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Metformin (biguanide) is a drug widely used for the treatment of type 2 diabetes. This drug has been used for 60 years as a highly effective antihyperglycemic agent. The search for the mechanism of action of metformin has produced an enormous amount of research to explain its effects on gluconeogenesis, protein metabolism, fatty acid oxidation, oxidative stress, glucose uptake, autophagy and pain, among others. It was only up the end of the 1990s and beginning of this century that some of its mechanisms were revealed. Metformin induces its beneficial effects in diabetes through the activation of a master switch kinase named AMP-activated protein kinase (AMPK). Two upstream kinases account for the physiological activation of AMPK: liver kinase B1 and calcium/calmodulin-dependent protein kinase kinase 2. Once activated, AMPK inhibits the mechanistic target of rapamycin complex 1 (mTORC1), which in turn avoids the phosphorylation of p70 ribosomal protein S6 kinase 1 and phosphatidylinositol 3-kinase/protein kinase B signaling pathways and reduces cap-dependent translation initiation. Since metformin is a disease-modifying drug in type 2 diabetes, which reduces the mTORC1 signaling to induce its effects on neuronal plasticity, it was proposed that these mechanisms could also explain the antinociceptive effect of this drug in several models of chronic pain. These studies have highlighted the efficacy of this drug in chronic pain, such as that from neuropathy, insulin resistance, diabetic neuropathy, and fibromyalgia-type pain. Mounting evidence indicates that chronic pain may induce anxiety, depression and cognitive impairment in rodents and humans. Interestingly, metformin is able to reverse some of these consequences of pathological pain in rodents. The purpose of this review was to analyze the current evidence about the effects of metformin in chronic pain and three of its comorbidities (anxiety, depression and cognitive impairment).
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La diabetes es una enfermedad crónica y compleja con demandas y desafíos que influyen en la calidad de vida relacionada a la salud. Objetivo: determinar la calidad de vida en los pacientes con diabetes mellitus tipo 2 que acuden a los servicios médicos de la UJAT durante el periodo junio- julio del 2017. Métodos: se realizó un estudio transversal en 80 sujetos con diagnóstico de diabetes mellitus tipo 2 que acuden a un primer nivel de atención en el sureste mexicano. Se diseñó un instrumento y se obtuvieron datos sociodemográficos, de calidad de vida, antropométrica, bioquímica y clínica. Las variables fueron analizadas a través de estadística descriptiva, además, se utilizó la prueba de Chi cuadrado para explorar asociación entre variables categóricas y para variables continuas la prueba de T, considerando los estadísticamente significativos los resultados de p<0,05. Resultados: la media de edad de los pacientes estudiados fue 57,8 años. El dominio de la calidad de vida principalmente afectado fue energía, funcionamiento sexual y movilidad, y los factores que tuvieron efecto sobre la calidad de vida fueron la escolaridad, las comorbilidades, la polifarmacia, el índice de masa corporal y la hiperglucemia. Discusión: los pacientes con diagnóstico de diabetes mellitus tipo 2 que acuden a un primer nivel institucional del sureste mexicano están principalmente afectados en 3 dominios: energía y movilidad, ansiedad y preocupación y funcionamiento sexual.
Diabetes is a chronic and complex disease with demands and challenges that influence the quality of life - related to health. Objective: To determine the quality of life in patients with type 2 diabetes in the first level of care in Tabasco, during June- July 2017. Methods: A cross-sectional study was carried out in 102 subjects with type 2 diabetes. An instrument collected sociodemographic, quality of life, anthropometric, biochemical, and clinical data. The variables analyzed through descriptive statistics, also, the Chi-square test to explore the association between categorical variables, and for continuous variables, the T-test. Finally, considering the statistically significant results of p <0,05. Results: The mean age of patients included was 57,8 years old. The domain of the quality of life principally affected were energy-mobility, anxiety-concern, and sexual function, and the factors that affected the quality of life were education, comorbidi-ties, polypharmacy, body mass index, and hyperglycemia. Discussion: Patients with type 2 diabetes in the first institutional level in the Mexican south are principally affected in three domains: energy-mobility, anxiety-concern, and sexual function.
Assuntos
Humanos , Pacientes , Qualidade de Vida , Diabetes Mellitus Tipo 2 , Ansiedade , Qualidade de Vida , Antropometria , Inquéritos e Questionários , Polimedicação , Fatores SociodemográficosRESUMO
UNLABELLED: Introduction and subject: The aim of the study was to determine the factors involved in the delayed medical care of patients with ST-Segment Elevation Myocardial Infarction. METHODS: A prospective observational study was conducted in patients admitted to the coronary care unit at Dr. Juan Graham Casasús hospital with a diagnosis of ST-Segment Elevation Acute Myocardial Infarction. In all patients, clinical data, type and time of reperfusion treatment, and factors associated with delay were identified. RESULTS: Between November 2012 and January 2015 we included 213 patients with ST-Segment Elevation Myocardial Infarction. Age, diabetes, atypical chest angina and patient arrival period (night or weekend), were more frequent in patients presenting after 12 hours of onset of symptoms of myocardial infarction. Of these, hospital admission at night or weekend was the only independent predictor for delay to the emergency room. CONCLUSIONS: This study shows that in a referral hospital in southeast of Mexico, the delay attributable to the patient was the most common factor associated with care in patients with ST-Segment Elevation Myocardial Infarction. Patient arrival period was associated with delay to medical care.
Assuntos
Reperfusão Miocárdica/métodos , Admissão do Paciente/estatística & dados numéricos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Unidades de Cuidados Coronarianos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , México , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
The aim of this study was to evaluate fosinopril-induced changes in hemodynamic parameters and tactile allodynia in a rat model of diabetes. Diabetes was induced by streptozotocin (STZ; 50 mg/kg, i.p.) in male Wistar rats. STZ produced hyperglycemia, weight loss, polydipsia, polyphagia, and polyuria as well as long-term arterial hypotension, bradycardia, and tactile allodynia at 10-12 weeks. Daily administration of the angiotensin converting enzyme inhibitor, fosinopril (25 mg/kg, p.o., for 11 weeks) partially reduced the loss of body weight, decreased hyperglycemia, and systolic blood pressure in diabetic rats. Likewise, systemic administration of fosinopril prevented the development and maintenance of tactile allodynia in STZ-induced diabetic rats. These data suggest that fosinopril may have a role in the pharmacotherapy of diabetic neuropathic pain.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Fosinopril/farmacologia , Hiperalgesia/prevenção & controle , Animais , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/fisiopatologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Hiperalgesia/sangue , Hiperalgesia/fisiopatologia , Hiperglicemia/sangue , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Hiperglicemia/fisiopatologia , Insulina/sangue , Masculino , Ratos , Ratos Wistar , Redução de Peso/efeitos dos fármacosRESUMO
BACKGROUND: Painful neuropathy is the most common and debilitating complication of diabetes and results in hyperalgesia and allodynia. Hyperglycemia clearly plays a key role in the development and progression of diabetic neuropathy. Current therapeutic approaches are only partially successful and they are only thought to reduce the pain associated with peripheral neuropathy. Some natural products offer combined antioxidant, anti-inflammatory and antinociceptive properties that may help to treat in a more integrative manner this condition. In this regard, the purpose of this study was to investigate the antineuropathic effect of 7-hydroxy-3,4-dihydrocadalin in streptozotocin-induced diabetic rats and mice without glucose control as well as the possible mechanism of action involved in this effect. METHODS: Rats and mice were injected with 50 or 200 mg/kg streptozotocin, respectively, to produce hyperglycemia. The formalin test and von Frey filaments were used to assess the nociceptive activity. Rota-rod was utilized to measure motor activity and malondialdehyde assay to determine anti-oxidative properties. RESULTS: After 3 weeks of diabetes induction, chemical hyperalgesia was observed in streptozotocin-injected rats. Oral acute administration of 7-hydroxy-3,4-dihydrocadalin (0.3-30 mg/kg) decreased in a dose-dependent manner formalin-evoked hyperalgesia in diabetic rats. In addition, methiothepin (non-selective 5-HT receptor antagonist, 1 mg/kg, i.p.) and ODQ (guanylyl cyclase inhibitor, 2 mg/kg, i.p.), but not naltrexone (opioid receptor antagonist, 1 mg/kg, s.c.), prevented 7-hydroxy-3,4-dihydrocadalin-induced antihyperalgesic effect. The anti-hyperalgesic effect of 7-hydroxy-3,4-dihydrocadalin was similar to that produced by pregabalin (10 mg/kg, p.o.). Furthermore, oral acute administration of 7-hydroxy-3,4-dihydrocadalin (30 mg/kg) reduced streptozotocin-induced changes in malondialdehyde concentration from plasma samples. Unlike pregabalin, 7-hydroxy-3,4-dihydrocadalin did not affect motor activity. Six weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. At this time, oral administration of 7-hydroxy-3,4-dihydrocadalin (30 mg/kg) or pregabalin (10 mg/kg) reduced in a similar way tactile allodynia in diabetic rats. Finally, chronic oral administration of 7-hydroxy-3,4-dihydrocadalin (30-300 mg/kg, 3 times/week, during 6 weeks), significantly prevented the development of mechanical hyperalgesia and allodynia in streptozotocin-induced diabetic mice. CONCLUSIONS: Data suggests that 7-hydroxy-3,4-dihydrocadalin has acute and chronic effects in painful diabetic neuropathy. This effect seems to involve antioxidant properties as well as activation of 5-HT receptors and inhibition of guanylyl cyclase enzyme.
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Analgésicos/administração & dosagem , Asteraceae/química , Diabetes Mellitus Experimental/complicações , Neuropatias Diabéticas/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Sesquiterpenos/administração & dosagem , Animais , Neuropatias Diabéticas/etiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ratos , Ratos Wistar , EstreptozocinaRESUMO
Intracellular pH is a fundamental parameter to cell function that requires tight homeostasis. In the absence of any regulation, excessive acidification of the cytosol would have the tendency to produce cellular damage. Mammalian Na(+)/H(+) exchangers (NHEs) are electroneutral Na(+)-dependent proteins that exchange extracellular Na(+) for intracellular H(+). To date, there are 9 identified NHE isoforms where NHE1 is the most ubiquitous member, known as the housekeeping exchanger. NHE1 seems to have a protective role in the ischemia-reperfusion injury and other inflammatory diseases. In nociception, NHE1 is found in neurons along nociceptive pathways, and its pharmacological inhibition increases nociceptive behavior in acute pain models at peripheral and central levels. Electrophysiological studies also show that NHE modulates electrical activity of primary nociceptive terminals. However, its role in neuropathic pain still remains controversial. In humans, NHE1 may be responsible for inflammatory bowel diseases since its expression is reduced in Crohn's disease and ulcerative colitis. The purpose of this work is to provide a review of the evidence about participation of NHE1 in the nociceptive processing.
RESUMO
Objetivo: Conocer las características de la oclusión primaria más frecuentes, alteraciones que predisponen y conllevan a la futura maloclusión, y las maloclusiones presentes en preescolares. Material y Métodos: Se determinó la frecuencia de las características de la oclusión en la dentición primaria de acuerdo a los principios de Baume. El grupo de estudio comprendió de 61 (76%) niños de edad preescolar. Cada niño fue explorado con luz natural para observar las características de la oclusión propias de su edad. Resultados: De los 61 (76%) niños solo el 12% de ellos presentaron las características de la oclusión primaria, el 67% presentó más de una alteración. La usencia de espacios de desarrollo en el 67%, de los casos, sobremordida horizontal el 15%, mientras que el 38% presento sobremordida vertical, en relación a la oclusión posterior el 3% presento planos terminales distales y el 2% mesial exagerada. De las maloclusiones estudiadas destacó la mordida abierta con el 32% seguidamente la mordida cruzada anterior con el 31%. Conclusiones: 1. La ausencia de espacios de desarrollo en la primera dentición, predice el apiñamiento dental en los permanentes. 2. La diferencia de dimensión en la sobremordida horizontal y vertical de los incisivos, limita el desarrollo y funcionalidad de los maxilares. 3. El plano terminal distal y mesial exagerado, determinan la clase molar II y III de Angle, la presencia de ellas afectan el comportamiento mesial del primer molar permanente. 4. La maloclusión de mordida abierta y la mordida cruzada anterior son signos que afectan complejo craneofaciodental de ambas denticiones.
Objective: Know the frequency in which the prescholar presents: characteristics of primary occlusion, alterations which lead to and predispose future malocclusions, and present malocclusions. Tools and Methodology: The frequency in occlusion characteristics in primary dentures was determined according to Doctor BaumeÆs principles. The study group consisted of 61 (76%) preschool children. Each child was explored with natural light in order to observe occlusion characteristics corresponding to their age. Results: Only 12% of the 61(76%) children presented primary occlusion characteristics, 67% presented more than one alteration. The absence of developmental spaces in 67% of cases was due to a horizontal overbite in 15%, while 38% presented a vertical overbite. Regarding posterior occlusions 3% presented terminal distal planes and 2% an exaggerated mesial. Of the malocclusions studied there was an outstanding 32% of cases with open bite followed by 31% presenting a crossed anterior bite. Conclusions: 1. The absence of developmental spaces in primary dentures predicts the conglomeration of future permanent dentures. 2. The difference in dimension of horizontal and vertical overbites found in incisors limits the development and functionality of maxillaries. 3. The terminal distal plane and exaggerated mesial determine de angle of the second and third molar, their presence affect the displacement of the first permanent molar. 4. The malocclusion of both the open and crossed anterior bite are signs which affect the craniofacial dental complex in both dentures.