nader sadigh

Amyloid-beta (Aβ) production is a normal physiological process, and an imbalance in Aβ production/excretion rate is the basis of the plaque load increase in AD. LRP1 is involved in both central clearance of Aβ from the CNS and transport of Aβ toward peripheral organs. In this study, the effect of silymarin combination compared to rosuvastatin and placebo on neuro-metabolites and serum levels of LRP1 and Aβ1-42 proteins and oxidative stress enzymes and lipid and cognitive tests of Iranian AD patients.

In this double-blind placebo-controlled study, thirty-six mild AD patients were divided into groups (n=12) of silymarin 140mg, placebo, and rosuvastatin 10mg. Medications were administered 3 times a day for 6 months. Clinical tests, lipid profile (TG, HDL, TC, and LDL), Aβ1-42, and LRP1 markers were measured at the beginning and end of the intervention. Magnetic resonance spectroscopy (MRS) was used to measure metabolites. Using SPSS software a one-way ANOVA test was used to compare the means of the quantitative variables and Pearson and Spearman's correlations to measure the correlation. GraphPad Prism software was used for drawing graphs. P < 0.05 was considered a significant.

The levels of LRP1 and Aβ1-42 in the silymarin group were significantly increased compared to the other groups (P < 0.05). NAA/mI in the silymarin group had a significant increase compared to both placebo and rosuvastatin groups (P < 0.05). Right and left hippocampal mI/Cr directly correlated with TG (r = 0.603, P = 0.003 and r = 0.595, P = 0.004, respectively). NAA/Cr of the right and left hippocampus was inversely related to TG (r = -0.511, P = 0.0033, and r = -0.532, P = 0.0021, respectively). NAA/Cr and NAA/mI of bilateral hippocampi directly correlated with HDL (P < 0.05). An inverse correlation was observed between the Aβ1-42 and mI/Cr of the right and left hippocampus (r = -0.661, P = 0.000 and r = -0.638, P = 0.000, respectively).

Donepezil and silymarin improved lipid profile associated with increased NAA/Cr, and decreased mI/Cr, in AD patients. Biomarker NAA/mI can be clinically significant in examining AD pathology. Measurement of the lipid factors and neurometabolites can be a suitable method for monitoring this disease.

Vesicoureteral reflux (VUR) is the most common congenital urinary tract abnormality in children. Renal parenchymal damage is the most devastating complication of severe undiagnosed VUR. Different diagnostic biomarkers have been introduced as alternatives for radiologic evaluation in these patients. This review article aimed to increase the knowledge about the role of urine neutrophil gelatinase-associated lipocalin (uNGAL) in children affected by primary VUR and renal parenchymal damage.

A systematic review of PubMed, Scopus, Web of Science, ProQuest, and Ovid was conducted in September 2022 to retrieve studies that investigated the correlation between uNGAL or uNGAL/Cr excretion and primary VUR in male/female patients younger than 18 years of age. Patients with secondary VUR, age older than 18 years, infectious or inflammatory disorders, obstructive uropathies, and acute or chronic kidney diseases were excluded. Two reviewers independently screened the titles and abstracts of the search results and then assessed the full texts selected from the pertinent studies. 

Eighteen research articles with a total sample of 699 patients were found to measure uNGAL in VUR or renal scarring. UNGAL or uNGAL/Cr had increased excretion in the majority of children with primary VUR or RPD, with a positive or no correlation to the severity of VUR. 

Several studies addressed uNGAL and uNGAL/Cr as putative biomarkers for the prediction of VUR or reflux-associated RPD.

Backgroundand

Production of a model of hepatic failure is used to evaluate the effectiveness and safety of alternative methods of liver transplantation. This study aimed to determine the appropriate dosage of carbon tetrachloride (CCl4) to induce acute hepatic failure in NMRI mice.

In this study, at first, a mixture of CCl4 dissolved in olive oil was administered intraperitoneally to 5 groups of 6 mice. After 24 hours, serum level of liver enzymes and the status of liver tissue were evaluated. To investigate the survival of mice, CCl4 (at doses of 0.5, 1, 1.5, 2, and 2.5ml/kg.bw) was administered to 6 new groups of mice, and these animals were monitored for 4 days. To assess the effect of the toxin in the next days, the determined dose was administered to 24 new mice, and serum and histological evaluations were repeated.

The serum level of liver enzymes and the degree of hepatic lesions were significantly increased with increased dose of CCl4. Values more than 1ml/kg of CCl4 induced acute liver damage. Also, the value of 1ml/kg decreased mortality rate and values more than 2ml/kg increased mortality rate. Maximum increase in serum levels of liver enzymes was observed 24 hours after injection of CCl4 (at the dose of 1.5ml/kg), which decreased gradually. The degree of liver damage in days after the injection was the same until the fourth day, but the liver regeneration phasewas initiated after 72 hours.

According to the results of this study, a single intraperitoneal administration of CCl4 at the dose of 1.5mL/kg CCl4 could be an appropriate dosage for the production of a model of acute hepatic failure in NMRI mouse.

Steroid-resistant nephrotic syndrome (SRNS) is uncommon in children, but often leads to ESRD. We report our experience with SRNS and its treatments and outcomes. We assessed 73 children with SRNS admitted to Ali Asghar Children Hospital in Tehran, Iran. Their clinical presentations, treatment, and disease courses were reviewed. The mean follow-up duration was 6.0 ± 4.2 years. Moreover, survival times were calculated and the Cox regression method was used to determine variables able to predict survival of the kidneys. Age at the onset of the disease, sex, and hematuria were not predictive of the response to treatment with immunosuppressive drugs in the children with SRNS. The type of resistance (early or late) was associated with the responsiveness to immunosuppressives. Response to any of the immunosuppressive drugs determined the responsiveness to other immunosuppressive drugs. Cyclosporine was more effective than cyclophosphamide as initial therapy. The mean kidney survival time was 11.62 years. Kidney survival rates were 94.6%, 70.0%, 56.0%, and 34.0% at 1, 5, 10, and 15 years, respectively, in patients with initial resistance to steroid, while these were 100%, 100%, 83.0%, and 83.0% in those with late resistance, respectively (P =. 03).We showed that patients with late steroid resistance had better response to immunosuprressive drugs than patients with early resistance. We also showed that resistance to immunosuppressive therapies increased the risk of resistance to other immunosuppressive drugs. Achievement of complete or partial remission with any therapy reduced the risk of ESRD.