Simple enzyme based fluorimetric biosensor for urea in human biofluids.

As an important biomarker for renal related diseases, detection of urea is playing a vital role in human biofluids on clinical diagnosis concern. In this work, a synthetic salicyaldehyde based imine fluorophore was synthesized using sonication method and conjugated with urease which was used as fluorescent biosensor for the detection of urea in serum samples. This enzyme based biosensor has shown a good selectivity and sensitivity towards urea with the linear range from 2 to 80 mM and the detection limit of 73 µM. The sensing response obtain is highly agreeing with existing analytical technique for urea detection which strongly recommends this biosensor for clinical application.

A study of size-selective renal elimination using a novel human model.

The recently discovered selective glomerular hypofiltration syndromes have increased interest in the actual elimination of molecules in the human kidney. In the present study, a novel human model was introduced to directly measure the single-pass renal elimination of molecules of increasing size. Plasma concentrations of urea, creatinine, C-peptide, insulin, pro-BNP, ß2-microglobulin, cystatin C, troponin-T, orosomucoid, albumin, and IgG were analysed in arterial and renal venous blood from 45 patients undergoing Transcatheter Aortic Valve Implantation (TAVI). The renal elimination ratio (RER) was calculated as the arteriovenous concentration difference divided by the arterial concentration. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI equations for both creatinine and cystatin C. Creatinine (0.11 kDa) showed the highest RER (21.0 ± 6.3%). With increasing molecular size, the RER gradually decreased, where the RER of cystatin C (13 kDa) was 14.4 ± 5.3% and troponin-T (36 kDa) was 11.3 ± 4.6%. The renal elimination threshold was found between 36 and 44 kDa as the RER of orosomucoid (44 kDa) was -0.2 ± 4.7%. The RER of creatinine and cystatin C showed a significant and moderate positive linear relationship with eGFR (r = 0.48 and 0.40). In conclusion, a novel human model was employed to demonstrate a decline in renal elimination with increasing molecular size. Moreover, RERs of creatinine and cystatin C were found to correlate with eGFR, suggesting the potential of this model to study selective glomerular hypofiltration syndromes.

Hepatogenic photosensitization in lambs supplemented with different levels of extruded urea in Brachiaria spp. pastures in the Brazilian Cerrado: Case report.

The aim was to report cases and risk factors for hepatogenous photosensitization in lambs kept on Brachiaria spp. pastures and supplemented with levels of extruded urea (EU). The herd consisted of 69 Texel crossbred lambs with known parentage (fathers and mothers adapted to the consumption of forage of the genus Brachiaria), randomly divided into 5 groups and distributed in individual paddocks for each group. The animals were supplemented with increasing levels of EU (Amireia® 200S): 0, 6, 12, 18, and 24 g of EU per 100 kg-1 of body weight (BW). The concentration of protodioscin was estimated in the mixed pastures of Brachiaria spp. (cv. Marandu and cv. Basilisk), structural components (leaf, stem, and dead material), samples of each cultivar, and in the months of December (2018), February, and April (2019). The animals were examined daily, and when behavioral changes were identified, they underwent clinical examinations and anamnesis. Weighing was performed every 14 days, followed by necropsy and serum biochemical analysis, including gamma-glutamyltransferase (GGT). The highest concentrations of protodioscin (p < 0.0001) were found in the pastures used by animals supplemented without extruded urea (7.07 ± 0.56), in the Basilisk cultivar (11.35 ± 0.06), in the leaf blade components (2.08 ± 0.05), and thatch (2.20 ± 0.00), and in the month of April (7.34 ± 0.29) (the month with the lowest rainfall), respectively. Fourteen (20.29%) cases of photosensitization were observed in lambs, of which six recovered, and eight died. Serum GGT levels ranged from 42.2 to 225 IU/L; however, in animals that died, values ranged from 209.4 to 225 IU/L. The use of levels 12 g and 18 g per 100 kg-1 of body weight of extruded urea may contribute to the lower occurrence of photosensitization, as the animals selected pastures with lower protodioscin content, presenting a smaller number of cases.

The correlation of urea and creatinine concentrations in sweat and saliva with plasma during hemodialysis: an observational cohort study.

OBJECTIVES: Urea and creatinine concentrations in plasma are used to guide hemodialysis (HD) in patients with end-stage renal disease (ESRD). To support individualized HD treatment in a home situation, there is a clinical need for a non-invasive and continuous alternative to plasma for biomarker monitoring during and between cycles of HD. In this observational study, we therefore established the correlation of urea and creatinine concentrations between sweat, saliva and plasma in a cohort of ESRD patients on HD. METHODS: Forty HD patients were recruited at the Dialysis Department of the Catharina Hospital Eindhoven. Sweat and salivary urea and creatinine concentrations were analyzed at the start and at the end of one HD cycle and compared to the corresponding plasma concentrations. RESULTS: A decrease of urea concentrations during HD was observed in sweat, from 27.86 mmol/L to 12.60 mmol/L, and saliva, from 24.70 mmol/L to 5.64 mmol/L. Urea concentrations in sweat and saliva strongly correlated with the concentrations in plasma (ρ 0.92 [p<0.001] and 0.94 [p<0.001], respectively). Creatinine concentrations also decreased in sweat from 43.39 µmol/L to 19.69 µmol/L, and saliva, from 59.00 µmol/L to 13.70 µmol/L. However, for creatinine, correlation coefficients were lower than for urea for both sweat and saliva compared to plasma (ρ: 0.58 [p<0.001] and 0.77 [p<0.001], respectively). CONCLUSIONS: The results illustrate a proof of principle of urea measurements in sweat and saliva to monitor HD adequacy in a non-invasive and continuous manner. Biosensors enabling urea monitoring in sweat or saliva could fill in a clinical need to enable at-home HD for more patients and thereby decrease patient burden.

Potential nephroprotective effects of angiotensin II type 2 receptor agonist Compound 21 in renal ischemia-reperfusion injury.

This study examined the reno-protective potential of Compound 21 during renal ischemia-reperfusion injury by regulating the PI3K expression. 20 adult male Swiss-albino mice, aged 8-12 weeks and weighing 20-30g, were randomly assigned to four equal groups: sham, control, vehicle, and Compound 21. Serum urea, creatinine, inflammatory mediators, tissue 8-isoprostane, and myeloperoxidase were quantified using ELISA. Compared to the sham group, blood levels of urea, creatinine, TNF-α, IL-6, and IL-10 were significantly higher in the ischemia-reperfusion group than in the sham group (p<0.05). However, these indicators were significantly lower in the Compound 21 group (p<0.05). Histological analysis revealed significant renal tissue damage in the ischemia-reperfusion group (p<0.05), which was significantly reduced in the Compound 21 group (p<0.05). PCR results showed that PI3K expression was significantly lower (p<0.05) in the control group compared to the sham group but significantly higher in the Compound 21 group (p<0.05). Furthermore, P-AKT expression levels in the control group were considerably lower than in the sham group (p<0.05). On the other hand, the level of P-AKT expression in the Compound 21 group was significantly upregulated compared to the control group (p<0.05). The findings revealed that Compound 21 could mitigate renal dysfunction induced by ischemia-reperfusion injury in male mice through modulation of the PI3K/AKT signaling pathway, resulting in decreased levels of pro-inflammatory cytokines and renal oxidative stress markers.

Higher urea-to-albumin ratio is associated with mortality risk in critically ill COVID-19 patients.

BACKGROUND: This study aimed to evaluate the ability of the urea-to-albumin ratio (UAR) to predict mortality in critically ill coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study included adult patients admitted with COVID-19 at two intensive care units (ICUs) at the University Hospital. Serum urea and albumin concentrations at ICU admission were used to calculate the UAR. All patients were followed up during hospitalization, and the ICU mortality rate was recorded. RESULTS: Two hundred and eleven patients were evaluated. The mean age was 57.8 ± 15.5 years, and 54% were male. Approximately 84.4% of patients were considered to be at nutritional risk by the NRS 2002, and the median UAR was 18.3 (10.5-34.8). The length of stay in the ICU was 10 (6-16) days, 38.4% of the patients required dialysis, and 64.9% died. Age, male sex, need of hemodialysis, lactate level, and inflammatory parameters were associated with higher mortality. Patients non-survivors had a higher UAR (23.7 [13.6-41.8] vs. 10.9 [8.5-16.8]; p < 0.001). The cutoff point with the best performance of UAR in the ROC curve for predicting mortality was ≥12.17 (AUC: 0.7201; CI 95%: 0.656-0.784). Additionally, the risk of mortality was 2.00-fold in the group of patients with UAR ≥12.17 (HR: 2.00 CI: 1.274-3.149; p = 0.003) and remained significant after adjusted analyzes (models 1 and 2). CONCLUSION: Our data suggest that a UAR ≥12.17 increased the risk of mortality by 2.00-fold in critically ill COVID-19 patients.

Association of the Urine-to-Plasma Urea Ratio With CKD Progression.

RATIONALE & OBJECTIVES: The urine-to-plasma (U/P) ratio of urea is correlated with urine-concentrating capacity and associated with progression of autosomal dominant polycystic kidney disease. As a proposed biomarker of tubular function, we hypothesized that the U/P urea ratio would also be associated with progression of more common forms of chronic kidney disease (CKD). STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 3,723 adults in the United States with estimated glomerular filtration rate (eGFR) of 20-70 mL/min/1.73 m2, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURE: U/P urea ratio, calculated from 24-hour urine collections and plasma samples at baseline. OUTCOME: Associations of U/P urea ratio with eGFR slope, initiation of kidney replacement therapy (KRT), and CKD progression, defined as 50% decline in eGFR or incident KRT. ANALYTICAL APPROACH: Multivariable linear mixed-effects models tested associations with eGFR slope. Cox proportional hazards models tested associations with dichotomous CKD outcomes. RESULTS: The median U/P urea ratio was 14.8 (IQR, 9.5-22.2). Compared with participants in the highest U/P urea ratio quintile, those in the lowest quintile had a greater eGFR decline by 1.06 mL/min/1.73 m2 per year (P < 0.001) over 7.0 (IQR, 3.0-11.0) years of follow-up observation. Each 1-SD lower natural log-transformed U/P urea ratio was independently associated with CKD progression (HR, 1.22 [95% CI, 1.12-1.33]) and incident KRT (HR, 1.22 [95% CI, 1.10-1.33]). Associations differed by baseline eGFR (P interaction = 0.009). Among those with an eGFR ≥30 mL/min/1.73 m2, each 1-SD lower in ln(U/P urea ratio) was independently associated with CKD progression (HR, 1.30 [95% CI, 1.18-1.45]), but this was not significant among those with eGFR <30 mL/min/1.73 m2 (HR, 1.00 [95% CI, 0.84-1.20]). LIMITATIONS: Possibility of residual confounding. Single baseline 24-hour urine collection for U/P urea ratio. CONCLUSIONS: In a large and diverse cohort of patients with common forms of CKD, U/P urea was independently associated with disease progression and incident kidney failure. Associations were not significant among those with advanced CKD at baseline.

Utilidad de la fórmula HUGE para el diagnóstico de enfermedad renal crónica en el anciano / Usefulness of the HUGE formula for the diagnosis of chronic kidney disease in the elderly

INTRODUCCIÓN: La enfermedad renal crónica se encuentra en ascenso.Prevenir o retardar su progresión mediante la aplicación de estrategias dirigidas al diagnóstico precoz es esencial. OBJETIVO: Evaluar la utilidad de la fórmula HUGE para el diagnóstico de Enfermedad Renal Crónica en el anciano. MATERIAL Y MÉTODO: Se realizó un estudio observacional descriptivo prospectivo y de corte longitudinal en 260 adultos mayores que ingresaron en los servicios de Geriatría y Medicina Interna del Hospital Clínico Quirúrgico "Hermanos Ameijeiras" en el período enero de 2019 y junio de 2020. RESULTADOS: El 58,5% de la muestra de estudio fueron mujeres. La edad promedio fue de 77,1 ± 7,3 años. La enfermedad renal crónica estuvo presente en el 64,2% de los pacientes. Se observó mayor frecuencia de pacientes con daño renal (32,7%) al emplear la formula CKD­ EPI en comparación con los identificados al emplear la fórmula HUGE (25,0%). Al estimar la concordancia entre ambas fórmulas se observó un estadístico kappa (k) de 0,814 (IC de 95%:0,7370 - 0,8909; p < 0,001). La sensibilidad de la fórmula de HUGE fue de un 76,5% (IC de 95%: 66,9% - 86,1%) y la especificidad de un 100% (99,7% - 100%). El valor predictivo positivo fue de 100 % (IC de 95%: 99,2% - 100%) y el negativo de 89,7% (85,2% - 94,2%). CONCLUSIONES: La fórmula CKD-EPI identifica daño renal en mayor porcentaje, en estadios precoces. Por el contrario, la fórmula de HUGE, detecta el daño renal en un porcentaje mayor en estadios más avanzados.La concordancia para diagnosticar daño renal entre la fórmula CKD-EPI y HUGE fue muy buena. La fórmula HUGE es útil, sensible y específica para evaluar la enfermedad renal crónica en los adultos mayores.

INTRODUCTION: Chronic kidney disease is on the rise. Preventing or delaying its progression through the application of strategies aimed at early diagnosis is essential. OBJECTIVE: To evaluate the usefulness of the HUGE formula for the diagnosis of Chronic Kidney Disease in the elderly. MATERIAL AND METHOD: A prospective, descriptive and longitudinal observational study was carried out in 260 older adults who were admitted to the Geriatrics and Internal Medicine services of the "Hermanos Ameijeiras" Surgical Clinical Hospital between January 2019 and June 2020. RESULTS: 58.5% of the study sample was women. The mean age was 77.1 ± 7.3 years. CKD was present in 64.2% of the patients. A higher frequency of patients with kidney damage (32.7%) was observed when using the CKD ­ EPI formula compared to those identified when using the HUGE (25.0%). When estimating the concordance between both formulas, a kappa statistic (k) of 0.814 (95% CI: 0.7370 - 0.8909; p < 0.001) was observed. The sensitivity of the HUGE formula was 76.5% (95% CI: 66.9% - 86.1%) and the specificity was 100% (99.7% - 100%). The positive predictive value was 100% (95% CI: 99.2% - 100%) and the negative predictive value was 89.7% (85.2% - 94.2%). CONCLUSIONS: The CKD-EPI formula identifies kidney damage in a higher percentage, in early stages. On the contrary, the HUGE formula detects kidney damage in a higher percentage in more advanced stages. The concordance to diagnose kidney damage between the CKD-EPI and HUGE formula was very good. The HUGE formula is useful, sensitive, and specific for evaluating chronic kidney disease in older adults.

TGF-ß1, NAG-1, and antioxidant enzymes expression alterations in Cisplatin-induced nephrotoxicity in a rat model: Comparative modulating role of Melatonin, Vit. E and Ozone.

Cisplatin (CP) is an anticancer medication that is commonly used to treat solid tumors. Its use is, however, dose-restricted due to nephrotoxicity. We planned to compare the nephroprotective effects of three major compounds, including melatonin (MN), Ozone, or vitamin E, against the CP-induced renal damage in rats. CP was given once intraperitoneally (10 mg/kg,) eliciting acute kidney injury as assured by several adverse histological changes; glomerulopathy, tubulopathy, and vasculopathy, an inflammatory response including elevated TNF-α, IL-6, and IL-1ß. Furthermore, biochemical alterations including, elevated plasma levels of urea, uric acid, creatinine, phosphorous, decreased plasma calcium levels, and gene expression abnormalities; upregulation of N-acetyl-ß-d-glucosaminidase (NAG) and Transforming growth factor-ß1 (TGF-ß1), downregulation of CAT and SOD. Concurrent supplementation with either MN (10 mg/kg per os) or Ozone (1.1 mg/kg ip) and Vit E given by oral gavage (1 g/kg) for five consecutive days prior to CP injection and five days afterward displayed variable significant nephroprotective effects by mitigating the pro-inflammatory secretion, augmenting antioxidant competence, and modulating the gene expression in the renal tissue. The obtained biochemical, histological, and gene expression data suggested that MN had foremost rescue effects followed by Ozone then Vit E. MN's ameliorative effect was augmented in many indices including TNF-α, IL-6 , IL1-ß, uric acid, creatinine, sNGAL and GGT, more than observed in Ozone, and Vit E therapy. A combination of these medications is expected to be more useful in relieving the damaging renal effects of CP given to cancer patients, pending further toxicological and pharmacological research.

Hypoxia preconditioning increases the ability of healthy but not diabetic rat-derived adipose stromal/stem cells (ASC) to improve histological lesions of streptozotocin-induced diabetic nephropathy.

BACKGROUND: Mesenchymal stromal cells (MSC) have demonstrated ability to improve diabetic nephropathy (DN) in experimental models, as well as by improving kidney endogenous progenitor cells proliferation and differentiation. Many studies have demonstrated the effect of hypoxia on MSC improving their functionality but the potential enhancement of the nephroprotective properties of MSC cultured under low oxygen concentration has been explored in few studies, none of them in the context of DN. On the other hand, diabetes is associated with abnormalities in MSCs functionality. These findings related to the hypoxia preconditioning ability to enhance adipose-tissue derived-MSC (ASC) performance have led us to wonder if hypoxia could increase the known beneficial effect of normal ASC in DN and if it could correct the expected inability of diabetic rat-derived ASC to exert this effect in vivo. To answer these questions, in the present study we have used ASC from healthy and diabetic-induced rats, cultured under standard conditions or hypoxia preconditioned, in a DN rat model induced by streptozotocin (STZ). METHODS: Diabetes was induced in Wistar-rats by 60 mg/kg streptozotocin (STZ) intraperitoneal injection. Fifteen days thereafter, five diabetic-induced rats and five healthy, previously injected with saline, were sacrificed and used as ASC donors . Both healthy and diabetic rat-derived ASC (cASC and dASC, respectively) were cultured under standard conditions (21%O2)(N) or were subjected to a 48 h conditioning period in hypoxia (3%O2)(H). Thus, four types of cells were generated depending on their origin (healthy or diabetic-induced rats) and the culture conditions(N or H):cASC-N, cASC-H, dASC-N and dASC-H. DN experimental study were carried out fifteen days after STZ induction of diabetes in fifty-two healthy rats. DN-induced-animals were randomly assigned to be injected with 200 µL saline as placebo or with 3 × 106 cASC-N, cASC-H, dASC-N or dASC-H, according to the study group. Serum glucose, urea and creatinine, and urine albumin levels were measured at 2-weeks intervals until day+ 45 after ND-induction.Animals were sacrificed and kidneys extracted for histopathological and transmission electron microcopy analysis RESULTS: None of the four study groups that received cell treatment showed significant changes in serum glucose, urea and creatinine levels, urine albumin concentration and body weight compared to placebo ND-induced group. Interestingly, only the group that received cASC-H showed a reduction in glucose and creatinine levels although it did not reach statistical significance.All DN-induced groups treated with ASC reduced significantly renal lesions such as mesangial expansion, mesangiolysis, microaneurysms and acute tubular necrosis compared to ND-induced placebo group (p ≤ 0.05). Renal injuries such as clear tubular cell changes, thickening of tubular basement membrane, tubular cysts and interstitial fibrosis significantly showed reduction in ND-induced rats treated with cASC-H regarding to their received cASCN (p ≤ 0.05). Non statistical differences were observed in the improvement capacity of cASC and dASC culture under standard condition.However, hypoxia preconditioning reduces the presence of tubular cysts (p ≤ 0.01). CONCLUSIONS: Hypoxia preconditioning enhances the ability of healthy rat-derived ASC to improve kidney injury in a rat model of DN. Moreover, diabetic-derived ASC exhibits a similar ability to healthy ASC which is clearly more than expected, but it is not significantly modified by hypoxia preconditioning.

Nitrogen recycling via gut symbionts increases in ground squirrels over the hibernation season.

Hibernation is a mammalian strategy that uses metabolic plasticity to reduce energy demands and enable long-term fasting. Fasting mitigates winter food scarcity but eliminates dietary nitrogen, jeopardizing body protein balance. Here, we reveal gut microbiome-mediated urea nitrogen recycling in hibernating thirteen-lined ground squirrels (Ictidomys tridecemlineatus). Ureolytic gut microbes incorporate urea nitrogen into metabolites that are absorbed by the host, with the nitrogen reincorporated into the squirrel's protein pool. Urea nitrogen recycling is greatest after prolonged fasting in late winter, when urea transporter abundance in gut tissue and urease gene abundance in the microbiome are highest. These results reveal a functional role for the gut microbiome during hibernation and suggest mechanisms by which urea nitrogen recycling may contribute to protein balance in other monogastric animals.

Lithium toxicity at therapeutic doses as a fallout of COVID-19 infection: a case series and possible mechanisms.

Lithium, a mood stabilizer used in the treatment of bipolar disorder is known for its anti-inflammatory properties with the discussion of its potential use in COVID-19 infection. The SARS-CoV-2 virus causing COVID-19 infection is known to enter the target cells through angiotensin converting enzyme-2 receptors present in abundance in the lung and renal tissue. Recent research supports the evidence for direct renal injury by viral proteins. Here we report two patients with bipolar disorder presenting with lithium toxicity in the presence of COVID-19 infection. Two patients with bipolar disorder, maintaining remission on lithium prophylaxis, presented to the psychiatric emergency with recent-onset fever and altered sensorium. Both the patient's investigations revealed lithium toxicity, elevated serum creatinine, urea and inflammatory markers. Hypernatremia, hyperkalaemia, and hyperchloremia were seen in one patient. Lithium and other psychotropic medications were stopped immediately, and COVID-19 treatment was initiated. Patient with clinical signs of lithium toxicity, hypernatremia, hyperkalaemia, and hyperchloremia developed ventricular tachycardia. He survived and regained consciousness after 2 weeks of aggressive conservative management. However, another patient died of acute respiratory failure on day 3. Possible direct infection of the kidney by SARS-CoV-2 viral proteins can manifest with acute kidney injury and lithium toxicity among patients on long-term lithium therapy. Health professionals treating COVID-19 infection among individuals on lithium therapy should be aware of the possibility of lithium toxicity in the background of renal injury.

Serum catestatin level is increased in women with preeclampsia.

Catestatin can inhibit catecholamine release from chromaffin cells and adrenergic neurons. Catestatin can also have a strong vasodilator effect. This may be useful in understanding the pathophysiology of preeclampsia and its treatment. In this study, we investigated the serum catestatin levels in pregnant women with and without preeclampsia. Fifty consecutive women with mild preeclampsia, 50 consecutive women with severe preeclampsia, and 100 consecutive pregnant women with a gestational age-matched (±1 week) uncomplicated pregnancy were evaluated in a cross-sectional study. Mean serum catestatin was significantly increased in the preeclampsia group compared to the control group (290.7 ± 95.5 pg/mL vs. 182.8 ± 72.0 pg/mL). Mean serum catestatin was comparable in mild and severe preeclampsia groups (282.7 ± 97.9 pg/mL vs. 298.7 ± 93.4 pg/mL, p = .431). Serum catestatin levels had positive correlations with systolic and diastolic blood pressure, urea, uric acid, and creatinine. In conclusion, serum catestatin levels are increased in preeclamptic pregnancies compared to gestational age-matched controls.IMPACT STATEMENTWhat is already known on this subject? The role of autonomic nervous system dysregulation in the pathophysiology of preeclampsia is known. The most obvious part of this dysregulation is the sympathetic nervous system activation. The adrenal medulla is one of the locations of the sympathetic nervous system in the body.What do the results of this study add? Serum catestatin levels were found to be correlated with clinical and laboratory data of preeclampsia. This highlights the importance of chromaffin cell secretions in the adrenal medulla in preeclampsia.What are the implications of these findings for clinical practice and/or further research? This study will help understand the role of the adrenal medulla in the autonomic nervous system dysregulation in preeclampsia. Also, control of serum catestatin levels may support the treatment of hypertension in preeclampsia.

Neurological and psychiatric presentations associated with COVID-19.

The objective is to investigate coronavirus disease 2019 (COVID-19)-associated neurological and psychiatric effects and explore possible pathogenic mechanisms. This study included 77 patients with laboratory-confirmed COVID-19 in Wuhan, China. Neurological manifestations were evaluated by well-trained neurologists, psychologists, psychiatric presentations and biochemical changes were evaluated using the Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire-9, Brief Psychiatric Rating Scale, and electronic medical records. Eighteen (23.4%) patients presented with neurological symptoms. Patients with neurological presentations had higher urea nitrogen, cystatin C, and high-sensitivity C-reactive protein levels and lower basophil counts. Among them, patients with muscle involvement had higher urea nitrogen and cystatin C levels but lower basophil counts. In addition, patients with psychiatric presentations were older and had higher interleukin (IL)-6 and IL-10 levels and higher alkaline phosphatase, R-glutamate transferase, and urea nitrogen levels. Moreover, patients with anxiety had higher IL-6 and IL-10 levels than those without, and patients with moderate depression had higher CD8 + T cell counts and lower CD4 + /CD8 + ratios than other patients. This study indicates that the central nervous system may be influenced in patients with COVID-19, and the pathological mechanisms may be related to direct virus invasion of the central nervous system, infection-mediated overreaction of the immune system, and aberrant serum pro-inflammatory factors. In addition, basophils and cystatin C may also play important roles during these pathological processes. Our findings suggest that neurological and psychiatric presentations should be evaluated and managed in patients with COVID-19. Further studies are needed to investigate the underlying mechanisms.

Verificación y transferencia de intervalos de referencia de variables bioquímicas de rutina / Verification and transfer of reference intervals of routine biochemical variables

Introducción. El correcto análisis en la interpretación de los resultados de cualquier analito biológico es esencial para la salud del paciente y está fuertemente ligado a contrastar dichos resultados con los intervalos biológicos referenciales que estén acorde a la población que está siendo analizada diariamente. El objetivo de este artículo, fue establecer intervalos referenciales (IR) en adultos para glicemia, urea, creatinina, ácido úrico, colesterol total y triglicéridos en un laboratorio clínico y comparar los valores obtenidos con los incluidos en los insertos para ese rango de edad. Metodología. La población fue de 561 adultos de ambos sexos, aparentemente sanos, que acudieron a Biomasterclin Laboratorio en Valencia, Venezuela, y cuyas edades fueron de 57,1±18,1 años. Resultados. Los IR obtenidos fueron glicemia 63,0-108,8 mg/dL, urea 17,7-54,9 mg/dL, creatinina 0,60-1,41 mg/dL, ácido úrico 0,89-7,26 mg/dL, colesterol total 78,5-251,1 mg/dL y triglicéridos 39,5-176,0 mg/dL. Los IR propuestos por la casa comercial empleada para la determinación de la glicemia y la creatinina pudieron ser transferidos a la población evaluada, mientras que el resto de los IR no. Conclusión. Debido a las diferencias que se presentan entre los IR en los estuches comerciales comparados con los de la población de individuos que acuden a los laboratorios clínicos, se hace necesario establecer IR para ser empleados en cada laboratorio clínico

The correct analysis in the interpretation of the results of any biological analyte is essential for the health of the patient and it is strongly linked to comparing those results with reference ranges that are in accordance with the population that is being analyzed on a daily basis. The objective of this study was to establish reference ranges in adults for glycemia, urea, creatinine, uric acid, total cholesterol and triglycerides in a clinical laboratory and compare the values obtained with those included in the inserts for the corresponding age group. Methodology. The population consisted of 561 apparently healthy adults of both sexes that attended Biomasterclin Laboratorio in Valencia, Venezuela, whose ages were 57.1±18.1 years. Results. The reference ranges obtained for glycemia were 63.0- 108.8 mg/dL, urea 17.7-54.9 mg/dL, creatinine 0.60-1.41 mg/dL, uric acid 0.89- 726 mg/dL, total cholesterol 78.5-251.1 mg/dL and triglycerides 39.5-176.0 mg/ dL. The reference ranges proposed by the commercial kits used for the determination of glycemia and creatinine could be transferred to the evaluated population, while the rest of the reference ranges could not. Conclusion. Due to the differences that occur between the reference ranges in commercial kits compared to those of the population of individuals who attend clinical laboratories, it is necessary to establish reference values in each clinical laboratory

Treadmill Exercise Training Ameliorates Functional and Structural Age-Associated Kidney Changes in Male Albino Rats.

Aging is a biological process that impacts multiple organs. Unfortunately, kidney aging affects the quality of life with high mortality rate. So, searching for innovative nonpharmacological modality improving age-associated kidney deterioration is important. This study aimed to throw more light on the beneficial effect of treadmill exercise on the aged kidney. Thirty male albino rats were divided into three groups: young (3-4 months old), sedentary aged (23-24 months old), and exercised aged (23-24 months old, practiced moderate-intensity treadmill exercise 5 days/week for 8 weeks). The results showed marked structural alterations in the aged kidney with concomitant impairment of kidney functions and increase in arterial blood pressure with no significant difference in kidney weight. Also, it revealed that treadmill exercise alleviated theses effects in exercised aged group with reduction of urea and cystatin C. Exercise training significantly decreased glomerulosclerosis index, tubular injury score, and % area of collagen deposition. Treadmill exercise exerted its beneficial role via a significant reduction of C-reactive protein and malondialdehyde and increase in total antioxidant capacity. In addition, exercise training significantly decreased desmin immunoreaction and increased aquaporin-3, vascular endothelial growth factor, and beclin-1 in the aged kidney. This study clarified that treadmill exercise exerted its effects via antioxidant and anti-inflammatory mechanisms, podocyte protection, improving aquaporin-3 and vascular endothelial growth factor expression, and inducing autophagy in the aged kidney. This work provided a new insight into the promising role of aerobic exercise to ameliorate age-associated kidney damage.

The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique.

BACKGROUND: A new UPLC-MS/MS technique for the determination of ripretinib in beagle dog plasma was developed, and the pharmacokinetic effects of voriconazole and itraconazole on ripretinib in beagle dogs were studied. METHODS: After extraction with ethyl acetate under alkaline conditions, ripretinib was detected using avapritinib as the internal standard (IS). The mobile phases were 0.1% formic acid-acetonitrile. The scanning method was multi-reaction monitoring using ESI+ source, and the ion pairs for ripretinib and IS were m/z 509.93→416.85 and 499.1→482.09, respectively. This animal experiment adopted a three period self-control experimental design. In the first period, ripretinib was orally administered to six beagle dogs at a dose of 5 mg/kg. In the second period, the same six beagle dogs were orally given itraconazole at a dose of 7 mg/kg, after 30 min, ripretinib was orally given. In the third period, voriconazole at a dose of 7 mg/kg was given orally, and then ripretinib was orally given. At different time points, the blood samples were collected. The concentration of ripretinib was detected, and the pharmacokinetic parameters of ripretinib were calculated. RESULTS: Ripretinib had a good linear relationship in the range of 1-1000 ng/mL. The precision, accuracy, recovery, matrix effect and stability met the requirements of the guiding principles. After erdafitinib combined with itraconazole, the Cmax and AUC0→t of ripretinib increased by 38.35% and 36.36%, respectively, and the t1/2 was prolonged to 7.53 h. After ripretinib combined with voriconazole, the Cmax and AUC0→t of ripretinib increased by 37.44% and 25.52%, respectively, and the t1/2 was prolonged to 7.33 h. CONCLUSION: A new and reliable UPLC-MS/MS technique was fully optimized and developed to detect the concentration of ripretinib in beagle dog plasma. Itraconazole and voriconazole could inhibit the metabolism of ripretinib in beagle dogs and increase the plasma exposure of ripretinib.

Evaluation of risk factors associated with first episode febrile seizure.

OBJECTIVE: Febrile convulsion (FC) is one of the most common neurological findings in children. This study was aimed to investigate the difference in laboratory parameters between Febrile Seizure and control groups. PATIENTS AND METHODS: In this study, 169 children admitted to the pediatric emergency department with their first episode of FS and 189 control groups were retrospectively analyzed. The demographic characteristics and laboratory parameters of children were obtained from their files. RESULTS: Upper respiratory tract infection (URTI) was determined the most common disease (81.6%) in the FC group followed by acute gastroenteritis (AGE) (15.4%) and urinary tract infection (UTI) (3%), respectively. Similarly, URTI was detected as the most common disease (81.8%) in control groups. It was determined that there was no statistically significant difference between the two groups in terms of diseases. The leukocyte and neutrophil counts of the children with FC were significantly higher but the mean corpuscular volume of lenfosit and lenfosit/neutrophil ratio was significantly lower than the control groups (p= 0.009, <0.001, 0.001, <0.001, <0.001, respectively). Children with FC had significantly higher blood glucose, urea, creatinine, creatine kinase, alkaline phosphatase and albumin levels compared with the control groups (p<0.001, in all parameters). On the other hand, the potassium, sodium and chlorine levels of the Children with FCs were significantly lower than control groups (p=0.017, <0.001, p <0.001, respectively). CONCLUSIONS: To conclude, febrile patients with high leukocyte counts, high neutrophil counts, and several biochemical parameters should be carefully monitored for FCs due to the increasing seizure risk.

Determination of risk factors for fever after transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma.

ABSTRACT: This study was to identify risk factors affecting postembolization fever (PEF) of CalliSpheres drug-eluting bead transarterial chemoembolization (DEB-TACE) in the treatment of primary hepatocellular carcinoma (HCC).One hundred eighty-eight consecutive patients with HCC who underwent DEB-TACE with fever between June 2017 and May 2019 were included in this retrospective study. The patients were divided into 4 groups based on the severity of posttransarterial chemoembolization (TACE) fever according to the degrees of body temperature. Univariate analysis and multivariate logistics regression were performed to identify potential risk factors for post-TACE fever.In the stepwise multiple regression analysis, pre-TACE blood urea, small particle size and Cental liqefction (P < .05) were independent risk factors of severe post-TACE fever (P < .05, respectively). Portal vein thrombosis (P < .01), Child-Pugh stage (P < .01), and cycles of DEB-TACE (P < .05) were independent risk factors for clinical death, PEF was not associated with clinical death (P = .754) and 6-month survival (P = .524) in the univariate analysis. Moreover, multivariate Cox regression was performed, and Child-Pugh stage (B vs A) (P = .040) and portal vein thrombosis (yes vs no) (P = .033) were independent factors predicting unfavorable overall survival in HCC patients.Pre-TACE blood urea, small particle size, and Cental liqefction were significantly correlated with the occurrence fever after DEB-TACE. Therefore, these factors should be taken into full consideration for the relief of fever. However, PEF after D-TACE was not associated with clinical death and 6-month survival rate.

Plasma concentrations of branched-chain amino acids differ with Holstein genetic strain in pasture-based dairy systems.

In pasture-based systems, there are nutritional and climatic challenges exacerbated across lactation; thus, dairy cows require an enhanced adaptive capacity compared with cows in confined systems. We aimed to evaluate the effect of lactation stage (21 vs. 180 days in milk, DIM) and Holstein genetic strain (North American Holstein, NAH, n = 8; New Zealand Holstein, NZH, n = 8) on metabolic adaptations of grazing dairy cows through plasma metabolomic profiling and its association with classical metabolites. Although 67 metabolites were affected (FDR < 0.05) by DIM, no metabolite was observed to differ between genetic strains while only alanine was affected (FDR = 0.02) by the interaction between genetic strain and DIM. However, complementary tools for time-series analysis (ASCA analysis, MEBA ranking) indicated that alanine and the branched-chain amino acids (BCAA) differed between genetic strains in a lactation-stage dependent manner. Indeed, NZH cows had lower (P-Tukey < 0.05) plasma concentrations of leucine, isoleucine and valine than NAH cows at 21 DIM, probably signaling for greater insulin sensitivity. Metabolic pathway analysis also revealed that, independently of genetic strains, AA metabolism might be structurally involved in homeorhetic changes as 40% (19/46) of metabolic pathways differentially expressed (FDR < 0.05) between 21 and 180 DIM belonged to AA metabolism.