Periodontopathic bacteria and herpesviruses in chronic periodontitis

Periodontal disease involves complex interactions of microorganisms and host defenses. This work investigated the associations between putative bacterial pathogens, herpesviruses and chronic periodontitis. Subgingival samples were collected from 40 periodontally healthy individuals and from 40 patients with chronic periodontitis with probing depths of ≤3 mm or ≥6 mm. Multiplex and nested polymerase chain reactions were used to identify bacterial pathogens and herpesviruses. Porphyromonas gingivalis, Tannerella forsythia, Epstein–Barr virus (EBV) type 1, cytomegalovirus (CMV), Aggregatibacter actinomycetemcomitans and EBV type 2 were detected in, respectively, 95, 75, 72.5, 50, 12.5 and 10% of sites with probing depths ≥6 mm. P. gingivalis, T. forsythia, EBV‐1 and CMV were statistically associated with probing depths ≥6 mm. A. actinomycetemcomitans and EBV‐2 showed no association with periodontitis sites, and no significant associations were found for any of the test infectious agents and probing depths ≤3 mm. Our results confirm an association between P. gingivalis, T. forsythia, EBV‐1 and CMV, and chronic periodontitis. These infectious agents may play an important synergistic role in the pathogenesis of chronic periodontitis.     

Pairwise network mechanisms in the host signaling response to coxsackievirus B3 infection

Signal transduction networks can be perturbed biochemically, genetically, and pharmacologically to unravel their functions. But at the systems level, it is not clear how such perturbations are best implemented to extract molecular mechanisms that underlie network function. Here, we combined pairwise perturbations with multiparameter phosphorylation measurements to reveal causal mechanisms within the signaling network response of cardiomyocytes to coxsackievirus B3 (CVB3) infection. Using all possible pairs of six kinase inhibitors, we assembled a dynamic nine-protein phosphorylation signature of perturbed CVB3 infectivity. Cluster analysis of the resulting dataset showed repeatedly that paired inhibitor data were required for accurate data-driven predictions of kinase substrate links in the host network. With pairwise data, we also derived a high-confidence network based on partial correlations, which identified phospho-IκBα as a central “hub” in the measured phosphorylation signature. The reconstructed network helped to connect phospho-IκBα with an autocrine feedback circuit in host cells involving the proinflammatory cytokines, TNF and IL-1. Autocrine blockade substantially inhibited CVB3 progeny release and improved host cell viability, implicating TNF and IL-1 as cell autonomous components of CVB3-induced myocardial damage. We conclude that pairwise perturbations, when combined with network-level intracellular measurements, enrich for mechanisms that would be overlooked by single perturbants.     

Effect of low-level laser therapy on mast cells in second-degree burns in rats

OBJECTIVE: This study sought to investigate whether low-level laser therapy (LLLT) with a helium-neon (He-Ne) laser would affect mast cell number and degranulation in second-degree burns in rats. Background Data: LLLT has been recently applied to stimulate the wound healing process. MATERIALS AND METHODS: Sixty-five rats were randomly allocated to one of five groups. A deep second-degree burn was inflicted on all rats except those in the control group. In the sham-exposed group burns remained untreated. In the two laser-treated groups, the burns were irradiated every day by LLLT, with energy densities of 1.2 and 2.4 J/cm(2). In the fifth group the burns were treated topically with 0.2% nitrofurazone cream every day. The unburned skin of the rats in the control group were used for baseline study. The effects on mast cell number and degranulation were assessed by counting the number of intact and degranulated mast cells in sections fixed in formalin and stained with toluidine blue. RESULTS: On the seventh and 16th days post-burn, the type 1 mast cell count in the 2.4-J/cm(2) laser-treated group was significantly higher than that of the control group. On the 30th day, the total numbers of mast cells in the laser-treated groups were lower than those in the control and sham-exposed groups. CONCLUSION: LLLT of deep second-degree cutaneous burns in rats significantly increased the number of intact mast cells during the inflammatory and proliferative phases of healing, and decreased the total number of mast cells during the remodeling phase.     

Multicentric Castleman's disease masquerading as HIV-related lymphoma

Patients with human immunodeficiency virus (HIV) infection are at increased risk for developing lymphoproliferative disorders. Multicentric Castleman's disease should always be kept in the differential diagnosis of HIV-positive patients suspected of having lymphoma to avoid misdiagnosis. We report the case of a 40-year-old HIV-positive homosexual man who presented with lower back pain and features highly suggestive of lymphoma including lymphadenopathy, elevated lactic dehydrogenase, and splenomegaly. The patient's plasma was positive by polymerase chain reaction for Kaposi sarcoma herpesvirus/human herpesvirus-8 (KSHV/ HHV8), and a lymph node biopsy revealed Multicentric Castleman's disease. He was started on highly active antiretroviral therapy, corticosteroids, valganciclovir, and rituximab. His back pain subsided, lymphadenopathy regressed, and he became KSHV/HHV8 negative. Albeit a rare condition, Castleman's disease should always be considered in immunocompromised patients suspected of having lymphoma.     

Is there evidence for dual causation between malaria and socioeconomic status? Findings from rural Tanzania

Malaria's relationship with socioeconomic status at the macroeconomic level has been established. This is the first study to explore this relationship at the microeconomic (household) level and estimate the direction of association. Malaria prevalence was measured by parasitemia, and household socioeconomic status was measured using an asset based index. Results from an instrumental variable probit model suggest that socioeconomic status is negatively associated with malaria parasitemia. Other variables that are significantly associated with parasitemia include age of the individual, use of a mosquito net on the night before interview, the number of people living in the household, whether the household was residing at their farm home at the time of interview, household wall construction, and the region of residence. Matching estimators indicate that malaria parasitemia is associated with reduced household socioeconomic status.     

Effect of low-level laser therapy on skin fibroblasts of streptozotocin-diabetic rats

OBJECTIVE: This study explored the effects of low-level laser therapy (LLLT) on cellular changes in cell culture and organ culture of skin from streptozotocin-diabetic (STZ-D) rats. BACKGROUND DATA: Growth of skin and its fibroblasts are impaired in diabetes. Therefore the healing of skin wounds is impaired in diabetic patients. The positive effects of LLLT on complications of diabetes in patients and animal models have been shown. METHODS: Diabetes was induced in rats by streptozotocin 30 days after its injection. Two sets of skin samples were extracted from skin under sterile conditions. Fibroblasts that were extruded from the samples were proliferated in vitro, and another set of samples were cultured as organ culture. A 24-well culture medium containing Dulbecco's modified minimum essential medium was supplemented by 12% fetal bovine serum. There were five laser-treated and five sham-exposed groups. A helium-neon laser was used, and 0.9-4 J/cm(2) energy densities were applied four times to each organ culture and cell culture. The organ cultures were analyzed by light microscopy and transmission electron microscopy examinations. Cell proliferation was evaluated by dimethylthiazol-diphenyltetrazolium bromide (MTT) assay. RESULTS: Statistical analysis revealed that 4-J/cm(2) irradiation significantly increases the fibroblast numbers compared to the sham-exposed cultures (p = 0.046). CONCLUSION: It is concluded that LLLT resulted in a significant increase of fibroblast proliferation of STZ-D rats in vitro.     

Double de novo mutations of ELA2 in cyclic and severe congenital neutropenia

Heterozygous mutations of ELA2, encoding the protease neutrophil elastase (NE), cause either autosomal dominant cyclic neutropenia or severe congenital neutropenia (SCN). Three hypotheses have been proposed for how allelic mutations produce these different disorders: 1) disruption of proteolytic activity; 2) mislocalization of the protein; or 3) destabilization of the protein resulting in induction of the unfolded protein response. As with other dominant diseases with reduced reproductive fitness, sporadic cases can result from new mutations not inherited from either parent. Here we report an exceptional genetic phenomenon in which both a cyclic neutropenia patient and an SCN patient each possess two new ELA2 mutations. Because of the rarity of the phenomenon, we investigated the origins of the mutations and found that both arise nonmosaically and in cis from the paternally-inherited allele. Moreover, these cases offer a unique opportunity to investigate molecular pathways distinguishing these two forms of hereditary neutropenia. We have characterized the mutants separately and in combination, with respect to their effects on proteolysis, subcellular trafficking, and induction of the unfolded protein response. Each pair of mutations acts more or less additively to produce equivalent net effects on reducing proteolytic activity and induction of the unfolded protein response, yet each has different and somewhat opposing effects on disturbing subcellular localization, thus offering support for a role for protein mistrafficking as a disease mechanism.