Cardiac autonomic denervation and expression of neurotrophins (NGF and BDNF) and their receptors during experimental Chagas disease.

Although cardiac dysautonomia is a distinctive feature of Chagas disease, its clinical and functional significance is still being speculated. Neurotrophic factors are potentially involved; however, studies of their effect in this infection are rare. Ultrastructural abnormalities in autonomic varicosities, levels of both nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF), as well as the expression of their receptors, were analysed in the heart of a rat model of Trypanosoma infection. Predominantly, at the early stage of the infection, cardiac autonomic varicosities displayed several signs of degeneration parallel to the elevation of cardiac levels of NGF, as well as expression of the receptors TrkA and p75NTR. For BDNF and TrkB, the changes were less conspicuous. Data obtained here can contribute to further clarify the factors related to the autonomic nervous system's adaptive changes that could determine the evolution of different clinical forms of Chagas disease; mainly, the cardiac form.

PnPP-19, a Synthetic and Nontoxic Peptide Designed from a Phoneutria nigriventer Toxin, Potentiates Erectile Function via NO/cGMP.

PURPOSE: We designed a peptide, PnPP-19, comprising the potential active core of the Phoneutria nigriventer native toxin PnTx2-6. We investigated its role on erectile function, and its toxicity and immunogenicity. MATERIALS AND METHODS: Erectile function was evaluated by the intracavernous pressure-to-mean arterial pressure ratio during electrical field stimulation on rat pelvic ganglia. Cavernous strips were contracted with phenylephrine and relaxation was induced by electrical field stimulation with or without PnPP-19 (10(-8) M). Activity on sodium channels was evaluated by electrophysiological screening of transfected channels on Xenopus oocytes and dorsal root ganglion cells. Antibodies were detected by indirect enzyme-linked immunosorbent assay in mice previously treated with the peptide. Histopathological studies were performed with mouse organs treated with different doses of PnPP-19. RESULTS: PnPP-19 was able to potentiate erection at 4 and 8 Hz in vivo and ex vivo. It showed no toxicity and low immunogenicity in mice, and did not affect sodium channels or rat hearts. PnPP-19 increased cyclic guanosine monophosphate levels at 8 Hz. This effect was inhibited by L-NAME (10(-4) M). Erectile function was partially inhibited by 7-nitroindazole (10(-5) M), a selective inhibitor of neuronal nitric oxide synthase. CONCLUSIONS: PnPP-19 potentiates erection in vivo and ex vivo via the nitric oxide/cyclic guanosine monophosphate pathway. It does not affect sodium channels or rat hearts and shows no toxicity and low immunogenicity. These findings make it a promising candidate as a novel drug in the therapy of erectile dysfunction.

Clotting factor XIII and desmopressin improve hemostasis in uncontrolled bleeding.

PURPOSE: To investigate hemostatic effects of supplementary factor XIII and desmopressin (DDAVP) in resuscitation of uncontrolled bleeding. METHODS: Fifty-four rabbits were randomized in nine groups: G1: Sham; G2: FXIII and normotensive resuscitation (NBP); G3: FXIII and permissive hypotension (PH) (MAP 60% baseline); G4: FXIII/DDAVP/NBP; G5: FXIII/DDAVP/PH; G6: NBP only; G7: FXIII no hemorrhage; G8: FXIII/DDAVP no hemorrhage; G9: PH only. Thromboelastometry and intra-abdominal blood loss were assessed. Scanning electron microscopy (EM) of the clots was performed. RESULTS: Compared to Sham, only G8 (FXIII/DDAVP w/o hemorrhage) showed clotting time (CT) significantly lower (p<0.05). NBP alone (G6) resulted in significantly prolonged CT compared to G2, G3 and G5 (p<0.05). Similarly, median alpha angle was significantly larger in G3,4,5, and 9 compared to G6 (p<0.05). Area under the curve was significantly greater in G5 than G2. Intra-abdominal blood loss was lower in G5 and G9 compared to G2 and G6. FXIII/DDAVP and PH resulted in more robust fibrin mesh by EM. CONCLUSIONS: Normotensive resuscitation provokes more bleeding and worsens coagulation compared to pH, that is partially reversed by factor XIII and desmopressin. FXIII and DDAVP can synergistically improve coagulation. Permissive hypotension reduces bleeding regardless of those agents.

Clotting Factor XIII and desmopressin improve hemostasis in uncontrolled bleeding

PURPOSE: To investigate hemostatic effects of supplementary factor XIII and desmopressin (DDAVP) in resuscitation of uncontrolled bleeding. METHODS: Fifty-four rabbits were randomized in nine groups: G1: Sham; G2: FXIII and normotensive resuscitation (NBP); G3: FXIII and permissive hypotension (PH) (MAP 60% baseline); G4: FXIII/DDAVP/NBP; G5: FXIII/DDAVP/PH; G6: NBP only; G7: FXIII no hemorrhage; G8: FXIII/DDAVP no hemorrhage; G9: PH only. Thromboelastometry and intra-abdominal blood loss were assessed. Scanning electron microscopy (EM) of the clots was performed. RESULTS: Compared to Sham, only G8 (FXIII/DDAVP w/o hemorrhage) showed clotting time (CT) significantly lower (p<0.05). NBP alone (G6) resulted in significantly prolonged CT compared to G2, G3 and G5 (p<0.05). Similarly, median alpha angle was significantly larger in G3,4,5, and 9 compared to G6 (p<0.05). Area under the curve was significantly greater in G5 than G2. Intra-abdominal blood loss was lower in G5 and G9 compared to G2 and G6. FXIII/DDAVP and PH resulted in more robust fibrin mesh by EM. CONCLUSIONS: Normotensive resuscitation provokes more bleeding and worsens coagulation compared to pH, that is partially reversed by factor XIII and desmopressin. FXIII and DDAVP can synergistically improve coagulation. Permissive hypotension reduces bleeding regardless of those agents. .

Animal models of neurodegenerative diseases.

The prevalence of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), increases with age, and the number of affected patients is expected to increase worldwide in the next decades. Accurately understanding the etiopathogenic mechanisms of these diseases is a crucial step for developing disease-modifying drugs able to preclude their emergence or at least slow their progression. Animal models contribute to increase the knowledge on the pathophysiology of neurodegenerative diseases. These models reproduce different aspects of a given disease, as well as the histopathological lesions and its main symptoms. The purpose of this review is to present the main animal models for AD, PD, and Huntington's disease.

Effects of Copaifera duckei Dwyer oleoresin on the cell wall and cell division of Bacillus cereus.

The aim of this work was to evaluate the antibacterial activity of Copaifera duckei oleoresin and to determine its possible mechanism of action against bacteria of clinical and food interest. The antibacterial activity was determined by agar diffusion and dilution methods; the mechanism of action by transmission electron microscopy and by SDS-PAGE; the bioactive compounds by bioautography; and the chemical analysis by GC/MS. Oleoresin showed activity against nine of the 11 strains of bacteria tested. Bacillus cereus was the most sensitive, with a MIC corresponding to 0.03125 mg ml(-1) and with a bactericidal action. Oleoresin acted on the bacterial cell wall, removing proteins and the S-layer, and interfering with the cell-division process. This activity probably can be attributed to the action of terpenic compounds, among them the bisabolene compound. Gram-negative bacteria tested were not inhibited. C. duckei oleoresin is a potential antibacterial, suggesting that this oil could be used as a therapeutic alternative, mainly against B. cereus.

Animal models of neurodegenerative diseases

The prevalence of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), increases with age, and the number of affected patients is expected to increase worldwide in the next decades. Accurately understanding the etiopathogenic mechanisms of these diseases is a crucial step for developing disease-modifying drugs able to preclude their emergence or at least slow their progression. Animal models contribute to increase the knowledge on the pathophysiology of neurodegenerative diseases. These models reproduce different aspects of a given disease, as well as the histopathological lesions and its main symptoms. The purpose of this review is to present the main animal models for AD, PD, and Huntington's disease.

Inflammatory changes in the central nervous system are associated with behavioral impairment in Plasmodium berghei (strain ANKA)-infected mice.

Experimental cerebral malaria is a neuroinflammatory condition that results from the host immune response to the parasite. Using intravital microscopy, we investigated leukocyte recruitment in the brain microcirculation and the temporal relationship of this process to the behavioral changes observed in Plasmodium berghei (strain ANKA)-infected C57Bl/6 mice. We found that leukocyte recruitment was increased from day 5 post-infection (p.i.) onwards. Histopathological changes and increased levels of inflammatory cytokines in the brain were also observed. Behavioral performance evaluated by the SHIRPA protocol showed functional impairment from day 6 p.i. onwards. Thus, early leukocyte migration into the brain and associated inflammatory changes may be involved in neurological impairment in parasite-infected C57Bl/6 mice.

Cardiac NGF and GDNF expression during Trypanosoma cruzi infection in rats.

In rats, autonomic nerve endings are damaged during Trypanosoma cruzi-induced myocarditis. Gradual recovery occurs after the acute phase. The present work shows the cardiac levels of glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF), and their cellular sources during T. cruzi infection in rats. Atrial and ventricular NGF levels (ELISA) increased significantly at day 20 post inoculation, the time-point of maximal sympathetic denervation. ELISA failed to show significant increase of cardiac GDNF levels. However immunohistochemistry showed a significant increase of anti-GDNF gold particles over atrial granules at day 20. Light microscopy showed stronger NGF immunostaining in atrial cardiomyocytes and several blood capillaries. In situ hybridization showed NGF and GDNF mRNAs in atrial and ventricular myocytes of both infected and uninfected animals. Endothelial cells exhibited NGF mRNA and protein only in infected rats. No evidence of neurotrophic factor expression by the infiltrating mononuclear cells was found. This is the first report on neurotrophic factor expression during T. cruzi infection. Our findings indicate an important role for NGF in the regenerative phenomena subsequent to a myocarditis able to damage sympathetic nerve endings, with preservation of preterminals and nerve trunks. GDNF could have a minor or a more transient participation.