Predominance of lineage I among Trypanosoma cruzi isolates from Venezuelan patients with different clinical profiles of acute Chagas' disease

Trypanosoma cruzi isolates from 23 acute chagasic patients from localities of Western Venezuela (state of Barinas) where Chagas' disease is endemic were typed using ribosomal and mini-exon gene markers. Results showed that isolates of the two major phylogenetic lineages, T. cruzi I and T. cruzi II, were isolated from these patients. Six isolates (26%) were typed as T. cruzi II and 17 (74%) as belonging to T. cruzi lineage I. Analysis of random amplified polymorphic DNA (RAPD) patterns confirmed these two groups of isolates, but did not disclose significant genetic intra-lineage polymorphism. Patients infected by both T. cruzi I or T. cruzi II showed different clinical profiles presenting highly variable signs and symptoms of acute phase of Chagas' disease ranging from totally asymptomatic to severe heart failure. The predominance of T. cruzi I human isolates in Venezuela allied to the higher prevalence of severe symptoms of Chagas' disease (heart failure) in patients infected by this lineage do not corroborate an innocuousness of T. cruzi I infection to humans. To our knowledge, this is the first study describing predominance of T. cruzi lineage I in a large number of acute chagasic patients with distinct and well-characterized clinical profiles.     

Histogenetic compartments of the mouse centromedial and extended amygdala based on gene expression patterns during development

The amygdala controls emotional and social behavior and regulates instinctive reflexes such as defense and reproduction by way of descending projections to the hypothalamus and brainstem. The descending amygdalar projections are suggested to show a cortico-striato-pallidal organization similar to that of the basal ganglia (Swanson [2000] Brain Res 886:113-164). To test this model we investigated the embryological origin and molecular properties of the mouse centromedial and extended amygdalar subdivisions, which constitute major sources of descending projections. We analyzed the distribution of key regulatory genes that show restricted expression patterns within the subpallium (Dlx5, Nkx2.1, Lhx6, Lhx7/8, Lhx9, Shh, and Gbx1), as well as genes considered markers for specific subpallial neuronal subpopulations. Our results indicate that most of the centromedial and extended amygdala is formed by cells derived from multiple subpallial subdivisions. Contrary to a previous suggestion, only the central--but not the medial--amygdala derives from the lateral ganglionic eminence and has striatal-like features. The medial amygdala and a large part of the extended amygdala (including the bed nucleus of the stria terminalis) consist of subdivisions or cell groups that derive from subpallial, pallial (ventral pallium), or extratelencephalic progenitor domains. The subpallial part includes derivatives from the medial ganglionic eminence, the anterior peduncular area, and possibly a novel subdivision, called here commissural preoptic area, located at the base of the septum and related to the anterior commissure. Our study provides a molecular and morphological foundation for understanding the complex embryonic origins and adult organization of the centromedial and extended amygdala.     

Efficacy of rifabutin-based triple therapy in Helicobacter pylori infected patients after two standard treatments

BACKGROUND AND AIM: Even with the current most effective treatment regimens for Helicobacter pylori infection, a considerable number of patients will be resistant to eradication. The aim of the present study was to evaluate the H. pylori eradication rate in patients resistant to standard therapies when treated with a triple therapy of pantoprazole, rifabutin and amoxicillin. METHODS: Ninety-two consecutive patients diagnosed with H. pylori infection resistant to two previous treatment regimens were treated with pantoprazole, rifabutin and amoxicillin for 10 days. The persistence or eradication of H. pylori was determined by a 13C-urea breath test performed 4 weeks after the treatment. RESULTS: Per protocol eradication was achieved in 62.2% of patients and the intention-to-treat eradication was 60.8%. Only two patients were excluded for adverse events related to the treatment. CONCLUSIONS: The eradication rate is acceptable as a third-line therapy, particularly in centers with high cure rate for first line therapy. Another important value of this study is the good tolerance for the treatment observed in our patients. It is possible that rifabutin-based triple therapy may be of use in hospital centers that do not have disposable culture and susceptibility methods against H. pylori.     

Melatonin protects the retina from experimental nonexudative age-related macular degeneration in mice

Nonexudative age-related macular degeneration (NE-AMD) represents the leading cause of blindness in the elderly. Currently, there are no available treatments for NE-AMD. We have developed a NE-AMD model induced by superior cervical ganglionectomy (SCGx) in C57BL/6J mice, which reproduces the disease hallmarks. Several lines of evidence strongly support the involvement of oxidative stress in NE-AMD-induced retinal pigment epithelium (RPE) and outer retina damage. Melatonin is a proven and safe antioxidant. Our aim was analysing the effect of melatonin in the RPE/outer retina damage within experimental NE-AMD. The treatment with melatonin starting 48 h after SCGx, which had no effect on the ubiquitous choriocapillaris widening, protected visual functions and avoided Bruch´s membrane thickening, RPE melanin content, melanosome number loss, retinoid isomerohydrolase (RPE65)-immunoreactivity decrease, and RPE and hotoreceptor ultrastructural damage induced within experimental NE-AMD exclusively located at the central temporal (but not nasal) region. Melatonin also prevented the increase in outer retina/RPE oxidative stress markers and a decrease in mitochondrial mass at 6 weeks post-SCGx. Moreover, when the treatment with melatonin started at 4 weeks post-SCGx, it restored visual functions and reversed the decrease in RPE melanin content and RPE65-immunoreactivity. These findings suggest that melatonin could become a promising safe therapeutic strategy for NE-AMD.     

Short-term cold exposure activates TRH neurons exclusively in the hypothalamic paraventricular nucleus and raphe pallidus

The neuropeptide thyrotropin releasing hormone (TRH) is necessary for adequate cold-induced thermogenesis. TRH increases body temperature via both neuroendocrine and autonomic mechanisms. TRH neurons of the hypothalamic paraventricular nucleus (PVN) regulate thermogenesis through the activation of the hypothalamic-pituitary-thyroid axis during cold exposure. However, little is known about the role that TRH neurons play in mediating the sympathetic response to cold exposure. Here, we examined the response of TRH neurons of rats to cold exposure in hypothalamic regions including the PVN, the dorsomedial nucleus and the lateral hypothalamus along with areas of the ventral medulla including raphe obscurus, raphe pallidus (RPa) and parapyramidal regions. Our results using a double immunohistochemistry protocol to identify TRH and c-Fos (as a marker of cellular activity) followed by analysis of preproTRH gene expression demonstrate that only TRH neurons located in the PVN and the RPa are activated in animals exposed to short-term cold conditions.