Brain Neuronal Degeneration Caused by Episodic Alcohol Intoxication in Rats: Effects of Nimodipine, 6,7-Dinitro-quinoxaline-2,3-dione, and MK-801

Rats repeatedly intoxicated with alcohol (ethanol, three times daily) over a 4-day period display neuronal degeneration in the dentate gyrus; entorhinal, piriform, insular, orbital, and perirhinal cortices; and in the olfactory nerve fibers and terminals in the olfactory bulb. Postulating a role for excitotoxicity, we have attempted to prevent the degeneration using antagonists that are neuroprotective in this type of brain damage. In an initial study, continuous subcutaneous infusion of a high dose of the glutamate/NMDA receptor antagonist MK-801 (2 mg/kg/day) by itself caused extensive neuronal degeneration in several brain regions and severe behavioral intoxication that precluded survival if combined with high blood alcohol levels (～300 mg/dl). Moreover, the lower, nonneurotoxic blood alcohol levels (～150 mg/dl) that were compatible with survival worsened the MK-801-induced brain damage. In a subsequent experiment, daily intraperitoneal injections of a lower dose of MK-801 (1 mg/kg/day) resulted in no MK-801 toxicity and, when combined with neurotoxic levels of alcohol, no reduction in alcohol-induced neurotoxicity. Nimodipine, a voltage-gated Ca²⁺ channel blocker, reduced the neuronal damage in the dentate gyrus, but greatly increased it in the piriform cortex when administered intragastrically at 600 mg/kg/day; it provided no protection from alcohol-dependent degeneration when given intragastrically at 100 mg/kg/day. Continuous intracere-broventricular delivery of 0.24 to 0.29 mg/day of 6,7-dinitro-quinoxa-line-2,3-dione, a glutamate/α-amino-3-hydroxy-5-methyl-4-isoxazole receptor antagonist, failed to diminish alcohol-dependent neuronal damage in any brain region. We conclude that brain damage from episodic “binge” alcohol intoxication is not primarily mediated by excitotoxic mechanisms, implying that other, nonexcrtotoxic pathophysiological mechanisms, are involved. Furthermore, MK-801, far from protecting from the alcohol-induced damage, at high doses causes widespread neuropathology that is significantly potentiated by alcohol.     

Imaging-Based Diagnosis of Autosomal Dominant Polycystic Kidney Disease

The clinical use of conventional ultrasonography (US) in autosomal dominant polycystic kidney disease (ADPKD) is currently limited by reduced diagnostic sensitivity, especially in at-risk subjects younger than 30 years of age. In this single-center prospective study, we compared the diagnostic performance of MRI with that of high-resolution (HR) US in 126 subjects ages 16–40 years born with a 50% risk of ADPKD who underwent both these renal imaging studies and comprehensive PKD1 and PKD2 mutation screening. Concurrently, 45 healthy control subjects without a family history of ADPKD completed the same imaging protocol. We analyzed 110 at-risk subjects whose disease status was unequivocally defined by molecular testing and 45 unaffected healthy control subjects. Using a total of >10 cysts as a test criterion in subjects younger than 30 years of age, we found that MRI provided both a sensitivity and specificity of 100%. Comparison of our results from HR US with those from a previous study of conventional US using the test criterion of a total of three or more cysts found a higher diagnostic sensitivity (approximately 97% versus approximately 82%) with a slightly decreased specificity (approximately 98% versus 100%) in this study. Similar results were obtained in test subjects between the ages of 30 and 40 years old. These results suggest that MRI is highly sensitive and specific for diagnosis of ADPKD. HR US has the potential to rival the diagnostic performance of MRI but is both center- and operator-dependent.     

Outcome of Transurethral Plasmakinetic Vaporization for Benign Prostatic Hyperplasia

Purpose

To assess the outcome of transurethral plasmakinetic vaporization (PKVP) in the management of benign prostatic hyperplasia (BPH).

Patients and methods

From August 2010 to May 2012, 60 patients with obstructive LUTS due to BPH were included in the study. All patients were evaluated by International Prostate Symptom Score (IPSS), general examination, digital rectal examination, PSA, routine laboratory examinations, pelvi-abdominal ultrasound, trans-rectal ultrasound, and uroflowmetry. Patients with Qmax of <10 mL/sec., an IPSS of >8 and a prostate volume of >40 mL underwent transurethral PKVP.

Results

Mean age of the patients was 66.8±4.5 years. The mean times of the operation, post-operative bladder irrigation, and post-operative catheterization were 63.8±13.9 minutes, 15.2±5.7 hours, and 23.9±5.2 hours, respectively. At 3 months of follow-up, there were significant reductions in the mean IPSS from 23.4±3.5 to 9.2±3.7 (P=0.4), mean PSA from 3.03±2.2 ng/mL to 1.2±1.04 ng/mL (P value=0.02), mean post voiding residual urine from 149.8±59.5 mL to 46.9±24.1 mL (P value <0.01), and mean prostate volume from 72.8±10.3 mL to 22.7±6.1 mL (P value <0.01). Also, there was a statistically significant increase in the mean Q max. from 8.7±2.4 mL/s to 19.5±3.5 mL/s (P value <0.01).

Conclusion

PKVP is an effective and safe treatment option in the management of symptomatic BPH.     

Inflammatory bowel disease in rats： Bacterial and chemical interaction

AIM：To develop a novel model of colitis in rats, using a combination of iodoacetamide and enteropathogenic E. coli（EPEC）, and to elucidate the pathophysiologic processes implicated in the development of ulcerative colitis （UC）.
METHODS： Hale Sprague-Dawley rats （/7 = 158） were inoculated intrarectally on a weekly basis with 4 different combinations： （a） 1% methylcellulose （HC）, （b） 100 μL of 6% iodoacetamide （IA） in 1% HC, （c） 200 p.L containing 4×10^8 colony factor units （CFU） of EPEC, and （d） combined treatment of （IA） followed by bacteria （13） after 2 d. Thirty days post treatment, each of the four groups was divided into two subgroups; the inoculation was stopped for one subgroup and the other subgroup continued with biweekly inoculation until the end of the experiment. Colitis was evaluated by the clinical course of the disease, the macroscopic and microscopic alterations, activity of myeloperoxidase （HPO）, and by TNF-α gene expression. RESULTS： Findings indicative of UC were seen in the combined treatment （IA ＋ B） as well as the IA continued treatment groups： the animals showed slow rate of increase in body weight, diarrhea, bloody stools, high colonic ulcer score, as well as histological alterations characteristic of UC, with an extensive inflammatory reaction. During the course of the experiment, the MPO activity was consistently elevated and the TNF-α gene expression was upregulated compared to the control animals.
CONCLUSION： The experimental ulcerative colitis model used in the present study resembles, to a great extent, the human disease. It is reproducible with characteristics indicative of chronicity.     

The Association of Diurnal Blood Glucose Variability With Subclinical Cardiac Disease in Patients With Type 2 Diabetes Mellitus

BackgroundThe relationship between glycemic control and the risk of cardiac disease in patients with Type 2 Diabetes Mellitus (T2DM) is controversial. 1,5-Anhydroglucitol (1,5-AG) is a biomarker of Glucose Variability (GV) and has been associated with clinical cardiovascular disease. However, its association with Subclinical Cardiac Disease (SCD) is unknown.Aim of the workStudy the association between GV and SCD.Subjects and methodsA cross-sectional study was conducted on 46 asymptomatic patients with T2DM as T2DM individuals group. Another 46 non-diabetic age and sex matched subjects were included as the healthy group. 1,5-AG was measured for all subjects. M-mode echocardiography in parasternal long axis view was used to measure Left Ventricular (LV) end diastolic dimension, LV end systolic dimension, ejection fraction, interventricular septum, LV posterior wall thickness, LV fractional shortening, left atrial dimension and aortic root dimension. Global Longitudinal Strain (GLS) was assessed by speckled tracking echocardiography.ResultsThere were no significant differences between both groups as regarding age, sex, BMI, AST, ALT, and serum creatinine. 1,5-AG was lower in T2DM individuals group. As regarding the echo parameters no significant difference found between both groups regarding left ventricular, left atrial and aortic root dimensions. T2DM individuals group showed a statistically significant higher mitral valve area, apical 2 chambers, apical 4 chambers, apical longitudinal axis and GLS. No correlation found between HbA1c and any echo parameters while 1,5-AG showed a significantly negative correlation with apical 2 chambers, apical 4 chambers, apical longitudinal axis and GLS. ROC curve analysis detected 1,5-AG less than 7.51 ng/ml as the best cut off value with sensitivity of 85.7%, specificity 75% to diagnose patients with T2DM and SCD.Conclusion1,5-AG might be used as an additional surrogate marker to identify patients with T2DM and SCD.     

Transgenerational sublethal effects of abamectin and pyridaben on demographic traits of Phytonemus pallidus (Banks) (Acari: Tarsonemidae)

In addition to determining the lethal effects, identifying sublethal effects of a pesticide is crucial to understanding the total impact a pesticide may have on a pest population. We determined the sublethal effects the two pesticides, abamectin and pyridaben, have on the cyclamen mite, Phytonemus pallidus (Banks) (Acari: Tarsonemidae)—a major pest of strawberry. Demographic traits of the P. pallidus progeny (F1 generation) produced by parents (F0 generation) treated with a low lethal concentration (LC₁₅) of abamectin and pyridaben were assessed using the age-stage, two-sex life table theory. The total longevity of the F1 generation (males = 10.78 days; female = 14.35 days) was the shortest in the progeny of the abamectin treated parents, differing significantly from the progeny of mites treated with pyridaben (males = 11.50 days, females = 15.63 days), and the control population (males = 13.50 days, females = 17.81 days). The intrinsic rates of increase (r) and the finite rates of increase (λ) of the progeny of abamectin (r = 0.0854 day⁻¹, λ = 1.0891 day⁻¹) and pyridaben (r = 0.0951 day⁻¹, λ = 1.0997 day⁻¹) treated parents were significantly lower than in the control mites (r = 0.1455 day⁻¹, λ = 1.1567 day⁻¹). The lowest fecundity (5.35 eggs/female), occurred in F1 female offspring of parents treated with LC₁₅ concentrations of abamectin, which was significantly lower than in the pyridaben (6.11 eggs/female) and control treatments (11.45 eggs/female). Transgenerational sublethal effects of abamectin and pyridaben in P. pallidus can be effectively used to for optimizing IPM programs against this pest on strawberries.