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1.
Cochrane Database Syst Rev ; 6: CD013106, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31232459

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is a liver disease caused by hepatitis B virus, which may lead to serious complications such as cirrhosis and hepatocellular carcinoma. People with HBV infection may also have coinfections including HIV and other hepatitis viruses (hepatitis C or D), and coinfections may increase the risk of all-cause mortality. Chronic HBV infection increases morbidity, psychological stress, and it is an economic burden on people with chronic hepatitis B and their families. Radix Sophorae flavescentis, a herbal medicine, is administered mostly in combination with other drugs or herbs. It is believed that it decreases discomfort and prevents the replication of the virus in people with chronic hepatitis B. However, the benefits and harms of Radix Sophorae flavescentis on patient-centred outcomes are unknown, and its wide usage has never been established with rigorous review methodology. OBJECTIVES: To assess the benefits and harms of Radix Sophorae flavescentis versus other drugs or herbs in people with chronic hepatitis B. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and seven other databases to December 2018. We also searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp), ClinicalTrials.gov (www.clinicaltrials.gov/), and the Chinese Clinical Trial Registry for ongoing or unpublished trials to December 2018. SELECTION CRITERIA: We included randomised clinical trials, irrespective of publication status, language, or blinding, comparing Radix Sophorae flavescentis versus other drugs or herbs for people with chronic hepatitis B. In addition to chronic hepatitis B, participants could also have had cirrhosis, hepatocellular carcinoma, or any other concomitant disease. We excluded polyherbal blends containing Radix Sophorae flavescentis. We allowed cointerventions when the cointerventions were administered equally to all intervention groups. DATA COLLECTION AND ANALYSIS: Review authors in pairs individually retrieved data from published reports and after correspondence with investigators. Our primary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our secondary outcomes were hepatitis B-related mortality, hepatitis B-related morbidity, and adverse events considered 'not to be serious'. We presented the meta-analysed results as risk ratios (RR) with 95% confidence intervals (CI). We assessed the risk of bias using domains with predefined definitions. We conducted Trial Sequential Analyses to control the risks of random errors. We used GRADE methodology to evaluate our certainty in the evidence (i.e. "the extent of our confidence that the estimates of the effect are correct or are adequate to support a particular decision or recommendation"). MAIN RESULTS: We included 10 randomised clinical trials with 898 participants. We judged all trials at high risk of bias. The trials covered oral capsules, intravenous infusion, intramuscular injection, and acupoint (a specifically chosen site of acupuncture) injection of Radix Sophorae flavescentis with a follow-up period from 1 to 12 months. The drugs being used as a comparator were lamivudine, adefovir, interferon, tiopronin, thymosin, or other Chinese herbs. Two trials included children up to 14 years old. Participants in one trial had cirrhosis in chronic hepatitis B. None of the trials reported all-cause mortality, health-related quality of life, serious adverse events, hepatitis B-related mortality, or morbidity. We are uncertain as to whether Radix Sophorae flavescentis has a beneficial or harmful effect on adverse events considered 'not to be serious' (RR 0.86, 95% CI 0.42 to 1.75; I2 = 0%; 2 trials, 163 participants; very low-certainty evidence), as well as if it decreases or increases the proportion of participants with detectable HBV-DNA (RR 1.14, 95% CI 0.81 to 1.63; I2 = 92%; 8 trials, 719 participants; very low-certainty evidence). Radix Sophorae flavescentis showed a reduction in the proportion of participants with detectable hepatitis B virus e-antigen (HBeAg) (RR 0.86, 95% CI 0.75 to 0.98; I2 = 43%; 7 trials, 588 participants; very low-certainty evidence).Two of the 10 trials were not funded, and one received academic funding. The remaining seven trials provided no information on funding.The randomisation process in another 109 trials was insufficiently reported to ensure the inclusion of any of these studies in our review. AUTHORS' CONCLUSIONS: The included trials lacked data on all-cause mortality, health-related quality of life, serious adverse events, hepatitis-B related mortality, and hepatitis-B related morbidity. The evidence on the effect of Radix Sophorae flavescentis on the proportion of participants with adverse events considered 'not to be serious' and on the proportion of participants with detectable HBV-DNA is still unclear. We advise caution regarding the results of Radix Sophorae flavescentis showing a reduction in the proportion of people with detectable HBeAg because the trials were at high risk of bias, because it is a non-validated surrogate outcome, and because of the very low certainty in the evidence. As we were unable to obtain information on a large number of studies regarding their trial design, we were deterred from including them in our review. Undisclosed funding may have influence on trial results and lead to poor design of the trial. In view of the wide usage of Radix Sophorae flavescentis, we need large, unbiased, high-quality placebo-controlled randomised trials assessing patient-centred outcomes.

2.
Complement Ther Med ; 44: 32-43, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31126573

RESUMO

OBJECTIVE: To assess the effects and associated risks of Chinese herbal medicine (CHM) for diabetic foot ulcer (DFU). METHODS: We systematically searched seven electronic databases for randomized controlled trials (RCTs) about Chinese herbal medicines for treating diabetic foot ulcers. The methodological quality of RCTs was assessed by the Cochrane risk of bias tool. Data was synthesized using review manager (RevMan) 5.3. Meta-analysis was conducted if the data were available. A summary of finding table was generated by The GRADEpro Guideline Development Tool (GDT) online. RESULTS: Forty-nine RCTs, all conducted in China, involving 3646 participants were included. Most of the included trials had unclear or high risk of bias. Twenty-six trials could be pooled in five Meta-analyses, the remaining trials could not be pooled due to the obvious clinical heterogeneity. Only low evidence showed CHM therapy may have 42%-60.4% participants healed completely after treatment, approximately twice (RR 1.42-1.76) as much as the healed rates in conventional therapy (or plus hot water foot bath) group. Majority of the included trials reported benefit of CHM group on shortening healing time (4-23 days) and reducing ulcer wound size (at least 2 cm2). No serious adverse events were reported related to the medication in all trials. CONCLUSION: Weak evidence showed benefit of CHM as add-on treatment of conventional therapy on increasing number of ulcer heals in patients with DFU. That's about twice the healing rate of the conventional treatment (or plus hot water foot bath) group. With insufficient information, we could not draw confirmative conclusion on safety of CHM administration. These findings need to be tested in further large, rigorous trials.

3.
Cochrane Database Syst Rev ; 4: CD013089, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30941748

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection, a liver disease caused by hepatitis B virus, may lead to serious complications such as cirrhosis and hepatocellular carcinoma. People with HBV infection may have co-infections including HIV and other hepatitis viruses (hepatitis C or D), and co-infection may increase the risk of all-cause mortality. Chronic HBV infection increases morbidity and psychological stress and is an economic burden on people with chronic hepatitis B and their families. Radix Sophorae flavescentis, an herbal medicine, is administered most often in combination with other drugs or herbs. It is believed that it decreases discomfort and prevents replication of the virus in people with chronic hepatitis B. However, the benefits and harms of Radix Sophorae flavescentis for patient-centred outcomes are not known, and its wide usage has never been established with rigorous review methodology. OBJECTIVES: To assess the benefits and harms of Radix Sophorae flavescentis versus placebo or no intervention in people with chronic hepatitis B. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), Wanfang Data, and SinoMed. We also searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp), ClinicalTrials.gov (www.clinicaltrials.gov/), and the Chinese Clinical Trial Registry for ongoing or unpublished trials. We conducted the last search in December 2018. SELECTION CRITERIA: We included randomised clinical trials, irrespective of publication status, language, or blinding, comparing Radix Sophorae flavescentis versus no intervention or placebo in people with chronic hepatitis B. We excluded polyherbal blends containing Radix Sophorae flavescentis. We allowed co-interventions when the co-interventions were administered equally to all intervention groups. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. Review authors in pairs retrieved data from individual published reports and after correspondence with investigators. Our primary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our secondary outcomes were hepatitis B-related mortality, hepatitis B-related morbidity, and adverse events considered 'not to be serious'. We presented meta-analysed results as risk ratios (RRs) with 95% confidence intervals (CIs). We assessed risk of bias using domains with pre-defined definitions. We conducted Trial Sequential Analyses to control the risk of random errors. We used GRADE methodology to evaluate our certainty in the evidence (i.e. "the extent of our confidence that the estimates of the effect are correct or are adequate to support a particular decision or recommendation"). MAIN RESULTS: We included 35 randomised clinical trials with 3556 participants. One trial compared Radix Sophorae flavescentis with placebo; the remaining 34 trials compared effects of Radix Sophorae flavescentis in addition to a co-intervention versus the same co-intervention. The included trials assessed heterogenous forms and ways of administering Radix Sophorae flavescentis (e.g. oral capsules, oral tablets, intravenous infusion, intramuscular injection, acupoint (a specifically chosen site of acupuncture) injection) with treatment duration of 1 to 24 months. Two of the trials included children up to 14 years old. Participants in two trials had cirrhosis in addition to chronic hepatitis B. All trials were assessed at high risk of bias, and certainty of the evidence for all outcomes was very low.Only one of the 35 trials assessed mortality; no deaths occurred. Ten trials assessed serious adverse events; no serious adverse events occurred. None of the trials reported health-related quality of life, hepatitis B-related mortality, or morbidity. Adverse events considered 'not to be serious' was an outcome in 19 trials; nine of these trials had zero events in both groups. Radix Sophorae flavescentis versus placebo or no intervention showed no difference in effects on adverse events considered 'not to be serious' (RR 1.10, 95% CI 0.76 to 1.59; I² = 49%; 10 trials, 1050 participants). Radix Sophorae flavescentis showed a reduction in the proportion of participants with detectable HBV-DNA (RR 0.61, 95% CI 0.55 to 0.68; I² = 56%; 29 trials, 2914 participants) and in the proportion of participants with detectable HBeAg (hepatitis B e-antigen) (RR 0.71, 95% CI 0.66 to 0.76; I² = 19%; 20 trials, 2129 participants).Seven of the 35 randomised clinical trials received academic funding from government or hospital. Four trials received no funding. The remaining 24 trials provided no information on funding.Additionally, 432 trials lacked the methodological information needed to ensure inclusion of these trials in our review. AUTHORS' CONCLUSIONS: The included trials lacked data on health-related quality of life, hepatitis B-related mortality, and hepatitis B-related morbidity. The effects of Radix Sophorae flavescentis on all-cause mortality and on the proportion of participants with serious adverse events and adverse events considered 'not to be serious' remain unclear. We advise caution in interpreting results showing that Radix Sophorae flavescentis reduced the proportion of people with detectable HBV-DNA and detectable HBeAg because the trials reporting on these outcomes are at high risk of bias and both outcomes are non-validated surrogate outcomes. We were unable to obtain information on the design and conduct of a large number of trials; therefore, we were deterred from including them in our review. Undisclosed funding may influence trial results and may lead to poor trial design. Given the wide usage of Radix Sophorae flavescentis, we need large, unbiased, high-quality placebo-controlled randomised trials in which patient-centred outcomes are assessed.


Assuntos
Medicamentos de Ervas Chinesas , Hepatite B Crônica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Sophora/química , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
4.
J Altern Complement Med ; 25(9): 957-973, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30883184

RESUMO

Objectives: To introduce a conceptualized visual error matrix tool to overview the validity of evidence by taking Radix Sophorae flavescentis for chronic hepatitis B as an example and to propose recommendations for improving clinical trial design and evidence quality. Methods: The randomized clinical trials and reviews were collected during the conduct of a Cochrane systematic review. The authors used a visual error matrix tool to overview the evidence validity by looking at systematic, random, and design error risks. Systematic errors were measured by the type of evidence. Random errors were expressed by the standard error (SE). Design errors were assessed on the priority of outcome measures and the adequacy of nine design components. Three-dimensional error matrix on benefits and harms were then constructed. Results: The authors included 6 meta-analyses and 28 randomized clinical trials. In terms of systematic errors, all reviews were at critically low quality, and all included randomized trials were assessed at high risk of bias. On this systematic error level, they found that there was substantial risk of random errors regarding all-cause mortality (SE 0.36), moderate risk regarding serious adverse events (SE 0.22), substantial risk regarding nonserious adverse events (SE 0.35), and small to moderate risk regarding surrogate outcomes such as detectable hepatitis B e-antigen (HBeAg) and detectable hepatitis B virus (HBV)-DNA (SE 0.16 and 0.21). No study reported results on quality of life, hepatitis B-related mortality, and morbidity. The design error risks were mainly misuse of outcomes (14/34), inadequate selection of participants (5/34), inadequate description of intervention (11/34) and control (9/34), single-center setting (33/34), and unclear study objective regarding superiority, equivalence, or noninferiority. Conclusion: The current evidence on Radix S. flavescentis for chronic hepatitis B showed high risks of systematic errors, moderate or high risks of random errors, and high risks of design errors. These findings suggest that more randomized trials at minimum risks of all three errors are needed to assess the benefits and harms of Radix S. flavescentis for chronic hepatitis B. The visual error matrix tool provides an overview of the reliability of evidence and may assist in design and conduct of future randomized trials.

6.
Complement Ther Med ; 41: 10-22, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30477824

RESUMO

OBJECTIVE: To evaluate the benefits and harms of pediatric Tui Na as a non-pharmaceutical Chinese medicine therapy for acute diarrhea in children under 5 years of age. DESIGN: Systematic review and meta-analysis of randomized clinical trials. METHODS: We searched seven major English and Chinese databases from their inception to January 2018 for randomized clinical trials (RCTs) comparing pediatric Tui Na therapy with conventional medicine (montmorillonite/diosmectite or probiotics used alone or in combination). Two authors extracted data and assessed the Cochrane risk of bias, independently. The primary outcomes are clinical cure rate and diarrhea duration from admission to the cessation of diarrhea. 'Clinical cure' is defined as the frequency, timing and character of stool back to normal status, as well as disappearance of diarrhea symptoms. We present dichotomous data as risk ratio (RR), and continuous data as mean difference (MD) with their 95% confidence interval (CI). We used the Cochrane's Revman software (v.5.3) for data analysis. Trial sequential analysis (TSA) was applied to calculate the required sample size in a meta-analysis and detect the robustness of the results. The GRADEpro was used to generate a summary of finding table. RESULTS: Totally 26 RCTs were included, involving 2410 children with acute diarrhea. Most of the included trials had high or unclear risk of bias in terms of random sequence generation, blinding, and incomplete outcome reporting. The pooled results demonstrated that pediatric Tui Na was superior to montmorillonite after three-session treatment (RR 1.45, 95% CI 1.29-1.62, n = 772, 10 trials), and also superior to montmorillonite combined with probiotics after three-session treatment (RR 2.04, 95% CI 1.49-2.78, n = 533, 7 trials) and after six-session treatment (RR 1.52, 95% CI 1.34-1.73, n = 631, 5 trials) in improving clinical cure rate. Pediatric Tui Na significantly decreased the duration of acute diarrhea (hrs) (MD -0.40 h, 95% CI -15.31 to -5.48 h, n = 410, 6 trials) and daily stool frequency (MD -1.71times, 95% CI -2.37 to -1.04, n = 217, 3 trials, after three-session treatment). No adverse event related to pediatric Tui Na was reported in the included trials. The quality of evidence of included trials was generally moderate to low. TSA for cure rate demonstrated that the pooled data reached a sufficient power regarding both numbers of trials and participants. CONCLUSIONS: This review shows pediatric Tui Na appears to be effective and safe in improving clinical cure rate and shortening diarrhea duration in childhood aged less than five years of age with acute diarrhea. However, rigorously designed well-reported RCTs are warranted to confirm the findings.

7.
BMC Complement Altern Med ; 18(1): 260, 2018 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-30257693

RESUMO

BACKGROUND: Due to limitations of conventional medicine for atopic eczema (AE), complementary and alternative medicine (CAM) is widely used as an alternative, maintaining, or simultaneous treatment for AE. We aimed to evaluate the beneficial and harmful effects of CAM for children with AE under 14 years old. METHODS: We searched for randomized trials on CAM in 12 Chinese and English databases from their inception to May 2018. We included children (< 14 years) diagnosed with AE, who received CAM therapy alone or combined with conventional medicine. We extracted data, and used the Cochrane "Risk of bias" tool to assess methodological quality. Effect was presented as relative risk (RR) or mean difference (MD) with 95% confidence interval (CI) using RevMan 5.3. RESULTS: Twenty-four randomized controlled trials involving 2233 children with AE were included. Methodological quality was of unclear or high risk of bias in general. The trials tested 5 different types of CAM therapies, including probiotics, diet, biofilm, borage oil, and swimming. Compared to placebo, probiotics showed improved effect for the SCORAD index (MD 9.01, 95% CI 7.12-10.90; n = 5). For symptoms and signs such as itching, skin lesions, CAM combined with usual care was more effective for symptom relief ≥95% (RR 1.47, 95% CI 1.30-1.68; n = 8), and for ≥50% symptoms improvement (RR 1.34, 1.25-1.45; n = 9) compared to usual care. There was no statistic significant difference between CAM and usual care on ≥95% improvement or ≥ 50% improvement of symptoms. However, swimming, diet and biofilm showed improvement of clinical symptoms compared with usual care. At follow-up of 8 weeks to 3 years, CAM alone or combined with usual care showed lower relapse rate (RR 0.38, 0.28-0.51, n = 2; RR 0.31, 0.24-0.40, n = 7; respectively) compared to usual care. Twelve out of 24 trials reported no occurrence of severe adverse events. CONCLUSIONS: Low evidence demonstrates that some CAM modalities may improve symptoms of childhood AE and reduce relapse rate. Safety remains unclear due to insufficient reporting. Further well-designed randomized trials are needed to confirm the potential beneficial effect and to establish safety use.


Assuntos
Terapias Complementares , Dermatite Atópica/terapia , Adolescente , Viés , Criança , Pré-Escolar , Dermatite Atópica/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Resultado do Tratamento
8.
Int J Mol Med ; 34(5): 1293-300, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25175177

RESUMO

In the diabetic state, the local rennin-angiotensin system (RAS) is activated in the pancreas, and is strongly associated with islet dysfunction. The angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7) [Ang(1-7)]/Mas axis is a protective, negative regulator of the classical renin-angiotensin system. In this study, we assessed the role of the ACE2/Ang(1­7)/Mas axis in pancreatic ß cell survival and function. ACE2 knockout and wild-type mice were fed a high-fat diet for 16 weeks. We then performed terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, and determined the expression levels of interleukin-1ß (IL-1ß) and inducible nitric oxide synthase (iNOS) in the pancreatic islets. The effects of Ang(1-7) or Mas receptor silencing on endothelial function were assessed in MS-1 cells. MIN6 cells were then co-cultured with the MS-1 cells to evaluate the effects of ACE2 on insulin secretion. The ACE2 knockout mice were more susceptible than the wild-type mice to high-fat diet-induced ß cell dysfunction. The TUNEL-positive area of the pancreatic islets and the expression levels of IL-1ß and iNOS were markedly increased in the ACE2 knockout mice compared with their wild-type littermates. The Mas-silenced MS-1 cells were more sensitive to palmitate-induced dysfunction and apoptosis in vitro. Ang(1-7) increased the activity of the Akt/endothelial NOS/nitric oxide (NO) pathway in the MS-1 cells, protected MIN6 cells against palmitate-induced apoptosis, and improved MIN6 insulin secretory function in the co-culture system. In conclusion, this study demonstrates that the ACE2/Ang(1-7)/Mas axis is a potential target for protecting the funcion of ß cells by improving the function of islet microvascular endothelial cells.


Assuntos
Angiotensina I/metabolismo , Células Endoteliais/metabolismo , Células Secretoras de Insulina/metabolismo , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Angiotensina I/genética , Animais , Linhagem Celular , Dieta Hiperlipídica , Inativação Gênica , Marcação In Situ das Extremidades Cortadas , Insulina/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Ilhotas Pancreáticas/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Fragmentos de Peptídeos/genética , Peptidil Dipeptidase A/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/metabolismo
9.
J Diabetes Res ; 2014: 391476, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24804268

RESUMO

This study aimed to explore the effect of angiotensin (1-7) (Ang (1-7)) on palmitate-induced apoptosis in islet endothelial cells and the mechanism of action. MS-1 cells were treated with palmitate in the presence or absence of Ang (1-7). The percentage of apoptotic cells was determined by DNA fragmentation and flow cytometry. Reactive oxygen species (ROS) production was measured using a Reactive Oxygen Species Assay Kit. Expression of AKT, eNOS, C-Jun N-terminal kinase (JNK), and p38 was detected by western blotting. Compared with palmitate treated group, palmitate-induced apoptosis was decreased in MS-1 cells which were preincubated with Ang (1-7) (P < 0.05). Palmitate decreased the phosphorylation of AKT and eNOS, and Ang (1-7) increased the phosphorylation of these kinases (P < 0.05), with a concomitant reduction in MS-1 cells apoptosis. Ang (1-7) also inhibited the palmitate-induced ROS production and attenuated the apoptosis-related signaling molecule JNK and p38 activation (all P < 0.05). PI3K/AKT, eNOS, p38 MAPK, and JNK inhibitors blocked the antilipoapoptosis of Ang (1-7) (all P < 0.05). Our findings suggest that Ang (1-7) reduces palmitate-induced islet endothelial cells apoptosis. AKT/eNOS/NO signaling and JNK and p38 pathway are involved in the Ang (1-7)-mediated modulation of islet endothelial cells lipoapoptosis.


Assuntos
Angiotensina I/farmacologia , Apoptose/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Ilhotas Pancreáticas/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Fragmentos de Peptídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/agonistas , Angiotensina I/antagonistas & inibidores , Angiotensina II/análogos & derivados , Angiotensina II/farmacologia , Animais , Anti-Hipertensivos/antagonistas & inibidores , Anti-Hipertensivos/farmacologia , Linhagem Celular Transformada , Endotélio Vascular/enzimologia , Endotélio Vascular/metabolismo , Ativação Enzimática/efeitos dos fármacos , Ácidos Graxos não Esterificados/antagonistas & inibidores , Ácidos Graxos não Esterificados/metabolismo , Ilhotas Pancreáticas/irrigação sanguínea , Ilhotas Pancreáticas/metabolismo , MAP Quinase Quinase 4/antagonistas & inibidores , MAP Quinase Quinase 4/química , MAP Quinase Quinase 4/metabolismo , Camundongos , Microvasos/efeitos dos fármacos , Microvasos/enzimologia , Microvasos/metabolismo , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/química , Ácido Palmítico/antagonistas & inibidores , Ácido Palmítico/metabolismo , Fragmentos de Peptídeos/antagonistas & inibidores , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas/agonistas , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Acoplados a Proteínas-G/agonistas , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/química , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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