Clinical and histologic evaluation of the periodontal response to restorative procedures in the dog

This study evaluated, in the dog, the periodontal response to resin-modified glass-ionomer cement or amalgam restorations placed in surgical windows and left for 124 days. Plaque control was performed in half of the sites. Histologic analyses showed that sites restored with amalgam were consistently more inflamed than sites restored with resin-modified glass-ionomer. Plaque control was associated with less inflammation in both cases. Some sites restored with resin-modified glass-ionomer presented bone repair and a connective tissue lining. The inflammatory response of the periodontium to resin-modified glass-ionomer restorations is less pronounced than that associated with amalgam restorations.     

Valproic acid modulates NCAM polysialylation and polysialyltransferase mRNA expression in human tumor cells

Polysialic acid (PSA) is a dynamically regulated carbohydrate modification of the neural cell adhesion molecule NCAM, which has been linked to cancer development and dissemination. Two enzymes, the polysialyltransferases ST8SiaIV and ST8SiaII, are known to be involved in the polysialylation of NCAM. The antiepileptic drug valproic acid (VPA) is associated with anti-cancer activity. In this study, VPA blocked the adhesion of several neuroectodermal tumor cell lines to human umbilical vein endothelial cells. Furthermore, VPA induced intracellular PSA accumulation and enhanced expression of PSA-NCAM on the cell surface. Using a semiquantitative RT-PCR strategy, VPA was shown to up-regulate ST8SiaIV mRNA, whereas ST8SiaII mRNA was down-regulated by this compound. Our data indicate that increased expression of ST8SiaIV enables accelerated polysialylation of NCAM, which might be coupled to a loss of adhesive functions of tumor cells.     

Gestational diabetes management: a multidisciplinary treatment algorithm

Effective treatment of gestational diabetes is important as an attempt to avoid unfavorable maternal and fetal outcomes. The objective of this paper is to describe the available therapies to optimize gestational diabetes treatment and to suggest a multidisciplinary approach algorithm. Nutrition therapy is the first option for the majority of these pregnancies; light to moderate physical activity is recommended in the absence of obstetrical contraindications. Medical treatment is recommended if glycemic control is not achieved or if excessive fetal growth is detected by ultrasound. Insulin is the standard treatment although oral antidiabetic drugs have recently been considered an effective and safe option. The monitoring of gestational diabetes treatment includes capillary glucose measurements and evaluation of fetal abdominal circumference by ultrasound performed around the 28th gestational week.     

Association between menopause status and central adiposity measured at different cutoffs of waist circumference and waist-to-hip ratio

OBJECTIVE: To assess the association between menopause status and central adiposity measured using two different cutoffs of waist circumference and waist-to-hip ratio, while controlling for body mass index and other confounding factors. DESIGN: Cross-sectional study of a representative population-based sample of 358 women from Passo Fundo, Southern Brazil. Medical students performed standardized interviews and anthropometric measurements under supervision. Menopause status was categorized as premenopausal for those with no change in menstrual frequency or flow; menopause transition for those who had these changes; and postmenopausal after 12 months of amenorrhea or bilateral oophorectomy. Obesity was defined by body mass index (BMI) equal or greater than 30 kg/m, whereas central adiposity was defined as a waist circumference equal or greater than 80 or 88 cm and a waist-to-hip-ratio equal or greater than 0.80 or 0.86. RESULTS: The anthropometric assessment showed that compared with postmenopausal women, premenopausal women were taller, had a thinner waist circumference, and had a lower waist-to-hip ratio. Postmenopausal women had five times the chance of having central adiposity than premenopausal women, even after controlling for BMI and other confounding factors. Women in the menopause transition had an increased BMI, but there was no independent association with central obesity. CONCLUSION: Postmenopausal women are at greater risk of central adiposity as detected by both waist circumference and waist-to-hip ratio.     

A resin-modified glass ionomer cement barrier for treating degree II furcation defects: a pilot study in dogs

OBJECTIVE: The aim of this study was to evaluate in an animal model the healing of degree II furcation defects treated with: an experimental barrier of resin-modified glass-ionomer cement (GIC), a polylactic acid barrier (GUI), and flap surgery (CTR). MATERIAL AND METHODS: In 3 beagles, 18 class II furcation defects were surgically produced in mandibular and maxillary premolars and exposed to plaque accumulation for 21 days. Following a full flap, notches were made at the base to the bone defect. GIC barriers were prepared immediately before use from a commercial product and fit to place with the same product. The GIC barriers were removed after 30 days and the dogs euthanized after 120 days. Histologic sections were analyzed in a computer-assisted microscope. Epithelium, new cementum with inserting fibers, and connective tissue lining the root surface in-between notches were measured and medians of percentage values calculated. RESULTS: In the GIC, epithelium constituted 3.5% (median values) of the notch-to-notch root area; new cementum was 83.6% and connective tissue 12.9%. These values were 0%, 73.6%, and 26.4% for the GUI group and 35.6%, 43.2%, and 0% for the CTR group. Bone fill median values were 54.3% for GIC, 20.6% for GUI, and 24.6% for CTR. CONCLUSION: GIC and GUI prevented epithelial migration and promoted the formation of new periodontal tissues in experimentally induced class II furcation defects in dogs.     

The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs

Osteoporosis and low bone mass are currently estimated to be a major public health risk affecting >50% of the female population over the age of 50. Because of their bone-selective pharmacokinetics, nitrogen-containing bisphosphonates (N-BPs), currently used as clinical inhibitors of bone-resorption diseases, target osteoclast farnesyl pyrophosphate synthase (FPPS) and inhibit protein prenylation. FPPS, a key branchpoint of the mevalonate pathway, catalyzes the successive condensation of isopentenyl pyrophosphate with dimethylallyl pyrophosphate and geranyl pyrophosphate. To understand the molecular events involved in inhibition of FPPS by N-BPs, we used protein crystallography, enzyme kinetics, and isothermal titration calorimetry. We report here high-resolution x-ray structures of the human enzyme in complexes with risedronate and zoledronate, two of the leading N-BPs in clinical use. These agents bind to the dimethylallyl/geranyl pyrophosphate ligand pocket and induce a conformational change. The interactions of the N-BP cyclic nitrogen with Thr-201 and Lys-200 suggest that these inhibitors achieve potency by positioning their nitrogen in the proposed carbocation-binding site. Kinetic analyses reveal that inhibition is competitive with geranyl pyrophosphate and is of a slow, tight binding character, indicating that isomerization of an initial enzyme-inhibitor complex occurs with inhibitor binding. Isothermal titration calorimetry indicates that binding of N-BPs to the apoenzyme is entropy-driven, presumably through desolvation entropy effects. These experiments reveal the molecular binding characteristics of an important pharmacological target and provide a route for further optimization of these important drugs.