Energy expenditure,body composition and dietary habits in progressive supranuclear palsy

Journal of Neurology - Little is known about metabolic changes in progressive supranuclear palsy. Goals of the present study are to: (1) investigate whether early progressive supranuclear palsy is...     

Long-Acting Atypical Antipsychotics: Characterization of the Local Tissue Response

Purpose

Long-acting injectables (LAIs) are increasingly recognized as an effective therapeutic approach for treating chronic conditions. Many LAIs are formulated to create a poorly soluble depot from which the active agent is delivered over time. This long residing depot can cause localized chronic-active inflammation in the tissue, which has not been well defined in the literature. The purpose of this work is to establish an experimental baseline for describing these responses.

Methods

Non-human primates and rodents were used to examine the response to LAI formulations of two clinically relevant atypical antipsychotics, aripiprazole monohydrate and olanzapine pamoate monohydrate.

Results

A foreign body response develops with elevations of key cytokines such as IL-1α, IL-1β, TNFα, and IL6 at the site of injection. However, the tissue response for the two atypical antipsychotics compounds diverge as evidenced by quantitative differences observed in cytokine levels at various time points after dosing.

Conclusions

Our studies show that, while the drugs are in the same therapeutic class, the response to each of these compounds can be distinguished qualitatively and quantitatively, supporting the idea that the injection site reaction involves a multiplicity of factors including the properties of the compound and cellular dynamics at the site of injection.     

Sildenafil citrate use in Addis Ababa: characteristics of users and pharmacists’ dispensing practices

International Journal of Clinical Pharmacy - Background Studies have reported misuse of sildenafil citrate for recreational purpose, not least by healthy young men. This is becoming a major...     

In vivo effects of Bothrops jararaca venom on metabolic profile and on muscle protein metabolism in rats

This study investigated the in vivo effects of the Bothrops jararaca venom (BjV) on general metabolic profile and, specifically, on muscle protein metabolism in rats. The crude venom (0.4 mg/kg body weight, IV) was infused in awake rats, and plasma activity of enzymes and metabolites levels were determined after 1, 2, 3, and 4 hours. BjV increased urea, lactate, and activities of creatine kinase, lactate dehydrogenase, and aspartate aminotransferase after 4 hours. The content of liver glycogen was reduced by BjV. Protein metabolism was evaluated by means of microdialysis technique and in isolated muscles. BjV induced increase in the muscle interstitial-arterial tyrosine concentration difference, indicating a high protein catabolism. The myotoxicity induced by this venom is associated with reduction of protein synthesis and increase in rates of overall proteolysis, which was accompanied by activation of lysosomal and ubiquitin-proteasome systems without changes in protein levels of cathepsins and ubiquitin-protein conjugates.     

Treatment of intestinal worms is associated with decreased HIV plasma viral load

BACKGROUND: We have previously suggested that helminthic infections make the host more susceptible to HIV infection and enhance its progression due to the chronic immune activation they cause. OBJECTIVE: To study the effect of antihelminthic treatment on HIV plasma viral load (VL) in HIV- and helminth-infected individuals living in Ethiopia. METHODS: Fifty-six clinically asymptomatic HIV-1-infected individuals, 31 (55%) of whom were also infected with helminths, were studied. All participants received antihelminthic treatment at baseline and at 3 and 6 months. Worm egg excretion, HIV plasma VL, and T-cell subsets were determined at baseline and 6 months after treatment. RESULTS: The mean age, number of CD4 T cells, and gender distribution were similar in the helminth-infected and -noninfected groups. At baseline, HIV plasma VL was strongly correlated to the number of eggs excreted (p <.001) and was higher in individuals infected with more than one helminth (5.28 +/- 0.35 versus 4.30 +/- 1.13 log RNA copies/mL, respectively; p =.16). After treatment of helminths, the 6-month change in HIV plasma VL was significantly different between the successfully treated group and the persistently helminth-positive group (p =.04) CONCLUSIONS: Helminth "load" is correlated to HIV plasma VL, and successful deworming is associated with a significant decrease in HIV plasma VL. The results of the current study, if confirmed in a larger study, may have important implications for slowing disease progression and reducing risks of transmission.     

Tissue engineering scaffolds containing embedded fluorinated-zeolite oxygen vectors

Efficient oxygen supply is a continuing challenge for the fabrication of successful tissue engineered constructs with clinical relevance. In an effort to enhance oxygen delivery we report the feasibility of using fluorinated zeolite particles embedded in three-dimensional (3-D) polyurethane scaffolds as novel oxygen vectors. First, 1H,1H,2H,2H-perfluorodecyltriethoxysilane was successfully coupled to zeolite framework particles to examine the dose-dependent dissolved oxygen concentration. Following this, the fluorinated-zeolite (FZ) particles were embedded in 3-D tissue engineering polyurethane scaffolds. Our data demonstrates an even distribution of FZ particles in the 3-D scaffolds without affecting the scaffold porosity or pore size. Human coronary artery smooth muscle cell (HCASMC) proliferation on FZ-containing polyurethane (PCU-FZ) scaffolds was significantly greater than on control scaffolds (P = 0.05). Remarkably, cell infiltration depths on the PCU-FZ scaffolds was double that on PCU control scaffolds. Taken together, our data suggest the potential of PCU-FZ scaffolds for tissue engineering with enhanced oxygen delivery to cells.