Brainstem application of melanocortin receptor ligands produces long-lasting effects on feeding and body weight

Recent evidence suggests that the central melanocortin (MC) system is a prominent contributor to food intake and body weight control. MC receptor (MC-R) populations in the arcuate and paraventricular nuclei are considered probable sites of action mediating the orexigenic effects of systemically or intracerebroventricularly administered ligands. Yet, the highest MC4-R density in the brain is found in the dorsal motor nucleus of the vagus nerve, situated subjacent to the commissural nucleus of the solitary tract, a site of pro-opiomelanocortin mRNA expression. We evaluated the contribution of the caudal brainstem MC system by (1) performing respective dose-response analyses for an MC-R agonist (MTII) and antagonist (SHU9119) delivered to the fourth ventricle, (2) comparing, in the same rats, the fourth intracerebroventricular dose-response profiles to those obtained with lateral intracerebroventricular delivery, and (3) delivering an effective dose of MTII or SHU9119 to rats before a 24 hr period of food deprivation. Fourth intracerebroventricular agonist treatment yielded a dose-dependent reduction of short-term (2 and 4 hr) and longer-term (24 hr) food intake and body weight. Fourth intracerebroventricular antagonist treatment produced the opposite pattern of results: dose-related increases in food intake and corresponding increases in body weight change for the 24-96 hr observation period. Comparable dose-response functions for food intake and body weight were observed when these compounds were delivered to the lateral ventricle. Results from deprived rats (no effect of MTII or SHU9119 on weight loss) support the impression derived from the dose-response analyses that the body weight change that follows MC treatments is secondary to their respective effects on food intake. Results support the relevance of the brainstem MC-R complement to the control of feeding.     

Management of infections due to antibiotic-resistant Streptococcus pneumoniae

Antibiotic-resistant strains of Streptococcus pneumoniae are becoming more prevalent throughout the world; this has resulted in modifications of treatment approaches. Management of bacterial meningitis has the greatest consensus. Strategies for treating other systemic infections such as pneumonia, bacteremia, and musculoskeletal infections are evolving, in part related to the availability of new antibiotics which are active in vitro against isolates resistant to penicillin and the extended-spectrum cephalosporins. However, there are currently very limited data related to the clinical efficacy of these new agents. The studies upon which current recommendations are based are reviewed. Otitis media represents the single most common infection due to S. pneumoniae. Recommendations for treatment of acute otitis media due to drug-resistant strains and the rationale for these recommendations are discussed.     

The envelope glycoprotein ectodomains determine the efficiency of CD4+ T lymphocyte depletion in simian-human immunodeficiency virus-infected macaques

CD4+ T lymphocyte depletion in human immunodeficiency virus type 1 (HIV-1)-infected humans underlies the development of acquired immune deficiency syndrome. Using a model in which rhesus macaques were infected with chimeric simian-human immunodeficiency viruses (SHIVs), we show that both the level of viremia and the structure of the HIV-1 envelope glycoprotein ectodomains individually contributed to the efficiency with which CD4(+) T lymphocytes were depleted. The envelope glycoproteins of recombinant SHIVs that efficiently caused loss of CD4(+) T lymphocytes exhibited increased chemokine receptor binding and membrane-fusing capacity compared with those of less pathogenic viruses. These studies identify the HIV-1 envelope glycoprotein ectodomains as determinants of CD4(+) T lymphocyte loss in vivo and provide a foundation for studying pathogenic mechanisms.     

Differential diagnosis of the transplant rejection and herpesvirus-related infections in kidney transplant recipients

An algorythm of differential diagnosis conduction of the transplant rejection reaction and the diseases caused by herpes viruses in recipients after the kidney transplantation was elaborated, basing on the analysis of results of the clinical, laboratory, immunological and serological examination methods.     

Topographic organization of connections between the hypothalamus and prefrontal cortex in the rhesus monkey

Prefrontal cortices have been implicated in autonomic function, but their role in this activity is not well understood. Orbital and medial prefrontal cortices receive input from cortical and subcortical structures associated with emotions. Thus, the prefrontal cortex may be an essential link for autonomic responses driven by emotions. Classic studies have demonstrated the existence of projections between prefrontal cortex and the hypothalamus, a central autonomic structure, but the topographic organization of these connections in the monkey has not been clearly established. We investigated the organization of bidirectional connections between these areas in the rhesus monkey by using tracer injections in orbital, medial, and lateral prefrontal areas. All prefrontal areas investigated received projections from the hypothalamus, originating mainly in the posterior hypothalamus. Differences in the topography of hypothalamic projection neurons were related to both the location and type of the target cortical area. Injections in lateral eulaminate prefrontal areas primarily labeled neurons in the posterior hypothalamus that were equally distributed in the lateral and medial hypothalamus. In contrast, injections in orbitofrontal and medial limbic cortices labeled neurons in the anterior and tuberal regions of the hypothalamus and in the posterior region. Projection neurons targeting orbital limbic cortices were more prevalent in the lateral part of the hypothalamus, whereas those targeting medial limbic cortices were more prevalent in the medial hypothalamus. In comparison to the ascending projections, descending projections from prefrontal cortex to the hypothalamus were highly specific, originating mostly from orbital and medial prefrontal cortices. The ascending and descending connections overlapped in the hypothalamus in areas that have autonomic functions. These results suggest that specific orbitofrontal and medial prefrontal areas exert a direct influence on the hypothalamus and may be important for the autonomic responses evoked by complex emotional situations.