A proof of principle investigation of a novel enzyme formulation on dental calculus deposition: a 4-week randomized human clinical trial.

Background: The dissolution of dental calculus, safely and at home, is among the more challenging issues facing the over-the-counter healthcare industry. Pontis Biologics, Inc. has developed novel model of calculus development and structure and has formulated a dentifrice (Tartarase™) using digestive enzymes as active ingredients that is shown to dissolve dental calculus in this Proof of Principle clinical trial.

Chromium Therapy for Insulin Resistance Associated with HIV-Disease.

Objective: With the advent of highly active anti-retroviral therapy, HIV disease has become a chronic condition, but with a number of metabolic complications including insulin resistance and diabetes mellitus, dyslipidemia and hypertension and an increased incidence of atherosclerosis. The aim of the current study was to test the safety and efficacy of chromium picolinate for HIV- associated insulin resistance.

Materials/methods: The study was a randomized, double-blind, placebo-controlled trial with subjects receiving 500μg of chromium picolinate or placebo twice daily for two months.

Expression of inflammatory cytokines by adipose tissue from patients with endometrial cancer.

Obesity results in increased mortality from many forms of cancer. We looked at the levels of gene expression for TNFalpha, IL-6, IkappaB kinase (inhibitor of NF-kappaB), CD 68 (glycoprotein expressed on macrophages) and leptin in samples of adipose tissue from individuals with endometrial cancer versus patients with benign conditions. This is a prospective study which included patients of a gynecologic oncology group.

Peripheral fat loss and decline in adipogenesis in older humans.

Objective: Aging is associated with a redistribution of body fat including a relative loss of subcutaneous peripheral fat. These changes in body fat can have important clinical consequences since they are linked to increased risk of metabolic complications. The causes and mechanisms of loss of peripheral fat associated with aging are not clear.

Rosiglitazone-Mediated Effects on Skeletal Muscle Gene Expression Correlate with Improvements in Insulin Sensitivity in Individuals with HIV-Insulin Resistance.

Rosiglitazone, an agonist of peroxisome proliferator activated receptor (PPARγ), improves insulin sensitivity by increasing insulin-stimulated glucose uptake into muscle tissue. This study was undertaken to assess changes in expression of PPAR-regulated genes in muscle tissue following treatment of HIV-associated insulin resistance with rosiglitazone. Muscle gene expression was assessed in twenty-two seronegative HIV subjects (control), 21 HIV-infected individuals with normal insulin sensitivity (HIV-IS) and 19 HIV-infected individuals with insulin resistance (HIV-IR).

Delivery of rosiglitazone from an injectable triple interpenetrating network hydrogel composed of naturally derived materials.

An in situ gelable and biodegradable triple-interpenetrating network (3XN) hydrogel, completely devoid of potentially cytotoxic extraneous small molecule crosslinkers, is formulated from partially oxidized dextran (Odex), teleostean and N-carboxyethyl chitosan (CEC). Both the rheological profile and mechanical strength of the 3XN hydrogel approximate the combined characteristics of the three individual hydrogels composed of the binary partial formulations (i.e.

Effect of ritonavir and atazanavir on human subcutaneous preadipocyte proliferation and differentiation.

Protease inhibitors (PIs) have been implicated in the development of HIV-associated lipodystrophy through a reduction in the differentiation of preadipocytes. While atazanavir (ATV) is associated with fewer clinical metabolic abnormalities in the short-term, the effects of long-term exposure are not known. ATV effects on preadipocyte replication or differentiation would indicate the potential for long-term problems.

Importance of the high-molecular-mass isoform of adiponectin in improved insulin sensitivity with rosiglitazone treatment in HIV disease.

The present study was designed to investigate the relationship of isoforms of adiponectin to insulin sensitivity in subjects with HIV-associated insulin resistance in response to treatment with the thiazolidinedione, rosiglitazone. The two isoforms of adiponectin, HMW (high-molecular-mass) and LMW (low-molecular-mass), were separated by sucrose-gradient-density centrifugation. The amount of adiponectin in gradient fractions was determined by ELISA.

Influence of age on the association of retinol-binding protein 4 with metabolic syndrome.

Objective: The relationships of retinol-binding protein 4 (RBP4) with insulin sensitivity and body fat distribution have been investigated in a few recent studies with conflicting results. This may have been due to differences in ages of the subjects in the different studies. The aim of this study was to investigate whether the association of RBP4 and insulin sensitivity and percent trunk fat are influenced by age.

Endothelial adhesion molecules are associated with inflammation in subjects with HIV disease.

Background: The presence of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1) is associated with elevated risk of cardiovascular disease. Subjects with human immunodeficiency virus (HIV) disease have multiple risk factors for cardiovascular disease, including elevated serum lipid levels, insulin resistance, and elevated levels of ICAM-1 and VCAM-1. This study assessed the variables associated with elevated adhesion molecule levels in this patient population.

Chromium picolinate for insulin resistance in subjects with HIV disease: a pilot study.

Aim: Multidrug regimens in HIV disease are associated with an increased incidence of insulin resistance, by as much as 50%. Not only does insulin resistance predisposes subjects to diabetes but also it is associated with the metabolic syndrome and increased risk of cardiovascular disease. Previous studies suggest that chromium picolinate can improve insulin resistance in patients with type 2 diabetes.

Limb fat to trunk fat ratio in elderly persons is a strong determinant of insulin resistance and adiponectin levels.

Background: Similar to lipodystrophy syndromes, aging results in increased visceral adiposity with loss of subcutaneous adipose tissue in the extremities. The hypothesis of this study is that the distribution of limb fat to trunk fat (LF/TF) ratio in elderly persons has a stronger correlation than trunk fat alone to insulin resistance and adiponectin levels.

Methods: Thirty-eight elderly participants were divided into an insulin-resistant (IR) group and an insulin-sensitive (IS) group.

Wall suction applied to needle muscle biopsy - a novel technique for increasing sample size.

Background: The needle biopsy technique described by Bergström is the most commonly used technique to obtain samples to assess muscle metabolism. Sampling of muscle, particularly the vastus lateralis, has become an essential tool in biomedical and clinical research. Optimal sample size is critical for availability of tissue for processing.

Retinol-binding protein 4 is associated with insulin resistance and body fat distribution in nonobese subjects without type 2 diabetes.

Background: Adipose tissue is responsible for releasing various adipokines that have been related to insulin resistance. Understanding the relationship of these adipokines to insulin resistance may foster the development of new treatments for diabetes.

Objectives: The primary objective of this study was to determine whether an association between retinol-binding protein 4 (RBP4) and insulin resistance exists in nonobese individuals without a family history or diagnosis of diabetes.

Chronic loss of subcutaneous adipose tissue in HIV-associated lipodystrophy may not be associated with accelerated apoptosis.

HIV-associated lipodystrophy (HIV-LD) is characterized by a loss of adipose tissue from the subcutaneous compartment. Previously reported data suggested that this loss of adipose tissue was the result of an increased rate of apoptosis in subcutaneous adipose tissue (SAT). The present study examined the rate of apoptosis in SAT with a sensitive ligase-mediated polymerase chain reaction technique to amplify DNA ladders.

Loss of subcutaneous adipose tissue in HIV-associated lipodystrophy is not due to accelerated apoptosis.

HIV-associated lipodystrophy is characterized by a loss of adipose tissue from the subcutaneous compartment. Previously reported data suggested that this loss of adipose tissue was the result of an increased rate of apoptosis in subcutaneous adipose tissue. The present study examined the rate of apoptosis in subcutaneous adipose tissue with a sensitive ligase-mediated polymerase chain reaction technique to amplify DNA ladders.

Adiponectin and leptin levels in HIV-infected subjects with insulin resistance and body fat redistribution.

In this study, we sought to determine the relationship between serum levels of leptin and adiponectin (Acrp30) in patients with HIV-associated lipodystrophy (HIV-LD). Three groups of subjects were studied; HIV-positive subjects with lipodystrophy (HIV-LD; n = 22), HIV-positive subjects without lipodystrophy (HIV; n = 17), and ethnicity- and body mass index-matched healthy control subjects (n = 20). Although total body fat from dual energy x-ray absorptiometry was similar in all three groups, the HIV-LD group had a significantly lower mean proportion of body fat in the limbs +/- SEM (37.

Improved insulin sensitivity and body fat distribution in HIV-infected patients treated with rosiglitazone: a pilot study.

The insulin-sensitizing drugs thiazolidinediones (TZDs), such as rosiglitazone, improve insulin sensitivity and also promote adipocyte differentiation in vitro. The authors hypothesized that TZDs might be beneficial to patients with HIV disease to improve insulin sensitivity and the distribution of body fat by increasing peripheral fat. The ability of rosiglitazone (8 mg/d) to improve insulin sensitivity (from hyperinsulinemic-euglycemic clamp) and to improve body fat distribution (determined from computed tomography measurements of visceral adipose tissue [VAT] and subcutaneous adipose tissue [SAT]) was determined in 8 HIV-positive patients.

Soluble tumour necrosis factor alpha receptor 2, a serum marker of resistance to the anabolic actions of growth hormone in subjects with HIV disease.

Therapies are still being sought for the prevention of loss of body weight and lean body mass in HIV disease. The purpose of the present study was to identify a serum marker that would help in selecting patients who may be appropriate candidates for the use of anabolic agents, such as growth hormone, to restore lean body mass. This study included 26 HIV-infected patients and nine healthy controls, assessed previously for the effectiveness of 2 weeks of growth hormone administration in the stimulation of protein synthesis in skeletal muscle.

Alanine scanning mutagenesis of a type 1 insulin-like growth factor receptor ligand binding site.

The high resolution crystal structure of an N-terminal fragment of the IGF-I receptor, has been reported. While this fragment is itself devoid of ligand binding activity, mutational analysis has indicated that its N terminus (L1, amino acids 1-150) and the C terminus of its cysteine-rich domain (amino acids 190-300) contain ligand binding determinants. Mutational analysis also suggests that amino acids 692-702 from the C terminus of the alpha subunit are critical for ligand binding.

Association of severe insulin resistance with both loss of limb fat and elevated serum tumor necrosis factor receptor levels in HIV lipodystrophy.

HIV-lipodystrophy (HIV-LD) is characterized by the loss of body fat from the limbs and face, an increase in truncal fat, insulin resistance, and hyperlipidemia, factors placing affected patients at increased risk for vascular disease. This study evaluated insulin sensitivity and inflammatory status associated with HIV-LD and provides suggestions about its etiology. Insulin sensitivity and immune activation markers were assessed in 12 control subjects and 2 HIV-positive groups, 14 without and 15 with LD syndrome.

Insulin-like growth factor system in patients with HIV infection: effect of exogenous growth hormone administration.

The purpose of this study was to characterize changes in the levels of insulin-like growth factor-I (IGF-I) and IGF binding proteins (BP) 1, 2, and 3 in HIV-infected adults throughout the course of their disease, and to assess the responsiveness of the IGF system components to growth hormone (GH) administration (6 mg/day) for 2 weeks. Healthy control study subjects (n = 10) were compared with patients who were either HIV-positive (n = 9), had AIDS without weight loss (n = 13), or had AIDS with >10% weight loss (n = 6), all of whom had been free of acute illness for at least 3 months. Under basal conditions, fasting serum concentrations of epinephrine, norepinephrine, cortisol, glucagon, insulin, IGF-I, and IGFBP-3 were not significantly different among the four groups.