly affected the risk of CMV infection with a higher incidence in higher VG levels (standard-dose: 357 patients, CMV: 33 cases (9.2 %); low-dose: 246 patients, CMV: 10 cases (4.1%). The occurrence of known risk factors: serologic risk distribution and rate of induction therapy were not statistically different between the 2 groups. Treatment of an acute rejection episode influenced the infection rate significantly in the standard-dose group. As a side effect of prophylaxis, leucopenia (<3G/L) was 2.46 times higher in standard-dose vs low-dose group. CONCLUSION: Low-dose VG administration is safe and non-inferior to the standard dose in the prophylaxis of CMV infection after KTx.

Cardioprotective and Antifibrotic Effects of Low-Dose Renin-Angiotensin-Aldosterone System Inhibitors in Type 1 Diabetic Rat Model.

Diabetic cardiovascular complications are associated with up to 50% mortality, and current therapies are not effective enough. Renin-angiotensin-aldosterone system inhibitors (RAASis) are the standard of care for diabetic patients with hypertension and albuminuria. Based on our previous studies reporting the renoprotective effects of low-dose RAASis, here, we hypothesized that low-dose RAASi treatment has cardioprotective and antifibrotic benefits in type 1 diabetes mellitus (T1DM). After five weeks of T1DM, adult male Wistar rats received low doses of ramipril, losartan, or eplerenone for two weeks. Heart rate, blood pressure, and pulse wave velocity (PWV) were recorded. Aortic intima-media thickness (IMT), collagen accumulation, and myocardial fibrosis were assessed. All RAASis reduced PWV elevation, prevented the progression of myocardial fibrosis, and normalized B-type natriuretic peptide, troponin I, and fibroblast growth factor 23 levels without affecting blood pressure. Interestingly, only eplerenone reversed the decline in Klotho levels and reduced IMT and fibrosis in the media of the aorta. Our comparative analysis suggests that mineralocorticoid receptor antagonists, particularly eplerenone, may offer superior efficacy in halting both the arterial and the myocardial injuries in T1DM compared to angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers.

The Sigma-1 Receptor Is a Novel Target for Improving Cold Preservation in Rodent Kidney Transplants.

Kidney transplantation is the preferred treatment for patients with end-stage kidney disease. Maintaining organ viability between donation and transplantation, as well as minimizing ischemic injury, are critically important for long-term graft function and survival. Moreover, the increasing shortage of transplantable organs is a considerable problem; thus, optimizing the condition of grafts is a pivotal task. Here, rodent models of kidney transplantation and cold storage were used to demonstrate that supplementation of a preservation solution with Sigma-1 receptor (S1R) agonist fluvoxamine (FLU) reduces cold and warm ischemic injury. Post-transplant kidney function was improved, histological injury was mitigated, and mRNA expression of two tubular injury markers-kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin-was robustly reduced. In addition, renal inflammation was diminished, as shown by reduced leukocyte infiltration and pro-inflammatory cytokine expression. In the cold ischemia model, FLU ameliorated structural injury profoundly after 2 h as well as 24 h. The reduced number of TUNEL-positive and Caspase 3-positive cells suggests the anti-apoptotic effect of FLU. None of these beneficial effects of FLU were observed in S1R-/- mice. Of note, organ damage in FLU-treated kidneys after 24 h of cold storage was similar to just 2 h without FLU. These results indicate that S1R agonists can prolong storage time and have great potential in improving organ preservation and in alleviating the problem of organ shortages.

Effects of Feeding Low Protein Diets with Different Energy-to-Protein Ratios on Performance, Carcass Characteristics, and Nitrogen Excretion of Broilers.

This study shows the effects of feeding low protein (LP) diets with different energy-to-protein ratios were evaluated on the production parameters, carcass composition, meat quality, nitrogen retention, and excreta composition of broilers. A total of 576-day-old Ross 308 broilers were fed a control diet (C) and three LP diets containing 1.5% less crude protein than diet C for 41 days. The LP1 treatment was isocaloric with diet C, while the dietary apparent metabolizable energy corrected by nitrogen (AMEn) levels in the case of the LP2 and LP3 treatments were reduced by 1.5% and 3%, respectively. The LP diets were supplemented with six crystalline essential amino acids (AA) to meet the standardized ileal digestible AA requirements of broilers. The LP1 treatment did not affect the performance parameters of broilers and increased the breast meat yield, the nitrogen retention and decreased drip loss of breast meat and the total-N and uric acid-N nitrogen excretion of birds in comparison with the C group. Although the energy-reduced LP2 and LP3 diets resulted in lower final body weight, they did not affect the carcass composition, breast meat quality, nitrogen retention, and excreta composition of birds compared with the control treatment.

An Overview of the Cardioprotective Effects of Novel Antidiabetic Classes: Focus on Inflammation, Oxidative Stress, and Fibrosis.

Metabolic diseases, particularly diabetes mellitus (DM), are significant global public health concerns. Despite the widespread use of standard-of-care therapies, cardiovascular disease (CVD) remains the leading cause of death among diabetic patients. Early and evidence-based interventions to reduce CVD are urgently needed. Large clinical trials have recently shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) ameliorate adverse cardiorenal outcomes in patients with type 2 DM. These quite unexpected positive results represent a paradigm shift in type 2 DM management, from the sole importance of glycemic control to the simultaneous improvement of cardiovascular outcomes. Moreover, SGLT2i is also found to be cardio- and nephroprotective in non-diabetic patients. Several mechanisms, which may be potentially independent or at least separate from the reduction in blood glucose levels, have already been identified behind the beneficial effect of these drugs. However, there is still much to be understood regarding the exact pathomechanisms. This review provides an overview of the current literature and sheds light on the modes of action of novel antidiabetic drugs, focusing on inflammation, oxidative stress, and fibrosis.

Diet Composition and Using Probiotics or Symbiotics Can Modify the Urinary and Faecal Nitrogen Ratio of Broiler Chicken's Excreta and Also the Dynamics of In Vitro Ammonia Emission.

The objective of this research was to determine whether diet composition, or adding probiotic or symbiotic feed additives to broiler diets can modify the N composition of the excreta and the dynamics of ammonia volatilization from the manure. A total of 574 one-day-old Ross 308 broiler chickens were fed four different diets. The treatments included a corn and soybean meal-based control diets (C), wheat-based and wheat bran containing diets (W), a multi-strain probiotic treatment (Broilact®; Br), and a symbiotic additive containing Bacillus subtilis, inulin, and Saccharomices cerevisiae (Sy). Feeding the wheat-based diet significantly improved the weight gain and FCR of chickens. Treatment W also significantly increased the dry matter content of the excreta compared with the probiotic and symbiotic treatments. Both Br and Sy tended to decrease the amount of excreted uric acid, which is the main substrate of ammonia. Treatment Sy reduced the urinary N ratio of the excreta in comparison with treatment W. The symbiotic additive resulted in significantly higher ammonia emission in the first two hours. On the other hand, the dynamics of the emission was slow at the beginning and increased steeply after 15 h when the wheat-based diets were fed. Based on our results, the wheat-based diets, containing soluble arabinoxylans, and the symbiotic treatments of broiler diets have an impact on the urinary and faecal nitrogen composition of the excreta, and also on the dynamics of ammonia release from the manure.

Case report: COVID-19 infection in a pregnant 33-year-old kidney transplant recipient.

Patients facing severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infections with comorbidities, especially patients whose immune system is weakened have higher chances to face severe outcomes. One of the main reasons behind the suppression of the immune system is iatrogenic, in patients who have autoimmune diseases and/or had an organ transplant. Although there are studies that are examining immunocompromised and/or transplanted patients with COVID-19 infection, furthermore there is a limited number of studies available which are dealing with COVID-19 in pregnant women; however, it is unique and is worth reporting when these factors are coexisting. In this study, we present the case of a 33-year-old Caucasian pregnant woman, who had a kidney transplant in 2009 and contracted the SARS-CoV-2 virus on the 26th gestational week, in 2021. After her infection, superimposed preeclampsia was diagnosed and due to the worsening flowmetric parameters, she gave birth to a premature male newborn with cesarean section. Our kidney transplant patient's case highlights how COVID-19 disease can lead to preeclampsia and artificial termination of gestation.

SGLT2 inhibitor dapagliflozin prevents atherosclerotic and cardiac complications in experimental type 1 diabetes.

INTRODUCTION: Cardiovascular disease (CVD) is two to five times more prevalent in diabetic patients and is the leading cause of death. Therefore, identification of novel therapeutic strategies that reduce the risk of CVD is a research priority. Clinical trials showed that reduction in the relative risk of heart failure by sodium-glucose cotransporter 2 inhibitors (SGLT2i) are partly beyond their glucose lowering effects, however, the molecular mechanisms are still elusive. Here we investigated the role of SGLT2i dapagliflozin (DAPA) in the prevention of diabetes-induced cardiovascular complications. METHODS: Type 1 diabetes was induced with streptozotocin (65 mg/bwkg, ip.) in adult, male Wistar rats. Following the onset of diabetes rats were treated for six weeks with DAPA (1 mg/bwkg/day, po.). RESULTS: DAPA decreased blood glucose levels (D: 37±2.7 vs. D+DAPA: 18±5.6 mmol/L; p<0.05) and prevented metabolic decline. Aortic intima-media thickening was mitigated by DAPA. DAPA abolished cardiac hypertrophy, and myocardial damage. Cardiac inflammation and fibrosis were also moderated after DAPA treatment. CONCLUSIONS: These data support the preventive and protective role of SGLT2i in diabetes-associated cardiovascular disease. SGLT2i may provide novel therapeutic strategy to hinder the development of cardiovascular diseases in type 1 diabetes, thereby improve the outcomes.

Effects of Probiotics and Wheat Bran Supplementation of Broiler Diets on the Ammonia Emission from Excreta.

Ammonia emission is a concern for the poultry industry from both environmental and animal welfare points of view. The objective of this research was to determine whether probiotics or wheat bran supplementation of broiler diets can modify the N composition of the excreta and the dynamics of ammonia volatilisation emission from the manure. A total of 120-day-old Ross 308 broiler chickens were fed six different diets. The treatments included a corn and soybean meal-based control diet (C) and diets containing wheat bran (WB). Both diets were fed alone and with supplementation of a lactic acid (Lactobacillus farciminis, LAB) and a butyric acid (Clostridium butyricum, BAB) producing bacterial strain. Treatment BAB had a significant effect on the dry matter content of the excreta and both probiotics decreased the amount of excreted uric acid. Treatment WB resulted in a significantly lower NH+4-N concentration of excreta and a tendency toward reduced uric acid content. Treatment LAB reduced the urinary N ratio of excreta. Among dietary treatments, WB resulted in the highest urease producing cell numbers in the excreta, but this difference was not significant. Based on our results, similar to pigs, the soluble fibre fraction of poultry diets can also modify the urinary to faecal N ratio of the excreta.

Long-term risks after kidney donation: how do we inform potential donors? A survey from DESCARTES and EKITA transplantation working groups.

BACKGROUND: Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation. METHODS: All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks. RESULTS: The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes. CONCLUSIONS: The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks.

Effects of Wheat Bran and Clostridium butyricum Supplementation on Cecal Microbiota, Short-Chain Fatty Acid Concentration, pH and Histomorphometry in Broiler Chickens.

Feed additives that can improve intestinal health and maintain a diverse and resilient intestinal microbiota of poultry are of great importance. Thus, the current study investigated the effects of a single strain butyric acid-producing Clostridium (C. butyricum) with (symbiotic) or without wheat bran supplementation on cecal microbiota composition and gut health characteristics of broiler chickens. In total, 384 male Ross 308 day-old chickens were divided into four dietary treatment groups and fed ad libitum until day 37 of life. Cecal samples were taken for Illumina sequencing and pH and short-chain fatty acid analyses, as well as for histological analysis at the end of the experimental period. Neither of the supplemented diets improved chicken growth performance. Caecum was dominated by the members of Bacteroidetes phyla followed by Firmicutes in each dietary group. At the genus level, Bacteroides, Oscillospira, Akkermansia, Faecalibacterium, Ruminococcus and Streptococcus genera exceeded 1% relative abundance. Dietary treatment influenced the relative abundance of the Akkermansia genus, which had a lower relative abundance in the C. butyricum group than in the other groups and in the symbiotic group compared to the wheat bran supplemented group. Dietary treatment also altered cecal crypt depth and had a trend to modify the cecal fermentation profile. Additive effects of wheat bran and C. butyricum supplementation were not detected. Our results suggest that Akkermansia muciniphila colonization in chicken can be influenced by diet composition.

Guidance on the special care of liver or kidney transplant recipients diagnosed with COVID-19 / Az új koronavírus (SARS-CoV-2) okozta fertozésben szenvedo vese- és májátültetett betegek ellátásának speciális szempontjai. (A COVID-19-pandémia orvosszakmai kérdései)

Due to the COVID-19 pandemic caused by infection with the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), transplant medicine also had to face a new, hitherto unknown challenge. To be prepared for any possibility, we consider it important to summarize the current knowledge regarding COVID-19 of liver and kidney transplant patients. Very early reports from Spanish and French registry recorded fatality rates of 18.6% and 13%, respectively, in renal patients which suggests a moderately worse outcome compared to the general population. In patients with positive PCR test but not showing clinical signs, the reduction of immunosuppression is not advised. In the case of gastrointestinal or respiratory signs with fever, the discontinuation of mycophenolate or mTOR inhibitors is recommended with decrease of the trough levels of calcineurin inhibitors to the lowest effective limit. Stop (kidney transplanted patients) or decrease (liver transplanted patients) immunosuppression and maintain corticosteroids when pulmonal injury develops and consider anti-IL1 and anti-IL6 monoclonal antibody use when hyperinflammatory syndrome is evolving. No proven effective treatment for SARS-CoV-2 exists currently. The use of lopinavir/ritonavir should be avoided because of the severe drug interaction with calcineurin inhibitors. The efficacy and tolerability of hidroxychloroquin remains to be also questionable; enroll patients into clinical trial with remdesivir or favipiravir if available. COVID-19 is characterized by virus-induced endothelial dysfunction, procoagulant state and renin-angiotensin-aldosteron system imbalance. Early thromboprofilaxis combination with low-molecular-weight heparin and low-dose aspirin is strongly recommended with the maintenance of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II-receptor blocker (ARB) therapy when they were prescribed earlier. Orv Hetil. 2020; 161(32): 1310-1321.

Reduced O-GlcNAcylation and tubular hypoxia contribute to the antifibrotic effect of SGLT2 inhibitor dapagliflozin in the diabetic kidney.

Diabetic kidney disease is a worldwide epidemic, and therapies are incomplete. Clinical data suggest that improved renal outcomes by Na+-glucose cotransporter 2 inhibitor (SGLT2i) are partly beyond their antihyperglycemic effects; however, the mechanisms are still elusive. Here, we investigated the effect of the SGLT2i dapagliflozin (DAPA) in the prevention of elevated O-GlcNAcylation and tubular hypoxia as contributors of renal fibrosis. Type 1 diabetes was induced by streptozotocin in adult male Wistar rats. After the onset of diabetes, rats were treated for 6 wk with DAPA or DAPA combined with losartan (LOS). The effect of hyperglycemia was tested in HK-2 cells kept under normal or high glucose conditions. To test the effect of hypoxia, cells were kept in 1% O2 for 2 h. Cells were treated with DAPA or DAPA combined with LOS. DAPA slowed the loss of renal function, mitigated renal tubular injury markers (kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin), and reduced tubulointerstitial fibrosis. DAPA diminished high glucose-induced protein O-GlcNAcylation and moderated the tubular response to hypoxia through the hypoxia-inducible factor pathway. DAPA alone was as effective as combined treatment with LOS in all outcome parameters. These data highlight the role of ameliorated O-GlcNAcylation and diminished tubular hypoxia as important benefits of SGLT2i treatment. Our results support the link between glucose toxicity, tubular hypoxia, and fibrosis, a vicious trio that could be targeted by SGLT2i in kidney diseases of other origins as well.

Oncological Screening of Kidney Transplant Patients: The Role of Ultrasound Examination.

INTRODUCTION: Immunosuppressive therapy used after organ transplantation represents a considerable oncological risk. Abdominal ultrasound examinations play an essential role in the oncological screening of organ transplant patients. Our aim was to study the effectiveness of the ultrasound screening protocol currently used in our clinic. METHODS: Reports of screening abdominal ultrasound examinations of kidney transplant recipients were processed at the Department of Transplantation and Surgery of Semmelweis University from January 2012 to December 2015. RESULTS: In 1478 studies, 14 patients were diagnosed with a malignant tumor, 11 of which were formed in the native shrunken kidney. The mean age for tumor diagnosis was 55.6 ± 12.6 years, and 80% of the patients diagnosed with tumor were male. On average, 7.5 ± 4.6 years passed between the transplantation and recognition of the tumor. All of the kidney tumors were diagnosed at an early stage: histologic examination of removed kidneys showed 73% pT1a- and 17% pT1b-stage tumors. CONCLUSION: In our study, early stage shrunken kidney cancers were outstandingly the most common post-transplant malignancies found by ultrasound screening. Annual ultrasound examinations as part of our current screening protocol allowed the detection of tumors at an early stage in kidney transplant recipients.

RAAS inhibitors directly reduce diabetes-induced renal fibrosis via growth factor inhibition.

KEY POINTS: Increased activation of the renin-angiotensin-aldosterone system (RAAS) and elevated growth factor production are of crucial importance in the development of renal fibrosis leading to diabetic kidney disease. The aim of this study was to provide evidence for the antifibrotic potential of RAAS inhibitor (RAASi) treatment and to explore the exact mechanism of this protective effect. We found that RAASi ameliorate diabetes-induced renal interstitial fibrosis and decrease profibrotic growth factor production. RAASi prevents fibrosis by acting directly on proximal tubular cells, and inhibits hyperglycaemia-induced growth factor production and thereby fibroblast activation. These results suggest a novel therapeutic indication and potential of RAASi in the treatment of renal fibrosis. ABSTRACT: In diabetic kidney disease (DKD) increased activation of renin-angiotensin-aldosterone system (RAAS) contributes to renal fibrosis. Although RAAS inhibitors (RAASi) are the gold standard therapy in DKD, the mechanism of their antifibrotic effect is not yet clarified. Here we tested the antifibrotic and renoprotective action of RAASi in a rat model of streptozotocin-induced DKD. In vitro studies on proximal tubular cells and renal fibroblasts were also performed to further clarify the signal transduction pathways that are directly altered by hyperglycaemia. After 5 weeks of diabetes, male Wistar rats were treated for two more weeks per os with the RAASi ramipril, losartan, spironolactone or eplerenone. Proximal tubular cells were cultured in normal or high glucose (HG) medium and treated with RAASi. Platelet-derived growth factor (PDGF) or connective tissue growth factor (CTGF/CCN2)-induced renal fibroblasts were also treated with various RAASi. In diabetic rats, reduced renal function and interstitial fibrosis were ameliorated and elevated renal profibrotic factors (TGFß1, PDGF, CTGF/CCN2, MMP2, TIMP1) and alpha-smooth muscle actin (αSMA) levels were decreased by RAASi. HG increased growth factor production of HK-2 cells, which in turn induced activation and αSMA production of fibroblasts. RAASi decreased tubular PDGF and CTGF expression and reduced production of extracellular matrix (ECM) components in fibroblasts. In proximal tubular cells, hyperglycaemia-induced growth factor production increased renal fibroblast transformation, contributing to the development of fibrosis. RAASi, even in non-antihypertensive doses, decreased the production of profibrotic factors and directly prevented fibroblast activation. All these findings suggest a novel therapeutic role for RAASi in the treatment of renal fibrosis.

[Diabetology and solid organ transplantation]. / Diabetológia és szervátültetés.

Diabetes increases the risk of different kidney diseases. The most important is diabetic nephropathy, however, ischemic kidney disease, chronic pyleonephritis and papilla necrosis may also develop. The prognosis of diabetic nephropathy has improved recently, however, it is still the primary cause of dialysis and transplantation. Cardiovascular diseases predict mostly mortality in diabetic patients, however, cerebrovascular insults and peripheral obstructive arterial diseases necessitating lower limb amputations are also important. Diabetic retinopathy is almost always present with diabetic nephropathy. Diabetic neuropathy may also develop, furthermore vascular complications often combine. All these urge complex workup, follow-up and early treatment. If transplantation is indicated, preemptive operation should be preferred, and living donation shows the best outcomes. Different forms of carbohydrate disorder may occur after transplantation: new-onset diabetes or diabetes known before transplantation may progress. Renal transplantation with pancreas transplantation may be indicated in type 1 diabetes with end-stage diabetic nephropathy, most often simultaneously. This may result in normoglycemia and insulin-independence and the progression of other complications may also halt. Transplant associated hyperglycemia occurs in most of the patients early, however, it is often transitory. Despite stabilization of the patient and of the immunosuppressive therapy, about one third of the patients may develop posttransplant diabetes. Insulin secretion disorder is the primary cause, but insulin resistance is also needed. Insulin administration may help, however, other antidiabetics can also be useful. Carbohydrate metabolism should be checked in both cadaveric and living donors. The authors make an attempt to summarize the above conditions with Hungarian relevance as well. Orv Hetil. 2018; 159(46): 1930-1939.

Soluble nondigestible carbohydrates improve intestinal function and increase caecal coliform load in broiler chickens.

Diets rich in various soluble nondigestible carbohydrates (sNDCs) were evaluated on different intestinal characteristics (histological, physico-chemical and microbiological) of chickens and compared with a maize-based diet as a control. A total of 160 Ross 308 male chickens were kept in deep litter pens (n = 40) and fed their appropriate diets from Day 1 to Day 35 of life. Four isocaloric and isonitrogenous diets, differing in their sNDC content, were composed; control (containing maize as the only cereal), maize-wheat-based (M + W) and maize-based supplemented with either 20 g/kg inulin (M + I) or 30 g/kg lactose (M + L). All of the diets tested decreased ileal crypt depth, ileal muscle layer thickness and increased caecal coliform counts relative to the control group. Villus-crypt ratio increased only in the M + L group. Ileal digesta of chickens fed the M + W diet had the highest ileal viscosity and the highest caecal butyrate, valerate and total short-chain fatty acid concentrations while the lowest pH was observed in caecal contents of chickens fed the M + I diet. The diet had no effect on ileal or caecal goblet cell and intraepithelial lymphocyte numbers. Lactobacillus counts in the caecal content remained unchanged. According to the present study, various sNDC sources may have beneficial gut health effects, however, some of the intestinal variables are dependent on the type of sNDCs.

The role of Sigma-1 receptor in sex-specific heat shock response in an experimental rat model of renal ischaemia/reperfusion injury.

We previously showed that female rats are more protected against renal ischaemia/reperfusion (I/R) injury than males, which is partly attributed to their more pronounced heat shock response. We recently described that Sigma-1 receptor (S1R) activation improves postischaemic survival and renal function. 17ß-estradiol activates S1R, thus here we investigated the role of sex-specific S1R activation and heat shock response in severe renal I/R injury. Proximal tubular cells were treated with 17ß-estradiol, which caused direct S1R activation and subsequent induction of heat shock response. Uninephrectomized female, male and ovariectomized female (Ovx) Wistar rats were subjected to 50-min renal ischaemia followed by 2 (T2) and 24 (T24) hours of reperfusion. At T24 renal functional, impairment was less severe and structural damage was less prominent in females versus males or Ovx. Postischaemic increase in S1R, pAkt, HSF-1, HSP72 levels were detected as early as at T2, while pHSP27 was elevated later at T24. Abundance of heat shock proteins was higher in healthy female rats and remained higher at T2 and T24 (female versus male or Ovx; resp.). We propose a S1R-dependent mechanism, which contributes to the relative renoprotection of females after I/R injury by enhancing the heat shock response.

Shear-wave elastography for the assessment of liver fibrosis in liver transplant recipients treated for hepatitis C virus recurrence.

OBJECTIVES: Direct-acting antiviral agents have revolutionized hepatitis C therapy, and are also found to be effective in the liver transplant setting. The extent of liver fibrosis influences patient management and is used to monitor therapeutic effects. Shear-wave elastography (SWE) is a relatively new imaging-based method that has not yet been studied extensively in liver transplant patients. Our aim was to study the effect of direct-acting antivirals in heaptitis C recurrence on liver stiffness determined by SWE. PATIENTS AND METHODS: A total of 23 liver transplant patients with hepatitis C recurrence were enrolled in this prospective study. The patients underwent 24 weeks of ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin combination therapy. Elastographic examinations, serological tests and laboratory tests were performed, and serum biomarkers of liver fibrosis were calculated the day before treatment (baseline) and at the end of the treatment. RESULTS: All our patients became hepatitis C virus RNA negative by the end of the treatment. Median liver stiffness values decreased significantly after treatment compared with baseline (8.72±3.77 vs. 7.19±2.4 kPa; P<0.001). Among the studied laboratory values, a significant decrease was observed in the levels of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase, whereas international normalized ratio levels increased. Serum biomarkers, namely aspartate aminotransferase-to-platelet ratio index and Fibrosis-4, decreased significantly after treatment compared with baseline. CONCLUSION: In the present study, SWE was succesfully used to monitor the beneficial therapeutic effects of direct-acting antivirals in hepatitis C recurrence following liver transplantation. We believe that SWE is a useful noninvasive diagnostic tool in the follow-up of hepatitis C treatment in liver transplant patients.