Association Between Serum Uric Acid Levels and Oxido-Inflammatory Biomarkers With Coronary Artery Disease in Type 2 Diabetic Patients.

BACKGROUND: Cardiovascular disease signifies a major cause of morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). Serum uric acid (SUA) levels are elevated during the initial phases of impaired glucose metabolism. This work was designed to explore the association between SUA levels, serum oxido-inflammatory biomarkers, and the risk of coronary artery disease (CAD) in T2DM patients as the primary outcome. The secondary outcome was to assess the prognostic role of SUA in the prediction of the risk of CAD in T2DM patients. METHODS: In this case-control study, we enrolled 110 patients with T2DM who were further divided into patients with CAD and without CAD. In addition, 55 control participants were stringently matched to cases by age. RESULTS: Diabetic patients with CAD had significantly higher serum levels of the inflammatory biomarkers and the oxidative malondialdehyde but significantly lower levels of serum total antioxidant capacity (TAC) compared with the controls and diabetic patients without CAD. Significant positive correlations existed between SUA levels and serum levels of the inflammatory biomarkers and malondialdehyde, while a significant negative correlation existed between SUA levels and serum TAC. SUA demonstrated an accepted discrimination ability. SUA can differentiate between T2DM patients with CAD and patients without CAD, an area under the curve of 0.759. CONCLUSIONS: Elevated serum levels of SUA and oxido-inflammatory biomarkers are associated with an increased risk of CAD in T2DM. SUA levels reflect the body's inflammatory status and oxidant injury in T2DM. SUA could be utilized as a simple biomarker in the prediction of CAD risk in T2DM.

Neutrophil-to-lymphocyte ratio versus platelet-to-lymphocyte ratio in predicting clinical outcomes in acute methanol poisoning.

Acute methanol poisoning is a global health concern. This study was designed to compare the prognostic roles of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and their combination in the prediction of clinical outcomes in methanol-intoxicated patients as well as to evaluate their associations with all initial patients' characteristics. We conducted a cross-sectional study among methanol-intoxicated patients. A total of 109 patients were enrolled in the study. Thirty-four (31%) patients died during hospital admission while 30 (27.5%) patients developed visual loss. Most of the unfavorable findings were evident in patients with high NLR and PLR. Neutrophil-to-lymphocyte ratio and PLR can excellently differentiate between survivors and non-survivors with an area under the curve (AUC) of 0.991 vs 0.923, respectively. Platelet-to-lymphocyte ratio showed an accepted discrimination ability to differentiate between patients who developed and patients who did not develop visual loss, AUC of 0.734, however, NLR showed no discrimination, AUC of 0.558. We concluded that NLR and PLR can serve as valuable tools in risk-stratifying patients and prognosticating outcomes in acute methanol poisoning. Platelet-to-lymphocyte ratio is superior to NLR as a predictive factor in patients with permanent visual impairment. However, a combination of NLR with PLR can develop a more powerful prediction for overall clinical outcomes.

Factors associated with time to successful weaning in mechanically ventilated organophosphate poisoned patients.

We designed this study to identify the factors associated with time to successful weaning in mechanically ventilated organophosphate (OP)-poisoned patients as the primary outcomes while duration of mechanical ventilation (MV) support, intensive care unit (ICU), and hospital length of stay (LOS) and in-hospital mortality as the secondary outcomes. We conducted a retrospective study of mechanically ventilated OP-poisoned patients admitted to the ICU of Poison Control Center of Ain Shams, Cairo, Egypt, starting from January 2019 to December 2019. Weaning was considered successful if the patient succeeded in the first spontaneous breathing trial of weaning and did not need reinstitution of MV. We used Cox proportional hazards regression models to identify factors associated with time to successful weaning in the studied patients. A total of 55 patients were enrolled in the study. Thirty-eight patients were weaned successfully. Lower initial red cell distribution width (RDW) levels [adjusted hazard ratio (HR), 0.299, 95% confidence interval (CI) (0.184-0.486)] and lower initial doses of atropine [adjusted HR, 0.97, 95% CI (0.935-0.999)] were independently associated with shorter time to achieve successful weaning. Successfully weaned patients had significantly longer hospital LOS (p = 0.019) and no reported in-hospital mortality (p < 0.001) compared with patients who failed to wean. We concluded that initial RDW and initial doses of atropine were found to be the strongest factors associated with time to successful weaning in mechanically ventilated OP-poisoned patients. RDW and atropine can be used as simple risk assessment tools in OP poisoning.

Subclinical nephrotoxicity in patients with beta-thalassemia: role of urinary kidney injury molecule.

We aimed to investigate the role of urinary kidney injury molecule-1 (KIM-1) in detection of subclinical nephrotoxicity in patients with Beta-thalassemia (ß-TM) in relation to chelation therapy and to correlate the urinary KIM-1 level with other clinical and laboratory findings. We conducted a cross-sectional study on 66 thalassemic patients. Their ages range from 7 to 22 years. Routine kidney indices and novel urinary KIM/creatinine ratio (UKIM-1/Cr) were measured. Estimated glomerular filtration rate (eGFR) was calculated. Results indicate that the level of serum creatinine was significantly higher in patients on deferasirox therapy than patients on deferoxamine and deferiprone therapy [median(IQR), 0.85(0.63-0.99), 0.50(0.34-0.58) and 0.44(0.36-0.45)] mg/dL, respectively, p < 0.001]. The median(IQR) level of eGFR was significantly lower in patients on deferasirox therapy than patients on deferoxamine and deferiprone therapy [63.3(56.5-92.1), 117.3(91.9-162) and 136.7(109.4-157.6)] ml/min/1.73 m2, respectively, p < 0.001]. The mean level of UKIM-1/Cr was significantly higher in patients on deferasirox therapy than patients on deferoxamine and deferiprone therapy (7.0 ± 1.9, 4.1 ± 1.7 and 4.2 ± 1.5) ng/mg creatinine, respectively, p < 0.001). We concluded that urinary KIM-1 is an early predictive biomarker for decline in eGFR in patients with ß-TM on deferasirox therapy. The appropriate chelation therapy and good monitoring of those patients are intensely needed for early detection of renal dysfunction and timely intervention.

Comparative cardioprotective effects of carvedilol versus atenolol in a rat model of cardiorenal syndrome type 4.

The incidence of chronic kidney disease is escalating; cardiorenal syndrome (CRS) type 4 is gaining a major health concern causing significant morbidity and mortality, putting major burdens on the healthcare system. This study was designed to compare the cardioprotective effects of carvedilol versus atenolol against CRS type 4 induced by subtotal 5/6 nephrectomy in rats and to explore the underlying mechanisms. Immediately after surgery, carvedilol (20 mg/kg/day) or atenolol (20 mg/kg/day) was added to drinking water for 10 weeks. Carvedilol was more effective than atenolol in improving kidney functions, decreasing elevated blood pressures, attenuating cardiac hypertrophy, reducing serum brain natriuretic peptide, and diminished cardiac fibrous tissue deposition. However, carvedilol was equivalent to atenolol in modulating ß1-adrenergic receptors (ß1ARs) and cardiac diacylglycerol (DAG) signaling, but carvedilol was superior in modulating ß-arrestin2, phosphatidyl inositol 4,5 bisphosphates (PIP2), and caspase 3 levels. Carvedilol has superior cardioprotective effects than atenolol in a rat model of CRS type 4. These protective effects are mediated through modulating cardiac ß1ARs/ß-arrestin2/PIP2/DAG as well as abating cardiac apoptotic signaling pathways (caspase3/pS473 protein kinase B (Akt)).

Assessment of serum aflatoxin B1 levels in neonatal jaundice with glucose-6-phosphate dehydrogenase deficiency: a preliminary study.

Aflatoxin (AF) contamination of food products is still a major health issue globally. Prior studies suggest that exposure to AFs during pregnancy has harmful fetal outcomes. This preliminary study was designed to assess serum AFB1 levels in neonatal jaundice (NNJ) secondary to glucose-6-phosphate dehydrogenase (G6PD) deficiency. Twenty-four full-term neonates with hemolytic jaundice secondary to G6PD deficiency were enrolled in the study. Erythrocyte G6PD status was assessed colorimetrically, and serum aflatoxin B1 (AFB1) concentrations were measured by high-performance liquid chromatography. The results revealed that AFB1 was detected in 58% (14/24) of the studied newborns while detected in 75% (18/24) of their mothers. AFB1 positive cases had a highly significantly lower birthweight and G6PD activity (P = 0.001, each). Birthweight (r = - 0.574, P = 0.032) and G6PD activity (r = - 0.585, P = 0.028) negatively correlated with serum AFB1 levels while serum alanine aminotransferase activity positively correlated with serum AFB1 levels (r = 0.536, P = 0.048). Maternal AFB1 exposure is associated with adverse birth outcomes as verified by the low birthweight and the evident decline in the activity of G6PD enzyme with the resultant hemolytic NNJ.

Silymarin in combination with chlorogenic acid protects against hepatotoxicity induced by doxorubicin in rats: possible role of adenosine monophosphate-activated protein kinase pathway.

Many xenobiotics are known to cause hepatic damage with subsequent significant morbidity and mortality. Doxorubicin (DOX) is a broad-spectrum antineoplastic agent. DOX is reported to cause hepatocellular damage. Previous studies verified the promising role of many natural antioxidant products against various models of hepatic dysfunction. We conducted this study to evaluate the possible hepatoprotective effect of silymarin (SILY) and/or chlorogenic acid (CGA) in a rat model of DOX-induced hepatotoxicity. For this purpose, we randomly divided 30 adult male rats into five equal groups as control, DOX, co-treated DOX with SILY, co-treated DOX with GCA and co-treated DOX with SILY and CGA groups. All treatments were administered every second day for 4 weeks. Our results showed that simultaneous SILY and CGA administration caused a significant decrease in hepatic apoptosis biomarkers (hepatic caspase-3 and nuclear factor-κB levels), a significant improvement in hepatic oxidant/antioxidant status (malondialdehyde and superoxide dismutase) and significant decrease in hepatic pro-inflammatory biomarkers (tumor necrosis factor-alpha and interlukin-1ß) compared with DOX treatment. We concluded that adding CGA to SILY acts as a hepatoprotective agent against DOX-induced liver injury through inhibiting apoptosis biomarkers, maintaining antioxidant enzyme levels, decreasing pro-inflammatory cytokines as well as regulating liver adenosine monophosphate-activated protein kinase signaling.

Comparative effectiveness of methylene blue versus intravenous lipid emulsion in a rodent model of amlodipine toxicity.

Context: Calcium channel blocker (CCB) poisonings are the leading cause of death from cardiovascular medication-related overdoses. Current treatments (calcium salts, vasopressors, inotropes) are often insufficient. Intravenous lipid emulsion (ILE) and methylene blue (MB) show promise in treating CCB overdoses unresponsive to conventional therapy. Objective: To compare the effectiveness of MB versus ILE in a rodent model of amlodipine (AML) poisoning with survival as the primary outcome and hemodynamic parameters as secondary outcomes. Materials and methods: Sixty-four adult male albino rats were anesthetized and cannulated for non-invasive hemodynamic measurement. Rats received amlodipine intraperitoneally (42 mg/kg). We then divided the rats into four groups: AML only without antidote, AML followed by ILE (24.8 mL/kg over 10 min), AML followed by normal saline (an equivalent volume of ILE), and AML followed by IV MB (2 mg/kg over 5 min). They received study treatments at 5, 30, and 60 minutes from the start of the protocol and with observation for 2 hours. Results: Survival time in ILE group was greater than in the control and NS groups. Differences between ILE and MB and between MB and NS were not significant. Hemodynamic parameters significantly increased in ILE group compared to the MB group at the 30, 60 and 120 min assessments but not after induction of AML poisoning and at 5 min assessment. Conclusions: Survival was greatest in rats treated with ILE. Both MB and NS had little effect on survival when compared to control animals. Both ILE and MB improved hemodynamics.