RESUMO
The Goldblatt model of hypertension (2K-1C) in rats is characterized by renal sympathetic nerve activity (rSNA). We investigated the effects of unilateral renal denervation of the clipped kidney (DNX) on sodium transporters of the unclipped kidneys and the cardiovascular, autonomic, and renal functions in 2K-1C and control (CTR) rats. The mean arterial pressure (MAP) and rSNA were evaluated in experimental groups. Kidney function and NHE3, NCC, ENaCß, and ENaCγ protein expressions were assessed. The glomerular filtration rate (GRF) and renal plasma flow were not changed by DNX, but the urinary (CTR: 0.0042 ± 0.001; 2K-1C: 0.014 ± 0.003; DNX: 0.005 ± 0.0013 mL/min/g renal tissue) and filtration fractions (CTR: 0.29 ± 0.02; 2K-1C: 0.51 ± 0.06; DNX: 0.28 ± 0.04 mL/min/g renal tissue) were normalized. The Na+/H+ exchanger (NHE3) was reduced in 2K-1C, and DNX normalized NHE3 (CTR: 100 ± 6; 2K-1C: 44 ± 14, DNX: 84 ± 13%). Conversely, the Na+/Cl- cotransporter (NCC) was increased in 2K-1C and was reduced by DNX (CTR: 94 ± 6; 2K-1C: 144 ± 8; DNX: 60 ± 15%). In conclusion, DNX in Goldblatt rats reduced blood pressure and proteinuria independently of GRF with a distinct regulation of NHE3 and NCC in unclipped kidneys.
Assuntos
Rim , Trocador 3 de Sódio-Hidrogênio , Animais , Rim/inervação , Rim/metabolismo , Ratos , Masculino , Trocador 3 de Sódio-Hidrogênio/metabolismo , Taxa de Filtração Glomerular , Denervação , Isquemia/metabolismo , Pressão Sanguínea , Ratos Wistar , Hipertensão/metabolismo , Canais Epiteliais de Sódio/metabolismo , Modelos Animais de Doenças , Trocadores de Sódio-Hidrogênio/metabolismoRESUMO
This retrospective cohort study described the obstetric and neonatal outcomes, antiseizure medication (ASM) use, and types of seizures in pregnant women with epilepsy (PWWE). Data collected from the medical records of 224 PWWE aged < 40 years with controlled or refractory seizures and 492 pregnant women without epilepsy (PWNE) control group from high-risk maternity hospitals in Alagoas between 2008 and 2021 were included in this study. The obstetric and neonatal outcomes observed in PWWE were pregnancy-related hypertension (PrH) (18.4%), oligohydramnios (10.3%), stillbirth (6.4%), vaginal bleeding (6%), preeclampsia (4.7%), and polyhydramnios (3%). There was a greater likelihood of PrH in PWWE with generalized tonic-clonic seizures (GTCS) and that of maternal intensive care unit (ICU) admissions in those with GTCS and status epilepticus, and phenytoin and lamotrigine use. PWWE with GTCS had a higher risk of stillbirth and premature delivery. PWWE with status epilepticus were treated with lamotrigine. Phenobarbital (PB) with diazepam were commonly used in GTCS and status epilepticus. Total 14% patients did not use ASM, while 50.2% used monotherapy and 35.8% used polytherapy. Total 60.9% of patients used PB and 25.2% used carbamazepine. This study described the association between the adverse obstetric and neonatal outcomes and severe seizure types in PWWE.
Assuntos
Epilepsia , Estado Epiléptico , Recém-Nascido , Feminino , Humanos , Gravidez , Lamotrigina/uso terapêutico , Gestantes , Estudos Retrospectivos , Natimorto/epidemiologia , Brasil/epidemiologia , Anticonvulsivantes/efeitos adversos , Convulsões/tratamento farmacológico , Convulsões/epidemiologia , Convulsões/induzido quimicamente , Epilepsia/tratamento farmacológico , Fenobarbital/uso terapêutico , Estado Epiléptico/induzido quimicamenteRESUMO
Diabetes promotes renal sympathetic hyperactivity, autonomic imbalance, and cardiovascular and renal dysfunction. Bilateral renal denervation (BRD) has emerged as a treatment for diabetes; however, the mechanisms that underlie the beneficial effects of BRD are unknown. AIMS: The present study evaluated the effects of BRD on autonomic, cardiovascular, metabolic, and renal function in streptozotocin-diabetic rats. MAIN METHODS: Wistar rats were separated into three experimental groups: control (CTR), diabetic (DM), and diabetic that underwent BRD (DM BRD). BRD was performed two weeks after STZ-diabetes induction, the experiments were performed four weeks after DM induction. This study evaluated sympathetic vasomotor nerve activity in different territories (renal, lumbar and splanchnic), arterial baroreceptor reflex, metabolic and renal function. KEY FINDINGS: BRD significantly reduced glycemia, glycosuria, albuminuria, and SGLT2 gene expression in the kidney in DM rats. Renal sympathetic nerve activity (rSNA) was significantly increased and splanchnic sympathetic nerve activity (sSNA) was significantly decreased in DM rats, without changes in lumbar sympathetic nerve activity (lSNA). BRD was able to normalize sSNA and significantly increase lSNA in DM rats compared to control rats. Additionally, cardiac baroreceptor sensitivity was impaired in DM rats, and BRD significantly improved baroreflex sensitivity. SIGNIFICANCE: Our data suggest that renal nerves play an important role in autonomic, cardiovascular, and renal dysfunction in STZ-DM rats. Thus, sympathetic renal hyperactivity should be considered a possible therapeutic target in diabetic patients.
Assuntos
Sistema Cardiovascular , Denervação , Diabetes Mellitus Experimental/metabolismo , Rim/inervação , Rim/metabolismo , Animais , Barorreflexo , Pressão Sanguínea/efeitos dos fármacos , Cateterismo , Diabetes Mellitus Experimental/fisiopatologia , Coração , Frequência Cardíaca/efeitos dos fármacos , Hematócrito , Masculino , Pressorreceptores/fisiologia , Ratos , Ratos Wistar , Transportador 2 de Glucose-Sódio/metabolismo , Estreptozocina , Sistema Nervoso Simpático/efeitos dos fármacosRESUMO
Novel coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its impact on patients with comorbidities is clearly related to fatality cases, and diabetes has been linked to one of the most important causes of severity and mortality in SARS-CoV-2 infected patients. Substantial research progress has been made on COVID-19 therapeutics; however, effective treatments remain unsatisfactory. This unmet clinical need is robustly associated with the complexity of pathophysiological mechanisms described for COVID-19. Several key lung pathophysiological mechanisms promoted by SARS-CoV-2 have driven the response in normoglycemic and hyperglycemic subjects. There is sufficient evidence that glucose metabolism pathways in the lung are closely tied to bacterial proliferation, inflammation, oxidative stress, and pro-thrombotic responses, which lead to severe clinical outcomes. It is also likely that SARS-CoV-2 proliferation is affected by glucose metabolism of type I and type II cells. This review summarizes the current understanding of pathophysiology of SARS-CoV-2 in the lung of diabetic patients and highlights the changes in clinical outcomes of COVID-19 in normoglycemic and hyperglycemic conditions.
RESUMO
Cyclo-Gly-Pro (CGP) attenuates nociception, however its effects on salivary glands remain unclear. In this study, we investigated the acute effects of CGP on salivary flow and composition, and on the submandibular gland composition, compared with morphine. Besides, we characterized the effects of naloxone (a non-selective opioid receptor antagonist) on CGP- and morphine-induced salivary and glandular alterations in mice. After that, in silico analyses were performed to predict the interaction between CGP and opioid receptors. Morphine and CGP significantly reduced salivary flow and total protein concentration of saliva and naloxone restored them to the physiological levels. Morphine and CGP also reduced several infrared vibrational modes (Amide I, 1687-1594cm-1; Amide II, 1594-1494cm-1; CH2/CH3, 1488-1433cm-1; C = O, 1432-1365cm-1; PO2 asymmetric, 1290-1185cm-1; PO2 symmetric, 1135-999cm-1) and naloxone reverted these alterations. The in silico docking analysis demonstrated the interaction of polar contacts between the CGP and opioid receptor Cys219 residue. Altogether, we showed that salivary hypofunction and glandular changes elicited by CGP may occur through opioid receptor suggesting that the blockage of opioid receptors in superior cervical and submandibular ganglions may be a possible strategy to restore salivary secretion while maintaining antinociceptive action due its effects on the central nervous system.
Assuntos
Gânglios Parassimpáticos/efeitos dos fármacos , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Peptídeos Cíclicos/farmacologia , Glândulas Salivares/efeitos dos fármacos , Analgésicos Opioides/farmacologia , Animais , Sítios de Ligação , Gânglios Parassimpáticos/metabolismo , Gânglios Parassimpáticos/fisiologia , Masculino , Camundongos , Morfina/farmacologia , Nociceptividade , Ligação Proteica , Receptores Opioides/química , Receptores Opioides/metabolismo , Saliva/metabolismo , Glândulas Salivares/metabolismo , Glândulas Salivares/fisiologiaRESUMO
Introducción: Los cambios funcionales resultantes de la evolución de la enfermedad pulmonar obstructiva crónica (EPOC) son progresivos e irreversibles, lo que provoca un aumento del trabajo del diafragma debido a la hiperinflación. Los nervios frénicos promueven la inervación del diafragma y pueden verse comprometidos en la condición de EPOC.Objetivo: Comparar la morfología de los nervios frénicos de los cadáveres con y sin EPOC, mediante microscopía óptica. Métodos: Estudio descriptivo, transversal y comparativo de muestras, tanto de los pulmones como de los nervios frénicos de 38 cadáveres, con diagnóstico de EPOC y sin esta condición. Las muestras de tejido fueron fijadas y procesadas por histología convencional con láminas histológicas de hematoxilina-eosina. Las muestras fueron compuestas por pacientes con EPOC (EPOC) y sin EPOC (CTR). Esta clasificación se realizó después del análisis histológico. Las láminas histológicas se analizaron mediante microscopía óptica por un patólogo, que fue un evaluador ciego al estudio. Resultados: De acuerdo con los criterios de inclusión, se incluyeron 31 cadáveres en el grupo de EPOC y 7 cadáveres en el grupo CTR. En el análisis de los nervios frénicos, 8 cadáveres, es decir 25,8% del grupo de EPOC, tuvieron cambios histopatológicos como edema perineural (75%, n=6), atrofia nerviosa (12,5%, n=1) e infiltrado eosinofílico perineural (12,5%, n=1). Conclusión: Los nervios frénicos de los cadáveres con EPOC tienen tendencia a alteraciones histopatológicas, siendo el edema perineural la principal modificación encontrada
Introducción: Los cambios funcionales resultantes de la evolución de la enfermedad pulmonar obstructiva crónica (EPOC) son progresivos e irreversibles, lo que provoca un aumento del trabajo del diafragma debido a la hiperinflación. Los nervios frénicos promueven la inervación del diafragma y pueden verse comprometidos en la condición de EPOC.Objetivo: Comparar la morfología de los nervios frénicos de los cadáveres con y sin EPOC, mediante microscopía óptica. Métodos: Estudio descriptivo, transversal y comparativo de muestras, tanto de los pulmones como de los nervios frénicos de 38 cadáveres, con diagnóstico de EPOC y sin esta condición. Las muestras de tejido fueron fijadas y procesadas por histología convencional con láminas histológicas de hematoxilina-eosina. Las muestras fueron compuestas por pacientes con EPOC (EPOC) y sin EPOC (CTR). Esta clasificación se realizó después del análisis histológico. Las láminas histológicas se analizaron mediante microscopía óptica por un patólogo, que fue un evaluador ciego al estudio. Resultados: De acuerdo con los criterios de inclusión, se incluyeron 31 cadáveres en el grupo de EPOC y 7 cadáveres en el grupo CTR. En el análisis de los nervios frénicos, 8 cadáveres, es decir 25,8% del grupo de EPOC, tuvieron cambios histopatológicos como edema perineural (75%, n=6), atrofia nerviosa (12,5%, n=1) e infiltrado eosinofílico perineural (12,5%, n=1). Conclusión: Los nervios frénicos de los cadáveres con EPOC tienen tendencia a alteraciones histopatológicas, siendo el edema perineural la principal modificación encontrada
RESUMO
Introducción: En la enfermedad pulmonar obstructiva crónica (EPOC), el diafragma y los músculos respiratorios esternocleidomastoideos (ECOM) funcionan contra el aumento de las cargas mecánicas debido a la limitación del flujo de aire y los cambios en la conformación del tórax debido a la condición de hiperinflación pulmonar. Objetivo: Evaluar los cambios histopatológicos presentes en los pulmones y los músculos respiratorios (diafragma y ECOM) de los cadáveres con Diagnostico de EPOC. El Estudio: Este es un estudio ciego y descriptivo con análisis de imágenes histológicas de biopsia. El historial de tabaquismo asociado con la presencia de antracosis pulmonar, engrosamiento septal y bullas enfisematosas comprendió los criterios de inclusión del estudio. La muestra consistió en biopsias de pulmón, diafragma y ECOM. El estudio se realizó mediante análisis microscópico óptico de lâminas histológicas obtenidas de 36 cadáveres con EPOC. El diagnóstico histopatológico fue realizado por un patólogo que desconocía los objetivos del estudio. Hallazgos: En el diafragma, hubo la presencia de tejido adiposo interpuesto, atrofia muscular, eliminación de las fibras musculares y fibrosis. En el ECOM, también se evidenció la eliminación de las fibras musculares, la atrofia muscular, el tejido adiposo interpuesto, la hipertrofia muscular y el engrosamiento de los tendones. Conclusiones: Los cambios encontrados en las biopsias musculares de diafragma y ECOM de los cadáveres con EPOC se evidenciaron como un mecanismo de compensación y/o disfunción del sistema respiratorio debido a alteraciones biomecánicas promovidas por la enfermedad.
Introduction: In chronic obstructive pulmonary disease (COPD), the diaphragm and sternocleidomastoid respiratory muscles (ECOM) work against increased mechanical loads due to limited air flow and changes in chest conformation due to the condition of pulmonary hyperinflation. Objective: To evaluate the histopathological changes present in the lungs and respiratory muscles (diaphragm and ECOM) of the corpses affected by COPD. Materials and methods: This is a blind and descriptive study with analysis of histological images of biopsy. The history of smoking associated with the presence of pulmonary anthracosis, septal thickening and emphysematous bullae included the inclusion criteria of the study. The study was conducted by optical microscopic analysis of histological sheets obtained from 36 corpses with COPD. The histopathological diagnosis was made by a pathologist who did not know the objectives of the study. Results: In the diaphragm, there was the presence of interposed adipose tissue, muscle atrophy, removal of muscle fibers and fibrosis. In ECOM, the elimination of muscle fibers, muscular atrophy, interposed adipose tissue, muscle hypertrophy and thickening of the tendons were also evident. Conclusions: The changes found in the diaphragm and ECOM muscle biopsies of the bodies with COPD were evidenced as a mechanism of compensation and / or dysfunction of the respiratory system due to biomechanical alterations promoted by the disease.
RESUMO
BACKGROUND: After serious epidemics of chikungunya (CHIKV) and Zika (ZIKV) in the Americas, dengue (DENV) have reemerged in most countries. We analyzed the incidence, incidence rates, and evolution of DENV cases in Honduras from 2015 to 2018 and the ongoing 2019 epidemic. METHODS: Using epidemiological weeks (EW) surveillance data on the DENV in Honduras, we estimated incidence rates (cases/100,000 population), and developed maps at national, departmental, and municipal levels. RESULTS: From January 1, 2016 to July 21, 2019, a total of 109,557 cases of DENV were reported, 28,603 in 2019, with an incidence rate of 312.32 cases/100,000 population this year; 0.13% laboratory-confirmed. The highest peak was reached on the EW 28°, 2019 (5299 cases; 57.89 cases/100,000 population). The department with the highest number of cases and incidence rate was Cortes (8404 cases, 479.68 cases/100,000 population in 2019). DISCUSSION: The pattern and evolution of DENV epidemic in 2019 in Honduras has been similar to that which occurred for in 2015. As previously reported, this epidemic involved the north and central areas of the country predominantly, reaching municipality incidences there >1000 cases/100,000 population (or 1%). Studies using geographical information systems linked with clinical disease characteristics are necessary to obtain accurate epidemiological data for public health systems. Such information is also useful for assessment of risk for travelers who visit specific areas in a destination country.
RESUMO
Respiratory infection can be exacerbated by the high glucose concentration in the airway surface liquid (ASL). We investigated the effects of salbutamol and phlorizin on the pulmonary function, oxidative stress levels and SGLT1 activity in lung, pulmonary histopathological damages and survival rates of rats with sepsis. Sepsis was induced by cecal ligation and puncture surgery (CLP). Twenty-four hours after surgery, CLP rats were intranasally treated with saline, salbutamol or phlorizin. After 2 hours, animals were anesthetized and sacrificed. Sepsis promoted atelectasis and bronchial inflammation, and led to increased expression of SGLT1 on cytoplasm of pneumocytes. Salbutamol treatment reduced bronchial inflammation and promoted hyperinsuflation in CLP rats. The interferon-ɤ and Interleucin-1ß concentrations in bronchoalveolar lavage (BAL) were closely related to the bronchial inflammation regulation. Salbutamol stimulated SGLT1 in plasma membrane; whereas, phlorizin promoted the increase of SGLT1 in cytoplasm. Phlorizin reduced catalase activity and induced a significant decrease in the survival rate of CLP rats. Taken together, sepsis promoted atelectasis and lung inflammation, which can be associated with SGLT1 inhibition. The loss of function of SGLT1 by phlorizin are related to the augmented disease severity, increased atelectasis, bronchial inflammation and a significant reduction of survival rate of CLP rats. Alternatively salbutamol reduced BAL inflammatory cytokines, bronchial inflammation, atelectasis, and airway damage in sepsis. These data suggest that this selective ß2-adrenergic agonist may protect lung of septic acute effects.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Albuterol/farmacologia , Florizina/farmacologia , Pneumonia/tratamento farmacológico , Sepse/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Animais , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Modelos Animais de Doenças , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Pneumonia/metabolismo , Ratos , Ratos Wistar , Sepse/metabolismo , Índice de Gravidade de Doença , Transportador 1 de Glucose-Sódio/metabolismoRESUMO
Sympathetic vasomotor activity is significantly increased in renovascular hypertension. Renal denervation (DnX) has emerged as a novel therapy for resistant hypertension to drug therapy. However, the underlying mechanisms regarding the reduction in blood pressure (BP) after DnX remain unclear. Thus, the aim of this study was to evaluate the effects of DnX of a clipped kidney on the baseline and baroreceptor reflex control of post-ganglionic sympathetic activity to the contralateral kidney (rSNA) and lumbar (lSNA) nerves in Goldblatt hypertensive rats (2K1C). Renal denervation of an ischaemic kidney (DxX - all visible bundles of nerves were dissected - 10% phenol) was performed 5weeks after clipping (gap width: 0.2mm). Ten days after DnX, BP was significantly reduced (16%) in the 2K1C compared with the undenervated 2K1C (p<0.05). DnX significantly reduced basal rSNA (control group (CT): 110±8, n=14; 2K1C: 150±8, n=12; 2K1C DnX: 89±7, spikes per second (spikes/s); p<0.05, n=8) and lSNA (CT: 137±8, n=8; 2K1C: 202±7, n=11; 2K1C DnX: 131±7, spikes/s; p<0.05, n=8) only in 2K1C rats. DnX significantly improved the arterial baroreceptor sensitivity of rSNA (CT: -2.3±0.2, n=11; 2K1C: -0.7±0.1, n=8; 2K1C DnX: -1.5±0.2, spikes/s/mmHg; p<0.05, n=5) and heart rate for tachycardic response (CT: -3.9±0.5, n=7; 2K1C: -1.9±0.1, n=8; 2K1C DnX: -3.3±0.4, bpm/mmHg; p<0.05, n=8), but not for lSNA in 2K1C rats. The results show that DnX normalized baseline sympathetic vasomotor activity to the lumbar and renal nerves, followed by a differential improvement in the arterial baroreceptor sensitivity. Whether the baroreceptor function sensitivity improvement induced by DnX is a cause or a consequence of BP reduction remains to be determined.
Assuntos
Barorreflexo/fisiologia , Hipertensão Renovascular/fisiopatologia , Rim/inervação , Pressorreceptores/fisiologia , Potenciais de Ação , Animais , Pressão Sanguínea/fisiologia , Denervação , Modelos Animais de Doenças , Frequência Cardíaca/fisiologia , Isquemia/fisiopatologia , Rim/fisiopatologia , Masculino , Ratos Wistar , Sistema Nervoso Simpático/fisiopatologiaRESUMO
High glucose concentration in the airway surface liquid (ASL) is an important feature of diabetes that predisposes to respiratory infections. We investigated the role of alveolar epithelial SGLT1 activity on ASL glucose concentration and bacterial proliferation. Non-diabetic and diabetic rats were intranasally treated with saline, isoproterenol (to increase SGLT1 activity) or phlorizin (to decrease SGLT1 activity); 2 hours later, glucose concentration and bacterial proliferation (methicillin-resistant Sthaphylococcus aureus, MRSA and Pseudomonas aeruginosa, P. aeruginosa) were analyzed in bronchoalveolar lavage (BAL); and alveolar SGLT1 was analyzed by immunohistochemistry. BAL glucose concentration and bacterial proliferation increased in diabetic animals: isoproterenol stimulated SGLT1 migration to luminal membrane, and reduced (50%) the BAL glucose concentration; whereas phlorizin increased the BAL glucose concentration (100%). These regulations were accompanied by parallel changes of in vitro MRSA and P. aeruginosa proliferation in BAL (r = 0.9651 and r = 0.9613, respectively, Pearson correlation). The same regulations were observed in in vivo P. aeruginosa proliferation. In summary, the results indicate a relationship among SGLT1 activity, ASL glucose concentration and pulmonary bacterial proliferation. Besides, the study highlights that, in situations of pulmonary infection risk, such as in diabetic subjects, increased SGLT1 activity may prevent bacterial proliferation whereas decreased SGLT1 activity can exacerbate it.