Benefit of Hemoadsorption Therapy in Patients Suffering Sepsis-Associated Acute Kidney Injury: A Case Series.

INTRODUCTION: Sepsis is defined as life-threatening organ dysfunction in result of the host's dysregulated response to infection and septic shock. Sepsis-associated kidney injury is usually defined as concurrent presence of acute kidney injury (AKI) and sepsis without other significant causative factors. METHOD: The current retrospective study was conducted to elucidate beneficial and side effects of CytoSorb®. A total of 17 patients were primarily treated with continuous renal replacement therapy in combination with CytoSorb. The demand for norepinephrine, mean arterial pressure, lactate, and procalcitonin (PCT) levels, as well as ICU length of stay, was measured. RESULT: The blood lactate levels decreased by 32.30% when comparing mean levels before and after treatment. All patients who survived (n = 14) had reduction in vasopressor demand to 68.96% of their initial dose before the start of treatment. Hospital survival was greater in patients who initially had higher vasopressor demand compared to their nonsurviving counterparts, but in whom vasopressor dosages were reduced significantly during their treatments. Mortality as predicted by APACHE II score in the overall patient population was 79.9%, whereas, the observed ICU mortality was 31%. The baseline PCT levels on patients received 1, 2, and 3 CytoSorbs were 27.08 ± 5.81 ng/mL, 13.28 ± 2.62 ng/mL, and 21.03 ± 6.56 ng/mL, respectively. Observed PCT levels at 24 h after the last treatment on patients received 1, 2, and 3 CytoSorb were 31.55 ± 15.70 ng/mL, 5.61 ± 1.77 ng/mL, and 8.11 ± 3.62 ng/mL, respectively. CONCLUSION: In conclusion, it seems that applying the CytoSorb in combination with CRRT in ICU septic patients with AKI, is related to a significant decrease in mortality, if the integrity and continuity of the treatment be kept, as much as possible. This study presented an effectively positive outcome with cytokine adsorber treatment as an adjuvant along with standard treatment in a high-risk mortality case of septic shock with organ failure.

Supplementary Prebiotics, Probiotics, and Thyme (Thymus vulgaris) Essential Oil for Broilers: Performance, Intestinal Morphology, and Fecal Nutrient Composition.

This experiment was performed to evaluate the effects of selected natural feed additives (thyme extract, organic acid, probiotic, and prebiotic) on performance, intestinal morphology, and composition of fecal nutrients with two crude protein levels diet (10% reduced crude protein level and the recommended level) in broilers. In this experiment, 388 Ross-308 strain broilers from 1 to 42 days in three experimental periods including starter (1 to 10 days), grower (11 to 24 days), and finisher (25 to 42 days) were used in a completely randomized design (8 treatments, 4 replicates, and 12 chickens in 5 × 2 factorial arrangements). According to the results, use of feed additives along with both levels of crude protein had significant effects on performance, intestinal morphology, and fecal nutrient levels (P < 0.05). A 10% decrease in crude protein level of diet caused to decrease in daily weight gain and an increase in feed conversion ratio in the starting period (P < 0.05). Decreased dietary crude protein levels in growing and finishing period had insignificant effects on chicken's performance (P > 0.05). During the experiment period, the use of feed additives on diets with lower than normal crude protein levels had no effect on the average feed intake, daily weight gain, and feed conversion ratio of chickens (P > 0.05). Lower crude protein level changed the intestinal morphology (P < 0.05). The use of feed additives had significant effects on the nutrient content of feces (P < 0.05). Overall, results showed that a 10% reduction in crude protein level of diet compared to normal crude protein levels changed the intestinal morphology and nutrient content of feces while having adverse effects on the performance of chickens.

The Effect of Using Bovine Colostrum and Probiotics on Performance, Egg Traits, Blood Biochemical and Antioxidant Status of Laying Japanese Quails.

The present paper aims to evaluate the effect of different levels of bovine colostrum and probiotic dietary supplementation on egg production performance, egg traits, carcass characteristics, blood biochemistry and antioxidant status of laying Japanese quails. For the trial, 240 laying quails, aged between 24 weeks and 30 weeks, were involved in a 3 × 2 factorial experimental design, with 3 levels of bovine fresh colostrum (0, 2, and 4 percent of the total ratio) and 2 levels of probiotics (0 and 0.01 percent of the total ratio) administration. The colostrum supplementation improved the egg production performance, egg traits, carcass characteristics, blood biochemistry, and antioxidant status (p < 0.01). Probiotics used without colostrum did not affect the investigated traits of laying Japanese quails (p > 0.05), but a synergistic effect was observed when combined with colostrum. The overall results recommended that using 4% of bovine colostrum in laying Japanese quails, with the addition of 0.01% of probiotic feed additive results in positive effects on egg production performance, egg traits, carcass characteristics, blood biochemistry, and antioxidant status of laying Japanese quails in the late laying period.

Protective effect of l-carnitine-loaded solid lipid nanoparticles against H2O2-induced genotoxicity and apoptosis.

L-carnitine (LC) is a highly water-soluble compound involved in the ß-oxidation of lipids and transportation of long-chain fatty acids across the membrane of mitochondria. However, the higher hydrophilicity of LC limits its free diffusion across the bilayer lipid membrane of intestinal epithelium in oral administration, decreasing oral bioavailability. Drug delivery with nanoparticles enhances cargo bioavailability and cellular uptake and improves therapeutic outcomes while decreasing unwanted side effects. Here, we proposed solid lipid nanoparticles (SLNs) as a hydrophobic carrier for LC delivery, aiming at increasing LC bioavailability and its protective role against intracellular oxidative stress damages. The LC-SLNs were prepared using the hot homogenization technique, and different physicochemical properties were investigated. The inhibition of H2O2-induced ROS generation in human umbilical vein endothelial cells (HUVECs) with plain LC and LC-SLNs was investigated. Moreover, various in vitro experiments were performed to assess whether LC-SLNs can protect HUVECs from H2O2-induced genotoxicity and apoptosis. The monodispersed and spherical blank SLNs and LC-SLNs were 104 ± 1.8 and 128 ± 1.5 nm, respectively with a drug loading (DL) of 11.49 ± 0.78 mg/mL and acceptable encapsulation efficiency (EE%) (69.09 ± 1.12) of LC-SLNs. The formulation process did not affect the antioxidant properties of LC. MTT assay and comet assay demonstrated that the LC-SLNs decreased cytotoxicity and genotoxicity of H2O2, respectively on HUVECs. Besides, LC-SLNs more inhibited ROS generation, along with apoptotic events in H2O2-treated HUVECs compared to the plain LC. Altogether, our findings affirmed the protective effects of LC-SLNs against H2O2-induced genotoxicity and apoptosis in HUVECs. In conclusion, LC-SLN formulation is a promising drug delivery system to overcome the bioavailability issue of hydrophilic LC, enhancing the antioxidant and biological properties of the plain LC.

The effects of L-carnitine-loaded solid lipid nanoparticles on performance, antioxidant parameters, and expression of genes associated with cholesterol metabolism in laying hens.

The purpose of this study was to investigate the production performance, antioxidant parameters, egg yolk cholesterol content, and expression of genes related to cholesterol metabolism in laying hens fed L-carnitine (LC) and L-carnitine-loaded solid lipid nanoparticles (LC-SLNs). A total of 350 Hy-Line (w-36) laying hens at 50 wk of age (1520.0 ± 0.7 g) were randomly assigned to 35 units (5 replicates and 50 hens in each treatment) with seven dietary treatments as a completely randomized design. The dietary treatments were corn-soybean meal-based diets, including 1) Control (basal diet); 2) Basal diet +50 mg/kg LC (50LC); 3) Basal diet +100 mg/kg LC (100LC); 4) Basal diet +150 mg/kg LC (150LC); 5) Basal diet +50 mg/kg LC-SLNs (50LC-SLNs); 6) Basal diet +100 mg/kg LC-SLNs (100LC-SLNs) and 7) Basal diet +150 mg/kg LC-SLNs (150LC-SLNs). Results showed that the 50LC-SLNs had the least feed conversion ratio (FCR) in all groups (P < 0.05). The dietary supplementation of 100LC-SLNs decreased (P < 0.01) the egg yolk cholesterol concentration from 14.71 to 11.76 mg/g yolk (25%). The 50LC-SLNs group produced the most total antioxidant capacity with a difference of 58.44% compared to the control group (P < 0.01). The greatest amount of total superoxide dismutase was found for 50LC-SLNs (P < 0.05), while the glutathione peroxidase was not affected by the experimental treatments (P > 0.05). Serum malondialdehyde levels were reduced by 50.52% in laying hens fed 50LC-SLNs compared to the control group (P < 0.05). The transcript level of 3-hydroxy-3-methylglutaryl coenzyme A reductase was significantly decreased (P < 0.01) in the LC and LC-SLNs groups. The expression of cholesterol 7α-hydroxylase was significantly increased (P < 0.01) in the plain LC (∼83%) and LC-SLNs (∼91%) groups. The inclusion of LC-SLNs in the diet increased (P < 0.05) the villus height and decreased villus width in all three parts of the small intestine. Dietary inclusion of LC was found to reduce egg yolk and serum cholesterol content by improving the production performance and antioxidant status. The LC-SLNs groups were more affected than the plain LC groups, which may be attributed to the increased bioavailability of LC.

Impacts of Continuous and Intermittent Use of Bovine Colostrum on Laying Japanese Quails: Egg Performance and Traits, Blood Biochemical and Antioxidant Status.

The Japanese quail (Coturnix japonica) is farmed for its eggs and meat across the globe. A series of experiments were conducted to evaluate the effect of the permanent or intermittent use of different levels of BC (bovine colostrum) on the egg performance and traits, carcass characteristics, blood biochemical and antioxidant status of laying Japanese quails. In this study, 200 laying quails were used for a duration of six weeks (week 24 to 30) to measure the selected parameters. Treatments included: (1) control (without BC); (2) 2% continuous BC; (3) 4% BC permanently; and (4) and (5) 2% and 4% BC intermittently (every other week), respectively. According to the results, performance, egg quality, carcass traits, biochemical indices and antioxidant status of BC-fed (continuous and intermittent mode) quails were improved compared to the control-diet-fed birds (p < 0.01). Per our observations, quails fed daily with 4% BC had the highest performance, best egg and carcass quality traits, best blood composition and best antioxidant status of serum, although the same parameters were also improved in birds fed intermittently with 4% BC. The final conclusion is that, although quails fed daily with 4% BC showed the best performance, intermittent feeding exerted comparable effects. Therefore, the intermittent-feeding approach could benefit the birds when colostrum preparation is limited due to the high cost of the related process. This approach could improve the economics of poultry breeding while reducing environmental problems, such as antibiotic resistance.

Targeted Next Generation Sequencing Revealed Novel Variants in the PKD1 and PKD2 Genes of Iranian Patients with Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD), one of the common inherited disorders in humans, is characterized by the development and enlargement of renal cysts, often leading to end-stage renal disease (ESRD). In this study, Iranian ADPKD families were subjected to high-throughput DNA sequencing to find potential causative variants facilitating the way toward risk assessment and targeted therapy. METHODS: Our protocol was based on the targeted next generation sequencing (NGS) panel previously developed in our center comprising 12 genes involved in PKD. This panel has been applied to investigate the genetic causes of 32 patients with a clinical suspicion of ADPKD. RESULTS: We identified a total of 31 variants for 32 individuals, two of which were each detected in two individuals. Twenty-seven out of 31 detected variants were interpreted as pathogenic/likely pathogenic and the remaining 4 of uncertain significance with a molecular diagnostic success rate of 87.5%. Among these variants, 25 PKD1/2 pathogenic/likely pathogenic variants were detected in 32 index patients (78.1%), and variants of uncertain significance in four individuals (12.5% in PKD1/2). The majority of variants was identified in PKD1 (74.2%). Autosomal recessive PKD was identified in one patient, indicating the similarities between recessive and dominant PKD. In concordance with earlier studies, this biallelic PKD1 variant, p.Arg3277Cys, leads to rapidly progressive and severe disease with very early-onset ADPKD. CONCLUSION: Our findings suggest that targeted gene panel sequencing is expected to be the method of choice to improve diagnostic and prognostic accuracy in PKD patients with heterogeneity in genetic background.

Serum levels of CTRP3 in diabetic nephropathy and its relationship with insulin resistance and kidney function.

BACKGROUND: C1q TNF related protein 3 (CTRP3) is an adipokine secreted from adipose tissue. Previous studies have suggested that CTRP3 improves insulin sensitivity and reduces inflammation. Human studies have evaluated circulating levels of this adipokine in patients with diabetes mellitus (DM), diabetic retinopathy, metabolic syndrome, and coronary artery diseases. However, circulating levels of this adipokine in patients with diabetic nephropathy have not been evaluated. The present study aimed to assess serum levels of CTRP3 in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (T2DM-NP) and its relationship with metabolic and inflammatory markers. METHODS: This cross-sectional study was performed on 55 controls, 54 patients with T2DM, and 55 patients with T2DM-NP. Serum levels of CTRP3, adiponectin, TNF-α, and IL-6 were measured by ELISA technique. RESULTS: Serum levels of CTRP3 were significantly lower in patients with T2DM (257.61 ± 69.79 ng/mL, p < 0.001) and T2DM-NP (222.03 ± 51.99 ng/mL, p < 0.001) compared to controls (328.17 ± 80.73 ng/mL), and those with T2DM-NP compared to T2DM group. CTRP3 was independently associated with HOMA-IR (r = -0.327, p < 0.05) and adiponectin (r = 0.436, p < 0.01) in T2DM group. In T2DM-NP patients, CTRP3 independently was associated with eGFR (r = 0.428, p < 0.01) and HOMA-IR (r = -0.436, p < 0.01). Furthermore, CTRP3 revealed a ability to differentiate T2DM-NP patients from controls (area under curve (95% confidence interval): 0.881 (0.820-0.943) and p < 0.001). CONCLUSION: Decreased serum levels of CTRP3 in patients with T2DM and diabetic nephropathy and its association with pathologic mechanism in these patients suggested a possible role for CTRP3 in pathogenesis of diabetic nephropathy; nevertheless, further studies are required in this regard.

Cyclosporine in the treatment of membranoproliferative glomerulonephritis.

BACKGROUND: Therapeutic approach to patients with idiopathic membranoproliferative glomerulonephritis is still controversial. Because it is more common in developing countries, the studies about it are limited. METHODS: We used cyclosporine to treat 18 patients with membranoproliferative glomerulonephritis who were resistant to other treatment protocols such as using aspirin, dipyridamole, or steroids. All patients were treated with cyclosporine plus low-dose prednisone and were followed for an average 108 weeks. RESULTS: Partial or complete remission of proteinuria occurred in 94% of the patients (P<0.01). Relapse occurred in one (14.2%) of remitters after discontinuation of the drug. But the remainder stayed in remission to the end of the observation period. There was a 507% decrease in the baseline creatinine clearance in one patient (5.5%). CONCLUSION: These results suggest that cyclosporine may be an effective therapeutic agent in the treatment of resistant idiopathic membranoproliferative glomerulonephritis. Although the response is appeared later than other types of glomerulonephritis, but a long-term decrease in proteinuria and preservation of filtration function were observed in a significant proportion of the treated patients.

Cytomegalovirus disease with atypical presentation in a renal transplant patient: case report.

Infection is a major problem after kidney transplantation. Cytomegalovirus (CMV) is the most common viral infection affecting transplant patients. This report presents a rare clinical manifestation of CMV in the form of a hemorrhoid in a 58-year-old woman. One week after undergoing an external hemorrhoidectomy, the patient presented with fever, leukopenia, and thrombocytopenia. Pathological analysis showed CMV in the hemorrhoidal tissue, which was confirmed via a positive PP65 antigenemia assay. Therapy with ganciclovir (250 mg IV b.i.d. for 2 weeks) was started. The patient's response to treatment was good, and she has been doing well since that time. Her plasma creatinine level 2 years later was 79.2 micromol/L (normal range, 53-106 micromol/L). Physicians must always be aware of the hazards of CMV in immunocompromised patients with typical, and even with atypical, presentations. Taking into consideration the statement, "prophylaxis precedes treatment," nephrologists must try to detect CMV in their patients (especially during the first 6 months after transplantation) prior to the appearance of any clinical manifestations. If CMV is detected, pre-emptive therapy with ganciclovir should be started.