Liposomes for HIV prophylaxis

There are approximately 33.4 million adults living with HIV worldwide of which an estimated 15.7 million are women. Although there has been enormous progress in the therapy of HIV/AIDS, treatment is not curative. Prevention is therefore of paramount importance, but vaccine-based and microbicidal approaches are still in their infancy. Since women acquire the virus largely through sexual intercourse, we developed liposomal systems potentially suitable for intra-vaginal use to prevent HIV-1 infection. We formulated liposomes from a range of naturally-occurring and synthetic lipids with varying physicochemical properties, and tested their ability to inhibit infection of transformed cells that express receptors specific to the virus. We identified formulations with the most favorable balance between decreasing HIV infection and causing cytotoxicity (i.e. therapeutic index). The therapeutic index improved with increasing cardiolipin content, and degree of unsaturation. Tissue reaction to these formulations was benign after intra-vaginal instillation in an in vivo female mouse model. These results support the potential use of cardiolipin-based liposomes enriched with synthetic lipids as microbicides for the prevention of HIV infection in women.     

The effect of degradable polymer surfaces on co-cultures of monocytes and smooth muscle cells

Strategies to optimize biomaterial chemistry for applications in vascular tissue engineering attempt to promote endothelial and smooth muscle cell recruitment into porous material constructs. The primary objective is to facilitate relevant tissue formation in a wound healing versus pro-inflammatory manner. The present work investigated the interactive co-cellular response of human monocytes and human vascular smooth muscle cells (VSMCs) with a novel degradable, polar/hydrophobic/ionic (D-PHI) polyurethane and compared it to a commercially available biomaterial, poly-lactic-glycolic acid (PLGA) as well as tissue culture polystyrene (TCPS). D-PHI triggered a smaller pro-inflammatory response (acid phosphatase, esterase, tumor necrosis factor-α) at later time points (>14?d) than PLGA suggesting that monocytes may be transitioning to a more wound-healing phenotype on the D-PHI surface. When D-PHI was coated with collagen, monocyte cell attachment did not differ with the native D-PHI; however, PLGA showed significant differences between collagen coated versus uncoated surfaces. There were more VSMCs and monocytes attached in co-culture to D-PHI when compared to PLGA. Co-cultures on D-PHI released more IL-10 (anti-inflammatory) than monocytes cultured alone, while the VSMCs retained the expression of its marker protein calponin. Together the above data suggest that co-culturing monocytes with VSMCs may aid in stimulating the attachment of VSMCs to D-PHI while eliciting the desired functional phenotypes for both monocytes (i.e. low inflammation based on IL-10 values) and VSMCs (expressing calponin, a marker of contractility). Moreover, the results of this study demonstrated that D-PHI performed equally or better to PLGA in terms of the assayed biological parameters.     

Novel methodology to characterize electromagnetic exposure of the brain

Due to the greatly non-uniform field distribution induced in brain tissues by radio frequency electromagnetic sources, the exposure of anatomical and functional regions of the brain may be a key issue in interpreting laboratory findings and epidemiological studies concerning endpoints related to the central nervous system. This paper introduces the Talairach atlas in characterization of the electromagnetic exposure of the brain. A hierarchical labeling scheme is mapped onto high-resolution human models. This procedure is fully automatic and allows identification of over a thousand different sites all over the brain. The electromagnetic absorption can then be extracted and interpreted in every region or combination of regions in the brain, depending on the characterization goals. The application examples show how this methodology enhances the dosimetry assessment of the brain based on results obtained by either finite difference time domain simulations or measurements delivered by test compliance dosimetry systems. Applications include, among others, the detailed dosimetric analysis of the exposure of the brain during cell phone use, improved design of exposure setups for human studies or medical diagnostic and therapeutic devices using electromagnetic fields or ultrasound.     

Efficacy of paroxetine in treating major depressive disorder in persons with multiple sclerosis

OBJECTIVE: The objective of this study was to evaluate the efficacy of paroxetine in treating major depressive disorder (MDD) in persons with multiple sclerosis (MS). METHOD: In this double-blind trial, 42 participants with MS and MDD were randomly assigned to one of two parallel 12-week treatment arms: paroxetine or placebo. The participants started at an initial dose of 10 mg/day paroxetine or placebo, titrated up to 40 mg daily based on symptoms response and side effects. The primary outcome measure was the Hamilton Rating Scale for Depression (HAM-D). Secondary outcomes included fatigue, anxiety and self-reported quality of life. RESULTS: Intent-to-treat analyses revealed that both groups improved from pretreatment to posttreatment. Although the treatment group improved more than the control group on most measures, few differences were statistically significant. For the primary outcome, 57.1% of participants in the treatment arm had at least a 50% reduction in HAM-D score, compared with 40% in the control group (nonsignificant). Treatment effects were greater among the participants who completed the study; 78.6% of completers had a treatment response compared with 42.1% of controls (P=.073). CONCLUSION: Although paroxetine may not be efficacious for all persons with MS and MDD, it appears to benefit some individuals.     

From ancient medicine to modern medicine: ayurvedic concepts of health and their role in inflammation and cancer

Recent statistics indicate that the overall cancer incidence in the United States, in spite of billions of dollars spent on research each year, has not changed significantly in the last half-century. Cancers of the prostate, breast, lung, and colon, although most common in the Western world, are least common in the Eastern world. Allopathic medicine commonly practiced currently is only 100 years old. Although traditional medicine has been around for thousands of years, no integration exists between it and allopathic medicine. Ayurveda, the science of long life and one of the most ancient medical systems still practiced on the Indian subcontinent, can be used in combination with modern medicine to provide better treatment of cancer. This review focuses on the ayurvedic concept of the causes of cancer and its linkage with inflammation, diagnosis, prevention, and treatment. How ayurvedic medicine can be integrated with allopathic medicine is also discussed in this review.     

Effect of a policy for restriction of selected classes of antibiotics on antimicrobial drug cost and resistance

Based on the instructions of the National Organization of Pharmaceutical Agents (Greece) from July 1, 2003, quinolones, 3( rd )and 4(th )generation cephalosporins, carbapenems, monobactams, glycopeptides, oxazolidinones, and streptogramins were considered as "restricted" antibiotics that could be used only with the approval of an Infectious Disease specialist. We analyzed the effect of the policy on the consumption and cost of antibiotics as a group and of specific classes, adjusted for the patient load, as well as on the antimicrobial resistance of isolated bacteria. We analyzed 5 trimesters (2 prior and 3 after the implementation of the new policy). A 20% and 16% reduction in adjusted consumption [in daily defined doses (DDDs)] and cost, respectively, of the restricted antibiotics was accomplished during the first trimester after implementation of the new policy. However, this was accompanied by a 36% and 56% increase in adjusted consumption and cost, respectively, of unrestricted antibiotics. A logistic regression model that we performed showed that the new policy had an independent positive effect on the in vitro antimicrobial susceptibility of Pseudomonas aeruginosa (p=0.051) but not of Acinetobacter baumannii and Escherichia coli isolates. Our data suggest that there are considerable limitations to the programs aiming to reduce the consumption of restricted antibiotics through the approval of their use by specialists, at least in some settings.