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1.
Braz. j. biol ; 83: e240842, 2023. tab
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1339375

RESUMO

Abstract This research aimed to investigate various mosquitocidal activities of Chenopodium botrys whole- plant n-hexane extract against Culex quinquefasciatus. The extract showed remarkable larvicidal, pupicidal, adulticidal, oviposition deterrent and adult emergence inhibitory activities against Cx. quinquefasciatus. During the larvicidal and pupicidal activities, the 24-hour lethal concentration (LC50) of extract against 2nd instar larvae, 4th instar larvae and pupae were 324.6, 495.6 and 950.8 ppm, respectively. During the CDC (Centers for Disease Control and Prevention) bottle bioassay for adulticidal activity, the median knockdown times (KDT50) at 1.25% concentration was 123.4 minutes. During the filter paper impregnation bioassay for adulticidal activity, the KDT50 value at 0.138 mg/cm2 concentration was 48.6 minutes. The extract was fractionated into 14 fractions through silica gel column chromatography which were then combined into six fractions on the basis of similar retention factor (Rf) value. These fractions were screened for adulticidal activity by applying CDC bottle bioassay. The fraction obtained through 60:40 to 50:50% n-hexanes-chloroform mobile phase with 0.5 Rf value showed 100% adulticidal activity at 0.2% concentration. During oviposition deterrent activity, the highest concentration (1000 ppm) showed 71.3 ± 4.4% effective repellence and 0.6 ± 0.1 oviposition activity index. During adult emergence inhibition activity, the median emergence inhibition (EI50) value was 312.3 ppm. From the outcome of the present investigation, it is concluded that the n-hexane extract of C. botrys whole- plant possesses strong larvicidal, pupicidal, adulticidal, oviposition deterrent and adult emergence inhibitory activities against Cx. quinquefasciatus.


Resumo Esta pesquisa teve como objetivo investigar várias atividades mosquitocidas do extrato n-hexano de planta inteira de Chenopodium botrys contra Culex quinquefasciatus. O extrato mostrou atividades larvicida, pupicida, adulticida, dissuasora de oviposição e inibidora da emergência de adultos contra a Cx. quinquefasciatus. Durante as atividades larvicida e pupicida, a concentração letal de 24 horas (CL50) do extrato contra larvas de 2º estádio, larvas de 4º estádio e pupa foi de 324,6, 495,6 e 950,8 ppm, respectivamente. Durante o bioensaio com frasco do CDC (Centros para Controle e Prevenção de Doenças) para adulticida, o tempo médio de desativação (KDT50) na concentração de 1,25% foi de 123,4 minutos. Durante o bioensaio de impregnação com papel de filtro para a atividade adulticida do extrato, o valor KDT50 na concentração de 0,138 mg / cm2 foi de 48,6 minutos. O extrato foi fracionado em 14 frações através de cromatografia em coluna de gel de sílica que foram então combinadas em seis frações com base em um valor de fator de retenção (Rf) semelhante. Essas frações foram selecionadas quanto à atividade adulticida por meio da aplicação do bioensaio com garrafa do CDC. A fração obtida através da fase móvel de n-hexanos-clorofórmio 60:40% a 50:50% com valor de 0,5 Rf apresentou atividade adulticida de 100% na concentração de 0,2%. Durante a atividade de dissuasão da oviposição, a maior concentração de extrato (1000 ppm) apresentou repelência efetiva de 71,3 ± 4,4% e índice de atividade de oviposição de 0,6 ± 0,1. Durante a atividade de inibição da emergência de adultos, o valor médio de inibição da emergência (EI50) foi de 312,3 ppm. A partir do resultado da presente investigação, conclui-se que o extrato de n-hexano da planta inteira de C. botrys possui fortes atividades larvicida, pupicida, adulticida, dissuasora da oviposição e inibidora da emergência de adultos contra a Cx. quinquefasciatus.

2.
STAR Protoc ; 2(4): 100925, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34755121

RESUMO

This protocol describes how to identify Dual Expressers (DEs), a rare type of lymphocyte that co-expresses B-cell receptors and T-cell receptors, by flow cytometry using a cocktail of four antibodies. It also shows the subsequent gating strategy for detecting and sorting DEs and the generation of EBV-immortalized DE lymphoblastoid cell lines and clones for antibody production and cloning antigen receptors. Use of this protocol maximizes detection of DEs and minimizes inclusion of doublets. For complete details on the use and execution of this protocol, please refer to Ahmed et al. (2019).

3.
Braz J Biol ; 83: e246904, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34706025

RESUMO

Hyperhydricity is a serious physiological disorder and affects In vitro propagation of many plants and as well of Salvia santolinifolia. The donor material to initiate the in vitro culture was the callus taken from the in vitro shoots produced on Murashig and Skoogs (MS) medium at 4.0 mg/l BA. This callus formed numerous hyperhydric shoots on culturing upon the medium of the same composition. The aim was to systematically evaluate the effect of cytokinins (Benzyladnine (BA) and N6-(-2-isopentenyl) adenine (2iP), culture vessels magnitude, medium solidification, source of nitrogen and calcium chloride for the alleviation of hyperhydricity. In the tissue cultures of S. santolinifolia BA and 2iP induced severe hyperhydricity, when other factors i.e. culture vessels magnitude and a suitable concentration of agar, ammonium nitrate (NH4NO3), potassium nitrate (KNO3) & calcium chloride (CaCl2.2H2O) were not optimized. After 30 days' culture, we observed 83.82% hyperhydric shoots at increased level (1.5 mg/l 2iP) and 81.59% at decreased levels (1.0 mg/l 2iP). On the other hand, hyperhydricity percentage at decreased (0.4%) and at increased (0.8%) levels of agar were 72.37% and 39.08%, respectively. MS medium modification with NH4NO3 (412 mg/l), KNO3 (475 mg/l) and CaCl2.2H2O (880 mg/l) was found the best medium to reduced hyperhydricity (23.6%).


Assuntos
Salvia , Meios de Cultura , Brotos de Planta
4.
Infect Dis Clin Pract (Baltim Md) ; 29(5): e287-e293, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34539163

RESUMO

Background: The decision of when it is safe to discontinue transmission-based precautions for SARS-CoV-2 coronavirus disease 2019 (COVID-19) hospitalized patients has been controversial. The Centers for Disease Control and Prevention offered reverse transcriptase polymerase chain reaction (PCR) diagnostic test- or symptom-based guidelines. Methods: A retrospective chart review of Vidant Health system, Eastern North Carolina, was conducted. Length of stay, days in isolation unit, and date appropriate for discharge or isolation discontinuation based on the symptom-based strategy were recorded. Results: Of 196 COVID hospitalized patients, 34 had repeated COVID PCR tests 3 or more days from their first positive test result. Half of these patients experienced delays in release from transmission-based precautions because of repeated positive PCR test results and use of the test-based approach. This resulted in an additional 166 days of hospitalization, costing an estimated $415,000. Furthermore, 2 subjects had a combined 16-day delay in necessary medical procedures. Most of the COVID PCR platforms yield quantitative results in the form of cycle threshold (Ct) values, the number of cycles needed to detect the genome. These values have also been used to assess whether patients are likely to remain contagious. None of our patients who met the criteria for symptom-based strategy for transmission-based precaution discontinuation had positive PCR test results with Ct values lower than 25, but 4 had Ct values lower than 30. Conclusions: Concerns surround immunocompromised patients and those treated with steroids who might be delayed or incapable of stopping viral replication and thus remain contagious. Our results suggest that clinicians use all available data including Ct values to evaluate the safety of discontinuation of transmission precautions.

5.
Braz J Biol ; 83: e240842, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34550279

RESUMO

This research aimed to investigate various mosquitocidal activities of Chenopodium botrys whole- plant n-hexane extract against Culex quinquefasciatus. The extract showed remarkable larvicidal, pupicidal, adulticidal, oviposition deterrent and adult emergence inhibitory activities against Cx. quinquefasciatus. During the larvicidal and pupicidal activities, the 24-hour lethal concentration (LC50) of extract against 2nd instar larvae, 4th instar larvae and pupae were 324.6, 495.6 and 950.8 ppm, respectively. During the CDC (Centers for Disease Control and Prevention) bottle bioassay for adulticidal activity, the median knockdown times (KDT50) at 1.25% concentration was 123.4 minutes. During the filter paper impregnation bioassay for adulticidal activity, the KDT50 value at 0.138 mg/cm2 concentration was 48.6 minutes. The extract was fractionated into 14 fractions through silica gel column chromatography which were then combined into six fractions on the basis of similar retention factor (Rf) value. These fractions were screened for adulticidal activity by applying CDC bottle bioassay. The fraction obtained through 60:40 to 50:50% n-hexanes-chloroform mobile phase with 0.5 Rf value showed 100% adulticidal activity at 0.2% concentration. During oviposition deterrent activity, the highest concentration (1000 ppm) showed 71.3 ± 4.4% effective repellence and 0.6 ± 0.1 oviposition activity index. During adult emergence inhibition activity, the median emergence inhibition (EI50) value was 312.3 ppm. From the outcome of the present investigation, it is concluded that the n-hexane extract of C. botrys whole- plant possesses strong larvicidal, pupicidal, adulticidal, oviposition deterrent and adult emergence inhibitory activities against Cx. quinquefasciatus.


Assuntos
Chenopodium , Culex , Inseticidas , Animais , Hexanos , Inseticidas/farmacologia , Larva , Extratos Vegetais/farmacologia , Folhas de Planta
6.
Braz J Biol ; 83: e246980, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468522

RESUMO

The study was aimed to evaluate the therapeutic effects of Zizyphus oxyphyla leaves methanolic (ZOX-LME), on serum liver, kidney and hematology along with other serum parameters in Carbon tetrachloride (CCl4) intoxicated rabbits. Experimental animals were divided into five groups, six rabbits in each. These were: group NC (normal control), group, TC (toxic control) and group ST i.e. silymarine administered group at dose rate (50) mg/kg body weight (BW). Group ET1 and group ET2 treated with (ZOX-LME) at dose 200 mg/kg BW and 400 mg/kg BW. CCl4 administration caused significant (P> 0.05) impairment in serum liver enzymes, blood factors and other serum indices. Treatment with (ZOX-LME) significantly (P<0.05) reduced and normalized the levels of serum alanine transaminase (ALT) aspartate transaminase (AST) and alkaline phosphatase (ALP) and hematological indices. Also significant (P< 0.05) reduction was observed in creatinine, urea, uric acid, blood urea nitrogen (BUN), and albumin and glucose concentrations. The altered levels of lipid profile and serum electrolytes (Ca, Mg, Cl, Na, K, and P) were significantly (P<0.05) change toward normal levels with (ZOX-LME) feeding. In addition (ZOX-LME) ingestion caused significant improvement in GSH, GST and CAT levels, while reducing the TBARS levels, exhibited antioxidant capacity. Also (ZOX-LME) showed increase inhibition against percent scavenging of 2, 2-diphenile-1-picrylehydrazyle (DPPH) free radical. Significant (P<0.05) normalizing effects were observed with high dose 400 mg/kg BW of (ZOX-LME and were equivalent to silymarine administered groups. The histological study of liver supported the hepatoprotective and renal curative activity of (ZOX-LME).


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Ziziphus , Animais , Antioxidantes , Biomarcadores , Rim , Extratos Vegetais/farmacologia , Coelhos
8.
J Health Pollut ; 11(31): 210912, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34434604

RESUMO

Background: Sawdust from Parkia biglobosa was prepared as an adsorbent for the adsorption of dye from aqueous solution. Objectives: The ability of sawdust to adsorb Congo red in a single dye system and binary dye system was examined. Methods: Effects of several variables (pH, contact time, initial dye concentration and adsorbent dose) were investigated and optimum conditions were established. The equilibrium data were subjected to kinetic and isotherm models. Results: Equilibrium time was observed at 600 mins while the optimum dose was 0.2 g and there was an increase in adsorption at low pH. The equilibrium data fitted the Freundlich isotherm model in both systems (coefficient correlation (R2) > 0.9). Harkin-Jura was the worst-fitted (R2 < 0.8). The qm in the single system (21.65) was lower than in BDS (27.17; 34.01). The values of 1/n show the heterogeneity on the surface of sawdust which reduced in the BDS. The increase in qm in the binary system showed that the presence of another dye (Reactive black 5) had a synergistic effect on the adsorption of Congo red. The kinetics of the process followed the pseudo-second-order model both in the single system and one of the binary systems. The dynamics of the process showed that the single system was non-spontaneous at low temperatures, endothermic and increased randomness on the surface of the adsorbent, while in the binary system, the process was exothermic and had little affinity for the adsorbent. Conclusions: Sawdust from Parkia biglobosa is a potential adsorbent for removing Congo red dye from aqueous solution in single and binary systems. Competing Interests: The authors declare no competing financial interests.

9.
J Environ Manage ; 294: 112960, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34116310

RESUMO

This study examined the impact of worldwide governance indicators on the sustainability of the bioenergy industry in selected European countries for the period 1996-2018. Applying the Fixed Effect (FE) Model, the results reveal that the bioenergy industry can significantly grow by improving the quality of worldwide governance indicators in European countries, especially in Western European Countries (WEC). Government effectiveness, rule of law, regulatory quality, and voice and accountability are found to be increasing the growth of the bioenergy industry. Precisely, the results further show that the magnitude of the effect of government effectiveness, voice and accountability, and Gross Domestic Product (GDP) on bioenergy output is higher in Western European Countries (WEC) as compared to the Central and Eastern European Countries (CEEC). Also, the findings further elaborate that the significant positive impact of regulatory quality and rule of law on bioenergy output is higher in CEEC countries compared to the WEC countries. The finding implies that the growth of the bioenergy industry in European countries can be effectively increased by improving the practice and quality of worldwide governance indicators. The study recommends for European countries to increase the efficiency of worldwide governance in their bioenergy industry to increase the sustainability of bioenergy production and reduce Dioxide Carbon (CO2) emissions. Policymakers in these countries should also invest more in worldwide governance to increase its effectiveness and transparency in the bioenergy industry. The authorities should equally emphasize the effectiveness and transparency of worldwide governance indicators to attain bioenergy security and lessen the dependence on fossil fuels.


Assuntos
Combustíveis Fósseis , Governo , Europa (Continente) , Produto Interno Bruto , Responsabilidade Social
10.
ESC Heart Fail ; 8(4): 3360-3368, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33938158

RESUMO

AIMS: The major cardiovascular (CV) adverse effects observed with sipuleucel-T from large multi-institutional clinical trials included thromboembolic events, myocardial infarction, and congestive heart failure in up to 0.3% of patients with CV risk factors. The incidence, outcomes, and mechanisms in real-world clinical settings of these CV adverse effects to date have not been fully elucidated. Our study identified a patient with sipuleucel-T-induced inflammatory cardiomyopathy, which led to the identification of CV adverse effects associated with sipuleucel-T from a large pharmacovigilance database and elucidation of its potential mechanisms. METHODS AND RESULTS: Using the MedDRA term 'cardiac disorders' (System Organ Class level), CV adverse events associated with sipuleucel-T versus all other drugs were reviewed from VigiBase, a large pharmacovigilance database. Disproportionality analysis was calculated by the information component (IC), a Bayesian disproportionality indicator. A positive IC025 (IC 95% lower end credibility interval) value (>0) is the traditional threshold used in statistical signal detection at the Uppsala Monitoring Centre. From VigiBase, the total number of CV adverse drug reaction reported with sipuleucel-T was 306 out of a total of 22 980 104 adverse drug reactions in VigiBase on 10/25/2020. MedDRA preferred terms levels were grouped into major CV adverse drug reaction categories where we observed significant reports of myocardial ischaemia, supraventricular tachycardia (particularly atrial fibrillation/atrial flutter), congestive heart failure, and valvular disorders. Myocardial ischemia included acute myocardial infarction (IC025 2.3) with n = 4/26 (15%) of these individual case safety reports considered fatal. Among patients with 'cardiac failure congestive' (IC025 1.5), 11 of these 43 cases (26%) were fatal with 42 (98%) of these cases considered to be solely due to sipuleucel-T. CONCLUSIONS: Patients with CV risk factors who are receiving sipuleucel-T may be at higher risk for congestive heart failure, myocardial ischemia, and supraventricular tachycardia. Electrocardiograms during weekly sipuleucel-T infusions and left ventricular function monitoring with echocardiogram should be considered in these patients. Our findings are suggestive of another rare presentation of T-cell-mediated CV toxicity with cancer immunotherapy.


Assuntos
Miocardite , Farmacovigilância , Sistemas de Notificação de Reações Adversas a Medicamentos , Teorema de Bayes , Humanos , Extratos de Tecidos
11.
J Community Hosp Intern Med Perspect ; 11(1): 72-75, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33552420

RESUMO

Kikuchi-Fujimoto disease (KFD) is a rare, benign, self-limiting necrotizing lymphadenitis of unknown etiology. The disease can affect people of all ages and of any sex and ethnicity. Tissue biopsy is needed for accurate diagnosis. The condition commonly masquerades as more sinister conditions such as malignancy and rheumatologic disorders, but has a much better prognosis. Treatment is generally supportive but patients may require corticosteroids with eventual spontaneous resolution. We discuss a case of KFD in a 34-year-old male and highlight the need for prompt and accurate diagnosis.

12.
Cell ; 184(3): 840-843, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33545037

RESUMO

We have recently identified a novel lymphocyte that is a dual expresser (DE) of TCRαß and BCR. DEs in T1D patients are predominated by a public BCR clonotype (clone-x) that encodes a potent autoantigen that cross-activates insulin-reactive T cells. Betts and colleagues were able to detect DEs but alleged to not detect high DE frequency, clone-x, or similar clones in T1D patients. Unfortunately, the authors did not follow our methods and when they did, their flow cytometric data at two sites were conflicting. Moreover, contrary to their claim, we identified clones similar to clone-x in their data along with clones bearing the core motif (DTAMVYYFDYW). Additionally, their report of no increased usage of clone-x VH/DH genes by bulk B cells confirms rather than challenges our results. Finally, the authors failed to provide data verifying purity of their sorted DEs, making it difficult to draw reliable conclusion of their repertoire analysis. This Matters Arising Response paper addresses the Japp et al. (2021) Matters Arising paper, published concurrently in Cell.


Assuntos
Diabetes Mellitus Tipo 1 , Linfócitos B , Células Clonais , Humanos , Receptores de Antígenos de Linfócitos T alfa-beta , Linfócitos T
14.
Heliyon ; 6(8): e04454, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32904237

RESUMO

The need for light intensity has made dye degradation very costly for industry. In this work, Fenton reagent was used for the efficient degradation of an aqueous solution of dye without the need for a light source. The influences of the pH of the media, the initial concentrations of Fe2+, H2O2, and methylene blue (MB) dye; in addition to temperature on the oxidation of MB dye were studied. The optimum amounts of the Fenton reagent were 4mM of Fe2+ and 70mM of H2O2 at 20 mg/L of dye. The optimum ratio of 0.05 of Fe2+/H2O2 was found to give the best result for the decolorization of dye. The Fenton process was effective at pH 3 with a maximum dye decolorization efficiency of 98.8% within 30 min of reaction, corresponding to a COD removal of 85%. The decolorization process was thermodynamically feasible, spontaneous, and endothermic. The activation energy (Ea) was 33.6 kJ/mol suggesting that the degradation reaction proceeded with a low energy barrier.

15.
J Family Med Prim Care ; 9(5): 2248-2252, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32754482

RESUMO

Teaching methodology has a great impact on the learning outcomes in an undergraduate's education. Objectives: 1. To assess the effectiveness of small group discussions (SGD) over lecture in learning the principles of family medicine among 2nd-year MBBS students. 2. To assess the perception of students on SGD over lecture in learning principles of family medicine among 2nd-year MBBS students. Materials and Methods: This medical education, quasi-experimental study was conducted at a medical college in north Kerala. Study subjects were the 2nd-year MBBS students of this college. They participated after giving informed consent and were divided into two groups using serial roll number. The study was conducted for 2 months after getting ethical clearance. Study tools included PowerPoint presentation slides, literature regarding principles of family medicine, structured questionnaire, and question paper for posttest. Statistical analysis was done with an independent sample Z-test and Mann-Whitney test, using SPSS 20 software. Results: SGD show a definite advantage over lecture-based learning in improving the attention span of students, understanding the principles of family medicine, and recall. The scores for the overall learning experience was found to be significantly higher for SGD. Evaluating the effectiveness of training on the Kirkpatrick model showed that learners show better satisfaction and learning in small groups. Conclusion: Students strongly preferred SGD over lectures as the teaching-learning methodology for principles of family medicine. SGD is a more effective instructional tool in improving the attention span of students, understanding the principles of family medicine, and recall. The overall learning satisfaction was found to be significantly higher with SGD for learning the principles of family medicine.

16.
Sci Rep ; 10(1): 14035, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32820192

RESUMO

Achieving the broadband response of metamaterial absorbers has been quite challenging due to the inherent bandwidth limitations. Herein, the investigation was made of a unique kind of visible light metamaterial absorber comprising elliptical rings-shaped fractal metasurface using tungsten metal. It was found that the proposed absorber exhibits average absorption of over 90% in the visible wavelength span of 400-750 nm. The features of perfect absorption could be observed because of the localized surface plasmon resonance that causes impedance matching. Moreover, in the context of optoelectronic applications, the absorber yields absorbance up to ~ 70% even with the incidence obliquity in the range of 0°-60° for transverse electric polarization. The theory of multiple reflections was employed to further verify the performance of the absorber. The obtained theoretical results were found to be in close agreement with the simulation results. In order to optimize the results, the performance was analyzed in terms of the figure of merit and operating bandwidth. Significant amount of absorption in the entire visible span, wide-angle stability, and utilization of low-cost metal make the proposed absorber suitable in varieties of photonics applications, in particular photovoltaics, thermal emitters and sensors.

18.
Indian Heart J ; 72(1): 7-13, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32423565

RESUMO

AIM: The primary objective of this review is to develop practice-based expert group opinions on the cardiovascular (CV) safety and utility of modern sulfonylureas (SUs) in cardiovascular outcome trials (CVOTs). BACKGROUND: The United States Food and Drug Administration issued new guidance to the pharmaceutical industry in 2008 regarding the development of new antihyperglycemic drugs. The guidance expanded the scope for the approval of novel antihyperglycemic drugs by mandating CVOTs for safety. A few long-term CVOTs on dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors have been completed, while others are ongoing. SUs, which constitute one of the key antihyperglycemic agents used for the management of type 2 diabetes mellitus (T2DM), have been used as comparator agents in several CVOTs. However, the need for CVOTs on modern SUs remains debatable. In this context, a multinational group of endocrinologists convened for a meeting and discussed the need for CVOTs of modern SUs to evaluate their utility in the management of patients with T2DM. At the meeting, CVOTs of modern SUs conducted to date and the hypotheses derived from the results of these trials were discussed. REVIEW RESULTS: The expert group analyzed the key trials emphasizing the CV safety of modern SUs and also reviewed the results of various CVOTs in which modern SUs were used as comparators. Based on literature evidence and individual clinical insights, the expert group opined that modern SUs are cardiosafe and that since they have been used as comparators in other CVOTs, CVOTs of SUs are not required. CONCLUSION: Modern SUs can be considered a cardiosafe option for the management of patients with diabetes mellitus and CV disease; thus CVOTs among individuals with T2DM are not required.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Prova Pericial , Compostos de Sulfonilureia/uso terapêutico , Humanos , Resultado do Tratamento
19.
World J Diabetes ; 11(4): 126-136, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32313611

RESUMO

BACKGROUND: Obesity is a disease state with serious adverse metabolic complications, including glucose intolerance and type 2 diabetes that currently has no cure. Identifying and understanding roles of various modulators of body composition and glucose homeostasis is required for developing effective cures. Syndecan-1 (Sdc1) is a member of the heparan sulfate proteoglycan family that has mainly been investigated for its role in regulating proliferation and survival of epithelia and tumor cells, but little is known about its roles in regulating obesity and glucose homeostasis. AIM: To examine the role of Sdc1 in regulating body fat and glucose metabolism. METHODS: We used female wild type and Sdc1 knockout (Sdc1 KO) mice on BALB/c background and multiple methods. Metabolic measurements (rates of oxygen consumption, carbon dioxide production, respiratory exchange ratio and energy expenditure) were performed using an open-flow indirect calorimeter with additional features to measure food intake and physical activity. Glucose intolerance and insulin resistance were measured by established tolerance test methods. RESULTS: Although our primary goal was to investigate the effects of Sdc1 deficiency on body fat and glucose homeostasis, we uncovered that Sdc1 regulates multiple metabolic parameters. Sdc1KO mice have reduced body weight due to significant decreases in fat and lean masses under both chow and high fat diet conditions. The reduced body weight was not due to changes in food intakes, but Sdc1 KO mice exhibited altered feeding behavior as they ate more during the dark phase and less during the light phase than wild type mice. In addition, Sdc1 KO mice suffered from high rate of energy expenditure, glucose intolerance and insulin resistance. CONCLUSION: These results reveal critical multisystem and opposing roles for Sdc1 in regulating normal energy balance and glucose homeostasis. The results will have important implications for targeting Sdc1 to modulate metabolic parameters. Finally, we offer a novel hypothesis that could reconcile the opposing roles associated with Sdc1 deficiency.

20.
Am J Physiol Renal Physiol ; 318(6): F1500-F1512, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32281417

RESUMO

Acute kidney injury (AKI) due to cisplatin is a significant problem that limits its use as an effective chemotherapeutic agent. T cell receptor+CD4-CD8- double negative (DN) T cells constitute the major T cell population in the human and mouse kidney, express programmed cell death protein (PD)-1, and protect from ischemic AKI. However, the pathophysiological roles of DN T cells in cisplatin-induced AKI is unknown. In this study, wild-type mice were treated with cisplatin (30 mg/kg) or vehicle, and the effects on kidney DN T cell numbers and function were measured. In vitro experiments evaluated effects of kidney DN T cells on cisplatin-induced apoptosis and PD ligand 1 (PD-L1) in renal epithelial cells. Adoptive transfer experiments assessed the therapeutic potential of DN T cells during cisplatin-induced AKI. Our results show that kidney DN T cell population increased at 24 h and declined by 72 h after cisplatin treatment. Cisplatin treatment increased kidney DN T cell proliferation, apoptosis, CD69, and IL-10 expression, whereas CD62L, CD44, IL-17A, interferon-γ, and TNF-α were downregulated. Cisplatin treatment decreased both PD-1 and natural killer 1.1 subsets of kidney DN T cells with a pronounced effect on the PD-1 subset. In vitro kidney DN T cell coculture decreased cisplatin-induced apoptosis in kidney proximal tubular epithelial cells, increased Bcl-2, and decreased cleaved caspase 3 expression. Cisplatin-induced expression of PD ligand 1 was reduced in proximal tubular epithelial cells cocultured with DN T cells. Adoptive transfer of DN T cells attenuated kidney dysfunction and structural damage from cisplatin-induced AKI. These results demonstrate that kidney DN T cells respond rapidly and play a protective role during cisplatin-induced AKI.


Assuntos
Injúria Renal Aguda/prevenção & controle , Transferência Adotiva , Apoptose , Cisplatino , Células Epiteliais/imunologia , Túbulos Renais Proximais/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Subpopulações de Linfócitos T/transplante , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/patologia , Animais , Antígeno B7-H1/imunologia , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Modelos Animais de Doenças , Células Epiteliais/patologia , Túbulos Renais Proximais/patologia , Masculino , Camundongos Endogâmicos C57BL , Fenótipo , Subpopulações de Linfócitos T/imunologia
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