Rabbits fed cholesterol-enriched diets exhibit pathological features of inclusion body myositis

Sporadic inclusion body myositis (IBM) is the most common age-related muscle disease in humans; however, its etiology is unknown, there are few animal models for this disease, and effective treatments have not been identified. Similarities between pathological findings in Alzheimer's disease brain and IBM skeletal muscle include increased levels of amyloid precursor protein (APP) and amyloid beta-protein (Abeta). Moreover, there have been suggestions that elevated levels of free cholesterol might participate in the pathogenesis of Alzheimer's disease and IBM due, in part, to its role in Abeta generation. Here, we tested the hypothesis that rabbits fed cholesterol-enriched diets might faithfully exhibit human-like IBM pathological features. In skeletal muscle of one-third of the female rabbits fed cholesterol-enriched diet but not control diet, we found features of IBM, including vacuolated muscle fibers, increased numbers of mononuclear inflammatory cells, increased intramuscular deposition of Abeta, hyperphosphorylated tau, and increased numbers of muscle fibers immunopositive for ubiquitin. The cholesterol-enriched diet increased mRNA and protein levels of APP, increased the protein levels of betaAPP cleaving enzyme, and shifted APP processing in favor of Abeta production. Our study has demonstrated that increased ingestion of high levels of dietary cholesterol can result in pathological features that resemble IBM closely and thus may serve as an important new model with which to study this debilitating disorder.     

Association of angiotensin-converting enzyme (ACE) gene insertion–deletion polymorphism with spondylarthropathies

Summary Low back pain (LBP) is a common medical problem. Interaction between genetic and environmental factors predisposes individuals to LBP even at an early age. Inflammatory back pain or spondylarthropathies include ankylosing spondylitis (AS), psoriatic arthritis (PSA), reactive arthritis enteropathic and undifferentiated arthropathies. Angiotensin-converting enzyme (ACE) plays an important role in circulatory homeostasis, physiology of vasculature and inflammation. The insertion–deletion (I/D) polymorphism of the ACE gene has been shown to determine the plasma and tissue levels of ACE especially in the synovial fluid. The aim of this study was to investigate an association between ACE gene I/D polymorphism and inflammatory back pain (spondylarthropathies) secondary to ankylosing spondylitis (AS), psoriatic arthritis, inflammatory bowel disease and undifferentiated spondylarthropathies. The prevalence of ACE gene I/D polymorphism genotypes was determined in 63 patients with inflammatory back pain by polymerase chain reaction (PCR) and compared with that in 111 healthy controls. Of the 63 patients studied, 45 (71.4%) were with AS, 13 (20.6%) were with PSA, 4 (6.3%) were with reactive arthropathy and 1 (1.6%) manifested undifferentiated arthropathy. There were 43 males and 20 females. Mean age of patients was 39.0 ± 11.36 years, age at onset of spondylarthropathy was 27.7 ± 7.49 years and disease duration was 10.3 ± 7.74 months. The controls were selected to match with the patients group in terms of gender ratio, age and ethnicity. The ACE gene polymorphism showed an overall significant difference between patients and controls (p = 0.050). When the ID and II genotype frequency was combined and compared with that for DD genotype amongst patient and control groups, a considerably higher incidence was detected for ID and II genotypes than the DD genotype in spondylarthropathy patients compared to that in the controls (p = 0.036). This study showed a significant association of the I-allele of ACE gene I/D polymorphism with spondylarthropathy in Kuwaiti Arabs.     

Tear cytokine and ocular surface alterations following brief passive cigarette smoke exposure

Purpose: To prospectively investigate the effects of acute passive cigarette smoke exposure on the ocular surface and tear film in healthy non-smokers. Methods: Twelve right eyes of 12 subjects without any ocular diseases were examined before, 5 min, and 24 h after 5 min of passive cigarette smoke exposure in a controlled smoke chamber. Tear samples were obtained before, 5 min and 24 h after smoke exposure to detect tear hexanoyl-lysine (HEL), acrolein and inflammatory cytokine concentrations. Tear evaporation rate, DR-1 tear film lipid layer interferometry, tear film break-up time (TBUT), ocular surface fluorescein staining (FS) and Rose Bengal staining (RB), Schirmer I test were performed before, 5 min, and 24 h after smoke exposure. Conjunctival impression cytology (IC) and brush cytology (BC) were carried out before and 24 h after smoke exposure. Results: Tear evaporation rate, tear lipid spread time, tear film break-up time, and vital staining scores showed significant worsening with passive smoke exposure. Tear HEL and IL-6 concentrations increased significantly 24 h after smoke exposure. Tear acrolein level showed an insignificant increase at 5 min. IC and RT-PCR revealed a significant reduction in goblet cell density, a shift toward higher squamous metaplasia grades and a significant downregulation of MUC5AC mRNA expression at 24 h. Conclusion: Even brief passive exposure to cigarette smoke in healthy non-smoker subjects was associated with adverse effects on the ocular surface health as evidenced by an increase of tear inflammatory cytokines, tear lipid peroxidation products and decrease of mucosal defense resulting in tear instability and damage to the ocular surface epithelia.     

Adsorption of Cd(II) ions from aqueous solutions using activated carbon prepared from olive stone by ZnCl2 activation

This study is aimed to remove Cd(II) ions from aqueous solutions by adsorption. As adsorbent, activated carbon prepared from olive stone, an agricultural solid by-product was used. Different activating agent (ZnCl(2)) amounts and adsorbent particle size were studied to optimize adsorbent surface area. The adsorption experiments were conducted at different parameters such as, adsorbent dose, temperature, equilibrium time and pH. According to the experiments results, the equilibrium time, optimum pH, adsorbent dosage were found 60 min, pH > 6 and 1.0 g/50 ml respectively. The kinetic data supports pseudo-second order model and intra-particle model but shows very poor fit for pseudo-first order model. Adsorption isotherms were obtained from three different temperatures. These adsorption data were fitted with the Langmuir and Freundlich isotherms. In addition, the thermodynamic parameters, standard free energy (DeltaG(0)), standard enthalpy (DeltaH(0)), standard entropy (DeltaS(0)) of the adsorption process were calculated. To reveal the adsorptive characteristics of the produced active carbon, BET surface area measurements were made. Structural analysis was performed using SEM-EDS. The resulting activated carbons with 20% ZnCl(2) solution was the best sample of the produced activated carbons from olive stone with the specific surface area of 790.25 m(2)g(-1). The results show that the produced activated carbon from olive stone is an alternative low-cost adsorbent for removing Cd(II).     

Intracerebroventricular serotonin reduces the degree of acute hypoxic ventilatory depression in peripherally chemodenervated rabbits

Hypoxia causes changes in the rate of synthesis or release of neurotransmitters in the brain. The accumulation of serotonin (5-HT) in the central nervous system might cause hypoxic respiratory depression. In the present study, we aimed to examine the role of central 5-HT on normoxic and acute hypoxic ventilatory depression (AHVD) in peripheral chemoreceptors denervated rabbits. All experiments were performed in peripherally chemodenervated rabbits anesthetized with intravenous injection of urethane (400 mg/kg) and alpha-chloralose (40 mg/kg). For intracerebroventricular (ICV) administration of 5-HT (20 microg/kg) and ketanserin (10 microg/kg), a cannula was placed in left lateral ventricle by stereotaxic method. Respiratory frequency (fR), tidal volume (VT), ventilation minute volume (VE) and systemic arterial bood pressure (BP) were recorded in each experimental phases and mean arterial pressure was calculated (MAP). Heart rate (HR) was also determined from the pulsation of BP. The effects of ICV serotonin and ICV ketanserin on the indicated parameters during air breathing (normoxia) and breathing of hypoxia (8% O2--92% N2) were investigated. During hypoxia, fR, VT, VE, MAP and HR decreased, and AHVD was thus obtained. ICV injection of 5-HT during normoxia caused significant increases in VT (P < 0.001) and in VE (P < 0.01). On the other hand, ICV 5-HT injection reduced the degree of AHVD in peripherally chemodenervated rabbits during hypoxia (fR; P < 0.05, VT; P < 0.05 and VE; P < 0.01). After ICV injection of ketanserin, the enhancement of 5-HT on VE was prevented during normoxia. On the breathing of hypoxic gas after ICV ketanserin, the degree of AHVD was augmented. In conclusion, our findings suggested that central 5-HT increases normoxic ventilation and reduces the degree of AHVD during hypoxia and that ICV ketanserin prevents the stimulatory effect of 5-HT on respiration and augments AHVD.     

Production, purification and characterization of beta-1,4-endoglucanase from a novel bacterial strain CTP-09 of a Bacillus sp

Bacillus strain CTP-09 yielded maximum productivity (1120 IU/L.h) of extracellular endoglucanase (CMCase) on 0.5% cellobiose after 10 h fermentation at 55 degrees C. The purified enzyme is mono-meric in nature and exhibits stability up to 80 degrees C and over a pH range (6.0-9.0). Activation energy, enthalpy and entropy of catalysis, and inactivation indicated that this CMCase is highly thermos-table. Purified enzyme possessed high power of defibrillation of textile and was minutely inhibited by anionic detergent and oxidizing agent comparable with inhibition by commercial enzyme. This polypeptide could be exploited for mass production and application in local industries.     

Formulation, Release Characteristics and Bioavailability Study of Oral Monolithic Matrix Tablets Containing Carbamazepine

This study examined the release of carbamazepine (CBZ) from hydrophobic (Compritol 888 ATO) and hydrophilic-hydrophobic matrix combination (Compritol 888 ATO-hydroxpropyl methylcellulose, HPMC). Hydrophobic matrix tablets were prepared by hot fusion technique, while hydrophilic-hydrophobic matrix tablets were prepared by wet granulation technique. The properties of the compressed matrix tablets were determined according to the US Pharmacopoeia. Both matrix formulations displayed a controlled-release profile when compared to the reference formulation (Tegretol CR 200). The bioavailability of CBZ formulations and Tegretol CR 200 were evaluated in beagle dogs. Carbamazepine presented a significant higher bioavailability from matrix tablets containing hydrophilic polymer (HPMC) than that obtained from Tegretol CR200. The average inter-subject plasma concentration variability CV% was the least with tablet containing hydrophilic polymer (HPMC) and was the highest with Tegretol CR 200 (33.8 and 54.1, respectively). Analysis of variance applied to log AUC(0-alpha) and log C(max) showed statistical significant differences among the three formulations (P < 0.05). Plotting the fraction of CBZ released in vitro and fraction absorbed showed a statistically significant relationship (R(2) = 0.935-0.975) for the three matrix tablets examined.     

The investigation of the antioxidative properties of the novel synthetic organoselenium compounds in some rat tissues

DMBA (7,12-dimethylbenz[a]anthracene) is a polycyclic aromatic hydrocarbon (PAH) known to cause tumors in rats. Selenium is an essential element with physiological non-enzymatic antioxidant properties. Because of the health problems induced by many environmental pollutants, many efforts have been undertaken in evaluating the relative antioxidant potential of selenium and synthetic organoselenium compounds. In this study, adult female Wistar rats were treated with DMBA and the novel organoselenium compounds (1-isopropyl-3-methylbenzimidazole-2-selenone [SeI] and 1,3-di-p-methoxybenzylpyrimidine-2-selenone [SeII]) in the determined doses. The protective effects of novel synthetic organoselenium compounds (SeI and SeII) against DMBA-induced changes in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities and total glutathione (GSH) and malone-dialdehyde (MDA) levels of rat heart and brain were investigated. It was determined that SeI and SeII fully or partially restored enzyme activity. It was also found that lipid peroxidation was also decreased in SeI and SeII treated groups. Consequently, it was determined that novel synthetic organoselenium compounds (SeI and SeII) provided protection of antioxidant activity, and protection against lipid peroxidation measured as MDA in SeI and SeII treated groups was provided by novel synthesized organoselenium compounds. The ability of the organoselenium compounds to prevent oxidative damage induced by DMBA in rats was rationalized.     

A novel genotype c.1228C>G/c.1448C-1498C (L371V/Rec-NciI) in a 3-year-old child with type 1 Gaucher disease

Gaucher disease (GD) is an autosomal recessive inborn error of metabolism, resulting from a deficiency of the enzyme glucocerebrosidase, causing an accumulation of the glycolipid glucocerebroside within lysosomes of macrophages in the reticuloendothelial system. Three major clinical forms have been assigned and more than 200 gene mutations have been identified. We herein report a Lebanese boy born with a novel combined mutation L371V/Rec-NciI, who presented with moderate-severe type 1 GD. An overview of the clinical and biomarker improvement following enzyme replacement therapy with imiglucerase is described in a follow-up of 30 months. Imiglucerase seems to be efficacious in decreasing the severity of the disease associated with this mutation. However, a high dose may be required to achieve optimal growth, platelet count, and hemoglobin level.