Epidemiology and risk factors for osteonecrosis of the jaw in cancer patients

Osteonecrosis of the jaw (ONJ), previously an entity associated with radiation therapy to the head and neck, has been observed in patients treated with bisphosphonates. Patients with metastatic breast cancer and myelomatous bone disease, commonly treated with high-potency nitrogen-containing bisphosphonates for a prolonged period of time, have the greatest risk of ONJ development. The reported frequency of ONJ ranges from 0.6% to 6.2% in breast cancer and from 1.7% to 15% in patients with multiple myeloma. Osteonecrosis of the jaw has also been observed in patients with other cancers such as prostate cancer and in benign bone disorders such as osteoporosis and Paget`s disease in which the incidence is low. Risk factors associated with the development of ONJ include dental extractions, length of bisphosphonate treatment, and the type of bisphosphonate used. In this review, we summarize the reported incidence and risk factors associated with ONJ.

Whole-Genome Characterization of Human and Simian Immunodeficiency Virus Intrahost Diversity by Ultradeep Pyrosequencing

Rapid evolution and high intrahost sequence diversity are hallmarks of human and simian immunodeficiency virus (HIV/SIV) infection. Minor viral variants have important implications for drug resistance, receptor tropism, and immune evasion. Here, we used ultradeep pyrosequencing to sequence complete HIV/SIV genomes, detecting variants present at a frequency as low as 1%. This approach provides a more complete characterization of the viral population than is possible with conventional methods, revealing low-level drug resistance and detecting previously hidden changes in the viral population. While this work applies pyrosequencing to immunodeficiency viruses, this approach could be applied to virtually any viral pathogen.

Increased number and function of natural killer cells in human immunodeficiency virus 1-positive subjects co-infected with herpes simplex virus 2

P>Natural killer (NK) cells bridge the interface between innate and adaptive immunity and are implicated in the control of herpes simplex virus 2 (HSV-2) infection. In subjects infected with human immunodeficiency virus 1 (HIV-1), the critical impact of the innate immune response on disease progression has recently come into focus. Higher numbers of NK cells are associated with lower HIV-1 plasma viraemia. Individuals with the compound genotype of killer cell immunoglobulin-like receptor (KIR) 3DS1 and human leucocyte antigen (HLA)-Bw4-80I, or who have alleles of KIR3DL1 that encode proteins highly expressed on the NK cell surface, have a significant delay in disease progression. We studied the effect of HSV-2 co-infection in HIV-1-infected subjects, and show that HSV-2 co-infection results in a pan-lymphocytosis, with elevated absolute numbers of CD4+ and CD8+ T cells, and NK cells. The NK cells in HSV-2 co-infected subjects functioned more efficiently, with an increase in degranulation after in vitro stimulation. The number of NK cells expressing the activating receptors NKp30 and NKp46, and expressing KIR3DL1 or KIR3DS1, was inversely correlated with HIV-1 plasma viral load in subjects mono-infected with HIV-1, but not in subjects co-infected with HSV-2. This suggests that HSV-2 infection mediates changes within the NK cell population that may affect immunity in HIV-1 infection.

Effect of diode laser on enzymatic activity of parotid glands of diabetic rats

The aim of this study was to evaluate the effect of laser irradiation (LI) on enzymatic activities of amylase, catalase and peroxidase in the parotid glands (PG) of diabetic and non-diabetic rats. Ninety-six female rats were divided into eight groups: D0; D5; D10; D20 and C0; C5; C10; C20, respectively. Diabetes was induced by administration of streptozotocin and confirmed later by the glycemia results. Twenty-nine (29) days after the induction, the PGs of groups D5 and C5; D10 and C10; D20 and C20, were irradiated with 5 J/cm(2), 10 J/cm(2) and 20 J/cm(2) of laser diode (660 nm/100 mW) respectively. On the following day, the rats were euthanized and the enzymatic activity in the PGs was measured. Diabetic rats that had not been irradiated (group D0) showed higher catalase activity (P < 0.05) than those in group C0 (0.14 +/- 0.02 U/mg protein and 0.10 +/- 0.03 U/mg protein, respectively). However, laser irradiation of 5 J/cm(2) and 20 J/cm(2) decreased the catalase activity of the diabetic groups (D5 and D20) to non-diabetic values (P > 0.05). Based on the results of this study, LI decreased catalase activity in the PGs of diabetic rats.

Diabetes induces metabolic alterations in dental pulp

Diabetes can interfere in tissue nutrition and can impair dental pulp metabolism. This disease causes oxidative stress in cells and tissues. However, little is known about the antioxidant system in the dental pulp of diabetics. Thus, it would be of importance to study this system in this tissue in order to verify possible alterations indicative of oxidative stress. The aim of this study was to evaluate some parameters of antioxidant system of the dental pulp of healthy (n = 8) and diabetic rats (n = 8). Diabetes was induced by streptozotocin in rats. Six weeks after diabetes induction, a pool of the dental pulp of the 4 incisors of each rat (healthy and diabetic) was used for the determination of total protein and sialic acid concentrations and catalase and peroxidase activities. Data were compared by a Student t test (p <= 0.05). Dental pulps from both groups presented similar total protein concentrations and peroxidase activity. Dental pulps of diabetic rats exhibited significantly lower free, conjugated, and total sialic acid concentrations than those of control tissues. Catalase activity in diabetic dental pulps was significantly enhanced in comparison with that of control pulps. The result of the present study is indicative of oxidative stress in the dental pulp caused by diabetes. The increase of catalase activity and the reduction of sialic acid could be resultant of reactive oxygen species production.

Lipophilic methotrexate conjugates with glucose-lipoamino acid moieties: Synthesis and in vitro antitumor activity

To obtain methotrexate (MTX) derivatives with a balanced hydrolipophilic character, we synthesized a series of conjugates in which the drug was linked to lipoamino acid (LAA)-glucose residues (LAAG-MTX). These conjugates displayed increased solubility in polar media compared with the corresponding LAA-MTX conjugates previously described. In vitro biological testing of LAAG-MTX indicated that the introduction of the sugar moiety decreased the biological activity of these MTX conjugates. The tetradecyl derivative 6b, however, was effective in inhibiting the dihydrofolate reductase activity in vitro and showed an inhibitory effect on human lymphoblastoid cell growth. (C) 2001 Wiley-Liss, Inc.