Transgenic expression of replication-restricted enteroviral genomes in heart muscle induces defective excitation-contraction coupling and dilated cardiomyopathy.

Numerous studies have implicated Coxsackievirus in acute and chronic heart failure. Although enteroviral nucleic acids have been detected in selected patients with dilated cardiomyopathy, the significance of such persistent nucleic acids is unknown. To investigate the mechanisms by which restricted viral replication with low level expression of Coxsackieviral proteins may be able to induce cardiomyopathy, we generated transgenic mice which express a replication-restricted full-length Coxsackievirus B3 (CVB3) cDNA mutant (CVB3DeltaVP0) in the heart driven by the cardiac myocyte-specific myosin light chain-2v (MLC-2v) promoter. CVB3DeltaVP0 was generated by mutating infectious CVB3 cDNA at the VP4/VP2 autocatalytic cleavage site from Asn-Ser to Lys-Ala. Cardiac-specific expression of this cDNA leads to synthesis of positive- and negative-strand viral RNA in the heart without formation of infectious viral progeny. Histopathologic analysis of transgenic hearts revealed typical morphologic features of myocardial interstitial fibrosis and in some cases degeneration of myocytes, thus resembling dilated cardiomyopathy in humans. There was also an increase in ventricular atrial natriuretic factor mRNA levels, demonstrating activation of the embryonic program of gene expression typical of ventricular hypertrophy and failure. Echocardiographic analysis demonstrated the presence of left ventricular dilation and decreased systolic function in the transgenic mice compared with wild-type littermates, evidenced by increased ventricular end-diastolic and end-systolic dimensions and decreased fractional shortening. Analysis of isolated myocytes from transgenic mice demonstrate that there is defective excitation-contraction coupling and a decrease in the magnitude of isolated cell shortening. These data demonstrate that restricted replication of enteroviral genomes in the heart can induce dilated cardiomyopathy with excitation-contraction coupling abnormalities similar to pressure overload models of dilated cardiomyopathy.     

Functional and ecological correlates of the primate jaw abductors

While the adductor musculature of the primate jaw has been extensively analyzed within the context of dietary and social ecology, little is known about the corresponding muscles of jaw abduction. Nonetheless, these muscles significantly contribute to a species' maximum gape potential, and thus might constrain dietary niche diversity and impact social display behaviors. In this study, we quantify the architectural properties of the digastric (a jaw abductor) and lateral pterygoid (a jaw abductor and anterior translator) across a broad sample of male and female anthropoid primates. We test the hypothesis that the abductor musculature reflects specialization to dietary and behavioral ecology. Our sample comprises 14 catarrhine and 13 platyrrhine species spanning a wide range of dietary and social categories. All specimens were sharp dissected and muscles subsequently chemically digested using a standardized protocol. Our findings demonstrate that relative fascicle lengths within the lateral pterygoid (but not the digastric) are significantly greater within species that habitually consume larger food items. Meanwhile, canine length is more strongly associated with fascicle lengths in the digastric than in the lateral pterygoid, particularly within males. Neither dietary mechanical resistance nor the intensity of social competition relates to the size or architectural properties of the jaw abductors. These findings suggest that dietary—and to a lesser extent, socioecological—aspects of a primate's life history may be reflected in the architecture of these muscles, albeit to varying degrees. This underlines the importance of considering the complete masticatory apparatus when interpreting the evolution of the primate jaw.     

Relationship between human immunodeficiency virus (HIV-1) infection and chronic periodontitis

Introduction: Current studies show that, even in the era of antiretroviral therapies, HIV-1 infection is associated with more severe and frequent refractory chronic periodontitis.

Areas covered: This review, based on a systematic analysis of the literature, intends to provide an update on factors that may be involved in the pathogenesis of periodontal disease in HIV-1-infected patients, including local immunosuppression, oral microbial factors, systemic inflammation, salivary markers, and the role of gingival tissue as a possible reservoir of HIV-1.

Expert commentary: The therapeutic revolution of ART made HIV-1 infection a chronic controllable disease, reduced HIV-1 mortality rate, restored at least partially the immune response and dramatically increased life expectancy of HIV-1-infected patients. Despite all these positive aspects, chronic periodontitis assumes an important role in the HIV-1 infection status for activating systemic inflammation favoring viral replication and influencing HIV-1 status, and also acting as a possible reservoir of HIV-1. All these issues still need to be clarified and validated, but have important clinical implications that certainly will benefit the diagnosis and management of chronic periodontitis in HIV-1-infected patients, and also contributes to HIV-1 eradication.     

Acute Liver Failure Induced by Carthamus tinctorius Oil: Case Reports and Literature Review

Background

Acute liver failure (ALF) is a clinical syndrome that results from the abrupt loss of liver function in a patient without previous liver disease. The most frequent causes are viral hepatitis, drug induced, and autoimmune disease, but in 20% of cases no cause is identified. Carthamus tinctorius (safflower) oil is used as a dietary supplement for weight loss and antioxidant. There are 4 cases described in the literature of ALF induced by the use of this substance. The objective of this study was to report 3 cases of ALF treated at the Clinical Hospital of the State University of Campinas that suggest the use of C tinctorius oil as a probable etiologic factor.

Susceptibility of Staphylococcus aureus to porphyrin-mediated photodynamic antimicrobial chemotherapy: an in vitro study

The ability of Staphylococcus aureus to develop multidrug resistance is well documented, and the antibiotic resistance showed by an increasing number of bacteria has shown the need for alternative therapies to treat infections, photodynamic therapy (PDT) being a potential candidate. The aim of this study was to determine the effect of photodynamic therapy as a light–based bactericidal modality to eliminate Staphylococcus aureus. The study investigated a technique based on a combination of light and a photosensitizer that is capable of producing oxidative species to induce a cytotoxic effect. A Staphylococcus aureus suspension was exposed to a light emitting diode (LED) emitting at 628 nm, 14.6 mW/cm², and energy density of 20J/cm², 40J/cm², or 60 J/cm² in the presence of different porphyrin concentrations (Photogem®). Three drug concentrations were employed: 12 μl/ml, 25 μl/ml, and 50 μl/ml. The treatment response was evaluated by the number of bacterial colony forming units (CFU) after light exposure. The results indicated that exposure to 60 J/cm² eliminated 100% (10 log¹⁰ scales) of bacteria, on average. The best PDT response rate to eliminate Staphylococcus aureus was achieved with exposure to LED light in combination with the photosensitizer at concentrations ranging from 25 μl/ml to 50 μl/ml. These data suggest that PDT has the potential to eliminate Staphylococcus aureus in suspension and indicates the necessary drug concentration and light fluency.     

In vitro initial immune response against Leishmania amazonensis infection is characterized by an increased production of IL-10 and IL-13

The initial encounter of Leishmania with its host's immune system is important in the outcome of infection. Previous studies have shown that PBMCs from healthy volunteers (HV) exposed to Leishmania differ in IFN-γ production. We have expanded such observations evaluating the profile and kinetics of cytokines (IFN-γ, IL-12p70, IL-10, IL-13), chemokines (CCL5, CCL3, CCL4, CXCL10), and chemokine receptors (CCR1,CCR5, CXCR3, CCR4) in vitro L. amazonensis-stimulated of HV?s PBMCs. HVs were divided in groups of high (HR) or low (LR) IFN-γ responders. In both groups, HR and LR, after L. amazonensis infection there was a predominance of IL-10 and IL-13 over IFN-γ production, while IL-12 was produced in similar amount. Regarding chemokines, a more striking difference was observed for CCL3 expression that was lower at 12 hours and 48 hours post infection in LR than in HR. Interestingly, a downregulation of CCR5 and a greater expression of CCR4 were found in low IFN-γ responders. These data suggest that early after L. amazonensis infection there is a cytokine milieu dominated by IL-13 and IL-10, and despite of this environment, IFN-γ is produced, supporting the complexity of the response. It is noteworthy that the pattern of immune response is mounted in first hours after Leishmania stimulation, with the definition of the differentiation of Th1 versus Th2 cells. It remains to be determined if such an in vitro difference has an in vivo counterpart in terms of susceptibility to infection.     

Arterial wall structure and dynamics in type 2 diabetes mellitus methodological aspects and pathophysiological findings

Type 2 Diabetes Mellitus (DM), or adult-onset diabetes, is being considered as a new pandemic. Cardiovascular disease is the major cause of morbidity and mortality in type 2 DM, due to arterial structure and functional changes. Assessment of arterial structure and biomechanics, by non-invasive methods and parameters, can be used to detect early alterations related to DM. Three markers of vascular disease may help to a better evaluation of vascular dysfunction in type 2 DM patients: carotid intimamedia thickness (IMTc), arterial stiffness, assessed by pulse wave velocity (PWV), and endothelial function, evaluated through the brachial artery flow-mediated dilation (FMD). Among these parameters, IMTc is considered a marker of structural vessel wall properties, and arterial stiffness reflects functional wall properties. Endothelial function represents the arterial way to actively regulate its diameter (smooth muscle-dependent actions) and its visco-elastic properties (wall elasticity and viscosity). IMTc is increased in patients with type 2 DM and other independent risk factors, such as: age, hyperlipidemia and duration of DM. Subjects with DM have shown increased arterial stiffness. Type 2 DM is associated with reductions in FMD (endothelial dysfunction), which has already been reported to be inversely and strongly related to the extent of hyperglycemia. The underlying patho-physiological mechanisms are complex and remain to be fully elucidated. A complete understanding of the association between arterial alterations and early detection, and type 2 DM, may be critical for the primary prevention of DM-related macro-vascular disease.