Value of carotid intimal–medial thickness as independent predictor of endothelial dysfunction in uremic patients

Background and aim of the workCardiovascular mortality and morbidity are significantly higher among uremic patients. Although the carotid intimal–medial thickness (C-IMT) as a predictor of endothelial dysfunction (ED) has a prognostic value that has been well demonstrated as an independent predictor of future cardiovascular events, its value in uremic patients need to be re-assisted in our locality. The aim of the work is to investigate a correlation between the brachial artery reactivity test (BART) and the carotid intimal–medial thickening (C-IMT) and their value as independent predictors of endothelial dysfunction in uremic patients.Subjects and methodsThe study involved 70 uremic patients, 40 men and 30 women, 36–56 years old, 40 of them on regular hemodialysis (HD) and 30 on conservative therapy, in addition to 30 healthy persons as a control group. They were selected from the General Medicine and Nephrology Departments, Al-Azhar Assiut University and Assiut University Hospitals over a period of 2 years. All of them were subjected to detailed history, thorough clinical examination, laboratory investigations including complete blood picture, renal function tests (urine analysis, blood urea, and serum creatinine), lipid profile, serum calcium and serum phosphorus, parathyroid hormone (PTH), fasting blood glucose, electrocardiography (ECG), high resolution B-mode ultra-sonography for C-IMT evaluation and brachial artery reactivity test (BART), and abdominal ultra-sonography.ResultsThe results of the present study showed: (1) uremic patients are at an increased risk for carotid atherosclerotic lesions, with significant increase in C-IMT than controls with more significant increase in HD patients. (2) Uremic patients are characterized by impaired endothelium dependent dilatation of the brachial artery (highly significant reduction in flow-mediated dilatation (FMD%)), an abnormality related to the renal failure severity and to the hemodialysis doses. The endothelial dysfunction in the brachial artery was more pronounced in HD patients than in patients on conservative therapy. (3) Significant positive correlation between increased C-IMT and reduction of the brachial FMD%. (4) Significant relation between C-IMT and plaque prevalence and HD duration, while no relations recorded between brachial FMD with HD duration.Conclusion(1) The study confirmed that carotid IMT and brachial artery FMD can be used in interventional studies in which cardiovascular risk is modified and increased in the uremic patients. (2) There was negative correlation between brachial FMD and C-IMT in the uremic patients.     

Endoscopic stapedotomy: Merits and demerits

A one-year-old baby girl with one-month history of recurrent pus fluid exuding from her left preauricular sinus orifice, who failed multiple courses of surgical drainage of the abscess and persistent debridement for the wound, presented with MRSA infection. The patient was treated with linezolid for three days. Her pain and paresthesia resolved, and C-reactive protein decreased to normal.     

Clinical characteristics,molecular profile and outcomes of myeloid sarcoma: a single institution experience over 13 years

Background: Myeloid sarcoma (MS) is characterized by extramedullary infiltration by immature myeloid cells. Owing to rarity of this disease, the clinical features and overall outcomes are yet to be clarified.

Objective: To define clinical characteristics, epidemiology, pathologic findings, treatment options and outcomes in MS.

Methods: We conducted a retrospective review of 23 patients diagnosed with MS at our institute over a period of 13 years (2002–2015).

Results: MS presented mostly as a manifestation of relapsed acute myeloid leukemia, seen in 39% of patients. Skin and subcutaneous soft tissues were the most common sites of anatomic involvement (69.5%). Ninety five percent (n?=?19) were positive for classical myeloid markers with either cytochemical staining (chloracetate-esterase, MPO), flow-cytometry (CD33, CD34, CD13 and CD117), or immunohistochemistry (CD34, CD43, CD68 and lysozyme). Of these, 52% were positive for CD33 (n?=?12), 35% for CD68 (n?=?8), 30% for CD34 (n?=?7), and 26% for lysozyme (n?=?6). Cytogenetic abnormalities were seen in 63% (n?=?12/19) patients on bone-marrow aspirate, with five patients displaying a complex (n?=?3) or monosomal (n?=?2) karyotype. Twenty seven percent patients with a normal karyotype had presence of deleterious mutations (FLT3, ASXL, STAG and JAK2) on further testing with myeloid mutation panel. The Median overall survival (OS) of the entire cohort was 15.9 months (95% CI, 7.4–24.4 months). The OS was significantly better for patients <65 years (24.6 vs. 3.4 months, p?=?0.009) of age, and for those attaining a complete remission (CR) to induction therapy (25.7 vs. 0.8 months, p?Conclusion: Failure to achieve CR with induction therapy, and age >65 years are associated with poor outcomes in MS. Allogeneic stem-cell transplant in first remission appears to be the most effective modality for achieving long-term remissions.     

Disturbance of zinc and glucose homeostasis by methyl tert-butyl ether (MTBE); evidence for type 2 diabetes

1.?The prevalence of diabetes and the other metabolic disorders has noticeably increased worldwide. A causal link between increasing risk of type 2 diabetes and exposure to environmental pollutants has been reported.

2.?We hypothesized that exposure to methyl tert-butyl ether (MTBE), an oxygenate additive to gasoline would hinder zinc and glucose homeostasis in rats.

3.?Male Sprague–Dawley rats received MTBE in drinking water for 90 days. At the end of the treatment, pancreas and blood samples were collected for biochemical and molecular examinations. Expression of four candidate genes, including Insulin1, Insulin2, MT1A, SLC30A8 by Real-Time Quantitative PCR (Q-PCR) as well as biochemical parameters, including fasting blood glucose (FBS), triglycerides (TG), cholesterol (CHO), low-density lipoprotein (LDL), high-density lipoprotein (HDL), copper (Cu²⁺) and calcium (Ca²⁺) levels as well as High-sensitive C-reactive protein were assessed as endpoints.

4.?This study suggested that MTBE exposure can be associated with disruption in zinc homeostasis and glucose tolerance.     

Experimental doxycycline overdose in rats causes cardiomyopathy

All reports of doxycycline‐induced cardiomyopathy to date have been limited to accidental oral poisoning in calves. Therefore, the current study investigated the cardiomyotoxic effect of experimental doxycycline overdose in rats as a toxicity model which could be monitored using histopathological and biochemical assays. A total of 38‐week‐old male Wistar rats were divided into three groups consisting of 10 each. The first group was an untreated control group (D₀), and the second group (D₅) received doxycycline hyclate 25 mg/kg intragastrically twice daily (8 AM and 8 PM), which is 5‐fold higher than the standard dose. The third group (D₁₀) received 50 mg/kg intragastrically twice daily (8 AM and 8 PM), which is 10‐fold higher than the standard dose. The dose continued for 10 consecutive days and revealed that the doxycycline toxicity was dose dependent. Mortality was recorded in the D₁₀ group only (30%). The D₅ rats exhibited minimal skeletal muscle injury and slight but significant increases in the skeletal muscle damage indicators creatine kinase (CK) and aspartate aminotransferase (AST) compared to controls. The cardiac muscle of the D₅ rats was histologically normal, and the D₅ rats also exhibited normal levels of troponin I (cTnI), an indicator of cardiac muscle damage. In contrast, the D₁₀ rats displayed cardiomyopathy, as well as significant increases in the muscle enzymes alanine aminotransferase (ALT), AST and CK and the cardiac damage indicator cTnI compared to control and D₅ groups. Pulmonary lesions were observed in the D₁₀ rats, primarily cardiac lesion‐related alveolar heart failure cells. Thus the present study is the first to demonstrate that oral doxycycline poisoning (10 times the therapeutic dose)‐induced cardiomyopathy is not limited to calves and could occur without any predisposing factors.     

Activation of central GABAB receptors offsets the cyclosporine counteraction of endotoxic cardiovascular outcomes in conscious rats

We have previously shown that cyclosporine (CSA) counteracts cardiovascular manifestations induced by endotoxemia (lipopolysaccharide, LPS) such as hypotension and cardiac autonomic dysfunction in conscious rats. In this study, we investigated whether the facilitation of central γ‐amino butyric acid (GABA) neurotransmission blunts these favorable influences of CSA. The LPS‐CSA interaction was determined in the absence and presence of drugs that activate GABA_A or GABA_B receptors or elevate synaptic GABA levels in the central nervous system. The consequent i.v. administration of CSA (10 mg/kg) blunted the LPS‐evoked hypotension, tachycardia, and reductions in time‐ and frequency‐domain indices of heart rate variability (measures of cardiac autonomic control) evoked by LPS (10 mg/kg i.v.). The ability of CSA to reverse the LPS effects disappeared in rats treated intracisternally (i.c.) with baclofen (selective GABA_B agonist, 2 μg/rat) but not muscimol (selective GABA_A agonist, 1 μg/rat), indicating a preferential compromising action for central GABA_B receptors on the advantageous effects of CSA. Moreover, the improvement by CSA of LPS‐evoked cardiovascular derangements was also eliminated after concurrent i.c. administration of vigabatrin (GABA transaminase inhibitor, 200 μg/rat) or tiagabine (GABA reuptake inhibitor, 100 μg/rat). These results demonstrate that the activation of central GABA_B receptors either directly via baclofen or indirectly following interventions that boost GABA levels in central synapses counterbalances the rectifying action of CSA on endotoxemia.     

Expression of thioredoxin and glutaredoxin in experimental hepatocellular carcinoma—Relevance for prognostic and diagnostic evaluation

Hepatocellular carcinoma (HCC), represents more than 85% of liver cancers. The diagnosis of HCC may be delayed due to the absence of early, sensitive and specific biomarkers. This study was conducted to investigate whether the expression of thioredoxin (Trx) and glutaredoxin (Grx) is helpful for HCC diagnosis in an experimental model. Twenty male albino rats were equally divided into two groups (HCC and control). Hepatocarcinogenesis was performed by single intraperitoneal (i.p) injection of 200?mg/kg of diethylnitrosamine (DENA). Two weeks later, 0.05% of phenobarbital (PB) was supplied in the drinking water for other 14 weeks. HCC was diagnosed by measuring serum alpha-fetoprotein (AFP) level and histopathological examination. Our results found that hepatic indices alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin were elevated but decreased total protein level. Lipid peroxidation was elevated through increasing hepatic content of MDA with decreased antioxidant parameters like hepatic SOD, CAT activities and GSH. The current study also found that Trx and Grx tissue genes were overexpressed in HCC group significantly, compared to control group. This study substantiated that increased expression of these enzymes may be predictive of outcomes in HCC.