ABSTRACT
Alzheimer's disease (AD) is a progressive and neurodegenerative disorder and one of the current therapies involves strengthening the cholinergic tone in central synapses. Neuroprotective properties for nicotine have been described in AD, through its actions on nicotinic receptors and the further activation of the PI3K/Akt/Bcl-2 survival pathway. We have tested a quinolizidine alkaloid extract (TM0112) obtained from Teline monspessulanna (L.) K. Koch seeds to evaluate its action on nicotinic acetylcholine receptor (nAChR) in a neuronal AD model. Our data show that PC-12 cells pretreated with amyloid-ß (Aß) peptide for 24 h in presence of TM0112 modified Aß-reduction on cellular viability (Aß = 80 ± 3%; +TM0112 = 113 ± 4%, n = 15). In addition, this effect was blocked with atropine, MLA, and α-BTX (+TM0112+atropine = 87 ± 4%; +TM0112+MLA = 86 ± 4%; +TM0112+α-BTX = 92 ± 3%). Furthermore, similar protective effects were observed in rat cortical neurons (Aß = 63 ± 6%; +TM0112 = 114 ± 8%), but not in HEK293T cells (Aß = 61.4 ± 6.1%; +TM0112 = 62.8 ± 5.2) that do not express α7 nAChR. Moreover, the frequency of synaptic activity in the neuronal network (Aß = 51.6 ± 16.9%; +TM0112 = 210.8 ± 47.9%, n > 10), as well as the intracellular Ca2+ transients were recovered by TM0112 (Aß = 61.4 ± 6.9%; +TM0112 = 112.0 ± 5.7%; n = 3) in rat hippocampal neurons. TM0112 increased P-Akt, up to 250% with respect to control, and elevated Bcl-2/Bax percentage (Aß = 61.0 ± 8.2%; +TM0112 = 105.4 ± 19.5%, n = 4), suggesting a coupling between nAChR activation and an intracellular neuroprotective pathway. Our results suggest that TM0112 could be a new potential source for anti-AD drugs.
Subject(s)
Alkaloids/pharmacology , Alzheimer Disease/drug therapy , Neurons/drug effects , Neuroprotective Agents/pharmacology , Quinolizidines/pharmacology , Receptors, Nicotinic/metabolism , Alzheimer Disease/physiopathology , Amyloid beta-Peptides/toxicity , Animals , Cell Survival/drug effects , Cells, Cultured , Cerebral Cortex/drug effects , Cerebral Cortex/physiopathology , Fabaceae , HEK293 Cells , Humans , Neurons/physiology , PC12 Cells , Peptide Fragments/toxicity , Phytotherapy , Plant Extracts/pharmacology , Rats , Rats, Sprague-Dawley , Seeds , Synaptic Transmission/drug effectsABSTRACT
Erection depends largely on the release of nitric oxide (NO) by vascular endothelial cells. Insulin resistance (IR) is a metabolic abnormality that produces endothelial dysfunction characterized by decreased synthesis and release of NO. The aim of this paper is to evaluate the effect of treatment with metformin on the response to sildenafil in patients with erectile dysfunction (ED) and IR enrolled in a prospective, randomized, controlled, double-blind placebo study. We included 30 male patients with ED, IR, and poor response to sildenafil. Exclusion criteria included pharmacologic, anatomic, or endocrine ED; diabetes; prostatic surgery; or chronic illnesses. Erectile function was rated according to the International Index of Erectile Function 5 (IIEF-5); IR was measured by homeostasis model assessment (HOMA; IR = HOMA ≥ 3). Patients were randomized to receive metformin (n = 17) or placebo (n = 13). After treatment with metformin, patients with ED showed a significant increase in IIEF-5 score and a significant decrease in HOMA, both occurring at month 2 (IIEF-5: 17.0 ± 6.0 vs 14.3 ± 3.9, P = .01; HOMA: 3.9 ± 1.6 vs 5.5 ± 2.4, P = .01) to 4 of treatment (IIEF-5: 19.8 ± 3.8 vs 14.3 ± 3.9, P = .005; HOMA: 4.5 ± 1.9 vs 5.5 ± 2.4, P = .04), with no changes in these parameters in patients with ED receiving placebo. Patients treated with metformin had more adverse events than those who received placebo: 61.5% compared with 7.7%, P = .03, respectively. Adverse events were mild, mainly gastrointestinal, and did not cause discontinuation of treatment. Treatment with metformin in patients with ED and poor response to sildenafil reduced the IR and improved erectile function.
Subject(s)
Erectile Dysfunction/drug therapy , Insulin Resistance , Metformin/therapeutic use , Piperazines/therapeutic use , Sulfones/therapeutic use , Aged , Double-Blind Method , Homeostasis , Humans , Male , Metformin/adverse effects , Middle Aged , Models, Biological , Penile Erection/drug effects , Pilot Projects , Purines/therapeutic use , Sildenafil CitrateSubject(s)
Male , Female , Humans , Latin America , Employment , Work , Uruguay , Economics , Occupational GroupsABSTRACT
Trichosporon species are emerging pathogens capable of causing severe infections in immunocompromised patients. In this paper, we report a case of systemic infection in a liver transplant patient caused by Trichosporon asahii to show the etiologic agent's aggressiveness and poor therapeutic results with the different antifungals employed.
Subject(s)
Immunocompromised Host , Liver Transplantation , Mycoses/microbiology , Mycoses/pathology , Trichosporon/isolation & purification , Adult , Fatal Outcome , Female , Humans , Microbial Sensitivity Tests , Mycoses/drug therapy , Mycoses/immunology , Trichosporon/drug effects , Young AdultABSTRACT
La presencia de aire en lugares del abdomen donde normalmente no tiene que haber aire representa, en general, un riesgo potencial de muerte para el paciente si no se hace un diagnóstico temprano y un manejo agresivo, ya sea médico o quirúrgico. El diagnóstico por imágenes juega un rol fundamental en estos casos. Las principales causas son la perforación de vísceras huecas y la producción de gas en procesos infecciosos. En general, el estudio de estos pacientes comienza con radiología o ecografía pero el método más sensible y específico es la TC, la que detecta muy bien la localización y la extensión del gas anormal.