Protective effects of copper against aluminum toxicity on acetylcholinesterase and catecholamine contents of different regions of rat’s brain

The probable protective effects of copper on the acetylcholinesterase activity and the catecholamine levels in cerebellum, cortex and mid-brain of rat, which was intoxicated by aluminum, were studied during short and long terms. In this respect, male Wistar rats weighing 200–250 g were received daily intraperitoneal doses of aluminum, copper and also combined doses of both metals for 15 days (Al 10 mg kg^?1 BW and Cu 1 mg kg^?1 BW), 30 days (Al 5 mg kg^?1 BW and Cu 0.5 mg kg^?1 BW) and 60 days (Al 1 mg kg^?1 BW and Cu 0.1 mg kg^?1 BW), respectively. The results obtained from the short period of exposure (15 days) showed that aluminum produced significant (P < 0.05) decreases in the acetylcholinesterase activity by 24.14, 23.30 and 25.81 %. Similarly, the catecholamine levels were reduced by 10.69, 12.25 and 12.64 % in cerebellum, cortex and mid-brain, respectively. Treatment with copper increases both acetylcholinesterase activity and catecholamine contents of cerebellum, cortex and mid-brain. Simultaneous injection of copper and aluminum increased both acetylcholinesterase activity and catecholamine contents in all three parts of rat brain when compared to aluminum-treated group. Same results were also observed following 30 and 60 days of exposures. In overall, it has been found that copper may have a protective-like ability to hinder aluminum toxicity in the brain.     

Visual consequences of electronic reader use: a pilot study

Background

With the increasing prevalence of electronic readers (e-readers) for vocational and professional uses, it is important to discover if there are visual consequences in the use of these products. There are no studies in the literature quantifying the incidence or severity of eyestrain, nor are there clinical characteristics that may predispose to these symptoms with e-reader use.

Purpose

The primary objective of this pilot study was to assess the degree of eyestrain associated with e-reader use compared to traditional paper format. The secondary outcomes of this study were to assess the rate of eyestrain associated with e-reader use and identify any clinical characteristics that may be associated with the development of eyestrain.

Methods

Forty-four students were randomly assigned to study (e-reader iPAD) and control (print) groups. Participant posture, luminosity of the room, and reading distance from reading device were measured during a 1-h session for both groups. At the end of the session, questionnaires were administered to determine symptoms.

Results

Significantly higher rates of eyestrain (p = 0.008) and irritation (p = 0.011) were found among the iPAD study group as compared to the print ‘control’ group. The study group was also 4.9 times more likely to report severe eyestrain (95 % CI [1.4, 16.9]). No clinical characteristics predisposing to eyestrain could be identified.

Conclusions

These findings conclude that reading on e-readers may induce increased levels of irritation and eyestrain. Predisposing factors, etiology, and potential remedial interventions remain to be determined.

     

Peroxisome proliferator-activated receptor-alpha agonist treatment in a transgenic model of type 2 diabetes reverses the lipotoxic state and improves glucose homeostasis

Abnormalities in insulin action are the characteristics of type 2 diabetes. Dominant-negative muscle-specific IGF-I receptor (MKR) mice exhibit elevated lipid levels at an early age and eventually develop type 2 diabetes. To evaluate the role of elevated lipids in the progression of the diabetic state, MKR mice were treated with WY14,643, a peroxisome proliferator-activated receptor (PPAR)-alpha agonist. WY14,643 treatment markedly reduced serum fatty acid and triglyceride levels within a few days, as well as muscle triglyceride levels, and subsequently normalized glucose and insulin levels in MKR mice. Hyperinsulinemic-euglycemic clamp analysis showed that WY14,643 treatment enhanced muscle and adipose tissue glucose uptake by improving whole-body insulin sensitivity. Insulin suppression of endogenous glucose production by the liver of MKR mice was also improved. The expression of genes involved in fatty acid oxidation was increased in liver and skeletal muscle, whereas gene expression levels of hepatic gluconeogenic enzymes were decreased in WY14,643-treated MKR mice. WY14,643 treatment also improved the pattern of glucose-stimulated insulin secretion from the perfused pancreata of MKR mice and reduced the beta-cell mass. Taken together, these findings suggest that the reduction in circulating or intracellular lipids by activation of PPAR-alpha improved insulin sensitivity and the diabetic condition of MKR mice.     

Genotype-phenotype correlation in Bruton's tyrosine kinase deficiency

Bruton's tyrosine kinase (Btk) belongs to the Tec family of nonreceptor protein tyrosine kinases. Mutations in the BTK gene cause X-linked agammaglobulinemia (XLA); a primary immunodeficiency disorder in human. No clear genotype-phenotype correlation has been established in XLA so far. To determine how differently mutations in BTK affect the severity of the disease and if BTK promoter polymorphic variant or intron 1 polymorphic variant in Tec, a cytoplasmic tyrosine kinase that might substitute for Btk, could contribute to the clinical phenotype, we analyzed the clinical and molecular findings in a cohort of XLA patients. Polymorphisms in BTK promoter and TEC intron 1 regions include substitutions of C>T (rs2071219) and T>C (rs2664019), respectively. Btk expression was evaluated by means of western immunoblotting and fluorescence-activated cell sorter analysis. Mutations were categorized as mild or severe and patients were evaluated for the clinical severity of disease. On the basis of the results, severe genotypes do not necessarily lead to severe phenotypes. More over, in a considerable number of patients with mild phenotype we showed a severe mutation with a tendency toward C substitution in the polymorphic site on TEC intron 1.     

Transplantation using hearts from primary pulmonary hypertensive donors for recipients with a high pulmonary vascular resistance

BACKGROUND: Transplantation for patients with a high pulmonary vascular resistance (PVR) carries an increased risk of mortality and right heart failure following heart transplantation and continues to be a major problem. We evaluated the use of hearts from patients who underwent heart and lung transplantation for primary pulmonary hypertension (PPH) as part of a domino procedure because these hearts have hypertrophied right ventricles used to increased pulmonary pressures, but could have a compromised left ventricle or irreversible damage of the right ventricle. METHODS: We reviewed 12 patients with PVR >4 Wood units who underwent orthotopic heart transplantation between 1989 and 1998 using hearts from donors with PPH as part of a domino procedure. RESULTS: We studied 10 men and 2 women, mean age 42.9 years. Mean PVR was 5.3 (range, 4-9) Wood units. Mean ischemia time was 85.3 minutes, and mean donor age was 32 years. Actuarial survival was 75% at 1 year and 75% at 5 years. In the early post-operative period, 3 patients had temporary arrhythmias, 2 required permanent pacemaker implantation, 1 had atrial fibrillation, and 1 had ventricular tachycardia that required defibrillator implantation. At a mean follow-up of 7.8 years, 2 patients had developed asymptomatic transplant coronary disease (both at 8.5 years after transplantation), 1 moderate and 1 very mild; the rest had none. Mean left ventricular ejection fraction at latest follow-up was 70.1% (range, 63%-78%). Right ventricular function assessed clinically and by echocardiography was adequate in the short and long term. CONCLUSIONS: Our results suggest that heart and lung recipients with PPH can provide useful donor hearts to patients with increased PVR and that these hearts function well in the intermediate and long term.     

Lithium and valproate protect against dextro-amphetamine induced brain choline concentration changes in bipolar disorder patients.

BACKGROUND: Lithium may affect brain choline concentrations, and this effect has been proposed to potentially explain its clinical efficacy. Since dextro-amphetamine is a useful human model of mania, we were interested in determining firstly whether dextro-amphetamine would alter brain choline concentrations, and secondly to determine if lithium would protect against any such changes in bipolar patients. In addition, we wanted to determine if valproate would also have any effects upon choline levels. METHODS: Healthy controls (n=18) were compared with euthymic Bipolar Disorder patients (Type I and Type II) who were taking lithium (n=14) or valproate (n=11). We utilized (1)H-magnetic resonance spectroscopy ((1)H-MRS) in a 3.0T scanner to examine brain choline/phosphocholine+creatine (Cho/Cr) ratios. Changes in this ratio were measured to determine any changes in choline concentrations in the temporal lobe. RESULTS: The results showed that administration of dextro-amphetamine decreased the Cho/Cr ratios. In contrast, in both the lithium-treated and valproate-treated patients this decrease was not seen; this attenuation in the change in Cho/Cr ratio changes was statistically significant. It should be noted that Cho/Cr ratios were significantly higher at baseline in the controls compared to both groups of patients, which may have influenced the results. CONCLUSIONS: These findings are the first to examine the effects of dextro-amphetamine on brain choline concentrations. They show that while in controls dextro-amphetamine decreases choline concentrations, lithium and valproate both appear to protect against this effect in bipolar patients. However, as brain ratios were measured rather than the absolute concentration of choline, and these ratios were lowered in patients at baseline, these results must be regarded as preliminary and require replication in future studies.     

Prenatal Exposure to Phthalic Acid Induces Increased Blood Pressure,Oxidative Stress,and Markers of Endothelial Dysfunction in Rat Offspring

Previous studies have reported the harmful effects of exposure to phthalic acid (PA) on heart. No studies have reported the effects of prenatal PA exposure on the structure or function of heart. The current study aimed to investigate the effects of prenatal PA exposure on the markers of oxidative stress and cardiac structure in rats’ offspring. Twenty-four pregnant rats were randomly categorized into three groups of control, exposed to 2.5 and 5 % PA. The morphometric properties of coronary arteries, markers of oxidative stress, and NOS activity were measured in offspring rats. By a dose-dependent manner, the body weight (BW), heart weight (HW), and HW/BW of the intervention groups were reduced and their heart rate and blood pressure were conversely increased compared to the control group. Also, the wall thickness, cross-sectional area of the aorta and septal branch of the descending left coronary artery were significantly increased in the intervention group. In addition, PA significantly increased the level of malondialdehyde and decreased the level of superoxide dismutase and glutathione peroxidase, compared to the control group. This study revealed that prenatal exposure of rats to PA causes vascular dysfunction, increasing oxidative stress, and reduction in cardiac nitric oxide synthetase activity among offspring rats.