RESUMEN
The vas deferens is a simple bioassay widely used to study the physiology of sympathetic neurotransmission and the pharmacodynamics of adrenergic drugs. The role of ATP as a sympathetic co-transmitter has gained increasing attention and furthered our understanding of its role in sympathetic reflexes. In addition, new information has emerged on the mechanisms underlying the storage and release of ATP. Both noradrenaline and ATP concur to elicit the tissue smooth muscle contractions following sympathetic reflexes or electrical field stimulation of the sympathetic nerve terminals. ATP and adenosine (its metabolic byproduct) are powerful presynaptic regulators of co-transmitter actions. In addition, neuropeptide Y, the third member of the sympathetic triad, is an endogenous modulator. The peptide plus ATP and/or adenosine play a significant role as sympathetic modulators of transmitter's release. This review focuses on the physiological principles that govern sympathetic co-transmitter activity, with special interest in defining the motor role of ATP. In addition, we intended to review the recent structural biology findings related to the topology of the P2X1R based on the crystallized P2X4 receptor from Danio rerio, or the crystallized adenosine A2A receptor as a member of the G protein coupled family of receptors as prototype neuro modulators. This review also covers structural elements of ectonucleotidases, since some members are found in the vas deferens neuro-effector junction. The allosteric principles that apply to purinoceptors are also reviewed highlighting concepts derived from receptor theory at the light of the current available structural elements. Finally, we discuss clinical applications of these concepts.
Asunto(s)
Unión Neuroefectora/fisiología , Conducto Deferente/fisiología , Animales , Epitelio/fisiología , Humanos , Masculino , Unión Neuroefectora/anatomía & histología , Receptores Purinérgicos/metabolismo , Conducto Deferente/anatomía & histologíaRESUMEN
BACKGROUND: The incidence of obesity and its most feared comorbidity, diabetes mellitus type 2, is increasing and there would not seem to be any medical treatment to help control these pandemics. However, there is a bariatric surgery technique, the Roux-en-Y Gastric Bypass (RYGB), which is safe and not only helps control excess weight, but produces encouraging results in the control and remission of diabetes. METHODS: We present 15 selected patients with a BMI between 30 and 35 kg/mt² and diabetes type 2 who underwent a laparoscopic RYGB with of one-year follow-up. RESULTS: A total of 14 women and one man were operated with the following average values: age: 37 years, weight: 88.3 kg, BMI: 32.8 kg/mt², blood glucose: 120 ± 38.8 mg%, HbA1c: 7.6 ± 0.73. Forty percent (40%) suffered from high blood pressure and 33.3% were dyslipidemic. Average surgical time was 75 minutes, hospital length of stay was two days, and there was a low rate of complications and no mortality. Diabetes remission was achieved in 93% of cases with significant drops in blood glucose and HbA1c (p ≤ 0.05 and p ≤ 0.001 respectively), dyslipidemia was 100% controlled and hypertension was 83.3% controlled. CONCLUSIONS: RYGB in selected patients with obesity type 1 and diabetes mellitus type 2 is a safe and effective technique for metabolic control and obesity control.
Asunto(s)
Anastomosis en-Y de Roux , Diabetes Mellitus Tipo 2/cirugía , Obesidad/complicaciones , Obesidad/cirugía , Adolescente , Adulto , Glucemia/metabolismo , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Obesidad/metabolismo , Resultado del Tratamiento , Adulto JovenRESUMEN
The anomalous aggregation of proteins into pathological filaments is a common feature of a many human diseases, often related to aging. In this context, neurodegenerative pathologies such as Alzheimer's disease (AD) account for a major part of these protein misfolding diseases. AD is characterized by pathological aggregation of two proteins, tau and Aß-amyloid. The intracellular neurofibrillary tangles (NFTs) and neuropil threads consists of filaments of the modified microtubule-associated protein tau, while extracellular amyloid plaques consists of filaments of Aß-peptide. It is noteworthy that tau oligomers with a prefilamentous structure appear to play a role at early stages of AD and tauopathies, but also in asymptomatic patients with Braak-stage I neuropathology, where clinical symptoms of AD and NFTs in frontal cortex are absent. This suggests that an increase in tau oligomers levels occurs before individuals manifest clinical symptoms of AD. NFTs are one of the hallmarks of Alzheimer disease and other tauphaties. These aggregates are thought to be toxic to neurons, either by causing some neurotoxic signalling defects or by obstructing the cell function. Factors contributing to accumulation of tau aggregates include the increased rate of protein misfolding, generation of amyloidogenic oligomers, underactivity of repair systems such as chaperones and ubiquitin-proteasome system, or a failure of energy supply and antioxidant defense mechanisms. There is not clear evidence if the aggregated tau or oligomers cause cellular damage, but on the basis of the emergent need to have an early and effective treatment, lowering the production or removal of these aggregates appears as a pathway toward alleviating the disease. In the context of some of most relevant reports, we analyze why tau protein seems to be an interesting target for AD treatment, and the importance to understand the pathways of tau. aggregation. This knowledge will allow us to identify and optimize potential inhibitors that interact with aggregated forms of tau and hyperphosphorylated tau before the formation of the NFTs, offering a possible therapeutic route for AD treatment.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Tauopatías/tratamiento farmacológico , Proteínas tau/metabolismo , Enfermedad de Alzheimer/metabolismo , Humanos , Ovillos Neurofibrilares/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fosforilación/efectos de los fármacos , Tauopatías/metabolismoRESUMEN
OBJECTIVE: To investigate the bioecological relationship between Chagas disease peridomestic vectors and reptiles as source of feeding. METHODS: In a three-story building, triatomines were captured by direct search and electric vacuum cleaner search in and outside the building. Then, age structure of the captured Triatoma maculata (T. maculata) were identified and recorded. Reptiles living in sympatric with the triatomines were also searched. RESULTS: T. maculata were found living sympatric with geckos (Thecadactylus rapicauda) and they bit residents of the apartment building in study. A total of 1 448 individuals of T. maculata were captured within three days, of which 74.2% (1 074 eggs) were eggs, 21.5% were nymphs at different stages, and 4.3% were adults. CONCLUSIONS: The association of T. maculata and T. rapicauda is an effective strategy of colonizing dwellings located in the vicinity of the habitat where both species are present; and therefore, could have implications of high importance in the intradomiciliary transmission of Chagas disease.