N-acetylcysteine effects on a murine model of chronic critical limb ischemia

During chronic limb ischemia, oxidative damage and inflammation are described. Besides oxidative damage, the decrease of tissue oxygen levels is followed by several adaptive responses. The purpose of this study was to determine whether supplementation with N-acetylcysteine (NAC) is effective in an animal model of chronic limb ischemia. Chronic limb ischemia was induced and animals were treated once a day for 30 consecutive days with NAC (30 mg/kg). After this time clinical scores were recorded and soleus muscle was isolated and lactate levels, oxidative damage and inflammatory parameters were determined. In addition, several mechanisms associated with hypoxia adaptation were measured (vascular endothelial growth factor - VEGF and hypoxia inducible factor - HIF levels, ex vivo oxygen consumption, markers of autophagy/mitophagy, and mitochondrial biogenesis). The adaptation to chronic ischemia in this model included an increase in muscle VEGF and HIF levels, and NAC was able to decrease VEGF, but not HIF levels. In addition, ex vivo oxygen consumption under hypoxia was increased in muscle from ischemic animals, and NAC was able to decrease this parameter. This effect was not mediated by a direct effect of NAC on oxygen consumption. Ischemia was followed by a significant increase in muscle myeloperoxidase activity, as well as interleukin-6 and thiobarbituric acid reactive substances species levels. Supplementation with NAC was able to attenuate inflammatory and oxidative damage parameters, and improve clinical scores. In conclusion, NAC treatment decreases oxidative damage and inflammation, and modulates oxygen consumption under hypoxic conditions in a model of chronic limb ischemia.     

Oxidative stress parameters in blood, liver, and kidney of diabetic rats treated with curcumin and/or insulin

This study evaluated the effects of curcumin and/or insulin on antioxidant enzyme activity in blood, liver, and kidney, as well as on lipid peroxidation and delta aminolevulinic dehydratase (δ-ALA-D) activity, and a histopathological analysis of streptozotocin-induced diabetic rats. The animals were divided into six groups (n = 6): control/saline (C); control/curcumin (CCur); diabetic/saline (D); diabetic/insulin (DIns); diabetic/curcumin (DCur); and diabetic/insulin/curcumin (DInsCur). After 30 days of treatment with curcumin and/or insulin, the animals were sacrificed and the liver, kidney, and serum were used for experimental determinations. Results of histopathological analysis showed that the treatment with insulin ameliorate renal and hepatic lesions from both DIns and DInsCur groups. TBARS levels were significantly increased in serum, liver, and kidney in D group and the administration of curcumin and insulin prevented this increase in DIns and DCur groups. The activities of catalase (CAT), superoxide dismutase, and δ-ALA-D presented a significant decrease in the liver and kidney D group when compared to C group (P < 0.05). The animals treated with curcumin and insulin presented an increase of CAT activity, revealing a positive interaction between both substances. The treatments with curcumin or insulin prevented oxidative stress in blood, through modulation of enzymatic antioxidant defenses. These findings contributed to the comprehension that antioxidants from medicinal plants could be used as adjuvant in the treatment of this endocrinopathy and not as single therapy.     

Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions.     

Dietary interventions in mice affect oxidative stress and gene expression of the Prlr and Esr1 in the adipose tissue and hypothalamus of dams and their offspring

Journal of Physiology and Biochemistry - Maternal diet is key to the progeny’s health since it may impact on the offspring’s adult life. In this study, mice dams received standard...     

Prevalence of temporomandibular disorders in a population of complete denture wearers

doi: 10.1111/j.1741‐2358.2011.00574.x
Prevalence of temporomandibular disorders in a population of complete denture wearers Background: Complete tooth loss among the elderly is still frequent in developing countries and the incidence of temporomandibular disorders (TMD) is a common finding in complete denture wearers. Objectives: The aim of this study was to evaluate the prevalence of temporomandibular disorders (TMD) in a population of complete denture wearers. Materials and Methods: The data were collected by four examiners for the diagnosis of use and need for complete dentures followed by the World Health Organization standards and interviews for TMD signs and symptoms evaluation. Exploratory variables included demographic, socio‐economic status and TMD prevalence. Results: The prevalence of TMD among denture wearers was 55.12%. Chi‐squared test showed no statistical difference between subjects with or without TMD for gender, geographical location and skin colour (p < 0.05). The number of subjects with TMD increased as the period of complete denture wear increased, although no statistical difference between groups were found (p < 0.05). Conclusions: There is a need of educational programmes aiming at the importance of health care and periodical change of a complete denture, and strategies with a preventive approach to quality general dental care.     

Nitric oxide inhibits neutrophil migration by a mechanism dependent on ICAM-1: role of soluble guanylate cyclase.

In the present study, we addressed the role of intercellular adhesion molecule type 1 (ICAM-1/CD54) in neutrophil migration to inflammatory site and whether the inhibitory effect of nitric oxide (NO) upon the neutrophil rolling, adhesion and migration involves down-modulation of ICAM-1 expression through a cyclic GMP (cGMP) dependent mechanism. It was observed that neutrophil migration induced by intraperitoneal administration of endotoxin (LPS), carrageenan (Cg) or N-formyl peptide (fMLP) in ICAM-1 deficient (ICAM-1-/-) is similar to that observed in wild type (WT) mice. The treatment of mice with NO synthase (NOS) inhibitors, NG-nitro-l-arginine, aminoguanidine or with a soluble guanylate cyclase (sGC) inhibitor, ODQ enhanced LPS- or Cg-induced neutrophil migration, rolling and adhesion on venular endothelium. These parameters induced by LPS were also enhanced by 1400 W, a specific iNOS inhibitor, treatment. On the other hand, the treatment of the mice with S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, reduced these parameters induced by LPS or Cg by a mechanism sensitive to ODQ pretreatment. The NOS inhibitors did not enhance LPS-, Cg- or fMLP-induced migration and adhesion in ICAM-1-/- mice. Moreover, genetic (iNOS-/- mice) or pharmacological inhibition of NOS or of sGC enhanced LPS-induced ICAM-1 expression on mesenteric microcirculation vessels of WT mice. By contrast, SNAP reduced the ICAM-1 expression by a mechanism dependent on cGMP. In conclusion, the results suggest that although during inflammation, ICAM-1 does not contribute to neutrophil migration, it is necessary for the down-modulatory effect of inflammation-released NO on the adhesion and transmigration of neutrophils. Moreover, these NO effects are mediated via cGMP.     

In vitro culture supplementation of EGF for improving the survival of equine preantral follicles

Folliculogenesis is a process of development and maturation of the ovarian follicles, being essential for the maintenance of fertility. In in vivo conditions, 99.9% of the follicles of an ovary do not ovulate and undergo atresia. In order to minimize this loss and to clarify the existing mechanisms, a technique was developed that allows for the in vitro follicular development. The objective of this study was to evaluate the effects of different epidermal growth factor (EGF) concentrations on the in vitro culturing of equine preantral follicles. Ovaries (n?=?10) were collected from a local slaughterhouse of mares in seasonal anestrus, washed with 70% alcohol and PBS, and transported. The inner portion of the ovary was divided into 11 fragments of approximately 3?×?3?×?1 mm. A fragment of each ovary was immediately fixed in Bouin (control group). The remaining 10 fragments were individually cultured for 2 and 6 d. The medium was supplemented with different concentrations of EGF (0, 10, 50, 100, and 200 ng/mL). After cultivation, the fragments were processed and classified according to the developmental stage and morphology. In total, 1065 slides containing 6105 tissue sections were evaluated. Within 2 d of culture, there was a higher proportion of intact follicles at the EGF concentrations of 0 and 100 ng/mL (p?>?0.05). After 6 d of culture, only the EGF concentration of 100 ng/mL demonstrated a difference when compared to the other treatments (0, 10, 50 and 200 ng/mL of EGF, p?>?0.05). There was follicular development after 2 d at all EGF concentrations. Thus, we suggest that EGF promotes follicular survival in equines at a concentration of 100 ng/mL in in vitro cultures of ovarian fragments for 2 d. In addition, we suggest that EGF promotes follicular survival in equines at a concentration of 100 ng/mL in situ cultivation.     

Synthesis, antitubercular activity, and SAR study of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides

Tuberculosis treatment remains a challenge that requires new antitubercular agents due to the emergence of multidrug-resistant Mycobacterium strains. This paper describes the synthesis, the antitubercular activity and the theoretical analysis of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides (8a-b, 8e-f, 8i-j and 8n-o) and new analogues (8c-d, 8g-h, 8l-m and 8p-q). These derivatives were synthesized in good yields and some of them showed a promising antitubercular profile. Interestingly the N-acylhydrazone (NAH) 8n was the most potent against the Mycobacterium tuberculosis H37Rv strain (MIC=2.5 μg/mL) similar to or better than the current drugs on the market. The theoretical structure-activity relationship study suggested that the presence of the furyl ring and the electronegative group (NO(2)) as well as low lipophilicity and small volume group at R position are important structural features for the antitubercular profile of these molecules. NMR spectra, IR spectra and elemental analyses of these substances are reported.