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Introdução:O diabetes mellitus é uma doença metabólica caracterizada pelo controle inadequado dos níveis de glicose no sangue, principalmente um estado crônico de hiperglicemia, causado por diferentes processos patogênicos, levando a complicaçõesdosistema nervoso do diabético queincluem axonopatias, doenças neurodegenerativas, doenças neurovasculares e comprometimento cognitivo geral.Objetivo:Avaliar as complicações clínicas da diabetes tipo 2 em mulheres. Metodologia:Tratou-se de um transversal, do tipo prevalência. Foram usados dois grupos de mulheres, onde todas as mulheres estavam com diagnóstico de diabetes Tipo 2 e idade de 40 e 60 anos, comotratamentooral -G1e com tratamentocominsulinoterapia ­G2,ambosfornecidospelarede pública Para comparação das variáveis estudadas foi utilizado o método de Mann-Whitney, adotando-se o nível de significância menor que 5% (p, valor ,0,05). Resultados:Aproporçãode pessoas com diabetes no Piauí, com consulta e hemoglobina glicada solicitada no primeiro quadrimestre de 2021, 2022, 2023, foi de18, 16 e 34 percentuais,respectivamenteeem Boa Hora nos mesmos quadrimestres foi 36, 39, 56 percentuais, respectivamente.Osprocedimentoshospitalares-por local de residência -Piauí foi de um total de 1.193e em Boa Hora 24. O grupo de mulheres estudadas mostrou uma diferença significativa para a glicemia em jejum e a Hemoglobina glicada quando comparados os grupos G1 e G2. Quase 100% da amostra estava obesa (IMC > 25), não fumava e não praticava atividade física.Conclusões:Concluiu-se que a as pacientes tiveram um agravamento do adoecimento ao longo dos anos com aumento de medicação. A ausência das boas práticas de promoção de saúde, atividade física e alimentação, podem ter contribuídocom o agravamento. Outrossim há necessidade urgente de uma intervenção para mudança de hábitos na população para que a medicalização seja diminuída para a promoção da saúde (AU).

Introduction: Diabetes mellitus is a metabolic disease characterized by inadequate control of blood glucose levels, mainly a chronic state of hyperglycemia, caused by different pathogenic processes, leading to complications of the nervous system including axonopathies, neurodegenerative diseases,neurovascular diseases and general cognitive impairment.Objective: To evaluate the clinical complications of type 2 diabetes in women.Methodology: This was a cross-sectional, prevalence study.Two groupsof women were used, where all women were diagnosed with Type 2 diabetes and aged between 40 and 60 years, with oral treatment -G1 and treatment with insulin therapy -G2, both provided by the public network .To compare the variables studied, the Mann-Whitney method was used, adopting a significance level of less than 5% (p, value 0.05).Results:The proportion of people with diabetes in Piauí, with consultation and glycated hemoglobin requested in the first four months of 2021, 2022, 2023, was 18, 16 and34 percentages, respectively and in Boa Hora in the same four months it was 36, 39, 56percentages, respectively.SUS hospital procedures -by place of residence -Piauí was a total of 1,193 and in Boa Hora 24. The group of women studied showed a significant difference in fasting blood glucose and glycated hemoglobin when comparing groups G1 and G2.Almost 100% of the sample was obese (BMI > 25), did not smoke and did not practice physical activity.Conclusions: It was concluded that the patients' illness worsened over the years with increased medication.The absence of good health promotion practices, physical activity and nutrition may have contributed to the worsening.Furthermore, there is an urgent need for intervention to change habits in the population so that medicalization is reduced to promote health (AU).

Introducción: La diabetes mellitus ecaracterizada por un control inadecuado de los niveles de glucosa en sangre, principalmente un estado crónico de hiperglucemia, causado por diferentes procesos patogénicos, derivando en complicaciones del sistema nervioso incluyendo axonopatías, enfermedades neurodegenerativas, enfermedades neurovasculares y deterioro cognitivo general.Objetivo: Evaluar las complicaciones clínicas de la diabetes tipo 2 en mujeres.Metodología: Se trata de un estudio transversal de prevalencia.Se utilizaron dos grupos de mujeres, donde todas fueron diagnosticadas con diabetes tipo 2 y con edades entre 40 y 60 años, con tratamiento oral -G1 y tratamiento con insulinoterapia -G2, ambos prestados por la red pública.Para comparar las variables estudiadas se utilizó el método de Mann-Whitney, adoptando un nivel de significancia inferior al 5% (p, valor 0,05).Resultados:La proporción de personas con diabetes en Piauí, con consulta y hemoglobina glucosilada solicitada en los primeros cuatro meses de 2021, 2022, 2023, fuede 18, 16 y 34 porcentajes, respectivamente y en Boa Hora en los mismos cuatro meses fue de 36 , 39, 56 porcentajes, respectivamente.Los procedimientos hospitalarios del SUS -por lugar de residencia -en Piauí fueron en total 1.193 y en Boa Hora 24. El grupo de mujeres estudiado presentó diferencia significativa en la glucemia en ayunas y en la hemoglobina glucosilada al comparar los grupos G1 y G2.Casi el 100% de la muestra era obesa (IMC > 25), no fumaba y no practicaba actividad física.Conclusiones:Se concluyó que la enfermedad de los pacientes empeoró con el paso de los años con el aumento de la medicación.La ausencia de buenas prácticas de promoción de la salud, actividad física y nutrición puede haber contribuido al empeoramiento.Además, es urgente intervenir para cambiar los hábitos de la población para promover la salud (AU).

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Holoprosencephaly (HPE) results from a lack of cleavage of the prosencephalon. It has a complex etiology, resulting from chromosome abnormalities or single gene variants in the Sonic hedgehog signaling pathway. A single variant, p.Arg535Cys in CNOT1, has been described in HPE in association with pancreatic agenesis and neonatal diabetes. Here, we report on a case of HPE and p.Arg535Cys in CNOT1 without pancreatic agenesis where the patient presented with diabetes mellitus in adolescence. This case reinforces the role of CNOT1 in pancreatic development. We suggest that individuals with p.Arg535Cys in CNOT1 with no pancreas abnormalities observed at birth should be screened for diabetes during follow-up.

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Skin wounds, primarily in association with type I diabetes mellitus, are a public health problem generating significant health impacts. Therefore, identifying the main pathways/mechanisms involved in differentiating fibroblasts into myofibroblasts is fundamental to guide research into effective treatments. Adopting the PRISMA guidelines, this study aimed to verify the main pathways/mechanisms using diabetic murine models and analyze the advances and limitations of this area. The Medline (PubMed), Scopus, and Web of Science platforms were used for the search. The studies included were limited to those that used diabetic murine models with excisional wounds. Bias analysis and methodological quality assessments were undertaken using the SYRCLE bias risk tool. Eighteen studies were selected. The systematic review results confirm that diabetes impairs the transformation of fibroblasts into myofibroblasts by affecting the expression of several growth factors, most notably transforming growth factor beta (TGF-beta) and NLRP3. Diabetes also compromises pathways such as the SMAD, c-Jun N-terminal kinase, protein kinase C, and nuclear factor kappa beta activating caspase pathways, leading to cell death. Furthermore, diabetes renders the wound environment highly pro-oxidant and inflammatory, which is known as OxInflammation. As a consequence of this OxInflammation, delays in the collagenization process occur. The protocol details for this systematic review were registered with PROSPERO: CRD42021267776.

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Introdução: As Doenças Crônicas não Transmissíveis constituem-se em um grande desafio de saúde pública. Dentro deste grupo, a Hipertensão Arterial e o Diabetes Mellitus merecem destaque, pois seu enfrentamento requer bastante dos serviços de saúde. Na realidade da Atenção Básica, tem-se destaque para as atividades educativas, em especial para a Educação Popular em Saúde, como a "Calçada Amiga". Objetivo: Abordar a experiência da atividade de educação popular em saúde intitulada "Calçada Amiga" como instrumento de proteção, prevenção e promoção da saúde na Hipertensão Arterial e no Diabetes Mellitus em um serviço de Atenção Primária à Saúde. Metodologia: Trata-se de um relato de Experiência de uma atividade de educação popular em saúde desenvolvida no território de uma Unidade Básica de Saúde do Município de Mossoró/Rio Grande do Norte, durante o ano de 2022.Resultados e Discussões: Foram realizadas 13 ações. Sobre a Hipertensão Arterial e o Diabetes Mellitus, notou-se uma certa dificuldade na adesão ao tratamento, com relatos tanto na prática do exercício físico quanto na alimentação adequada, além do uso das medicações. Ainda sobre as dificuldades na adesão, muitos deles afirmavam uma subutilização dos serviços de saúde, em especial a UBS. Foi possível observar a validade da Educação Popular em Saúde por meio de afirmações de avaliação positiva sobre o método adotado para as atividades, com boa aceitação, frequência e retorno da comunidade. Conclusões: A atividade permitiu o fortalecimento do vínculo entre a Unidade Básica de Saúde e a comunidade por meio da imersão no território com momentos de diálogos horizontais e escuta ativa, facilitando a compreensão por parte dos profissionais sobre a realidade dos sujeitos assistidos no serviço. Para a comunidade, permitiu um momento de fala e escuta, expressando seus anseios, medos e dificuldades sobre as condições, tornando-se ativa no processo de saúde/doença (AU).

Introduction: Chronic non-communicable diseases are a major public health challenge. Within this group, Hypertension and Diabetes Mellitus deserve to be highlighted, because coping with it requires a lot of health services. In the reality of Primary Care, there is emphasis on educational activities, especially for Popular Health Education, such as "Calçada Amiga".Objective:To address the experience of popular health education activity entitled "Calçada Amiga" as an instrument of protection, prevention and health promotion in Hypertension and Diabetes Mellitus in a Primary Health Care service.Methodology:This is an experience report of a popular health education activity developed in the territory of a Basic Health Unit of the Municipalityof Mossoró/ Rio Grande do Norte during the year 2022.Results and Discussion:13 actions were performed. Regarding Hypertension and Diabetes Mellitus, there was some difficulty in adherence to treatment, with reports both in the practice of physical exercise and in proper nutrition, in addition to the use of medications. Still on the difficulties in adherence, many of them stated an underutilization of health services, especially the UBS. It was possible to observe the validity of Popular Health Education through affirmations of positive evaluation of the method adopted for the activities, with good acceptance, frequency and community return.Conclusions:The activity allowed the strengthening of the bond between the Basic Health Unit and the community through immersion in the territory with moments of horizontal dialogues and active listening, professionals about the reality of the subjects assisted in the service. For the community, it allowed a moment of speech and listening, expressing their desires,fears and difficulties about the conditions, becoming active in the health/disease process (AU).

Introducción: Las Enfermedades Crónicas no Transmisibles se constituyen en un gran desafío de salud pública. Dentro de este grupo, la Hipertensión Arterial y el Diabetes Mellitus merecen destaque, pues su enfrentamiento requiere bastante de los servicios de salud. En realidad de la Atención Básica, se ha destacado para las actividades educativas, en especial para la Educación Popular en Salud, como la "Calçada Amiga". Objetivo: Abordar la experiencia de la actividad de educación popular en salud titulada "Calçada Amiga" como instrumento de protección, prevención y promoción de la salud en la Hipertensión Arterial y en la Diabetes Mellitus en un servicio de Atención Primaria de Salud.Metodología: Se trata de un relato de experiencia de una actividad de educación popular en salud desarrollada en el territorio de una Unidad Básica de Salud del Municipio de Mossoró/ Rio Grande do Norte durante el año 2022.Resultados y Discusión: Fueron realizadas 13 acciones. Sobre la Hipertensión Arterial y la Diabetes Mellitus, se notó una cierta dificultad en la adhesión del tratamiento, con relatos tanto en la práctica del ejercicio físico como en la alimentación adecuada, además del uso de las medicaciones. También sobre las dificultades en la adhesión, muchos de ellos afirmaban una infrautilización de los servicios de salud, en especial la UBS. Fue posible observar la validez de la Educación Popular en Salud por medio de afirmaciones de evaluación positiva sobre el método adoptado para las actividades, con buena aceptación, frecuencia y retorno de la comunidad.Conclusiones: La actividad permitió el fortalecimiento del vínculo entre la Unidad Básica de Salud y la comunidad por medio de la inmersión en el territorio con momentos de diálogos horizontales y escucha activa, facilitando la comprensión por parte de los profesionales de la realidad de los sujetos asistidos en el servicio. Para la comunidad, permitió un momento de habla y escucha, expresando sus anhelos, miedos y dificultades sobre las condiciones, haciéndose activa en el proceso de salud/enfermedad (AU).

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BACKGROUND: Longitudinal associations of noninvasive 2-dimensional phase-contrast magnetic resonance imaging (2D-PC-MRI) velocity markers of the superficial femoral artery (SFA) were analyzed along with the characteristics of peripheral artery disease (PAD). We hypothesized that the 2-year differences in MRI-based measures of SFA velocity were associated with longitudinal changes in markers of PAD. METHODS: A total of 33 (11 diabetic, 22 nondiabetic) patients with PAD with baseline and 2-year follow-up MRI scans were included in this secondary analysis of the Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT). Electrocardiographically gated 2D-PC-MRI was performed at a proximal and a distal location of the distal SFA territory. SFA lumen, wall, and total vessel volumes and the normalized wall index (NWI) were analyzed. RESULTS: Baseline characteristics did not differ between diabetic and nondiabetic PAD patients. Maximum proximal and distal SFA velocity measures did not differ between baseline and 2 years (41.98 interquartile range (IQR) (23.58-72.6) cm/s vs. 40.31 IQR (26.69-61.29) cm/s; P = 0.30). Pooled analysis (N = 33) showed that the 24-month change in the NWI was inversely associated with the 24-month change in the proximal maximal SFA velocity (beta = -168.36, R2 = 0.150, P value = 0.03). The 24-month change of the maximum velocity differences between the proximal and distal SFA locations was inversely associated with the 24-month changes in peak walking distance (beta = -0.003, R2 = 0.360, P value = 0.011). CONCLUSION: The 2-year change of SFA plaque burden is inversely associated with the 2-year change of proximal peak SFA blood flow velocity. 2D-PC-MRI measured SFA velocity may be of interest in assessing PAD longitudinally.

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Hyperglycemia leads to microvascular lesions in various tissues. In diabetic nephropathy-DN, alterations in usual markers reflect an already installed disease. The study of new biomarkers for the early detection of diabetic complications can bring new prevention perspectives. Rats were divided into diabetic adult-DMA-or elderly-DME and control sham adult-CSA-or control sham elderly-CSE. Blood and urine samples were collected for biochemical analysis. Bulbar region, cardiac, hepatic and renal tissues were collected for target gene expression studies. As result, DMA showed decreased TNFR1, MCT1 and CD147 expression in the bulbar region, TNFR1 in the heart, VEGFA and CD147 in the kidney and TNFR1 in blood. Positive correlations were found between TNFR1 and MCT1 in the bulbar region and HbA1c and plasma creatinine, respectively. DME showed positive correlation in the bulbar region between TNFR1 and glycemia, in addition to negative correlations between CD147 in the heart versus glycemia and urea. We concluded that the initial hyperglycemic stimulus already promotes changes in the expression of genes involved in the inflammatory and metabolic pathways, and aging alters this profile. These changes prior to the onset of diseases such as DN, show that they have potential for early biomarkers studies.

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An impaired healing response underlies diabetic foot wound chronicity, frequently translating to amputation, disability, and mortality. Diabetics suffer from underappreciated episodes of post-epithelization ulcer recurrence. Recurrence epidemiological data are alarmingly high, so the ulcer is considered in "remission" and not healed from the time it remains epithelialized. Recurrence may result from the combined effects of behavioral and endogenous biological factors. Although the damaging role of behavioral, clinical predisposing factors is undebatable, it still remains elusive in the identification of endogenous biological culprits that may prime the residual scar tissue for recurrence. Furthermore, the event of ulcer recurrence still waits for the identification of a molecular predictor. We propose that ulcer recurrence is deeply impinged by chronic hyperglycemia and its downstream biological effectors, which originate epigenetic drivers that enforce abnormal pathologic phenotypes to dermal fibroblasts and keratinocytes as memory cells. Hyperglycemia-derived cytotoxic reactants accumulate and modify dermal proteins, reduce scar tissue mechanical tolerance, and disrupt fibroblast-secretory activity. Accordingly, the combination of epigenetic and local and systemic cytotoxic signalers induce the onset of "at-risk phenotypes" such as premature skin cell aging, dysmetabolism, inflammatory, pro-degradative, and oxidative programs that may ultimately converge to scar cell demise. Post-epithelialization recurrence rate data are missing in clinical studies of reputed ulcer healing therapies during follow-up periods. Intra-ulcer infiltration of epidermal growth factor exhibits the most consistent remission data with the lowest recurrences during 12-month follow-up. Recurrence data should be regarded as a valuable clinical endpoint during the investigational period for each emergent healing candidate.

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Abstract Pterocarpus santalinoides is used in Nigerian ethnomedicine to treat diabetes mellitus. This study aimed to establish the antidiabetic property of the plant, and isolate and characterize its active principle. Dried and pulverized leaves (500 g) of P. santalinoides were extracted with 1.8 L of 80 % hydromethanol by cold maceration. The dried extract (10 g) was partitioned into n-hexane, ethyl acetate (EtOAc), n-butanol, and water. Antidiabetic activitiy-guided isolation by column chromatographic separation of the EtOAc soluble and purification of the sub-fractions by repeated preparative thin layer chromatography (pTLC) yielded a C-glycosyl flavonoid, identified as isovitexin. The chemical structure was elucidated based on high-resolution mass spectroscopy, 1D, and 2D nuclear magnetic resonance spectroscopic analyses. Alloxan-induced diabetic rat model was adopted for antidiabetic screening. The extract of P. santalinoides (100-200 mg/kg), fraction F4 (50 mg/kg), sub-fraction F4.3 (10 mg/kg), and the semi-purified compound F4.3.2 (5 mg/kg) significantly (p<0.05) reduced the fasting blood glucose of alloxan-induced diabetic rats, causing 48.4, 69.4, 57.7 and 64.5 % antidiabetic activity respectively, compared with > 68 % recorded in glibenclamide (2 mg/kg) control. These results reveal that isovitexin is the antidiabetic principle in P. santalinoides

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Abstract Diabetes is a metabolic disorder caused by insulin resistance or a defect in the pancreatic beta cells in insulin secretion. The aim of this study was to evaluate the possible effectiveness of long-term administration of resveratrol on inflammatory and oxidative stress markers in the pancreatic tissue of diabetic rats. Male Wistar rats (n = 24) were randomly divided into four groups of six animals, namely a healthy group, a healthy group receiving resveratrol, a diabetic control group, and a diabetic group receiving resveratrol. Diabetes was induced by single dose injection of streptozotocin (50 mg/kg; ip), 15 min after injection of nicotinamide (110 mg/kg; ip). Resveratrol was also administered by gavage (5 mg/kg/day) for 4 months. Administration of resveratrol alleviated hyperglycemia, weight loss and pancreatic ß cell function measured by HOMA-ß. Resveratrol improved oxidative stress (nitrate/nitrite, 8-isoprostane and glutathione) and proinflammatory markers (tumor necrosis factor α, cyclooxygenase 2, interleukin 6 and nuclear factor kappa B) in the pancreatic tissue of diabetic rats. Resveratrol administration had no significant effect on the activity of superoxide dismutase and catalase enzyme. These observations indicate that resveratrol administration may be effective as a beneficial factor in improving pancreatic function and reducing the complications of diabetes

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Objective: To investigate the effects of vibration therapy on fracture healing in diabetic and non-diabetic rats. Methods: 148 rats underwent fracture surgery and were assigned to four groups: (1) SHAM: weight-matched non-diabetic rats, (2) SHAM+VT: non-diabetic rats treated with vibration therapy (VT), (3) DM: diabetic rats, and (4) DM+VT: diabetic rats treated with VT. Thirty days after diabetes induction with streptozotocin, animals underwent bone fracture, followed by surgical stabilization. Three days after bone fracture, rats began VT. Bone healing was assessed on days 14 and 28 post-fracture by serum bone marker analysis, and femurs collected for dual-energy X-ray absorptiometry, micro-computed tomography, histology, and gene expression. Results: Our results are based on 88 animals. Diabetes led to a dramatic impairment of bone healing as demonstrated by a 17% reduction in bone mineral density and decreases in formation-related microstructural parameters compared to non-diabetic control rats (81% reduction in bone callus volume, 69% reduction in woven bone fraction, 39% reduction in trabecular thickness, and 45% in trabecular number). These changes were accompanied by a significant decrease in the expression of osteoblast-related genes (Runx2, Col1a1, Osx), as well as a 92% reduction in serum insulin-like growth factor I (IGF-1) levels. On the other hand, resorption-related parameters were increased in diabetic rats, including a 20% increase in the callus porosity, a 33% increase in trabecular separation, and a 318% increase in serum C terminal telopeptide of type 1 collagen levels. VT augmented osteogenic and chondrogenic cell proliferation at the fracture callus in diabetic rats; increased circulating IGF-1 by 668%, callus volume by 52%, callus bone mineral content by 90%, and callus area by 72%; and was associated with a 19% reduction in circulating receptor activator of nuclear factor kappa beta ligand (RANK-L). Conclusions: Diabetes had detrimental effects on bone healing. Vibration therapy was effective at counteracting the significant disruption in bone repair induced by diabetes, but did not improve fracture healing in non-diabetic control rats. The mechanical stimulus not only improved bone callus quality and quantity, but also partially restored the serum levels of IGF-1 and RANK-L, inducing bone formation and mineralization, thus creating conditions for adequate fracture repair in diabetic rats.

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O Ardor Bucal Secundário (ABS) pode estar relacionado a diferentes doenças e condições que afetam a mucosa oral, ou representar uma manifestação oral de um quadro sistêmico. O propósito deste estudo foi investigar se existe associação entre o ABS queixa de Ardor Bucal e condições sistêmicas presentes na história médica do paciente. Foi realizado um estudo retrospectivo, constituído por 102 pacientes com ABS apresentando HAS ou DM tipo II, e o grupo controle constituído por 102 pacientes pareados por idade e sexo, com HAS ou DM tipo II e sem ABS. Na comparação entre os grupos, foram empregados os testes Qui-Quadrado de Pearson (χ2) e Exato de Fisher, além da obtenção da razão de chances (Odds ratio, OR) e seu respectivo intervalo de confiança (IC) de 95%. Foi aplicado, ainda, o modelo de regressão logística multivariada, para obtenção dos Odds ratio ajustados (ORa). Após análise multivariada, a gastrite foi identificada como fator de risco para ABS (ORa=2,50; IC 95% = 1,32­4,74; p=0,005). O uso de subclasses de anti-hipertensivos, tais como betabloqueadores (ORa = 0,36; IC 95% = 0,16-0,80; p=0,012), inibidores da enzima conversora de angiotensina (ECA) (ORa = 0,19; IC 95% = 0,06-0,56; p=0,003) e bloqueadores dos receptores da angiotensina (BRA) (ORa = 0,26; IC 95% = 0,14-0,49; p<0,001), revelou-se menos associado para o ABS. O presente estudo demonstrou que os pacientes com HAS e DM tipo II não obtiveram associação com o ABS. Todavia, nos pacientes portadores de gastrite foi observado 2,5 vezes mais chances de desenvolver a ABS. Além disso, os medicamentos antihipertensivos, inibidores da ECA, BRA e betabloqueadores, foram menos associados ao ABS (AU).

Secondary Burning Mouth (SBM) can be related to different diseases that affect the oral mucosa or represent an oral manifestation of a systemic condition presented by the patient. This study aimed to investigate whether there is an association between the complaint of SBM Complaint of Burning Mouth and Systemic Conditions presents in the patient's medical history. It was a retrospective case-control study of 102 patients with BMS and SAH or type II DM and a control group of 102 patients matched by age and sex, with SAH or type II DM and without ABS. Pearson's Chi-Square (χ2) and Fisher's Exact tests were applied to compare the groups, in addition to obtaining the odds ratio (OR) and its respective confidence interval (CI) of 95%. The multivariate logistic regression model was also applied to obtain the adjusted odds ratio (ORa). After multivariate analysis, gastritis was identified as a risk factor for SBM (ORa=2.50; 95% CI = 1.32­4.74; p=0.005). The use of antihypertensive subclasses, such as beta-blockers (ORa = 0.36; 95% CI = 0.16-0.80; p=0.012), angiotensin-converting enzyme (ACE) inhibitors (ORa = 0.19; 95% CI = 0.06- 0.56; p=0.003) and angiotensin receptor blockers (ARB) (ORa = 0.26; 95% CI = 0.14-0.49; p<0.001), proved to be less associated for ABS. The present study demonstrated that SAH and type II DM were not associated with SBM. A 2.5-fold greater chance of developing SBM was observed in patients with gastritis. In addition, antihypertensive drugs from the groups of ACE inhibitors, ARBs, and beta-blockers were shown to be less associated for SBM (AU).

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La mucormicosis es una infección fúngica rara, con alta morbilidad y mortalidad. Se presenta principalmente en pa- cientes con diabetes mellitus no controlada, inmunocompro- metidos, con tratamiento crónicos con esteroides, entre otros. Actualmente, se cree que la pandemia de COVID-19 y los tratamientos con corticosteroides podrían estar implicados en el aumento de casos de esta micosis. Este hongo invade el sistema vascular, ocluyendo el flujo sanguíneo arterial y generando una rápida trombosis e isque- mia, lo que provoca la necrosis de los tejidos duros y blandos, con invasión rápida a los tejidos circundantes. Hay varias formas clínicas. En la cavidad bucal se presenta la variante rino-orbito-cerebral, que afecta el paladar en forma de lesión eritematosa o grisácea que puede progresar hacia la formación de una masa necrótica o ulceración con muy escaso sangrado de mucosa. Se manifiesta con síntomas típicos de una rinosinusitis con fiebre y dolor en las piezas dentarias superiores. El tratamiento consta de tres pilares fundamentales: el diagnóstico, un manejo adecuado de las comorbilidades y la combinación de las terapias antifúngica y quirúrgica. Desde el año 2020, la mucormicosis asociada a COVID-19 pasó a ser un evento de notificación obligatoria inmediata al Sistema Nacional de Vigilancia de la Salud (SNVS2.0) me- diante el Sistema Integrado de Información Sanitaria Argen- tina (SISA). Es importante destacar que se han reportado casos de mu- cormicosis luego de extracciones dentales; lo que impulsa a afianzar los conocimientos sobre esta enfermedad, extremar las medidas preventivas e incentivar el diagnóstico precoz en la atención odontológica, debido a la rapidez en la evolución de la patología (AU))

Mucormycosis is a rare fungal infection, with high mor- bidity and mortality. It occurs mainly in patients with uncon- trolled diabetes mellitus, immunocompromised, on chronic treatment with steroids, among others. Currently, it is believed that the COVID-19 pandemic and the corticosteroid treatments could be one of the causes of increased cases. This fungus invades the vascular system, occluding arteri- al blood flow and generating rapid thrombosis and ischemia, which causes necrosis of hard and soft tissues, with rapid in- vasion to the surrounding tissues. There are several clinical forms. In the oral cavity, the rhino-orbito-cerebral variant presents itself affecting the pal- ate in the form of an erythematous or grayish lesion that can progress towards the formation of a necrotic mass or ulcera- tion with very little mucosal bleeding. It manifests itself with typical symptoms of rhinosinusitis, with fever and pain in the upper teeth. The treatment consists of three fundamental pillars: diag- nosis, proper management of comorbidities and the combina- tion of antifungal and surgical therapies. Since 2020, COVID-19 associated mucormycosis became an event of mandatory immediate notification to the National Health Surveillance System (SNVS2.0,) through the Argentina Integrated Health Information System (SISA). It is important to emphasize that mucormycosis cases had been reported following tooth extractions, which drives to strengthen knowledge about this disease, extreme preventive measures and encourage early diagnosis in dental care, due to the speed of the evolution of the pathology (AU))

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BACKGROUND: Diabetic retinopathy (DR) is a specific microvascular complication arising from diabetes, and its pathogenesis is not completely understood. tRNA-derived stress-induced RNAs (tiRNAs), a new type of small noncoding RNA generated by specific cleavage of tRNAs, has become a promising target for several diseases. However, the regulatory function of tiRNAs in DR and its detailed mechanism remain unknown. RESULTS: Here, we analyzed the tiRNA profiles of normal and DR retinal tissues. The expression level of tiRNA-Val was significantly upregulated in DR retinal tissues. Consistently, tiRNA-Val was upregulated in human retinal microvascular endothelial cells (HRMECs) under high glucose conditions. The overexpression of tiRNA-Val enhanced cell proliferation and inhibited cell apoptosis in HRMECs, but the knockdown of tiRNA-Val decreased cell proliferation and promoted cell apoptosis. Mechanistically, tiRNA-Val, derived from mature tRNA-Val with Ang cleavage, decreased Sirt1 expression level by interacting with sirt1 3'UTR, leading to the accumulation of Hif-1α, a key target for DR. In addition, subretinal injection of adeno-associated virus to knock down tiRNA-Val in DR mice ameliorated the symptoms of DR. CONCLUSION: tiRNA-Val enhance cell proliferation and inhibited cell apoptosis via Sirt1/Hif-1α pathway in HRMECs of DR retinal tissues.

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Individuals with diabetes mellitus (DM) are affected four times more by tendinopathies than non-diabetics. On the other hand, physical activity helps to DM control. However, the effects of physical exercise in water (PEW) on the fibrocartilages present in the tendons of animals affected by DM are unknown. In this sense, the aim of this study was to analyze the structural organization and chemical composition of fibrocartilage present in the intermediate region of the deep digital flexor tendon (DDFT) of Wistar rats with alloxan-induced DM. Diabetic and non-diabetic animals were randomly separated into four experimental groups (n = 10): Non-Trained Control (NTC), Trained Control (TC), Non-Trained Diabetic (NTD), and Trained Diabetic (TD). TC and TD animals underwent the exercise protocol (total weekly training load - week 1: 14,375; 2: 16,500; 3: 18,375; 4: 20,000) and then were euthanized to collect tendon samples for analysis. The matrix basophilia was more intense in the TC and TD groups. The Decorin immunohistochemical test results showed greater intensity in the NTD and TD groups. The wet weight of the fibrocartilaginous region of the tendon (NTC:19.9 ± 0.06; TC:22.3 ± 0.05; NTD:20.3 ± 0.08; TD:21.8 ± 0.04 mg - p = 0.048), glycosaminoglycan amounts (NTC:3.21 ± 0.18; TC:3.98 ± 0.44; NTD:3.32 ± 0.19; TD:3.79 ± 0.28 µg/mg of fresh tissue - p = 0.046), and intumescence in water (NTC:13.8 ± 3.8; TC:24.3 ± 3.9; NTD:14.9 ± 3.9; TD:28.2 ± 5.3 % w/w - p = 0.042) were higher in the TC and TD groups. The TD group showed the highest levels of type I collagen and matrix metalloproteinase (MMP)-13. The TC group showed the highest and TD the lowest TGF-ß1 levels. In conclusion, the PEW was able to stimulate the deposition of proteoglycans, without inducing chemical changes that would cause histopathological modifications in fibrocartilage in the DDFT of adult rats. Thus, PEW preserves the structural organization of these tissues in tendons of animals affected by DM.

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BACKGROUND: Diabetic retinopathy (DR) is a specific microvascular complication arising from diabetes, and its pathogenesis is not completely understood. tRNA-derived stress-induced RNAs (tiRNAs), a new type of small noncoding RNA generated by specific cleavage of tRNAs, has become a promising target for several diseases. However, the regulatory function of tiRNAs in DR and its detailed mechanism remain unknown. RESULTS: Here, we analyzed the tiRNA profiles of normal and DR retinal tissues. The expression level of tiRNA-Val was significantly upregulated in DR retinal tissues. Consistently, tiRNA-Val was upregulated in human retinal microvascular endothelial cells (HRMECs) under high glucose conditions. The overexpression of tiRNA-Val enhanced cell proliferation and inhibited cell apoptosis in HRMECs, but the knockdown of tiRNA-Val decreased cell proliferation and promoted cell apoptosis. Mechanistically, tiRNA-Val, derived from mature tRNA-Val with Ang cleavage, decreased Sirt1 expression level by interacting with sirt1 3'UTR, leading to the accumulation of Hif-1α, a key target for DR. In addition, subretinal injection of adeno-associated virus to knock down tiRNA-Val in DR mice ameliorated the symptoms of DR. CONCLUSION: tiRNA-Val enhance cell proliferation and inhibited cell apoptosis via Sirt1/Hif-1α pathway in HRMECs of DR retinal tissues.

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Abstract Neuropathic pain (NP) affects more than 8% of the global population. The proposed action of the transient receptor potential ankyrin 1 (TRPA1) as a mechanosensor and the characterization of the transient receptor potential melastatin 8 (TRPM8) as a cold thermosensor raises the question of whether these receptors are implicated in NP. Our study aimed to evaluate the involvement of TRPA1 and TRPM8 in cold and mechanical signal transduction to obtain a comparative view in rat models of streptozotocin-induced diabetes (STZ) and chronic constriction injury of the sciatic nerve (CCI). The electronic von Frey test showed that STZ rats presented mechanical allodynia that was first evidenced on the 14th day after diabetes confirmation, and four days after CCI. This phenomenon was reduced by the intraplantar (ipl) administration of a TRPA1 receptor antagonist (HC-030031; 40 µL/300 µg/paw) in both NP models. Only CCI rats displayed cold hyperalgesia based on the cold plate test. The pharmacological blocking of TRPA1 through the injection of the antagonist attenuated cold hyperalgesia in this NP model. STZ animals showed a reduction in the number of flinches induced by the intraplantar injection of mustard oil (MO; TRPA1 agonist; 0.1%/50 µL/paw), or intraplantar injection of menthol (MT; TRPM8 agonist; 0.5% and 1%/50 µL/paw). The response induced by the ipl administration of MT (1%/50 µL/paw) was significantly different between the CCI and SHAM groups. Together, these data suggest a different pattern in nociceptive behavior associated with different models of NP, suggesting a variant involvement of TRPA1 and TRPM8 in both conditions

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Para que os fármacos possam ser comercializados economicamente, a sua escala de produção deve ser aumentada para atender à demanda do mercado. Atualmente, a maior parte dos fármacos são sintetizados em processos batelada que possuem limitações quanto à eficiência de mistura, temperatura e pressão. O uso de microrreatores surge como alternativa na indústria químico-farmacêutica, aumentando a eficiência dos processos de maneira segura. Ferramentas utilizadas no segmento computacional multidisciplinar teórico, como o DFT (Density Functional Theory), podem prever e compreender o comportamento das reações químicas, podendo ter grande utilidade na síntese de novos fármacos economizando tempo, investimento e reduzindo a geração de resíduos. A diabetes mellitus é uma doença de caráter epidêmico, que a cada ano vem aumentando o número de casos. O emprego de fármacos derivados das glitazonas no tratamento de diabetes mellitus tipo 2 é recomendado devido ao excelente controle glicêmico que esta classe de fármacos oferece. Neste trabalho, foi sintetizada a Rosiglitazona, um fármaco derivado das glitazonas, que auxilia no tratamento da diabetes mellitus tipo 2, sendo estudadas duas rotas de síntese distintas, que foram otimizadas com o intuito de maximizar o rendimento de seus intermediários, obtendo a Rosiglitazona com pureza de cerca de 94%. Foi realizada, para os intermediários, aqui denominados, 1R, 2R2 e 3R2 a síntese one-pot e para os intermediários 1R, 2R1 e 3R2 foi realizada a transposição do processo usual em batelada para fluxo contínuo no microrreator, com rendimentos de até 93%. Com o auxílio da química quântica computacional, a reação de síntese do intermediário 1R, foi elucidada teoricamente e determinadas as grandezas termodinâmicas (ΔH‡, ΔG‡ e ΔS‡) no estado de transição, que foram comparadas com os valores experimentais, sendo constatada uma boa concordância, com desvio máximo de 14%

In order for drugs to be commercialized economically, their production scale must be increased to meet market demand. Currently, most drugs are synthesized in batch processes that have limitations in terms of mixing efficiency, temperature and pressure. The use of microreactors appears as an alternative in the chemical-pharmaceutical industry, increasing the efficiency of the synthesis processes in a safe way. Tools used in the theoretical multidisciplinary computational segment, such as DFT (Density Functional Theory), can predict and understand the behavior of chemical reactions, and can be very useful in the synthesis of new drugs, saving time, investment and reducing waste generation. Diabetes mellitus is an epidemic disease that has been increasing the number of cases every year. The use of drugs derived from glitazones in the treatment of type 2 diabetes mellitus is recommended due to the excellent glycemic control that this class of drugs offers. In this work, Rosiglitazone, a drug derived from glitazones, which helps in the treatment of type 2 diabetes mellitus, was synthesized. Two different synthetic routes were studied and optimized in order to maximize the yield of its intermediates, obtaining Rosiglitazone with purity of about 94%. One-pot synthesis was performed to 1R, 2R2 and 3R2 intermediates, and the transposition from the usual batch process to continuous flow in microreactor was performed to 1R, 2R1 and 3R2 intermediates, with yields of up to 93%. With the aid of computational quantum chemistry, the intermediate 1R synthesis reaction was theoretically elucidated and the thermodynamic properties were determined (ΔH‡, ΔG‡ and ΔS‡) in the transition state, which were compared with the experimental results, obtaining good agreement, with a maximum deviation of 14%.

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Introduction: Glycemic decompensation in diabetes is one of the major factors for the development of chronic disease complications. Factors involved in the adequate control of diabetes include adherence to pharmacological treatment and knowledge about the disease.Methods: Cross-sectional study on the factors associated with adherence to drug treatment and knowledge about diabetes in diabetic patients treated at Hospital Universitário de Santa Maria between 2018 and 2019, based on the validated Morisky-Green test and on the Diabetes Knowledge Questionnaire.Results: A total of 201 patients diagnosed with diabetes were included, the majority (85.6%) of which had type 2 diabetes and were white (75.6%), with a mean age of 59.4 years. An association between insufficient knowledge about diabetes and patients with type 2 diabetes was observed. An association was found between patients with type 2 diabetes using insulin and non-adherence to drug treatment compared with patients with type 2 diabetes who did use insulin. The research also showed that non-adherence to drug treatment was associated with higher occurrence of hypoglycemia compared with patients who adhered to drug treatment.Conclusion: The data obtained in our study allows us to conclude that non-adherence to pharmacological treatment makes diabetes therapy more complicated and worsens the prognosis.

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Abstract Metabolic syndrome (MetS), an epidemic defined as a group of interconnected physiological, biochemistry, clinical, and metabolic factors, directly increases the risk of cardiovascular disease, atherosclerosis, type 2 diabetes, and death. MetS therapy includes diet, physical exercise, and a poly-pharmacological intervention. Cannabis is mainly recognized for its recreational uses and has several medical applications for neurological diseases, due to its hypnotic, anxiolytic, antinociceptive, anti-inflammatory, and anticonvulsant activities. Although several clinical observations in Cannabis smokers suggest metabolic effects, its utility in metabolic disorders is unclear. This review aims to determine under what conditions Cannabis might be useful in the treatment of MetS. Cannabis contains 120 phytocannabinoids, of which Δ9-THC mediates its psychoactive effects. Cannabinoids exert biological effects through interactions with the endocannabinoid system, which modulates several physiologic and metabolic pathways through cannabinoid receptors (CB1/CB2). Signaling through both receptors inhibits neurotransmitter release. In general, endocannabinoid system stimulation in Cannabis smokers and Δ9-THC signaling through CB1 have been implicated in MetS development, obesity, and type 2 diabetes. In contrast, CB1 antagonists and non-psychotropic phytocannabinoids like cannabidiol reduce these effects through interactions with both cannabinoid and non-cannabinoid receptors. These pharmacological approaches represent a source of new therapeutic agents for MetS. However, more studies are necessary to support the therapeutic potential of Cannabis and cannabinoids in metabolic abnormalities

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