Plasma Uric Acid Levels Research Articles

A Study of Uric Acid Level as a Marker of Severity in Malaria

Context: Malaria is an inflammatory condition triggered by the infection of parasite Plasmodium on erythrocytes. It is characterised by periodic fever with chills due to rupture of erythrocytes to release the progeny parasites. It is marked by release of variety of cytokines like IL-6, IL-12, IFN-Ɣ, TNF—α etc. Uric acid is one of the emerging inflammatory markers in malaria that demands attention. One of the proposed mechanisms is that there is accumulation of uric acid and its precursor, hypoxanthine in the infected erythrocytes. These are released into the blood on rupture of the schizont. 
 Aim: To find association of serum uric acid level with severity of malaria.Settings and Design: This was a hospital based longitudinal study conducted at a tertiary care centre in Kolkata, India.
 Materials and Methods: We measured the plasma levels of uric acid and various inflammatory markers {Ferritin, C-reactive protein(CRP), LDH, C3, C4} in eighty eight patients admitted with microscopically proven malaria (severe or non-severe type). The levels of uric acid were compared with the disease severity and the inflammatory markers stated above.
 Statistical Analysis used: The data was analyzed using MedCalc software and Microsoft Excel 2010 and further graphically plotted.
 Results: The serum uric acid levels were raised in 18.51% of patients with severe malaria compared to only 4.91% with non-severe variety (p= 0.04). The uric acid levels demonstrated a positive correlation with CRP (r=0.3334, p=0.0015); procalcitonin & ferritn (r=0.3701, p<0.0005). However, it was negatively correlated with C3 (r= -0.3780, p= 0.0003) and C4 (r=0.3180, p<0.005). A univariate regression analysis supported our results to establish the correlation. However, multiple logistic regression analysis demonstrated significant association between serum uric acid levels on day 1 and C3 decrement as a marker of disease severity.
 Conclusion: Thus, it can be concluded that there is a definite association between the severity of malaria and plasma uric acid levels. Although, this study does not establish the causation, it acts as a cornerstone for further research into this field.

Is there an association between inflammatory/anti-oxidant markers and the presence of psychotic symptoms or severity of illness in mood and psychotic disorders? A multi-centric study on a drug-free sample

The immune and antioxidant systems are intimately connected and their role in the etiology of major psychiatric disorders is currently under study. The aim of this study was to evaluate the potential associations between inflammatory/antioxidant peripheral markers and presence of psychotic symptoms or severity of illness in patients affected by major psychiatric disorders.One hundred and twenty-six drug-free patients were included. A blood sample was collected to measure total/B/T lymphocytes and plasma levels of albumin, total bilirubin, uric acid, C-reactive protein, and vitamins A and E. Severity of illness was assessed using psychometric scales. Groups of patients divided according to diagnosis were compared in terms of measured markers using multivariate analyses of variance (MANOVAs). Linear and logistic regression analyses were performed to investigate the potential association between markers and severity of illness or presence/absence of psychotic symptoms.Albumin plasma levels were higher in patients with substance-induced psychotic disorder (SIPD) than subjects affected by schizophrenia (F ​= ​4.923; p ​= ​0.003). Lower vitamin E (OR ​= ​0.81; p ​= ​0.014) and T lymphocyte (OR ​= ​0.99; p ​= ​0.048) plasma levels were predictive of lifetime psychotic symptoms. Lower vitamin A levels were associated with higher Montgomery-Åsberg Depression Rating Scale scores (β ​= ​-24.26; p ​= ​0.029), independent of diagnosis.Patients with SIPD may be less vulnerable to oxidative stress. The severity of depressive symptoms, inversely associated with vitamin A plasma levels, is likely to be modulated by the degree of inflammation. Patients presenting with lifetime psychotic symptoms may be more vulnerable to oxidative stress and may have a higher activation of humoral immunity.

Abstract 116: Clinical and biochemical predictors in early pregnancy for development of gestational diabetes mellitus

Background: Early prediction of GDM is vital. Current risk prediction models are based on maternal and clinical parameters, lacking a strong predictive value.Objective: To identify clinical and biochemical parameters in early pregnancy for prediction of GDM.Methods: In this prospective cohort study, we screened 581 consecutive healthy women with singleton pregnancy for GDM during their first antenatal visit. Fasting blood samples were collected and stored at -800C. Detailed history and clinical assessment were done for each patient and findings were noted in a pre-specified proforma. GDM was diagnosed as per IADPSG criteria at 24-28 weeks. During prospective follow up, 55 patients developed GDM. A total of 110 age and BMI matched controls were recruited for comparison. We measured OGTT, fasting insulin, HbA1c, hsCRP, uric acid and Lipid Profile. HOMA-IR, HOMA-β and QUICKI were used to estimate insulin sensitivity and β-cell function.Results: Significant higher proportion of subjects in GDM cohort had presence of Acanthosis nigricans, positive family history of T2DM in 1st degree relative. GDM cohort had significantly higher waist circumference, 2 hr plasma glucose, HbA1c, fasting insulin, HOMA-IR, uric acid and serum triglyceride levels. The area under the curve were as follows: HbA1c - 0.71 (95%CI: 0.628–0.793), Fasting Insulin - 0.748 (95%CI: 0.671–0.826), hsCRP - 0.634 (95%CI: 0.546 - 0.722) and Uric acid - 0.693 (95%CI: 0.606–0.780). Multiple regression analysis revealed HbA1c (OR 4.225; 95%CI – 1.421-12.561), 2 hr PPG (OR 1.026; 95%CI – 1.003-1.049), Insulin (OR 1.057; 95%CI – 1.006-1.111) and uric acid (OR 1.039; 95%CI – 1.026-2.793) to be independently associated with GDM outcome.Conclusions: Fasting Insulin, HbA1c, HOMA-IR, hsCRP and Uric acid levels are significantly altered in early pregnancy in individuals who develop GDM subsequently. Hence utilization of these parameters may identify at risk group in routine clinical care and help in improving feto-maternal outcome.

Epidemiology of gout and hyperuricemia in New Caledonia.

New Caledonia is a Pacific island of 270,000 inhabitants with mixed ethnicities, including Polynesians (10.2%), people from European ancestry (27.2%), and Melanesians (39.1%),. This study aimed at determining the prevalence of gout and hyperuricemia in the general population and the various ethnicities of New Caledonia. A 3-degree random sample of the population aged 18 to 60 years was adjusted according to the 2014 New Caledonia census. Face-to-face planned interviews and physical measurements were performed by trained nurses. All consenting participants underwent capillary measurement of creatinine; all consenting men and only women older than 40 years underwent point-of-care uricemia testing. Gout was defined by a validated algorithm. Two definitions of hyperuricemia were used: capillary level equivalent to plasma uric acid level>360μmol/l (6mg/dl) and>420μmol/l (7mg/dl) and/or urate-lowering drug treatment for both thresholds. We included 1144 participants (adjusted mean age 37.7±12.0 years; adjusted sex ratio 50.4% men). The adjusted prevalence of gout was 3.3% (95% confidence interval 2.2-4.9). Prevalence was 6.7% (2.5-16.8), 4.1% (1.8-8.9), and 2.6% (1.4-4.7) for Polynesians, Europeans and Melanesians, respectively, and 1.9% (0.5-6.6) for other ethnicities. Prevalence of hyperuricemia, determined in 658 participants, was 67.0% (61.9-71.6) and 37.0% (32.3-42.0) for the 360- and 420-μmol/l thresholds, respectively, and was significantly greater for Polynesians and Melanesians than Europeans for both thresholds. The prevalence of gout and hyperuricemia in New Caledonia was high, including in patients of European descent.

Gender differences in clinical and biochemical parameters of patients consecutively hospitalized for unipolar depression

Major Depressive Disorder (MDD) is a medical illness twice as common in women than in men lifetime. Purpose of this study is to identify gender differences in clinical and biochemical parameters in subjects affected by MDD to implement individualized treatment strategies. We recruited 234 patients (112 males and 122 females) consecutively hospitalized for MDD in Milan (Italy). Data were obtained through a screening of the clinical charts and blood analyses. Univariate analyses, binary logistic regressions and a final logistic regression model were performed. The final logistic regression model showed that female patients (compared to males) had lower plasmatic levels of hemoglobin (p = 0.020) and uric acid (p = 0.002), higher levels of cholesterol (p < 0.001), had been treated with a lower number of antidepressants (p = 0.011), presented lower red blood cells (p < 0.001) and showed more frequently comorbidity with hypothyroidism (p = 0.036). Univariate analyses identified also that women had an earlier age at onset (p = 0.043), were less likely to have comorbidity with diabetes (p = 0.002) and were less frequently treated with a psychiatric polytherapy (p < 0.001). Finally, female patients had achieved more frequently remission in the last depressive episode (p = 0.001) and were more likely to have family history for psychiatric disorders (p < 0.001) than males. Female patients globally have a better response to treatments, but they seem to be more vulnerable to specific metabolic abnormalities as showed by more frequent hypercholesterolemia and lower plasma levels of uric acid. These results have to be confirmed by further studies.

Effects of supplementing diet with Thyme (Thymuas vulgaris L.) essential oil and/or selenium yeast on production performance and blood variables of broiler chickens.

BackgroundOrganic products for animals are becoming more widely accepted by consumers. Using herbal additives may lead to more healthy animal products. In this research, it is hypothesized that thyme essential oil (TEO) and/or selenium yeast (SY) would be helpful to enhance production performance in broilers.ObjectiveIn the current study, the effects of adding TEO and/or SY to the diet on broiler performance and blood parameters were evaluated in broiler chickens.MethodsA total of 480 chicks were distributed in 24 cages with 20 chicks (10 males and 10 females) each and assigned to be fed four iso‐caloric and iso‐nitrogenous diets including two levels (0 and 250 mg/kg) of TEO and two levels (0 and 0.3 mg/kg) of SY in a 2 × 2 factorial arrangement with six replicates.ResultsAdding SY significantly decreased feed intake in finishing period (22–42 d) (p < 0.05). Supplementation with SY and TEO significantly decreased plasma uric acid and triglyceride levels, respectively (p < 0.05). However, neither of the supplements had any influence on the plasma glucose and albumin levels (p > 0.05). The lowest level of plasma cholesterol was detected in the birds fed the TEO‐supplemented diet (p < 0.05). Addition of SY significantly increased blood glutathione peroxidase activity (p < 0.05).ConclusionsDietary supplemental TEO has a favourable effect on feed intake, weight gain, and body weight values. Besides, SY may decrease blood concentration of uric acid, as well as blood glutathione peroxidase activity. An interaction is detected between TEO and SY on blood cholesterol.

The Allium triquetrum L. Leaves Mitigated Hepatotoxicity and Nephrotoxicity Induced by Lead Acetate in Wistar Rats.

The aim of this study was to scrutinize the possible mitigating role of leaves' Allium triquetrum L. against the toxicity of lead acetate on liver and kidney markers of Wistar rat. Lead acetate (Pb) and leaves' aqueous extracts (L) were orally administrated for 3 weeks. Rats were divided into the control, Pb group (500 mg/kg body weight/day), positive controls L (2g, 3g, 4g/kg BW/day), along with three combined groups of the same doses (Pb-L1, Pb-L2, Pb-L3). The levels of plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total proteins (TP), albumin (ALB), urea, creatinine (Cr), and uric acid (UA), as well as the hepatic and the renal malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GPx), were estimated. Results exhibited a significant increase in plasma AST, ALT, ALP, urea, creatinine, uric acid, and MDA levels of the Pb group compared to the control, with the exception of TP, ALB, GSH levels, and GPx activities that were significantly diminished, though the co-administration of garlic extracts (Pb-L) revealed a significant decrease in all mentioned markers, excluding the TP, ALB, GSH, and GPx levels. Likewise, Pb caused histological injuries in the hepatic and renal tissues of rats, while the co-administration of leaves' wild garlic has reduced such effect. Thought, the Pb-L has attenuated the Pb-induced toxicity in a dose-dependent manner. In conclusion, the aqueous extracts of A. triquetrum have the potential to alleviate Pb hepatotoxicity and nephrotoxicity through the modulation of most biomarkers in Wistar rat.

Association of plasma uric acid levels with cognitive function among non-hyperuricemia adults: A prospective study

The neuroprotective roles of uric acid are still controversial. One possible explanation is that previous studies included participants with hyperuricemia, which might interfere with clarifying the association. Therefore, this study aimed to investigate the prospective association between plasma uric acid levels and cognitive function among non-hyperuricemia adults. A total of 7828 participants from the China Health and Retirement Longitudinal Study (CHARLS) who were free from hyperuricemia, brain damage, mental retardation, or memory-related diseases at baseline were included. According to the baseline plasma uric acid levels, participants were classified into low (<3.5mg/dL for men and <2.5mg/dL for women), low-normal (3.5-4.9mg/dL for men and 2.5-3.9mg/dL for women), and high-normal groups (4.9-7.0mg/dL for men and 3.9-6.0mg/dL for women). Cognitive function tests covered the domains of executive function (time orientation, numerical ability, and drawing) and episodic memory (immediate and delayed word recall). We used generalized estimating equation models to evaluate the average difference in cognitive function within 4-years' follow-up across different uric acid groups. Compared with the high-normal group, participants with lower uric acid levels were associated with poorer cognitive performance during 4-years' follow-up. The corresponding level of difference was-0.24 (95% CI:-0.47,-0.01) for low group, and-0.13 (95% CI:-0.26,-0.01) for low-normal group. The associations were significant and similar for the specific domain of executive function (P<0.001). In addition, a stronger association was observed among participants with baseline age ≥60 years (P<0.05 for interaction). Our study supports a potential detrimental role of low levels of plasma uric acid on cognitive function among Chinese adults without hyperuricemia. More research is warranted to confirm this finding and identify the optimal plasma uric acid level for cognitive benefits.

A Phase I, Randomized, Single-Ascending-Dose, Multiple-Dose, and Food-Effect Trial of the Safety, Efficacy, and Pharmacokinetics of Topiroxostat in Healthy Chinese Participants

Abstract Background: As the structure of the human diet changes, the prevalence of hyperuricemia is increasing each year. Hyperuricemia and its comorbidities, such as gout, severely affect quality of life. Moreover, hyperuricemia causes renal impairment and is associated with chronic kidney disease. Topiroxostat, a selective xanthine oxidoreductase inhibitor, has been approved to treat hyperuricemia or gout in Japan. Topiroxostat has shown good tolerance and efficacy in the Japanese population. However, its pharmacokinetic (PK) characteristics, efficacy, and safety in the Chinese population remains unknown. Objective: This trial evaluated the PK profile, safety, efficacy, and food effects of Topiroxostat in healthy Chinese participants. Methods: The major endpoint was determination of the PK profile of Topiroxostat. Topiroxostat concentrations were detected with LC-MS/MS. PK parameters were calculated in Phoenix WinNonlin 8.1. Minor endpoints were safety and efficacy assessments. Assessment of adverse events and safety was performed by clinicians. Plasma uric acid concentration (ΔECmax and ΔAUEC) was determined as the pharmacodynamic index. This study consisted of three arms: single ascending dose (20, 40, and 80 mg, N = 10), multiple dose (80 mg BID, 7 days, N = 10), and food effects (40 mg single dose, fasting-fed cross-over design, N = 10). Results: In the single-ascending-dose arm, Topiroxostat showed rapid absorption and excretion, with Tmax &lt;1.6 h and T1/2 2.49–3.72 h. Additionally, Topiroxostat showed a wide distribution, on the basis of moderate Vz/F (242.8–336.36 L). The main PK parameters Cmax, AUC0-t, and AUC0-C showed a linear relationship with dose (R2 = 0.5146, 0.8416, 0.8386, respectively). In the multiple-dose arm, no significant differences were observed in Cmin on days 3–6 (P = 0.265). No serious adverse events were observed. Regarding efficacy, plasma uric acid levels were controlled to low levels during multiple-dose administration. In the food-effects arm, the fed group showed a lower Cmax than the fasting group (316.00 ± 135.81 vs. 478.40 ± 175.42 ng/mL, P = 0.033) but demonstrated better efficacy (ΔECmax, P &lt; 0.001; ΔAUEC, P &lt; 0.001). Conclusions: Topiroxostat showed rapid absorption and a broad distribution in healthy Chinese adults. Additionally, it showed good safety and tolerance in the Chinese population. Moreover, the pharmacodynamic profile indicated that post cibum administration increased the efficacy of Topiroxostat.

The effect of stevia sweetener on diabetic nephropathy in rats

Diabetic nephropathy (DN) is considered a clinical syndrome, which is a diabetic kidney disease characterized by increasing blood pressure, albuminuria, and chronic kidney disease. The current study aimed to determine the effect of sweetener (Stevia rebaudiana ) on diabetic nephropathy in a diabetic rat model. Four groups (n=7) of male albino rats (Rattus norvegicus): the control group, diabetic control group (induced streptozotocin intraperitoneally), two diabetic rat groups treated with 2 doses of stevia (200 and 400 mg/kg body weight) for 4 weeks. Biomarkers of nephropathy were measured in plasma and kidneys at the end of the experiment. The levels of plasma glucose, urea, uric acid, creatinine, renal malondialdehyde (MDA), and caspase-3 significantly increased in diabetic rats and levels of insulin, renal catalase, superoxide dismutase, and vascular endothelial growth factor A (VEGF-A) were significantly decreased. After treating the diabetic rats with natural sweetener (stevia), the kidney and plasma biochemical parameters were improved significantly. These results indicated the major role of stevia in diabetic nephropathy.

Trace elements and antioxidant status in human immunodeficiency virus positive patients

Objectives: This study was conducted to determine the plasma levels of the antioxidants and mineral trace elements in three severity groups of human immunodeficiency virus (HIV) patients compared with non-HIV-infected controls. Methods: The plasma levels of antioxidants (Total antioxidant, albumin, bilirubin, uric acid) and trace elements (Mg, Fe, Zn, Mn, Cu, Cr, Cd and Se) were estimated in spectrophotometrically in controls and patients with CD4 counts &lt;200; 200–499 and ≥500 cells/µL. Results: Plasma uric acid and plasma zinc (Zn) were significantly high, while vitamin E and all the micro trace elements (except Zn) were significantly lower in HIV-infected patients compared to healthy controls human beings. The higher level of plasma uric acid was observed in those with CD4 counts &lt;200 cells/µL. All the trace elements (except Zn) were high levels in HIV subjects with a CD4 count of 200–499 cells/µL compared to &gt;500 cells/µL. Only plasma uric acid and zinc showed significant correlation with CD4 cell count. Conclusion: Routine assessment of antioxidant/ trace element levels in HIV subjects is recommended. This supplementation is given to strengthen the immune system and reduce the adverse consequences of HIV related oxidative stress and sometimes suggests that assessing antioxidant levels or enzymes activities of patients infected with HIV should be considered during therapy. Keywords: trace elements; human immunodeficiency virus; antioxidants; CD4 cell; AIDS; oxidative stress

Green synthesized Zinc Oxide Nanoparticles Elicited a Prominent Suppression of Oxidative and Inflammatory Distortions in Rats Exposed to Carbon Tetrachloride

This study centered on Zinc oxide nanoparticles capped with Pterocarpus mildbraedii leaf extracts (PmZnONPs) as a potent antioxidant and anti-inflammatory agent against carbon tetrachloride (CCl4) ‐ induced hepatorenal toxicity in rats. PmZnONPs were characterized by Fourier transform infrared spectroscopy (FTIR), Brunauer–Emmett–Teller (BET), scanning electron microscopy (SEM), X-ray diffraction pattern (XRD), and transmission electron microscopy (TEM) techniques. The FTIR results revealed the presence of various functional groups in PmZnONPs, while the BET showed a surface area of 1.55 mg-2. In vitro, PmZnONPS showed comparable 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH), and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS) radicals scavenging activities as Vitamin C. After that, PmZnONPs (1 and 3 mg/kg) were administered (p.o.) into six groups of rats, using CCl4 as the toxicant. The obtained results demonstrated that PmZnONPS significantly prevented CCl4‐induced elevations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma‐glutamyl transferase (GGT), alkaline phosphatase (ALP), bilirubin (BIL), creatinine, and urea. Moreover, PmZnONPs restored the levels of plasma uric acid, hepatorenal antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, glutathione transferase, and glutathione that were significantly decreased by CCl4 treatment. Immunohistochemical studies showed that PmZnONPs significantly suppressed the high immunoreactivity of nuclear factor kappa B (NF‐κB), cyclooxygenase‐2 (COX-2), and interleukin‐6 (IL-6) arising from CCl4 intoxication. Thus our data hint that PmZnONPs suppressed CCl4‐induced toxicity in the liver and kidney of rats via its combined antioxidant and anti‐inflammatory properties.

Altered structural changes of podocytes, glomerular basement membrane in patients with type 2 diabetes mellitus

Diabetic nephropathy is a one of the microvascular complication in patients with type 2 diabetes mellitus due to increased production of free radicals and decreased levels of anti oxidants. The seviority of the disease totally depends on due to damage of foot process of podocytes. Hence, we need to evaluate the altered structural changes of podocytes, glomerular basement membrane in patients with type 2 diabetes mellitus. A total 60 type 2 diabetes mellitus patients were included in the present study and again sub classified into 2 types (Normoalbuminuria 30, Microalbuminuria 30) based on their urinary ACR. Basic laboratory investigations and radio graphical data were collected from the all subjects. A statistical was performed by using SPSS Version 21.0 and P value considers &amp;#60; 0.05 is statistically significant. The significantly elevated levels of plasma FBS, PPBS, Serum Urea, Creatinine, Uric Acid and HbA1c, Urinary albuminuria observed in type 2 diabetes mellitus with microalbuminuria when compared to normoalbuminuria. The radiographical data showed a significantly damaged foot process of podocytes and glomerular basement membrane are observed in patients with microalbuminuria when compared to normoalbuminuria. The increased levels blood sugar and HbA1c, Urinary Albuminuria directly indicates the damage of podocytes and glomerular basement membrane in the kidney. This study suggest continuous monitoring of these parameters may helpful for progression of type 2 diabetes mellitus complications.

Bromuconazole caused genotoxicity and hepatic and renal damage via oxidative stress process in Wistar rats.

Bromuconazole is a triazole pesticide used to protect vegetables and fruits against diverse fungi pathologies. However, its utilization may be accompanied by diverse tissue injuries. In this study, we evaluated the biochemical and histopathological modifications, and we analyzed genotoxic and oxidative stress, in the aim to examine bromuconazole effects in the liver and kidney. We subdivided animals into four groups, each one contains six adult male Wistar rats. Untreated rats received daily a corn oil (vehicle) orally. Three oral bromuconazole doses were tested (1, 5, and 10 % of LD50) daily for 28 days. Bromuconazole increased the plasma activities of alkaline phosphatase, lactate dehydrogenase, and transaminases. It also increased the plasma levels of creatinine and uric acid. Histopathological check showed that bromuconazole caused organ damage. This study makes known that bromuconazole caused conspicuous DNA damage either in hepatic or kidney tissues, with a significant increase in the levels of malondialdehyde and protein carbonyl followed by an enhancement in catalase and superoxide dismutase enzymatic activities, and these increases are in a dose-dependent manner. In other side, we found that Glutathione-S-transferase and peroxidase activities raised. Our outcomes highlight that bromuconazole exposure induced genotoxic damage and organ damage which may be caused by the disturbances of oxidative stress statue in the liver and kidney.

Relation between Exogenous Insulin and Cognitive Function in Type 2 Diabetes Mellitus.

Background and objectives: Although the role of insulin in the periphery is well understood, not as much is known about its multifactorial role in the brain. The aim of this study is to determine whether exogenous insulin, evaluated by daily insulin requirement, has an impact on mild cognitive impairment (MCI), and whether this relationship is mediated by insulin doses and other risk factors. Materials and methods: A sample of 100 participants with type 2 diabetes aged 40 and over was divided into case and control groups, according to their insulin requirement. Patients with an insulin requirement >1 IU/kg/day were assessed as the case group whereas those with an insulin dose <1 IU/kg were used as the control group. All participants underwent cognitive testing using MoCA questionnaire scoring and blood analysis to determine lipid and uric acid levels in plasma. Subjects were categorized as having normal cognitive function or MCI. Results: Results showed that the prevalence of MCI in Lithuanian elderly diabetic patients was high in the groups with a normal insulin requirement or high insulin requirement at 84.8% and 72.5%, respectively (p = 0.14). Age (p = 0.001) and insulin dose (p < 0.0001) were related to the MCI. Using ROC curve analysis, the highest rate risk of MCI occurred when the insulin dose was lower than 144 IU/d. Conclusions: In summary, the results of this study provided evidence that increased exogenous insulin supply improves cognitive function. Higher insulin dose (>144 IU/d) demonstrated a positive effect on cognitive function, especially in individuals with poorly controlled diabetes (HbA1c ≥ 9%). Finally, the prevalence of MCI in the T2DM population was found to be very high. Future research is needed to determine whether high exogenous insulin doses have a protective effect on MCI.

Biopharmaceutical Study on Nobiletin-Loaded Amorphous Solid Dispersion with Improved Hypouricemic Effect.

The present study aimed to develop an amorphous solid dispersion of nobiletin (ASD/NOB) using hydroxypropyl cellulose-SSL (HPC-SSL) to improve the pharmacokinetic properties and hypouricemic effect of NOB. ASD/NOB was prepared by the freeze-drying method (ASD/NOB). ASD/NOB was characterized with a focus on crystallinity, dissolution, pharmacokinetic behavior, and hypouricemic action in a rat model of hyperuricemia. ASD/NOB showed significant improvement in dissolution behavior, as evidenced by a 4.4-fold higher dissolved NOB concentration than crystalline NOB at 2 h in distilled water. After the oral administration of ASD/NOB (50 mg NOB/kg) in rats, higher systemic exposure to NOB was observed with an 18-fold enhancement in oral bioavailability, and the Tmax value of orally administered ASD/NOB was 60% shorter than that of orally administered crystalline NOB. In a rat model of hyperuricemia, orally dosed ASD/NOB showed an improved hypouricemic effect by a 16% reduction in the plasma uric acid level compared with orally administered crystalline NOB. Based on these findings, ASD/NOB may be an efficacious dosage option to improve the nutraceutical potential of NOB for the treatment of hyperuricemia.

Impact of Lisinopril on Cardiometabolic Risk Factors in Men With Hypertension and Early-onset Androgenetic Alopecia: A Pilot Study.

Women with polycystic ovary syndrome are at a high cardiometabolic risk. Early-onset male-pattern baldness is considered the phenotypic equivalent of polycystic ovary syndrome in men. The aim of this study was to assess whether early-onset androgenetic alopecia modifies cardiometabolic effects of lisinopril in men with arterial hypertension. The study population consisted of 62 young men with grade 1 hypertension, 31 of whom were diagnosed with early-onset male-pattern baldness (group A). Thirty-one blood pressure-matched men with normal hair growth (group B) served as a control group. All participants were treated with lisinopril (10-40 mg daily). Blood pressure, glucose homeostasis markers, urinary albumin-to-creatinine ratio (UACR), as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, total and calculated free testosterone, dehydroepiandrosterone sulfate, and estradiol were assessed before lisinopril treatment and 6 months later. At baseline, levels of all cardiometabolic risk factors were higher in group A than group B. Although lisinopril reduced systolic and diastolic blood pressure, UACR, hsCRP, and fibrinogen in both study groups, these effects were stronger in group B than in group A. Only in group B, the drug decreased levels of uric acid and homocysteine, as well as improved insulin sensitivity. The impact of lisinopril on uric acid, hsCRP, fibrinogen, homocysteine, and UACR correlated weakly with its hypotensive properties, androgen levels, and insulin sensitivity. The obtained results suggest that cardiometabolic effects of lisinopril in men are less pronounced in case of coexisting early-onset androgenetic alopecia.

Chitosan Oligosaccharide Alleviates Abnormal Glucose Metabolism without Inhibition of Hepatic Lipid Accumulation in a High-Fat Diet/Streptozotocin-Induced Diabetic Rat Model.

This study investigated the effects of chitosan oligosaccharide (COS) on glucose metabolism and hepatic steatosis in a high-fat (HF) diet/streptozotocin-induced diabetic rat model. Male Wistar rats were divided into: (1) normal control (NC group), (2) HF diet (HF group), (3) streptozotocin (STZ)-induced diabetes with HF diet (DF group), and DF group supplemented with (4) 0.5% COS (D0.5F group), (5) 1% COS (D1F group), and (6) 5% COS (D5F group) for 4 weeks. COS supplementation significantly decreased the plasma glucose, BUN, creatinine, uric acid, triglyceride (TG), and total cholesterol (TC) levels, and hepatic glucose-6-phosphatase activity, and significantly increased hepatic hexokinase activity and glycogen content in diabetic rats; but the increased hepatic TG and TC levels could not be significantly decreased by COS supplementation. Supplementation of COS increased superoxide dismutase activity and decreased lipid peroxidation products in the diabetic rat livers. COS supplementation significantly increased phosphorylated AMP-activated protein kinase (AMPK) protein expression, and attenuated protein expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and phosphorylated p38 and renal sodium-glucose cotransporter-2 (SGLT2) in diabetic rats. These results suggest that COS may possess a potential for alleviating abnormal glucose metabolism in diabetic rats through the inhibition of hepatic gluconeogenesis and lipid peroxidation and renal SGLT2 expression.

RBP4 Is Associated With Insulin Resistance in Hyperuricemia-Induced Rats and Patients With Hyperuricemia.

ObjectiveHyperuricemia (HUA) is strongly associated with abnormal glucose metabolism and insulin resistance (IR). However, the precise molecular mechanism of HUA-induced IR is still unclear. Retinol binding protein 4 (RBP4) has been shown to induce IR in type 2 diabetes mellitus. This study was designed to clarify the relationship between RBP4 and HUA-induced IR and its potential mechanisms.MethodsPatients with HUA were collected to detect the levels of plasma RBP4 and clinical biochemical indicators. Rats were fed with 10% high yeast and oteracil potassium (300 mg/kg) via intraperitoneal injection once daily for eight weeks, and gavage with adenine (100 mg/kg) once daily from the fifth week to induce the HUA model. Glucose consumption testing was performed to determine the capacity of glucose intake and consumption in 3T3-L1 adipocytes. Real-time polymerase chain reaction (RT-PCR) and western blot were used to detect the mRNA and protein level of RBP4 and insulin receptor substrate-phosphatidylinositol 3-kinase-active protein kinase (IRS/PI3K/Akt) signaling pathway-related proteins.ResultsThe levels of plasma RBP4 in both HUA patients and HUA rat models were significantly higher than that in the control groups. The level of plasma RBP4 was positively correlated with plasma uric acid, creatinine, fasting insulin, IR index, total cholesterol and triglyceride levels in patients with HUA. In HUA rats, the level of plasma RBP4 was positively correlated with plasma uric acid, IR index, and triglycerides. HUA rats also exhibited IR. After inhibition of RBP4 expression, the phosphorylation levels of the IRS/PI3K/Akt signaling pathway were increased, and IR was significantly improved.ConclusionHUA induced IR both in vitro and in vivo. RBP4 may be involved in HUA-induced IR by inhibiting IRS/PI3K/Akt phosphorylation. Our findings may provide a new insight for the treatment of IR caused by HUA.

Angiotensin involvement in kidney injury induced by rheumatoid arthritis in rat.

Renal injury induced by rheumatoid arthritis is not clear and may be related to the angiotensin II. We aim to investigate the adjuvant-induced arthritis (AIA) injury in rat kidney, focusing the angiotensin II/AT1 pathway. Male Wistar rats were allocated in to three groups: Control, AIA and AIA plus losartan. The AIA was induced by injection of 100µL of an emulsion of dissected Mycobacterium tuberculosis (50mg/mL) on the paw. Treatment with losartan was initiated on the first day of immunization (daily subcutaneous injection, 1mg/kg). After 60days post immunization, we evaluated kidney function by plasma creatinine, urea and uric acid levels and creatinine depuration; kidney injury by apoptosis analysis and inflammation markers such as macrophages, transforming growth factor beta (TGF-β) and inducible nitric oxide synthase (iNOS) expression; oxidative stress by plasma thiobarbituric acid reactive substances (TBARS); renal expression of angiotensin receptors subtype 1 (AT1 ) and 2 (AT2 ) and plasma concentration of angiotensin II. AIA rats showed elevated plasma levels of creatinine, urea, uric acid, TBARS and Ang II and reduced creatinine depuration, and enhanced kidney macrophage number, TGF-β, caspase-3, iNOS and AT1 /AT2 receptors expression. The losartan reduced plasma creatinine and its clearance, reduced macrophages and the expression of TGF-β and iNOS in renal tissues, and reduced plasma TBARS. We conclude that AIA causes kidney injury by a physiopathological mechanism that involves AT1 stimulation in renal tissue, elevating the presence of macrophages, the expression of TGF-β and iNOS, as well the local oxidative stress, which contribute to renal function deterioration.