Antibody-Mediated Osseous Regeneration for Bone Tissue Engineering in Canine Segmental Defects.

Among many applications of therapeutic monoclonal antibodies (mAbs), a unique approach for regenerative medicine has entailed antibody-mediated osseous regeneration (AMOR). In an effort to identify a clinically relevant model of craniofacial defect, the present study investigated the efficacy of mAb specific for bone morphogenetic protein- (BMP-) 2 to repair canine segmental mandibular continuity defect model. Accordingly, a 15 mm unilateral segmental defect was created in mandible and fixated with a titanium plate. Anorganic bovine bone mineral with 10% collagen (ABBM-C) was functionalized with 25 µg/mL of either chimeric anti-BMP-2 mAb or isotype-matched mAb (negative control). Recombinant human (rh) BMP-2 served as positive control. Morphometric analyses were performed on computed tomography (CT) and histologic images. Bone densities within healed defect sites at 12 weeks after surgery were 1360.81 ± 10.52 Hounsfield Unit (HU), 1044.27 ± 141.16 HU, and 839.45 ± 179.41 HU, in sites with implanted anti-BMP-2 mAb, rhBMP-2, and isotype mAb groups, respectively. Osteoid bone formation in anti-BMP-2 mAb (42.99% ± 8.67) and rhBMP-2 (48.97% ± 2.96) groups was not significantly different but was higher (p < 0.05) than in sites with isotype control mAb (26.8% ± 5.35). In view of the long-term objective of translational application of AMOR in humans, the results of the present study demonstrated the feasibility of AMOR in a large clinically relevant animal model.

Diabetes, trekking and high altitude: recognizing and preparing for the risks.

Although regular physical activity is encouraged for individuals with diabetes, exercise at high altitude increases risk for a number of potential complications. This review highlights our current understanding of the key physiological and clinical issues that accompany high-altitude travel and proposes basic clinical strategies to help overcome obstacles faced by trekkers with Type 1 or Type 2 diabetes. Although individuals with diabetes have adaptations to the hypoxia of high altitude (increased ventilation, heart rate, blood pressure and hormonal responses), elevated counter-regulatory hormones can impair glycaemic control, particularly if mountain sickness occurs. Moreover, high-altitude-induced anorexia and increased energy expenditure can predispose individuals to dysglycaemia unless careful adjustments in medication are performed. Frequent blood glucose monitoring is imperative, and results must be interpreted with caution because capillary blood glucose meter results may be less accurate at high elevations and low temperatures. It is also important to undergo pre-travel screening to rule out possible contraindications owing to chronic diabetes complications and make well-informed decisions about risks. Despite the risks, healthy, physically fit and well-prepared individuals with Type 1 or Type 2 diabetes who are capable of advanced self-management can be encouraged to participate in these activities and attain their summit goals. Moreover, trekking at high altitude can serve as an effective means to engage in physical activity and to increase confidence with fundamental diabetes self-management skills.

Preventive effect of methanolic extract of Zataria Multiflora Boiss on liver toxicity of paracetamol in rats.

Background: The analgesic paracetamol causes a potentially fatal, centrilobular hepatic necrosis when taken in misuse and overdose. This research aimed to evaluate the protective effects of methanolic extract of Zataria Multiflora Boiss (Z. Multiflora) against hepatic damage induced by paracetamol-induced hepatotoxicity in male Wistar rats. Methods: for this purpose, paracetamol was administrated orally at a dose of 2 g/ kg body weight (b.w.)/ day on the seventh day after the oral administration of a methanolic extract of Z. Multiflora at doses of 100 mg/ kg, 200 mg/ kg and 400 mg/ kg b.w. The lipid peroxidation level and activities of liver aminotransferases and enzymes contributing to the oxidative damage were measured in serum, and a histopathological examination of liver sections was also performed. Results and Discussion: The results showed that Z. Multiflora reduced the activity of aminotransferases in rats treated with paracetamol. This extract also inhibited lipid peroxidation and protein carbonylation by an increase in the activity of the antioxidant enzyme and the elevation of glutathione content of the liver. Conclusion: These effects are related to the antioxidant compounds of Z. Multiflora. The methanolic extract of this herb exhibits protective effects against paracetamol-induced hepatotoxicity.

Hepatoprotective effect of Zataria Multiflora Boisson cisplatin-induced oxidative stress in male rat.

Background: This research aimed to evaluate the protective effects of methanolic extract of Zataria Multiflora Boiss (Z. Multiflora) against hepatic damage induced by cisplatin in male Wistar rats. Methods: Hepatotoxicity was induced in Wistar male rats by a single intraperitoneal administration of cisplatin, 7 g/ kg body weight. A methanolic extract of Z. Multiflora was administered orally at doses of 50 mg/ kg, 100 mg/ kg, 200 mg/ kg and 400 mg/ kg body weight daily for seven days after being cisplatin-induced. The study included the histopathological examination of the liver sections. The activity of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were evaluated as markers of liver damage. The superoxide dismutase (SOD), the activity of Catalase (CAT), and glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) and nitric oxide (NO) content in serum were measured as an oxidative stress factor. Results: The results showed that rat treated with cisplatin resulted in a significant increase in serum activity, AST, ALT and ALP in treated mice. Management with Z. Multiflora reduced the business of these enzymes to nearly normal levels. In parallel with these changes, this extract reduced cisplatin-induced oxidative stress by inhibiting lipid peroxidation and protein carbonylation, and restoring the antioxidant enzyme (SOD, CAT, and GSH-Px) and elevation of the glutathione level. Conclusion: Biochemical and histological observations showed the hepatoprotective effect was found in a dose-dependent manner in Z. Multiflora methanolic extract. This protective effect can be attributed to the antioxidant compounds.

Review of evidence for dietary influences on atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting children and adolescents worldwide. The relationship of AD to diet has been a matter of curiosity for many years. Here we look at the evidence in the literature of the association between AD and diet, and the effectiveness of elimination diets and diet supplementation in the management of AD. Several studies have found an association between clinical food allergy and AD, and more recent investigations have also suggested that dietary elements may promote late AD exacerbations. Diet elimination trials in select patients who are clinically allergic to eggs have shown promise in reducing symptoms. Additionally, elimination of food additives in a subgroup of patients was found to be beneficial. Finally, diet supplementations with evening primrose oil and an omega-3 fatty acid (docosahexaenoic acid) may be appropriate in certain AD candidates.

A systematic review on the nerve-muscle electrophysiology in human organophosphorus pesticide exposure.

This article presents a systematic review of the recent literature on the scientific support of electromyography (EMG) and nerve conduction velocity (NCV) in diagnosing the exposure and toxicity of organophosphorus pesticides (OP). Specifically, this review focused on changes in EMG, NCV, occurrence of intermediate syndrome (IMS), and OP-induced delayed polyneuropathy (OPIDN) in human. All relevant bibliographic databases were searched for human studies using the key words "OP poisoning", "electromyography", "nerve conduction study," and "muscles disorders". IMS usually occurs after an acute cholinergic crisis, while OPIDN occurs after both acute and chronic exposures. Collection of these studies supports that IMS is a neuromuscular junction disorder and can be recorded upon the onset of respiratory failure. Due to heterogeneity of reports on outcomes of interest such as motor NCV and EMG amplitude in acute cases and inability to achieve precise estimation of effect in chronic cases meta-analysis was not helpful to this review. The OPIDN after both acute and low-level prolonged exposures develops peripheral neuropathy without preceding cholinergic toxicity and the progress of changes in EMG and NCV is parallel with the development of IMS and OPIDN. Persistent inhibition of acetylcholinesterase (AChE) is responsible for muscle weakness, but this is not the only factor involved in the incidence of this weakness in IMS or OPIDN suggestive of AChE assay not useful as an index of nerve and muscle impairment. Although several mechanisms for induction of this neurodegenerative disorder have been proposed as were reviewed for this article, among them oxidative stress and resulting apoptosis can be emphasized. Nevertheless, there is little synchronized evidence on subclinical electrophysiological findings that limit us to reach a strong conclusion on the diagnostic or prognostic use of EMG and NCV for acute and occupational exposures to OPs.

Mechanisms of muscular electrophysiological and mitochondrial dysfunction following exposure to malathion, an organophosphorus pesticide.

Muscle dysfunction in acute organophosphorus (OP) poisoning is a cause of death in human. The present study was conducted to identify the mechanism of action of OP in terms of muscle mitochondrial dysfunction. Electromyography (EMG) was conducted on rats exposed to the acute oral dose of malathion (400 mg/kg) that could inhibit acetylcholinesterase activity up to 70%. The function of mitochondrial respiratory chain and the rate of production of reactive oxygen species (ROS) from intact mitochondria were measured. The bioenergetic pathways were studied by measurement of adenosine triphosphate (ATP), lactate, and glycogen. To identify mitochondrial-dependent apoptotic pathways, the messenger RNA (mRNA) expression of bax and bcl-2, protein expression of caspase-9, mitochondrial cytochrome c release, and DNA damage were measured. The EMG confirmed muscle weakness. The reduction in activity of mitochondrial complexes and muscular glycogen with an elevation of lactate was in association with impairment of cellular respiration. The reduction in mitochondrial proapoptotic stimuli is indicative of autophagic process inducing cytoprotective effects in the early stage of stress. Downregulation of apoptotic signaling may be due to reduction in ATP and ROS, and genotoxic potential of malathion. The maintenance of mitochondrial integrity by means of artificial electron donors and increasing exogenous ATP might prevent toxicity of OPs.

Effect of fasting in Ramadan on body composition and nutritional intake: a prospective study.

BACKGROUND: The present study aimed to assess the effects of Ramadan intermittent fasting on body weight and composition and the effects of age and sex. METHODS: Body weight, height, waist and hip circumferences were measured, body mass index (BMI) was calculated and fat mass, fat-free mass and percentage body fat were assessed by bioelectrical impedance on 240 adult subjects (male: 158) who fasted between sunrise and sunset for at least 20 days. Measurements were taken 1 week before and 1 week after Ramadan. Energy and macronutrient intakes were assessed using a 3-day food frequency questionnaire on a sub-sample of subjects before and during Ramadan. RESULTS: Subjects were grouped according to age and sex: ≤35 years (n = 82, males: 31) and 36-70 years (n = 158, males: 127). There were significant reductions in weight and BMI (P < 0.001) in almost all subjects, with the biggest being in males ≤35 years [-2.2% (SE 2.2%), P < 0.001]. Waist and hip circumferences fell in most subjects, except females aged 36-70 years. Fat mass fell in most subjects, ranging from 2.3% to 4.3% from baseline, except in females aged 36-70 years who did not experience a significant change. Fat-free mass was significantly reduced in all subjects (P < 0.001), whereas percentage body fat was lower only in males by 2.5% (SE 3.2%) (P = 0.029) in those aged ≤35 years and by 1.1% (SE 1.5%) (P < 0.001) in those aged 36-70 years. Dietary intake was similar before and during Ramadan, except in males whose protein intake fell during Ramadan (P = 0.032). CONCLUSIONS: Ramadan fasting leads to weight loss and fat-free mass reductions. Body composition changes vary depending on age and sex.

Effect of Ramadan fasting on glycemic control in patients with Type 2 diabetes.

BACKGROUND: Although Muslim patients with Type 2 diabetes may be exempt from fasting during Ramadan for medical reasons, a high proportion of them fast. AIM: To investigate the association between Ramadan fasting and glycemic control in patients with Type 2 diabetes. SUBJECTS AND METHODS: A prospective cohort clinical trial was designed. Eighty-eight patients with Type 2 diabetes (45 male, 43 female, age 51±10 yr) who opted to fast for at least 10 days during the month of Ramadan were recruited. Fasting blood samples were taken at the beginning and end of Ramadan, and 1 month after Ramadan, to assess fasting blood glucose (FBG), fasting insulin, full blood count, glycated hemoglobin (HbA(1c)) and fasting lipid profile. Insulin resistance was estimated using the homeostatic model assessment. Anthropometrics and blood pressure were also measured. RESULTS: There was a significant deterioration in FBG and HbA(1c) (p=0.002 and p≤0.001, respectively) and significant improvements in HDL and LDL cholesterol and body mass index after Ramadan (p<0.001). Interestingly, HbA(1c) showed a reduction 1 month after Ramadan (9.4±2% at the end of Ramadan vs 8.4±2.5% 1 month after Ramadan; p<0.001). CONCLUSION: Results from this study showed that fasting during Ramadan deteriorated the glycemic control in Type 2 diabetes patients. This was more evident in patients using oral hypoglycemic medication than diet- controlled patients. However, Ramadan fasting had small positive effects on lipid profile and body weight.

Extraction and purification of crocin from saffron stigmas employing a simple and efficient crystallization method.

In this study, total crocin was extracted from saffron stigmas using crystallization method. Ethanol 80% was selected as the best extraction solvent. Crystallization process was carried out in one and two steps at different temperatures. Ethanol 80% was used as crystallization medium. Crocin crystals obtained from the first crystallization had low purity and thus were subjected to the second crystallization. The higher purity crystals were yielded in the second crystallization at -5 degrees C. The purity of crocin crystals was studied using UV-visible spectrophotometery and HPLC in comparison with Fluka product and methanolic extract of saffron stigmas. The results indicated that its purity was extremely higher, about 13 times, more than Fluka product. In spite of our expectation, the Fluka product was not a pure alpha-crocin sample; five other types of crocins in addition to an unknown impurity were seen in its chromatogram. The purity of crystallized total crocin in this work was more than 97%.

Determination of polychlorinated biphenyl congeners in water and sediment in North West Persian Gulf, Iran.

Polychlorinated biphenyl (PCB) was detected as isomer groups (congener numbers 28, 52, 101, 118, 138, 153 and 180) in the coastal water and sediment of four stations around Shadegan wetland protected area in the northwestern part of the Persian Gulf. Total PCB concentration range was 8-375 ng/L in water and 3.4-50.2 µg/g in sediment. Concentration of different congeners and chromatogram indicates that the source of PCB in this area can be Clophen A60; it used for long time in Iranian electronic industries. Other chlorinated hydrocarbons such as lindane, DDT and their metabolites were also present in the samples.

Isolation, characterization and study of enhancing effects on nasal absorption of insulin in rat of the total saponin from Acanthophyllum squarrosum.

OBJECTIVE: Isolation of the total saponins from Acanthophyllum squarrosum Boiss. and investigation of its surface activity, haemolytic effects on human erythrocytes as well as enhancing potentials on intranasal insulin absorption in rat in comparison with two other enhancers i.e. Quillaja total saponin (QTS) and sodium cholate (SC). MATERIALS AND METHODS: The decrease in blood glucose levels in five fasting rats following nasal administration of regular insulin solutions in the presence or absence of enhancers was determined by glucometric strips and used as an indication of insulin absorption. RESULTS: The results showed that ATS decreased surface tension of water to about 50 dyne.cm(-1) and caused complete haemolysis of human RBCs at a concentration of 250 microg.ml(-1). Following the instillation of solutions containing insulin and different absorption enhancers into the right nostril of rats, the percentage decrease in initial blood glucose was as follows: 72.46% (+/- 2.39%) for ATS, 63.22 % (+/-11.06%) for QTS and 60.06% (+/-14.93%) for SC. Percentage lowering in initial blood glucose concentrations against time showed that ATS exhibits a stronger effect than the two other enhancers although the difference was not statistically significant (p>0.05). CONCLUSION: ATS has a considerable absorption enhancing effect and can possibly be used to increase insulin bioavailability via nasal route. However the potential toxic effects of this saponin on nasal mucosa should be further evaluated.