RESUMEN
BACKGROUND: Solanum lycocarpum is a medicinal plant used in Brazil with hypoglycemic activity by its fruits use. However, the fruits production is restricted in some periods of the year, differently of leaves. OBJECTIVE: To evaluate the effects of hydroalcoholic extracts of S. lycocarpum leaves in alloxan-induced diabetic mice. METHODS: Hydroalcoholic extract of S. lycocarpum was characterized by phytochemical and GCMS analysis. The Antidiabetic activity was assessed following treatment for 22 days with S. lycocarpum extract at 125, 250, and 500 mg/kg. Bodyweight, water, and food intake, glycemia, biochemical parameters, anatomy-histopathology of the pancreas, liver and kidney, and expression of target genes were analyzed. In addition, oral acute toxicity was evaluated. RESULTS: Animals treated showed a significant reduction (p < 0.05) in glycemia following a dose of 125 mg/kg. Food intake remained similar for all groups. Decreased polydipsia symptoms were observed after treatment with 250 (p < 0.001) and 500 mg/kg (p < 0.01) compared with diabetic control, although normal rates were observed when 125 mg/kg was administered. A protective effect was also observed in the pancreas, liver, and kidneys, through the regeneration of the islets. Hypoglycemic activity can be attributed to myo-inositol, which stimulates insulin secretion, associated with α-tocopherol, which prevents damage from oxidative stress and apoptosis of ß-pancreatic cells by an increased Catalase (CAT) and Glutathione peroxidase 4 (GPX4) mRNA expression. The toxicological test demonstrated safe oral use of the extract under the present conditions. CONCLUSION: Hydroalcoholic extract of S. lycocarpum promotes the regulation of diabetes in the case of moderate glycemic levels, by decreasing glycemia and exerting protective effects on the islets.
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Complicaciones de la Diabetes/tratamiento farmacológico , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Solanum/química , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/metabolismo , Aloxano/administración & dosificación , Animales , Aspartato Aminotransferasas/metabolismo , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Catalasa/metabolismo , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/patología , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Hipoglucemiantes/química , Inositol/farmacología , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Páncreas/patología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Extractos Vegetales/química , Hojas de la Planta/química , alfa-Tocoferol/farmacologíaRESUMEN
Emphysematous pyelonephritis (EPN) is a necrotizing infection characterized by the production of gas in the renal parenchyma, collecting system or perirenal tissue. Meanwhile, emphysematous cystitis (EC) is a clinical entity characterized by the presence of gas inside and around the bladder wall. Interestingly, although both diseases are common in patients with diabetes mellitus, these are rarely combined. We report a rare case of a 56-year-old diabetic male suffering from fever, headache and vomiting and in which a diagnosis of septic shock was established due to coexistence of EC and bilateral EPN. The emphysematous diseases improved with a conservative treatment approach using antibiotic therapy and glycemic control, we highlight that the nephrectomy was not necessary in our patient despite the fact that he presented risk factors that predict the failure of conservative treatment.
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Cistitis/complicaciones , Complicaciones de la Diabetes/microbiología , Enfisema/diagnóstico por imagen , Pielonefritis/complicaciones , Choque Séptico/diagnóstico , Adulto , Anciano , Antibacterianos/uso terapéutico , Tratamiento Conservador , Cistitis/diagnóstico , Cistitis/tratamiento farmacológico , Cistitis/microbiología , Complicaciones de la Diabetes/patología , Enfisema/etiología , Escherichia coli/aislamiento & purificación , Femenino , Fiebre/diagnóstico , Fiebre/etiología , Cefalea/diagnóstico , Cefalea/etiología , Humanos , Masculino , Persona de Mediana Edad , Pielonefritis/diagnóstico , Pielonefritis/tratamiento farmacológico , Pielonefritis/microbiología , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Vómitos/diagnóstico , Vómitos/etiologíaAsunto(s)
Complicaciones de la Diabetes/patología , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/patología , Infarto del Miocardio sin Elevación del ST/complicaciones , Infarto del Miocardio sin Elevación del ST/patología , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/patología , Diabetes Mellitus/patología , Electrocardiografía , Resultado Fatal , Humanos , Masculino , Persona de Mediana Edad , Radiografía TorácicaRESUMEN
BACKGROUND: The accuracy of different laboratory tests for diagnosis of diabetes mellitus (DM) and prediabetes (preDM) in populations exposed to tuberculosis (TB) remains poorly understood. Here, we examined the prevalence of DM and preDM in TB affected people in Lima, Peru. METHODS: A prospective cohort study of patients affected TB and their household contacts (HHC), was conducted between February and November 2017 in Lima, Peru. Fasting plasma glucose (FPG), HbA1c and oral glucose tolerance test (OGTT) were used to detect DM and preDM in a prospective cohort of TB patients (n = 136) and household contacts (n = 138). Diagnostic performance of the laboratory tests was analyzed. Potential effects of sociodemographic and clinical factors on detection of dysglycemia were analyzed. RESULTS: In TB patients, prevalence of DM and preDM was 13.97 and 30.88% respectively. Lower prevalence of both DM (6.52%) and preDM (28.99%) were observed in contacts. FPG, HbA1c and OGTT had poor agreement in detection of preDM in either TB cases or contacts. TB-DM patients had substantially lower hemoglobin levels, which resulted in low accuracy of HbA1c-based diagnosis. Classic sociodemographic and clinical characteristics were not different between TB patients with or without dysglycemia. CONCLUSION: High prevalence of DM and preDM was found in both TB patients and contacts in Lima. Anemia was strongly associated with TB-DM, which directly affected the diagnostic performance of HbA1c in such population.
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Diabetes Mellitus/diagnóstico , Estado Prediabético/diagnóstico , Tuberculosis/patología , Adulto , Glucemia/análisis , Complicaciones de la Diabetes/patología , Diabetes Mellitus/epidemiología , Femenino , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Perú , Estado Prediabético/complicaciones , Estado Prediabético/epidemiología , Prevalencia , Estudios Prospectivos , Tuberculosis/complicacionesRESUMEN
Objective: To assesses microvascular complications in renal transplant recipients with posttransplant diabetes mellitus (PTDM). Research Design and Methods: In this observational study, patients with ≥5 years of PTDM were included from a cohort of 895 kidney recipients transplanted from 2000 through 2011. Diabetic retinopathy was evaluated by fundus photographs and optical coherence tomography (OCT). Diabetes kidney disease was evaluated by protein to creatinine ratio (PCR) and estimated glomerular filtration rate (eGFR). Distal polyneuropathy was assessed by Michigan Protocol and 10 g-monofilament feet examinations. The Ewing protocol identified cardiovascular autonomic neuropathy. Renal transplant recipients without PTDM diagnosis (NPTDM) were considered controls. Results: After 144.5 months of follow-up, 135 (15%) patients developed PTDM, and 64 had a PTDM duration ≥5 years. None of the patients with PTDM presented diabetic retinopathy at fundus photographs, but thinning of inner retinal layers was observed with OCT. More than 60% of patients with PTDM had distal polyneuropathy (OR, 1.55; 95% CI, 1.26 to 1.91; P < 0.001). Cardiovascular reflex tests abnormalities were similar between patients with PTDM and NPTDM (P = 0.26). During the first year and 8.5 ± 3.0 years after renal transplantation, eGFR and PCR did not differ significantly between patients with PTDM or NPTDM. Conclusions: This longitudinal study assesses microvascular complications in renal transplant patients with PTDM. A lower than expected prevalence as well as a different clinical course of the complications was observed. PTDM seems to be a unique type of diabetes, and its consequences may be milder than expected in type 1 and type 2 diabetes.
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Complicaciones de la Diabetes/epidemiología , Trasplante de Riñón/efectos adversos , Microvasos/patología , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Complicaciones de la Diabetes/etiología , Complicaciones de la Diabetes/patología , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/patología , Prevalencia , Estudios Retrospectivos , Receptores de Trasplantes/estadística & datos numéricosRESUMEN
Type 1 diabetes mellitus (T1DM) is a disorder resulting from chronic autoimmune destruction of insulin-producing pancreatic ß-cells, lack of insulin production and hyperglycaemia. The aim of this study was to evaluate the hypothesis that streptozotocin-diabetic mice treated with Saccharomyces boulardii THT 500101 strain present improvement of glucose and triglycerides metabolism, reduction of liver inflammation concomitant with a beneficial impact in the gut microbiota profile. C57BL/6 male mice were randomly assigned into three groups: Control, Diabetes, Diabetes+Probiotic, and were euthanised 8 weeks after probiotic chronic administration. Mice submitted to treatment presented reduced glycemia in comparison with the diabetic group, which was correlated with an increase in C-peptide level and in hepatic glycogen content. Fat metabolism was significantly altered in streptozotocin-induced diabetic group, and S. boulardii treatment regulated it, leading to a decrease in serum triglycerides secretion, increase in hepatic triglycerides storage and modulation of inflammatory profile. The phenotypic changes seen from chronic S. boulardii treatment were found to be broadly associated with the changes in microbioma of diabetic animals, with increased proportion in Bacteroidetes, Firmicutes and Deferribacteres, and a decreased proportion of Proteobacteria and Verrucomicrobia phylum. Thus, the data presented here show up a novel potential therapeutic role of S. boulardii for the treatment and attenuation of diabetes-induced complications.
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Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus Experimental/inducido químicamente , Microbioma Gastrointestinal/efectos de los fármacos , Probióticos/farmacología , Probióticos/uso terapéutico , Saccharomyces boulardii/fisiología , Estreptozocina/toxicidad , Animales , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Glucemia/efectos de los fármacos , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/patología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Dislipidemias/prevención & control , Hiperglucemia/prevención & control , Inflamación , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Probióticos/administración & dosificación , Triglicéridos/metabolismoRESUMEN
BACKGROUND: Little is known about diabetes-related major lower extremity amputations (DMLEA) burden in México. AIM OF THE STUDY: To describe DMLEA hospitalization rates, in-hospital survival rates, characteristics associated with all-cause in-hospital mortality and direct costs of hospitalization during the 2005-2015 period, in the two principal Health Institutions in Mexico: the Mexican Institute of Social Security (IMSS) and the Ministry of Health (MoH). METHODS: A secondary data analysis was conducted using hospital discharge information obtained from administrative databases. Non-traumatic DMLEA hospitalizations in adults aged 20 years and over were analyzed. Hospitalization characteristics and in-hospital all-cause mortality risk were also assessed. Direct costs of hospitalization including length of hospital stay, surgical procedure, wound care and medical emergency consultation were accounted in U.S. dollars (USD, 2015). RESULTS: There were 34,051 DMLEA hospitalizations and 1,268 in-hospital deaths. DMLEA hospitalizations rates increase from 4.71-6.12 × 100,000 affiliates during 2005 and 2015 respectively for both institutions together. Females and age ≥60 years were associated with all-cause in-hospital death. The all-period direct costs of hospitalization amounted to $132.51 million USD ($86.30 in the IMSS and $46.21 in the MoH), and showed a sustained increment: from $4.14 million USD in 2005 to $24.84 million USD in 2015 (percentage increase 499.3%). CONCLUSIONS: In-hospital mortality was 3.7%. Female sex and age ≥60 years were characteristics associated with all-cause in-hospital death. The increase in the number of DMLEA hospitalizations and their direct costs, reflects a negative progression of diabetes in the two largest Health Institutions in Mexico.
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Amputación Quirúrgica/estadística & datos numéricos , Diabetes Mellitus/patología , Hospitalización/economía , Extremidad Inferior/cirugía , Adulto , Complicaciones de la Diabetes/mortalidad , Complicaciones de la Diabetes/patología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , México , Persona de Mediana Edad , Seguridad Social , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: To analyze costs associated with dementia based on a cross-sectional study in the Brazilian health system. METHODS: Direct and indirect costs were estimated by conducting comprehensive interviews on the use of resources in a sample of 156 patients with dementia treated at an outpatient memory clinic of a tertiary hospital. A regression model was used to determine the main determinants of costs associated with dementia. RESULTS: Global costs of dementia were US$1,012.35; US$1,683.18 and US$1,372.30 per patient/month for mild, moderate and severe stages, respectively. Indirect costs ranged from US$536.62 to US$545.17 according to severity. Dementia costs were influenced by medication, FAST score, and educational level of caregiver. DISCUSSION: The study represents an original contribution toward establishing direct and indirect costs of dementia in Brazil. Results indicate significant economic impacts, including projection of annual costs of US$16,548.24 per patient.
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Costo de Enfermedad , Demencia/economía , Anciano , Anciano de 80 o más Años , Brasil , Enfermedades Cardiovasculares/complicaciones , Cuidadores/economía , Demencia/complicaciones , Demencia/patología , Complicaciones de la Diabetes/patología , Femenino , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Centros de Atención TerciariaRESUMEN
Chronic or intermittent hyperglycemia is associated with the development of diabetic complications. Several signaling pathways can be altered by having hyperglycemia in different tissues, producing oxidative stress, the formation of advanced glycation end products (AGEs), as well as the secretion of the pro-inflammatory cytokines and cellular death (pathological autophagy and/or apoptosis). However, the signaling pathways that are directly triggered by hyperglycemia appear to have a pivotal role in diabetic complications due to the production of reactive oxygen species (ROS), oxidative stress, and cellular death. The present review will discuss the role of cellular death in diabetic complications, and it will suggest the cause and the consequences between the hyperglycemia-induced signaling pathways and cell death. The signaling pathways discussed in this review are to be described step-by-step, together with their respective inhibitors. They involve diacylglycerol, the activation of protein kinase C (PKC) and NADPH-oxidase system, and the consequent production of ROS. This was initially entitled the "dangerous metabolic route in diabetes". The historical usages and the recent advancement of new drugs in controlling possible therapeutical targets have been highlighted, in order to evaluate the evolution of knowledge in this sensitive area. It has recently been shown that the metabolic responses to stimuli (i.e., hyperglycemia) involve an integrated network of signaling pathways, in order to define the exact responses. Certain new drugs have been experimentally tested-or suggested and proposed-for their ability to modulate the possible biochemical therapeutical targets for the downregulation of retinopathy, nephropathy, neuropathy, heart disease, angiogenesis, oxidative stress, and cellular death. The aim of this study was to critically and didactically evaluate the exact steps of these signaling pathways and hence mark the indicated sites for the actions of such drugs and their possible consequences. This review will emphasize, besides others, the therapeutical targets for controlling the signaling pathways, when aimed at the downregulation of ROS generation, oxidative stress, and, consequently, cellular death-with all of these conditions being a problem in diabetes.
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Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/patología , Especies Reactivas de Oxígeno/metabolismo , Animales , Muerte Celular , Humanos , Modelos Biológicos , Estrés Oxidativo , Transducción de SeñalRESUMEN
Diabetic skin manifestations, previous to ulcers and wounds, are not highly accounted as part of diagnosis even when they represent the first symptom of vascular damage and are present in up to 70% of patients with diabetes mellitus type II. Here, an application for skin macules characterization based on a three-stage segmentation and characterization algorithm used to classify vascular, petechiae, trophic changes, and trauma macules from digital photographs of the lower limbs is presented. First, in order to find the skin region, a logical multiplication is performed on two skin masks obtained from color space transformations; dynamic thresholds are stabilised to self-adjust to a variety of skin tones. Then, in order to locate the lesion region, illumination enhancement is performed using a chromatic model color space, followed by a principal component analysis gray-scale transformation. Finally, characteristics of each type of macule are considered and classified; morphologic properties (area, axes, perimeter, and solidity), intensity properties, and a set of shade indices (red, green, blue, and brown) are proposed as a measure to obviate skin color differences among subjects. The values calculated show differences between macules with a statistical significance, which agree with the physician's diagnosis. Later, macule properties are fed to an artificial neural network classifier, which proved a 97.5% accuracy, to differentiate between them. Characterization is useful in order to track macule changes and development along time, provides meaningful information to provide early treatments, and offers support in the prevention of amputations due to diabetic feet. A graphical user interface was designed to show the properties of the macules; this application could be the background of a future Diagnosis Assistance Tool for educational (i.e., untrained physicians) and preventive assistance technology purposes.
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Complicaciones de la Diabetes/diagnóstico por imagen , Diabetes Mellitus Tipo 2/complicaciones , Procesamiento de Imagen Asistido por Computador/métodos , Pierna/diagnóstico por imagen , Trastornos de la Pigmentación/diagnóstico por imagen , Piel/diagnóstico por imagen , Algoritmos , Color , Gráficos por Computador , Complicaciones de la Diabetes/patología , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Pie Diabético/complicaciones , Humanos , Pierna/patología , Redes Neurales de la Computación , Fotograbar , Trastornos de la Pigmentación/patología , Análisis de Componente Principal , Púrpura/patología , Piel/patología , Anomalías Cutáneas/diagnóstico por imagen , Pigmentación de la Piel , Programas Informáticos , Interfaz Usuario-ComputadorRESUMEN
The aim of the present study was to investigate the mechanism of action of a sulfonamide derivative on glucose uptake in adipose tissue, as well as to characterize the effects of this compound on intestinal disaccharidases and advanced glycation end-products (AGEs) formation. Camphoryl-benzene sulfonamide (CS) was able to stimulate glucose uptake in isolated adipocytes, adipose tissue, and in soleus muscle. The stimulatory effect of the compound (10 µM) on glucose uptake on adipose tissue was blocked by diazoxide, wortmannin, U73122, colchicine, and N-ethylmaleimide. On the other hand, the effects of CS were not blocked by glibenclamide, an inhibitor of the K+ -ATP channel, or even by the inhibitor of protein p38 MAPK, SB 203580. In vivo, this compound reduced intestinal disaccharidase activity, while, in vitro, CS reduced the formation of AGEs at 7, 14, and 28 days of incubation. The stimulatory effect of CS on glucose uptake requires the activation of the K+ -ATP channel, translocation, and fusion of GLUT4 vesicles to the plasma membrane on adipocytes for glucose homeostasis. In addition, the inhibition of disaccharidase activity contributes to the glucose homeostasis in a short-term as well as the remarkable reduction in AGE formation indicates that the CS may prevent of complications of late diabetes.
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Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Membrana Celular/metabolismo , Glucosa/metabolismo , Sulfonamidas/farmacología , Adipocitos/patología , Tejido Adiposo/patología , Animales , Membrana Celular/patología , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/patología , Complicaciones de la Diabetes/prevención & control , Disacáridos/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Masculino , Ratas , Ratas WistarRESUMEN
Chronic hyperglycemia increases production of reactive oxygen species, which favors carcinogenesis. The association between diabetes and prostate cancer is controversial. Melatonin has antioxidant, anti-inflammatory, and antiproliferative properties. We investigated whether low doses of melatonin prevent the tissue alterations caused by diabetes and alter prostate histology of healthy rats. We also investigated whether experimental diabetes promoted the development of pathological lesions in the ventral prostate of rats. Melatonin was provided in drinking water (10 µg/kg/day) from age 5 weeks until the end of experiment. Diabetes was induced at 13 weeks by administration of streptozotocin (40 mg/kg, ip). Rats were euthanized at 14 or 21 weeks. Histological and stereological analyses were carried out and the incidence and density of malignant and pre-malignant lesions were assessed. Immunohistochemical assays of α-actin, cell proliferation (PCNA), Bcl-2, glutathione S-transferase (GSTPI), and DNA methylation (5-methylcytidine) were performed. Melatonin did not elicit conspicuous changes in the prostate of healthy animals; in diabetic animals there was a higher incidence of atrophy (93%), microinvasive carcinoma (10%), proliferative inflammatory atrophy, PIA (13%), prostatitis (26%), and prostate intraepithelial neoplasia, PIN (20%) associated with an increase of 40% in global DNA methylation. Melatonin attenuated epithelial and smooth muscle cell (smc) atrophy, especially at short-term diabetes-and normalized incidence of PIN (11%), inflammatory cells infiltrates, prostatitis (0%) and PIA (0%) at long-term diabetes. MLT was effective in preventing inflammatory disorders and PIN under diabetic condition. Although MLT has antioxidant action, it did not influence DNA methylation and not avoid carcinogenesis at low doses.
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Metilación de ADN/efectos de los fármacos , Complicaciones de la Diabetes/genética , Diabetes Mellitus Experimental/genética , Melatonina/farmacología , Próstata/efectos de los fármacos , Neoplasias de la Próstata/patología , Animales , Antioxidantes/metabolismo , Proliferación Celular/efectos de los fármacos , Complicaciones de la Diabetes/inducido químicamente , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/patología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Masculino , Próstata/metabolismo , Próstata/patología , Prostatitis , RatasRESUMEN
Aim: The aim of this study was to assess the effects of pancreas transplantation on the progression of testicular lesions in diabetic rats. Methods: Diabetic rats were subjected to pancreas transplantation and sacrificed after 6, 14, 26 and 50 weeks of follow-up, using non-diabetic and untreated diabetic rats as controls. Results: Successful pancreas transplantation corrected all of the metabolic changes observed in diabetic rats, including low levels of testosterone. The testicular mass was decreased, and the relative weight of the testes was high in diabetic rats. The seminiferous tubules of diabetic rats showed progressive atrophy of the germinal epithelium, with cytoplasmic vacuolization, detachment of germ cells to the tubular lumen and the appearance of giant cells. Leydig cells were abnormally distributed, and hyperplasia of Sertoli cells was observed. Sperm were not detectable within the tubular lumen in late follow-up. The diameter, total area, lumen area, and germinal epithelium area of the seminiferous tubules were low, and tubular density was high in diabetic rats. Ultrastructural changes were also observed in these rats, compromising the cytoplasm, organelles and cellular nuclei of the germ, Sertoli, and Leydig cells. The most frequent changes consisted of accumulation of lipid droplets and electron-dense dark material in the cell cytoplasm, cellular degeneration and apoptosis. Similar to non-diabetic rats, pancreas-transplanted rats showed progressive testicular lesions, but they were much less severe and occurred much later than in the untreated diabetic controls. Conclusion: Diabetes causes morphological and ultrastructural changes in rat testes, but the progression of lesions can be significantly delayed by successful pancreas transplantation, which may have a positive impact on male infertility due to diabetes.
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Complicaciones de la Diabetes , Diabetes Mellitus Experimental , Trasplante de Páncreas , Enfermedades Testiculares , Testículo , Animales , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/patología , Complicaciones de la Diabetes/cirugía , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/cirugía , Masculino , Ratas , Ratas Endogámicas Lew , Espermatogénesis , Enfermedades Testiculares/etiología , Enfermedades Testiculares/metabolismo , Enfermedades Testiculares/patología , Enfermedades Testiculares/cirugía , Testículo/metabolismo , Testículo/patologíaRESUMEN
Diabetes mellitus (DM) induces a variable degree of muscle sarcopenia, which may be related to protein degradation and to the expression of both E3 ubiquitin ligases and some specific microRNAs (miRNAs). The present study investigated the effect of diabetes and acute muscle contraction upon the TRIM63 and FBXO32 expression as well as the potential involvement of some miRNAs. Diabetes was induced by streptozotocin and studied after 30 days. Soleus muscles were harvested, stimulated to contract in vitro for twitch tension analysis (0.5 Hz), 30 min later for tetanic analysis (100 Hz), and 30 min later were frozen. TRIM63 and FBXO32 proteins were quantified by western blotting; Trim63 mRNA, Fbxo32 mRNA, miR-1-3p, miR-29a-3p, miR-29b-3p, miR-133a-3p, and miR-133b-3p were quantified by qPCR. Diabetes induced sarcopenia by decreasing (P < 0.05) muscle weight/tibia length index, maximum tetanic contraction and relaxation rates, and absolute twitch and tetanic forces (P < 0.05). Diabetes decreased (P < 0.05) the Trim63 and Fbxo32 mRNAs (30%) and respective proteins (60%), and increased (P < 0.01) the miR-29b-3p (2.5-fold). In muscle from diabetic rats, acute contractile stimulus increased TRIM63 protein, miR-1-3p, miR-29a-3p, and miR-133a/b-3p, but decreased miR-29b-3p (P < 0.05). Independent of the metabolic condition, after muscle contraction, both TRIM63 and FBXO32 proteins correlated significantly with miR-1-3p, miR-29a/b-3p, and miR-133a/b-3p. All diabetes-induced regulations were reversed by insulin treatment. Concluding, the results depict that muscle wasting in long-term insulinopenic condition may not be accompanied by increased proteolysis, pointing out the protein synthesis as an important modulator of muscle sarcopenia in DM.
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Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus Experimental/metabolismo , Regulación de la Expresión Génica , MicroARNs/metabolismo , Proteínas Musculares/biosíntesis , Proteínas Ligasas SKP Cullina F-box/biosíntesis , Sarcopenia/metabolismo , Proteínas de Motivos Tripartitos/biosíntesis , Ubiquitina-Proteína Ligasas/biosíntesis , Animales , Complicaciones de la Diabetes/patología , Diabetes Mellitus Experimental/patología , Masculino , Ratas , Ratas Wistar , Sarcopenia/patologíaRESUMEN
Mucormycosis is an invasive infection caused by opportunistic fungi. Rhizopus, Lichtheimia, Mucor and Rhizomucor are the most common isolated genera. Primary cutaneous mucormycosis is usually related to traumatic injuries, but immunocompromised cases are associated with underlying conditions such as diabetes mellitus and malignancies. The treatment of choice is surgical debridement and liposomal amphotericin B. We present a 40-year-old male with fever and a painful necrotic lesion on the middle back and history of poorly controlled diabetes mellitus. Rhizopus oryzae was isolated and identified using an internal transcribed spacer regions ITS1 and ITS2. An initial good response to treatment was observed; however, 7 days later a diabetic ketoacidosis due to poor adherence to treatment caused a lethal outcome.
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Dermatomicosis/diagnóstico , Dermatomicosis/patología , Mucormicosis/diagnóstico , Mucormicosis/patología , Rhizopus/clasificación , Rhizopus/aislamiento & purificación , Adulto , ADN de Hongos/química , ADN de Hongos/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Dermatomicosis/microbiología , Complicaciones de la Diabetes/diagnóstico , Complicaciones de la Diabetes/microbiología , Complicaciones de la Diabetes/patología , Histocitoquímica , Humanos , Masculino , Microscopía , Mucormicosis/microbiología , Rhizopus/genética , Análisis de Secuencia de ADN , Piel/microbiología , Piel/patologíaRESUMEN
INTRODUCTION: We have previously shown that long-term type 1 diabetes affects the structural organization, contractile apparatus and extracellular matrix (ECM) of the myometrium during early pregnancy in mice. OBJECTIVE: This study aimed to identify which myometrial ECM components are affected by diabetes, including fibril-forming collagen types I, III and V, as well as proteoglycans, decorin, lumican, fibromodulin and biglycan. METHODS: Alloxan-induced type 1 diabetic female mice were divided into subgroups D1 and D2, formed by females that bred 90-100 and 100-110 days after diabetes induction, respectively. The deposition of ECM components in the myometrium was evaluated by immunohistochemistry/immunofluorescence. RESULTS: The subgroup D1 showed decreased deposition of collagen types I and III in the external muscle layer (EML) and decreased collagen types III and V in the internal muscle layer (IML). Collagen types I and III were decreased in both muscle layers of the subgroup D2. In addition, increased deposition of collagen types I and III and lumican as well as decreased collagen type V were observed in the connective tissue between muscle layers of D2. Lumican was decreased in the EML of the subgroups D1 and D2. Fibromodulin was repressed in the IML and EML of both D1 and D2. In contrast, decorin deposition diminished only in muscle layers of D2. No changes were noticed for biglycan. CONCLUSIONS: Subgroups D1 and D2 showed distinct stages of progression of diabetic complications in the myometrium, characterized by both common and specific sets of changes in the ECM composition.
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Colágeno/metabolismo , Complicaciones de la Diabetes/patología , Miometrio/patología , Complicaciones del Embarazo/etiología , Proteoglicanos/metabolismo , Animales , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patología , Modelos Animales de Enfermedad , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Femenino , Ratones , Miometrio/metabolismo , Embarazo , Complicaciones del Embarazo/patologíaRESUMEN
BACKGROUND: The diabetic cardiomyopathy occurs in both type 1 and type 2 diabetes mellitus. Hyperglycemia and associated metabolic changes participate in the pathogenesis of this disease. OBJECTIVE: To characterizes various pathological changes occurring during the development of diabetic cardiomyopathy in rats. METHODS: Diabetic rats were used for streptozotocin administration. At 7, 14, 21 and 30 days after toxic administration, the heart was obtained and placed in a Hartman solution and 4% p-formaldehyde. Five-micrometer thick sections were stained with hematoxylin-eosin, Masson trichrome and immunocytochemistry using anti-ß-tubulin antibody. RESULTS: At 14 days after application of streptozotocin, dilated sinusoids with endothelial lining in the myocardium and collagen deposits in the cardiac interstitium and between the Purkinje fibers were observed. At 21 days there was a slight decrease of the arteriolar lumen due to hyperplasia of the medial layer. It is important to note that cardiac sinusoids as well as collagen deposits became more evident at 30 day of the study, as well as a major derangement of the microtubular system of the cardiomyocytes. CONCLUSIONS: Cardiac sinusoids representing fetal vascular pattern and interstitial fibrosis in the myocardium and the microtubular derangement of cardiomyocytes support the fact that the pathophysiological mechanism of diabetic cardiomyopathy begins in the coronary microcirculation due to changes in cardiac metabolism, contributing to the development of myocardial dysfunction in diabetes.
Antecedentes: la miocardiopatía diabética ocurre en ambos tipos de diabetes mellitus y en su patogenia intervienen la hiperglucemia y los cambios metabólicos asociados. Objetivo: caracterizar los diferentes cambios patológicos que aparecen durante la evolución de la miocardiopatía diabética en la rata. Material y métodos: estudio transversal comparativo en dos grupos de ratas diabéticas por la administración de estreptozotocina. A los 14, 21 y 30 días de la administración del tóxico se obtuvieron los corazones, que se colocaron en p-formaldehído al 4%. Se efectuaron cortes de 5 µm y se tiñeron con hematoxilina-eosina, tricrómica de Masson e inmunocitoquímica con anticuerpos anti ß-tubulina. Resultados: a los 14 días de la aplicación de la estreptozotocina se observaron en el miocardio sinusoides dilatadas y depósito de colágena entre las fibras de Purkinje e intersticio cardiaco. A los 21 días disminuyó la luz arteriolar por hiperplasia de la capa media. A los 30 días del estudio se hicieron más evidentes los sinusoides cardiacos y los depósitos de colágena y un importante desarreglo del sistema microtubular de los cardiomiocitos. Conclusiones: los sinusoides cardiacos, que representan un patrón vascular fetal y la fibrosis intersticial en el miocardio y el desarreglo microtubular de los cardiomiocitos, apoyan el hecho de que el mecanismo fisiopatológico de la miocardiopatía diabética se inicia en la microcirculación coronaria debido a cambios en el metabolismo cardiaco que contribuyen a la disfunción miocárdica durante el estado diabético.
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Cardiomiopatías/patología , Complicaciones de la Diabetes/patología , Diabetes Mellitus Experimental/patología , Animales , Glucemia/análisis , Peso Corporal , Capilares/patología , Cardiomiopatías/etiología , Colágeno/análisis , Circulación Coronaria , Citoesqueleto/ultraestructura , Angiopatías Diabéticas/patología , Ingestión de Alimentos , Fibrosis , Masculino , Microcirculación , Microtúbulos/ultraestructura , Miocitos Cardíacos/patología , Ratas , Ratas Wistar , Estreptozocina , Tubulina (Proteína)/análisisRESUMEN
Diabetes mellitus (DM) is considered a risk factor for the development of Alzheimer disease (AD); however, how DM favors evolution of AD is still insufficiently understood. Hyperglycemia in DM is associated to an increase in mitochondrial reactive oxygen species (ROS) generation, as well as damage of hippocampal cells, reflected by changes in morphological and mitochondrial functionality. Similar mitochondrial damage has been observed when amyloid beta (Aß) accumulates in the brain of AD patients. In DM, the excess of glucose in the brain induces higher activity of the hexosamine biosynthesis pathway (HBP), it synthesizes UDP-N-acetylglucosamine (UDP-GlcNAc), which is used by O-linked N-acetylglucosamine transferase (OGT) to catalyze O-GlcNAcylation of numerous proteins. Although O-GlcNAcylation plays an important role in maintaining structure and cellular functionality, chronic activity of this pathway has been associated with insulin resistance and hyperglycemia-induced glucose toxicity. Three different forms of OGT are known: nucleocytoplasmic (ncOGT), short (sOGT), and mitochondrial (mOGT). Previous reports showed that overexpression of ncOGT is not toxic to the cell; in contrast, overexpression of mOGT is associated with cellular apoptosis. In this work, we suggest that hyperglycemia in the diabetic patient could induce greater expression and activity of mOGT, modifying the structure and functionality of mitochondria in hippocampal cells, accelerating neuronal damage, and favoring the start of AD. In consequence, mOGT activity could be a key point for AD development in patients with DM.
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Enfermedad de Alzheimer/etiología , Péptidos beta-Amiloides/metabolismo , Complicaciones de la Diabetes/enzimología , Hipocampo/enzimología , Mitocondrias/enzimología , N-Acetilglucosaminiltransferasas/metabolismo , Enfermedad de Alzheimer/enzimología , Enfermedad de Alzheimer/patología , Animales , Glucemia/metabolismo , Complicaciones de la Diabetes/sangre , Complicaciones de la Diabetes/complicaciones , Complicaciones de la Diabetes/patología , Glicosilación , Hipocampo/patología , Humanos , Mitocondrias/patología , Procesamiento Proteico-Postraduccional , Factores de RiesgoRESUMEN
To evaluate the effect of diabetes mellitus and of sildenafil citrate on female urethral function. Twenty nine female rats were divided into four groups: G1 - (n=9), normal rats; G2 - (n=6), normal rats treated with sildenafil citrate; G3 - (n=9) rats with alloxan-induced diabetes; G4 - (n=5) rats with alloxan-induced diabetes treated with sildenafil citrate. Under anesthesia, urodynamic evaluation was performed by cystometry and urethral pressure simultaneously. A significant increase in urethral pressure was observed during micturition. Sildenafil citrate can partially reduced urethral pressure in diabetic female rats.
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Animales , Ratas , Alloxanum , Complicaciones de la Diabetes/patología , Vejiga Urinaria , Uretra/anatomía & histología , Ratas/clasificaciónRESUMEN
To evaluate the effect of diabetes mellitus and of sildenafil citrate on female urethral function. Twenty nine female rats were divided into four groups: G1 - (n=9), normal rats; G2 - (n=6), normal rats treated with sildenafil citrate; G3 - (n=9) rats with alloxan-induced diabetes; G4 - (n=5) rats with alloxan-induced diabetes treated with sildenafil citrate. Under anesthesia, urodynamic evaluation was performed by cystometry and urethral pressure simultaneously. A significant increase in urethral pressure was observed during micturition. Sildenafil citrate can partially reduced urethral pressure in diabetic female rats.(AU)