The signaling and apoptotic effects of TNF-related apoptosis-inducing ligand in HIV-1 associated dementia

HIV-1 Associated Dementia (HAD) develops during progressive HIV-1 infection and is characterized by cognitive impairments, behavioral disorders and potential progressive motor abnormality. Abnormal inflammation within the central nervous system (CNS), activation of macrophage/microglia and involvement of proinflammatory cytokines have been suggested as primary factors in the pathogenesis of HAD. Impairment of neuronal function and neuronal cell death are believed to be the end pathophysiological result of HAD. TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF family of cytokines, was suggested to participate in apoptotic cell death during HAD. As a death ligand, TRAIL was originally thought to target only tumor cells. TRAIL is not typically present in CNS; however, emerging data show that TRAIL can be induced by immune stimuli on macrophage and microglia, major disease effector cells during HAD. Upregulated TRAIL may then cause neuronal apoptosis through direct interaction with TRAIL receptors on neurons or through macrophage death-mediated release of neurotoxins. In this review, we summarize the pivotal role of TRAIL in HAD and TRAIL-initiated intracellular death cascades that culminate in neuronal apoptosis as observed in HAD.     

Bioequivalence evaluation of lansoprazole 30-mg capsules (Lanfast and Lanzor) in healthy volunteers.

The bioequivalence of two lansoprazole 30-mg capsules was determined in healthy human, adult volunteers after a single dose in a randomized cross-over study. The study was conducted at Pharmaconsult, Flemington Pharmaceutical Corp., New Jersey, USA. Reference (Lanzor, Laboratoires Houde, Paris, France) and test (Lanfast, Julphar, UAE) were administered to volunteers with 240 ml water after overnight fasting. Blood samples were collected at specified time intervals, plasma was separated and analyzed for lansoprazole using a validated HPLC method. The pharmacokinetic parameters AUC(0-t), AUC(0-~), C(max), T(max), T(1/2) and elimination rate constant were determined from plasma concentration-time profile of both formulations and found to be in good agreement with previously reported values. The calculated pharmacokinetic parameters were compared statistically to evaluate bioequivalence between the two brands, using the statistical modules recommended by the Food and Drug Administration. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals fell within the acceptable range (80-120%) for bioequivalence. Based on these statistical inferences it was concluded that the two formulations exhibited comparable pharmacokinetic profiles and that Julphar's Lanfast is bioequivalent to Lanzor of Lab. Houde.     

Micromechanics-Based Conversion of CT Data into Anisotropic Elasticity Tensors, Applied to FE Simulations of a Mandible

Computer Tomographic (CT) image data have become a standard basis for structural analyses of bony organs. In this context, regression functions between stiffness components and Hounsfields units (HU) from CT, related to X-ray attenuation coefficients, are widely used for the definition of the (actually inhomogeneous and anisotropic) material behavior inside the organ. Herein, we suggest to derive the functional dependence of the fully orthotropic stiffness tensors on the Hounsfield units from the physical information contained in the X-ray attenuation coefficients: (i) Based on voxel average rules for the X-ray attenuation coefficients, we assign to each voxel the volume fraction occupied by water (marrow) and that occupied by solid bone matrix. (ii) By means of a continuum micromechanics representation for bone, which is based on voxel-invariant (species and whole bone-specific) stiffness properties of solid bone matrix and of water, we convert the aforementioned volume fractions into voxel-specific orthotropic stiffness tensor components. The micromechanics model, in combination with the average rule for X-ray attenuation coefficients, predicts a quasi-linear relationship between axial Young’s modulus and HU, and highly nonlinear relationships for both circumferential and radial Young’s moduli as well as for the shear moduli in all principal material directions. Corresponding whole-organ Finite Element (FE) analyses of a partially edentulous human mandible characterized by atrophy of the alveolar ridge show that volumetric strain concentrations/peaks within the organ are decreased when considering material anisotropy, and increased when considering material inhomogeneity.

Systemic social practice of nurses in luhmann's perspective

The objective was to understand the meaning of the social practice of nurses in Luhmann's perspective and allow for a discussion about the construction of a specific code for nursing; one that would go beyond the traditional health-disease code prevalent in the health system, whose relevant social communication is the disease. The Grounded Theory was the methodological framework. Data collection was performed by interviewing the 35 participants between May and December 2007. Data coding and analysis resulted revealed that assuming that nursing is as a functionally differentiated system implies on developing a binary code to enhance health as socially relevant communication and human beings as social beings who are part of a complex and multidimensional reality.     

Novel indications for phosphodiesterase type 5 inhibitors]

Phosphodiesterase type 5 (PDE5) induces the breakdown of cyclic guanosine monophosphate (cGMP) in smooth muscle cells. Hence, PDE5 inhibitors promote vasodilative effects by enhancing intracellular cGMP levels. Three PDE5 inhibitors, sildenafil, vardenafil, and tadalafil, have been approved for the treatment of "erectile dysfunction" (ED). All three show an excellent effectiveness regarding ED therapy, but differ from one another regarding their pharmacokinetic properties. Recent experimental studies and clinical trials indicate that PDE5 inhibitors are also effective in the treatment of various other diseases such as pulmonary arterial hypertension (PAH), Raynaud's disease, gastrointestinal disorders, and stroke, and furthermore exert cardioprotective effects. This review describes the cardiovascular safety of PDE5 inhibitors and provides an overview of the current literature regarding potential novel indications.     

Management of enterocutaneous fistulas using negative-pressure dressings

Fifteen patients with enterocutaneous fistulas (ECFs) not amenable to surgical treatment were treated with negative-pressure dressings over the abdominal wound and ECF. Closure of the ECF and time to closure were examined. In 11 patients who had no visible intestinal mucosa on examination, the closure rate was 100%, with a mean time to closure of 14 days. In 4 patients who did have grossly visible intestinal mucosa, no closure occurred. This represents an overall closure rate of 73%. Fistula output rate did not have a significant effect on outcome. These results confirm the efficacy of negative-pressure dressings in the closure of ECFs. Presence or absence of visible intestinal mucosa is the single most important clinical factor when considering the use of a negative-pressure dressing in the management of a patient with ECF.