Higher Urea Levels Research Articles

Severe Human Illness Caused by Rift Valley Fever Virus in Mauritania, 2015.

Background.Rift Valley Fever epizootics are characterized by numerous abortions and mortality among young animals. In humans, the illness is usually characterized by a mild self-limited febrile illness, which could progress to more serious complications.Objectives. The aim of the present prospective study was to describe severe clinical signs and symptoms of Rift Valley Fever in southern Mauritania.Patients and methods.Suspected cases were enrolled in Kiffa (Assaba) and Aleg (Brakna) Hospital Centers from September 1 to November 7, 2015, based on the presence of fever, hemorrhagic or meningoencephalitic syndromes, and probable contact with sick animals. Suspected cases were confirmed by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR).Results.There were thirty-one confirmed cases. The sex ratio M/F and the average age were 2.9 and 25 years old [range, 4-70 years old], respectively. Mosquito bites, direct contact with aborted or dead animals, and frequent ingestion of milk from these animals were risk factors observed in all patients. Hemorrhagic and neurological manifestations were observed in 81% and 13% of cases, respectively. The results of laboratory analysis showed high levels of transaminases, creatinine, and urea associated with thrombocytopenia, anemia, and leukopenia. All patients who died (42%) had a hemorrhagic syndrome and 3 of them had a neurological complication. Among the cured patients, none had neurologic sequelae.Conclusion.The hemorrhagic form was the most common clinical manifestation of RVF found in southern Mauritania and was responsible for a high mortality rate. Our results justify the implementation of a continuous epidemiological surveillance.

Prevalence and lethality among patients with histoplasmosis and AIDS in the Midwest Region of Brazil.

Histoplasmosis is a systemic mycosis that is considered an important public health problem. In this work, we performed a descriptive, observational, cross-sectional and retrospective study with a secondary data analysis of medical records from 2000 to 2012 at a tertiary hospital. The study sample consisted of 275 patients with laboratory-confirmed Disseminated Histoplasmosis (DH)/AIDS. The results showed that the prevalence of DH associated with AIDS was 4.4%. The majority of patients were young adult men with fever in 84.2%, cough in 63.4%, weight loss in 63.1%, diarrhoea in 44.8% and skin manifestations in 27.6% of patients. In the overall cohort, the CD4 counts were low, but not significantly different in survivors and non-survivors. Higher levels of urea and lower levels of haemoglobin and platelets were observed in non-survivor patients (<.05). The global lethality was 71.3% (196/275). The results with high prevalence and lethality highlight the need to adopt measures to facilitate early diagnosis, proper treatment and improved prognosis.

Tributyltin-mediated hepatic, renal and testicular tissue damage in male Syrian hamster (Mesocricetus auratus): a study on impact of oxidative stress

Organotin compounds are a versatile group of organometallic chemicals that are used in a variety of industrial and agricultural applications. Tributyltin (TBT), a common organotin, brings about severe spermatotoxic and organotoxic effects. However, information about the adverse effects of TBT on liver, kidney and testis is scanty. Hence, the present study was undertaken to elucidate the TBT-mediated oxidative stress-induced impairments in these organs. Administration of TBT through oral route at increasing doses of 50, 100 and 150 ppm for 65 days to male Syrian hamsters resulted in drastically decreased activities of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase and decreased mean levels of non-enzymatic antioxidants (reduced glutathione, vitamin C, and vitamin E) followed by a dramatic increase in the levels of lipid peroxidation in the liver, kidney and testis as compared to the control animals. Significantly high levels of serum urea, creatinine, uric acid and bilirubin were observed in TBT-treated hamsters. Also, TBT treatment induced drastic histopathological changes in the liver, kidney and testis combined with remarkable changes in serum levels of tissue injury marker enzymes Aspartate transaminases, Alkaline phosphatase and Alanine transaminase. These data affirm that exposure to TBT can lead to oxidative stress-induced damage to liver, kidney and testis.

Clinical manifestations and pulmonary radiological findings of primary anti-neutrophil cytoplasmic antibody-associated vasculitis

Objective To analyze the clinical features and pulmonary radiological findings of primary anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis (AAV). Methods Clinical data of 271 ANCA positive primary AAV patients admitted in Shanghai Ruijin Hospital from January 2003 to November 2015 were retrospectively analyzed. Among 271 patients, there were 211 myeloperoxidase (MPO)-ANCA positive cases (MPO subgroup), 52 proteinase 3 (PR3)-ANCA positive cases (PR3 subgroup), and 8 dual positive cases (dual subgroup) according to ANCA classification. The demography, clinical characteristics, pulmonary radiological manifestation and renal function were compared among three subgroups. Results MPO subgroup had more renal (χ2=4.968, P=0.026) and constitutional symptoms (χ2=8.901, P=0.003) than PR3 group, while PR3 group had more ENT symptoms (χ2=19.843, P<0.001), cough (χ2=6.623, P=0.010), hemoptysis (χ2=8.656, P=0.003), dyspnea (χ2=5.127, P=0.024) , buccal and ocular mucosal symptoms (χ2=4.818, P=0.028) than MPO group. In lung radiology, interstitial manifestations were displayed more frequently in MPO than PR3 group (χ2=4.237, P=0.040), while pulmonary nodules was more frequent in PR3 than MPO group (χ2=4.503, P=0.034). Dual subgroup tended to have more nervous, respiratory and renal impairment. Renal function showed that MPO subgroup had higher creatinine (Z=-5.529, P<0.001), urea (Z=-4.646, P<0.001) and uric acid levels (Z=-2.331, P=0.020) than PR3 subgroup. Dual subgroup had higher creatinine (Z=-3.251, P=0.001) and urea (Z=-2.882, P=0.004) levels than PR3 subgroup, but there was no difference with MPO subgroup. Conclusion There are significant differences in both clinical and pulmonary radiological manifestations between the MPO and PR3-ANCA subgroup of primary AAV. Key words: Anti-neutrophil cytoplasmic antibody-associated vasculitis; Peroxidase; Proteinase 3; Clinical characteristics; Pulmonary computed tomography

Predictive factors of early mortality after percutaneous endoscopic gastrostomy placement: The importance of C-reactive protein

Percutaneous endoscopic gastrostomy (PEG) is considered one of the preferred routes for long-term enteral feeding. However, early mortality after PEG placement is high. We aimed at analyzing overall and early mortality in patients who underwent PEG insertion and at identifying risk factors of increased mortality after the procedure. Retrospective study which included patients who had a PEG insertion at our department between May 2007 and January 2013. Variables analyzed: demographic, Charlson's co-morbidity index, past aspiration pneumonia, indication for PEG, hemogram, ionogram, urea, creatinine, albumin and C-reactive protein (CRP). death. Kaplan-Meier survival analysis was used to calculate mortality after PEG placement. Predictive factors of overall mortality were identified by univariate and multivariate analysis and of 30-day, 90-day and 180-day mortality by logistic regression. The AUROC analysis for CRP levels was performed. Inclusion of 135 patients: 51.9% female, mean age of 73±17 years, 90.4% with neurological dysphagia and 9.6% with tumors compromising oral intake. The median survival time was 272 days. The 30-day, 90-day and 180-day mortality was 0.14±0.06 (95% CI 0.08-0.20), 0.29±0.08 (95% CI 0.21-0.37) and 0.43±0.08 (95% CI 0.35-0.51), respectively. Patients with higher levels CPR (hazard ratio (HR) 1.009 95% CI 1.002-1.160, p=0.012) and higher levels of urea (HR 1.009 95% CI 1.002-1.160, p=0.012) had worse outcome and those with higher sodium levels (HR 0.945 95% CI 0.908-0.983, p=0.005) had better prognosis. Higher CRP levels was the only independent predictive factor for 30-day mortality (odds ratio (OR) 1.008 95% CI 1.001-1.014, p=0.029), and was also a risk factor for 90-day and 180-day mortality (OR 1.013 95% CI 1.005-1.021, p=0.002 and OR 1.009 95% CI 1.001-1.018, p=0.026, respectively). CRP levels ≥35.9mg/dL could predict death at 30 days with a sensitivity of 0.810 and a specificity of 0.614. The early mortality after PEG placement is high. CRP, an indicator of acute illness, is a useful parameter at identifying patients with increased probability of dying after PEG insertion. High CRP levels should be considered in the decision making process.

Ablation of the Renal Urea Transporters UT‐A1 and UT‐A3 Replicates the Benefits of a Low‐protein Diet in Attenuating Diabetic Nephropathy

Diabetic nephropathy (DN) is a leading cause of kidney failure worldwide. Progression of DN can be slowed with a low‐protein diet; however, Western diets exceed the amount of protein physiologically needed, thus excess urea is generated and excreted by the kidney. Urea is reabsorbed in the inner medulla by the urea transporters UT‐A1 and UT‐A3. Although regulation of urea handling by these transporters controls urine concentration, the impact of these transporters on DN has not been explored. We induced DN in wild type (WT) and UT‐A1/A3 null mice (KO) using low‐dose streptozotocin injections and fed the mice a low (LP; 14%)‐, normal (NP; 25%)‐ or high (HP; 40%)‐protein diet over 10 wk. All DN mice demonstrated glycosuria and polyuria regardless of diet or genotype. Creatinine clearance was dampened in DN WT mice on LP and NP diets and was significantly decreased in DN WT mice on a HP diet. Interestingly, DN KO mice did not have diminished creatinine clearance rates regardless of diet suggesting the inability to reabsorb urea preserves renal function in DN. Histological analysis showed advanced interstitial fibrosis in WT DN mice fed a NP and HP diet; however, diabetic KO mice on the same diets had minimal fibrosis. Both DN and high urea levels are associated oxidative stress, prompting us to investigate multiple markers of oxidative stress. We found that DN KO mice fed HP diet were protected from the oxidative stress observed in DN WT mice on the same diet. Our data indicate in the absence of UT‐A1 and UT‐A3, the collecting duct fails to reabsorb the excess urea from a high protein diet and in doing so, prevents the interstitial fibrosis that occurs as a consequence of increased oxidative stress in the diabetic kidney.Support or Funding InformationHHMI Science Education Program Award #52006923

Cardiotrophin-1 therapy prevents gentamicin-induced nephrotoxicity in rats

Aminoglycosides are very effective antibiotics for the treatment of severe infections, but they rank among the most frequent causes of drug-induced nephrotoxicity. Thus, prevention of aminoglycoside nephrotoxicity is an unmet therapeutic objective. Cardiotrophin-1 (CT-1), a member of the IL-6 family of cytokines, has been reported to protect the kidney against toxic and ischemic acute kidney injury (AKI). We have assessed the effect of rat CT-1 in the severity of gentamicin (G)-induced AKI. Groups of male Wistar rats received the following for 6 consecutive days: i) isotonic saline solution (group CONT), ii) G, 150mg/kg/day, i.p. (group G), iii) CT-1, 100μg/kg/day i.v. (group CT-1), or iv) G and CT-1 at the doses described above. The G group showed a manifest AKI characterized by low creatinine clearance, high plasma creatinine and urea levels, increased urinary excretion of proteins, glucose and AKI markers such as N-acetyl-glucosaminidase, neutrophil gelatinase-associated lipocalin, kidney-injury molecule-1 and T-gelsolin, increased kidney levels of CD-68, iNOS, IL-1β and TNF-α, and markedly higher histological renal damage and leukocyte infiltration than the CONT and CT-1 groups. Administration of CT-1 together with G reduced almost all of the above-described manifestations of G-induced AKI. The results of this study have potential clinical application, as CT-1 is near to being used as a drug for organ protection.

Study of Serum urea and Creatinine in Diabetic and non-diabetic patients in in a tertiary teaching hospital

Introduction: Diabetes is on the rise worldwide and India has more number of diabetics with more than 60 million people diagnosed to suffer from the disease in 2013. Approximately 20% to 30% of all diabetics will develop evidence of nephropathy, although a higher percentage of type 1 patients progress to end stage renal disease. Diabetic nephropathy (DN) is characterised by macro albuminuria and abnormal renal function as represented by a reduction in glomerular filtration and rise in serum urea and creatinine. Aim &amp; Objectives: The aim of this study was to study the relationship between blood levels of urea and creatinine with blood glucose levels in diabetic and non-diabetic subjects for their utility in diagnosis of diabetic nephropathy and their comparison with glycemic status. Material and Methods: Diabetic and non-diabetic subjects; 100 in each group; attending out- patient department during 15 May to 15 September 2015 were studied. Patients with known kidney disease were excluded. Blood samples were analysed for blood sugar (glucose), serum urea and creatinine to determine presence of kidney disease and hyperglycemia on basis of reference laboratory standards in the institute. Results: Out of 100 diabetes samples, 18 had high urea level whereas 15 had increased creatinine level. In control group of 100 sample, there was no one with high urea value and 2 had high creatinine level. There was statistically significant increase in urea level with increased blood sugar level (p&lt;0.05, 95%CI). Conclusion: Serum urea and creatinine are useful, simple biomarkers as predictor and prognostic tests of renal failure in diabetic patients, despite some limitations.

Effects of L-Arginine Supplementation on Lactating Mares and the Development of Foals

Background: Most animal species are able to produce Arginine (Arg) under normal conditions. However, in some situations, its degradation can be higher than its production. For example, during a period of lactation or disease, there is an increase in the consumption of Arg. In this case, endogenous production is not enough for the animal’s demands. Indeed, Arg supplementation in animals has several benefits for the animal’s body, such as the increase of angiogenesis, improvements in immunity and the reproductive system, as well as the stimulation of lactogenesis. During the early phase of growth, a deficiency of Arg could cause a reduction in the growth rate and metabolic activity of animals. Therefore, this amino acid is considered essential in some phases of the life of animals. However, very few studies of the supplementation of this amino acid in horses have been carried out. The aim of the present study was to characterize the effects of supplementing lactating mares and their foals with Arg.Materials, Methods &amp; Results: Lactating mares (n = 10) were divided into two groups (control group: n = 3 / supplemented group: n = 7) and maintained exclusively under grazing. The supplemented group received 50 g of Arg during the lactation period. Samples of milk and blood from mares and blood from foals were collected at different phases of the lactation period. The following parameters were measured in milk: Glutamine (Gln); Glutamate (Glu); protein; fat; casein; lactose; urea and total solids. The following parameters were measured in blood: Gln; Glu; total plasmatic protein (TPP); albumin; urea; creatinine; uric acid; triglycerides; total cholesterol; calcium (C); phosphorous (P); magnesium (Mg) and ferrous (Fe). In addition, the biometric parameters of Wither Height (WH), Chest Perimeter (CP), Cannon Bone Circumference (CBC) and Fat Percentage (FP) of foals were obtained. A significant increase of Gln was observed in the milk in both groups (P &lt; 0.05). The highest concentration of Gln was detected in the third month of the lactation period in the supplemented group (~ 2.26 mmol/mL), and the control group (~ 1.91 mmol/mL) during the same period. Gln did not alter in the blood (P &gt; 0.05), although Glu was higher in the control group in the first month of the lactation period (~ 0.21 mmol/mL) (P &lt; 0.05). An increase in uric acid (~ 0.19 mmol/L) in both groups on the day of birth (P &lt; 0.05). In the supplemented group, increases in triglycerides (~ 0.60 mmol/L), Ca (~ 2.90 mmol/L) and Mg (~ 0.52 mmol/L) were observed in the first month of the lactation (P &lt; 0.05). At birth, foals exhibited high levels of urea (~ 4.67 mmol/L) and uric acid (~ 0.21 mmol/L), and low levels of P (~ 2.02 mmol/L) (P &lt; 0.05). The levels of Gln in the blood of foals remained between 0.50 and 0.70 mmol/mL throughout the lactation period (P &gt; 0.05). Even when they were added (Gln + Glu), no differences were observed (P &gt; 0.05). However, when the biometric parameters were analyzed, significant variations were detected in almost all characteristics (weight, WH, CP and CBC). In particular, the control group exhibited higher body mass and CP in the fifth month, when compared with the group of foals born from supplemented mares (P &lt; 0.05). The FP did not alter in either of the groups analyzed (P &gt; 0.05).Discussion: The results indicate that the supplementation of lactating mares with Arg produced few alterations in the parameters analyzed for both mares and foals. In addition, the supplementation did not produce side effects among the supplemented animals.

Uremic pruritus – a review

Uremic pruritus remains a frequent concern for hemodialysis patients with the most frustrating and disabling symptoms. The word uremic may denote that patients suffer from acute renal injury. Hence it is preferred to use the recent term “chronic kidney disease associated pruritus” (CKD- associated pruritus). The prevalence of CKD-associated pruritus in patients ranges from 15%-90% in various studies. Interestingly, in CKD associated pruritus the skin lesions are not found. The various skin lesions which range from excoriations, impetigo, linear crusts, papules and ulcers are secondary. Other co-existing diseases like cardiovascular diseases, diabetes, hypothyroidism, chronic liver or hematological diseases may challenge the diagnosis and management. The pathophysiology remains unexplained. There may be an imbalance between the antagonistic activities of µ- and] κ-opioid receptors. Itch sensation are correlated with the activation of certain areas in the brain, spatial and temporal aspects may be processed in the primary somatosensory cortex, planning of scratch response in the pre-motor and supplementary motor cortices, and affective and motivational aspects in the anterior cingulate cortex. A number of different mechanisms have been proposed like xerosis, transdermal water loss, accumulation of pruritogenic substances, increase in parathyroid hormone levels, high levels of urea, calcium, phosphate, β-2 microglobulin but none are convincing. Because of the poorly understood patho-physiological mechanisms the treatment of this condition, have been largely empirical. Reduced hydration may be alleviated by simple emollient therapy. Antihistamines have been widely prescribed in spite of lack of best evidence. UVB phototherapy helps many patients. Anti convulsant, gabapentin may have beneficial effect. Other ole remedies include fish oil, omega 3 fatty acids, IV heparin, thalidomide, lidocaine and mexitine. Recent studies demonstrated that nalfurafine as a systemic agent for two weeks would benefit most patients. All these treatment modalities are best only in addition to the dialysis related treatment like renal dialysis, erythropoietin and renal transplantation.

Does the course of laboratory parameters help us to predict the outcome of CCHF?

This study was performed to identify the characteristics distinguishing fatal and nonfatal cases of patients diagnosed with Crimean-Congo hemorrhagic fever (CCHF). A total of 92 patients with confirmed diagnosis of CCHF in 2009-2013 were included in the study. A high level of urea and aPTT on the third day of hospital stay, diarrhea, somnolence, and the interval from the beginning of the symptoms to hospital admission were independently associated with fatality. Each 10-unit increase in aPTT and urea levels increased the fatality rate by 3.379-fold and 1.236-fold, respectively. Delay in hospital admission increased the fatality rate 1.453-fold for each day of delay. When comparing first and third admission-day laboratory values, the increase in leukocyte counts and the decrease in CPK, urea, creatinine, aPTT, PT, INR, and hemoglobin levels were significant in nonfatal cases. This study showed that the course of these laboratory tests helps us to predict the outcome of the disease. In a few days of hospitalization, persistence or progress of the abnormal laboratory parameters may warn us about poor prognosis.

Genetic variation in WDR1 is associated with gout risk and gout-related metabolic indices in the Han Chinese population.

Gout is the most common form of inflammatory arthritis affecting men, and current evidence suggests that genetic factors contribute to its progression. As a previous study identified that WD40 repeat protein 1 (WDR1) is associated with gout in populations of European descent, we sought to investigate its relationship with this disease in the Han Chinese population. We genotyped six WDR1 single nucleotide polymorphisms in 143 gout cases and 310 controls using Sequenom MassARRAY technology. The SPSS 16.0 software was used to perform statistical analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression, with adjustments for age and gender. In an analysis using an allelic model, we identified that the minor alleles of rs3756230 (OR = 0.64, 95%CI = 0.450-0.911, P = 0.013) and rs12498927 (OR = 1.377, 95%CI = 1.037-1.831, P = 0.027) were associated with gout risk. In addition, we found that the "A/A" genotype of rs12498927 was associated with increased risk of gout under codominant (OR = 2.22, 95%CI = 1.12- 4.40, P = 0.042) and recessive models (OR = 2.24, 95%CI = 1.20-4.17, P = 0.012). We also determined the "A/G" genotype of rs12498927 to be significantly associated with higher urea levels in gout patients (P = 0.017). Our data shed new light on the association between genetic variations in the WDR1 gene and gout susceptibility in the Han Chinese population.

Infusum Daun Alpukat Sebagai Inhibitor Kristalisasi Kalsium Oksalat pada Ginjal

Urine crystal is a crystal nucleus which tend to form urine stone. The case of urine stone seems to beincreased every year. Crystallization could induce acute tubular necrosis which impact on renal dysfunction.The signs of this condition are high level of urea, creatinine and decrease glomerulus filtration rate. Theobjective of this research was to evaluate the effects of infusum Persea americana Mill as an inhibitorcrystallization which induced by ethylene glycol on white male rats. 20 male rats were divided into 4groups; K1 as negative group received only distilled water ad libitum, K2 as positive group receiveddistilled water containing ethylene glycol, K3 (dose 5%) and K4 (dose 10%) as treatment groups receivedwater containing ethylene glycol and avocado leaves infusion. Phytochemsitry screening of infusion avocadoleaves consisted of flavonoid, saponin, tanine and quinone. Result of analysis showed that the level ofureum and creatinine on K2 was higher than K3 and K4 group. The increased level could be inhibited byinfusion avocado leaves. The measurement of glomerular filtration rate in treatment groups wassignificantly different (p<0.05). Descriptive histopathology observation showed that renal lesio in grouptreatment (K3 and K4) were declined. Large crystal calcium oxalate on K2 group was observed by usingpolarized microscope, whereas small crystal calcium oxalate were seen in the infusion of avocado leavesgroups. These result showed the ability of infusion of avocado leaves as an inhibitor on the growth ofcrystallization calcium oxalate

BIOCHEMICAL MARKERS OF RENAL DYSFUNCTIONS IN CRITICALLY ILL FULL - TERM NEWBORNS

Introduction. Full - term newborns with clinical signs of severe perinatal pathology constitute a high risk group of the formation of urinary system functional disorders, the diagnostic of which in the early neonatal period is complicated.&#x0D; Objective of the research was to study the condition of renal functions in critically ill full - term newborns during the first week of their life by means of detection of specific biomarkers level in the blood serum and urine.&#x0D; Materials and methods. A comprehensive clinical - paraclinical examination of 36 critically ill newborns (the main group) and 37 conditionally healthy newborns (the control group) has been conducted. Laboratory methods ofexamination included detection of the levels of creatinine, urea, sodium and potassium ions in the blood and urine, as well as protein, albumin, immunoglobulin G, a - - microglobulinand $ - microglobulinin urine.&#x0D; Results and discussion. The neonates of the main group as compared to the control one presented statistically significant higher levels of creatinine (р&lt;0,01) and urea (р&lt;0,001) in the blood serum against the ground of lower glomerular filtration rate (р&lt;0,05) and the level ofpotassium ions (р&lt;0,01); in the urine — statistically significant lower level of creatinine (р&lt;0,01), higher levels of urea (р&lt;0,001) and sodium ions (р&lt;0,05). Evaluation of urineproteinogramin the main group of newborns as compared to the control group enabled to find statistically significant higher levels of protein (р&lt;0,01), albumin (р&lt;0,01), immunoglobulin G (р&lt;0,05), a - - microglobulin (р&lt;0,01), $ - - microglobulin (р&lt;0,01).&#x0D; Conclusions. Critically ill full - term newborns with perinatal pathology receiving treatment in the Intensive Care Unit are under conditions of a complex influence of potentially nephrotoxic factors (hypoxia, reoxygenation - reperfusion, infection, artificial lung ventilation, infusion, inotropic, transfusion and antibacterial therapy). Severity of general condition, morpho - functional immaturity of the organism, multiple organ failure due to underlying perinatal pathology “obscure” renal symptoms and complicate the diagnostics of renal function disorders. The biochemical changes found in critically ill newborns require timely diagnostics to correct therapeutic measures on the stage of intensive therapy with the aim to prevent the development of severe renal pathology and chronic renal failure in future.

Histopathological analysis of the olfactory epithelium of zebrafish (Danio rerio) exposed to sublethal doses of urea.

Chronic renal disease is known to alter olfactory function, but the specific changes induced in olfactory organs during this process remain unclear. Of the uraemic toxins generated during renal disease, high levels of urea are known to induce hyposmic conditions. In this study, the effects of environmental exposure to elevated concentrations of urea (7, 13.5 and 20 g L(-1)) on the sensory mucosa of zebrafish in acute toxicity and chronic toxicity tests were described. It was observed that lamellae maintained structural integrity and epithelial thickness was slightly reduced, but only following exposure to the highest concentrations of urea. Pan-neuronal labelling with anti-Hu revealed a negative correlation with levels of urea, leading to investigation of whether distinct neuronal subtypes were equally sensitive. Using densitometric analysis of immunolabelled tissues, numbers of Gα olf-, TRPC2- and TrkA-expressing cells were compared, representing ciliated, microvillous and crypt neurons, respectively. The three neuronal subpopulations responded differently to increasing levels of urea. In particular, crypt cells were more severely affected than the other cell types, and Gα olf-immunoreactivity was found to increase when fish were exposed to low doses of urea. It can be concluded that exposure to moderate levels of urea leads to sensory toxicity directly affecting olfactory organs, in accordance with the functional olfactometric measurements previously reported in the literature.

Uremic frost: a harbinger of impending renal failure.

Uremic frost is a striking cutaneous finding seen in patients with severe kidney disease. Familiarity with this condition can be a life-saving signal to initiate urgent dialysis. Uremic frost generally occurs at blood urea nitrogen levels of approximately 200 mg/dl, although it may arise with less severe uremia. Recently confirmed urea transporters in the skin may play a role in the development of uremic frost. Alternatively, damage to the cutaneous microvasculature and pilosebaceous units, as seen in chronic kidney disease, could account for the high levels of urea deposited outside the skin. The treatment of uremic frost is largely aimed at correcting the underlying cause of uremia and the other life-threatening conditions associated with renal failure.

Leukotriene C4 increases the susceptibility of adult mice to Shiga toxin-producing Escherichia coli infection

Shiga toxin-producing Escherichia coli (STEC) is a food-borne pathogen that causes hemorrhagic colitis. Under some circumstances, Shiga toxin (Stx) produced within the intestinal tract enters the bloodstream, leading to systemic complications that may cause the potentially fatal hemolytic-uremic syndrome (HUS). Despite STEC human infection is characterized by acute inflammation of the colonic mucosa, little is known regarding the role of proinflammatory mediators like cysteine leukotrienes (cysLTs) in this pathology. Thus, the aim of this work was to analyze whether leukotriene C4 (LTC4) influences STEC pathogenesis in mice. We report that exogenous LTC4 pretreatment severely affected the outcome of STEC gastrointestinal infection. LTC4-pretreated (LTC4+) and STEC-infected (STEC+) mice showed an increased intestinal damage by histological studies, and a decreased survival compared to LTC4-non-pretreated (LTC4−) and STEC+ mice. LTC4+/STEC+ mice that died after the infection displayed neutrophilia and high urea levels, indicating that the cause of death was related to Stx2-toxicity. Despite the differences observed in the survival between LTC4+ and LTC4− mice after STEC infection, both groups showed the same survival after Stx2-intravenous inoculation. In addition, LTC4 pretreatment increased the permeability of mucosal intestinal barrier, as assessed by FITC-dextran absorption experiments. Altogether these results suggest that LTC4 detrimental effect on STEC infection is related to the increased passage of pathogenic factors to the bloodstream.Finally, we showed that STEC infection per se increases the endogenous LTC4 levels in the gut, suggesting that this inflammatory mediator plays a role in the pathogenicity of STEC infection in mice, mainly by disrupting the mucosal epithelial barrier.

Metabolomics and microbiological profile of Italian mozzarella cheese produced with buffalo and cow milk

Italian buffalo mozzarella (BM) cheese metabolite profile and microbial communities were characterised and compared to cow mozzarella (CM). Polar metabolite profiles were studied by gas-chromatography mass-spectrometry (GC–MS) and results elaborated by multivariate analysis (MVA). BM produced using natural whey starter cultures (NWS) exhibited a higher microbial diversity with less psychrotrophic bacteria. BM samples were higher in threonine, serine, valine, and lower in orotic acid and urea. CM produced with commercial starters (CMS) had the highest count of Streptococcus thermophilus and higher levels of galactose and phenylalanine. CM obtained by direct acidification (CMA) had lower microbial counts and higher levels of urea and sugars. Orotic acid was the only metabolite linked to milk animal origin. Results indicated that this metabolite pool well reflects the different production protocols and microbial complexity of these dairy products. This approach can help to protect the designation of origin of Italian buffalo mozzarella.

Serum Kreatinin Seviyelerinin Perkütan Nefrolitotripside Kanama Üzerine Etkisi

Purpose: Percutaneous Nephrolithotomy (PNL), has been a breakthrough in urology practice; it can be performed in various centers, with high success rates and low morbidity and mortality rates. In this study, we aimed to investigate the effect of plasma creatinine levels upon the hemorrhage on PNL procedures. Material and Methods: Patients underwent PNL were categorized as having high plasma urea and creatinine levels. Patient age, stone size, gender, hematocrit levels and additional co-morbidities were recorded and a matching group was designed using same variables. Group 1 consisted of patients with high creatinine levels and Group 2 consisted of normal creatinine levels. Body mass index, stone size, hematocrit levels, plasma creatinine levels before and after the operation, coagulation parameter (aPTT, INR), number of access tracts, operative time, preoperative platelet number, stone free rates and transfusion rates were recorded and compared. Results: Mean plasma creatinine levels were 2,11 ± 0,44 and 0,98 ± 0,27 for Groups 1 and 2, respectively. For Groups 1 and 2, stone sizes were 29,41 ± 3,83 mm, and 29,49 ± 2,99 (p=0,317). Mean peroperative hematocrit levels were 44,88 ± 5,61 and 47,51 ± 4,61 (p=0,381) for Groups 1 and 2, respectively. Those levels were 30,27 ± 7,01 and 37,74 ± 7,11 (p=0,044) for Groups 1 and 2 post operatively. Conclusion: In conclusion, having high levels of plasma creatinine preoperatively for PNL was seen to be a risk factor for hemorrhage. If a patient has high creatinine levels preoperatively, he/she may be more prone to bleeding after PNL

Alternatively activated macrophages attenuate influenza-induced acute lung injury in mice heterozygous for the F508del mutation in CFTR. (INC6P.314)

Abstract Infection with influenza A virus can result in acute lung injury (ALI), characterized by pulmonary edema and hypoxemia. We found that influenza-induced ALI in C57BL/6 (WT) mice was associated with increased bronchoalveolar epithelial cell Cl- secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Influenza-induced ALI was highly attenuated in C57BL/6-congenic mice that are heterozygous for the F508del CFTR mutation (HETs), which exhibit a 50% reduction in CFTR expression and CFTR-mediated Cl- transport. This beneficial phenotype was alveolar macrophage (AM)-dependent and was not due to differences in viral replication between mouse strains. The aim of this study was to evaluate the role of HET AMs in the attenuation of influenza-induced ALI. We hypothesized that ALI attenuation in influenza-infected HET mice results from “alternative” activation (M2 polarization) of HET AMs in response to infection. Compared to WT AMs, Arginase 1 (Arg1) protein expression was higher while inducible nitric oxide synthase (iNOS) protein was lower in HET AMs following infection. Arg1 enzymatic activity was also higher in HET AM lysates. BALF from HET mice contained higher levels of urea and lower levels of nitrate/nitrite (end-products of Arg1 and iNOS, respectively) than WT. These findings indicate that reduced CFTR expression/activity promotes an anti-inflammatory, M2 AM polarization response to influenza infection, which contributes to ALI attenuation.