RESUMO
Background: Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is associated with oxidative stress (OS), which is the main risk factor for renal diseases. This study aimed to investigate the mechanisms responsible for renal injury in a hyperandrogenemic female rat model. Methods: This study was conducted from December 2019 to September 2021 at Shiraz Nephro-Urology Research Centre, Shiraz University of Medical Sciences (Shiraz, Iran). Thirty female Sprague-Dawley rats were randomly divided into three groups (n=10), namely control, sham, and dehydroepiandrosterone (DHEA). Plasma total testosterone, plasma creatinine (Cr), and blood urea nitrogen (BUN) levels were measured. In addition, total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), and histopathological changes in the ovaries and kidneys were determined. Data were analyzed using the GraphPad Prism software, and P<0.05 was considered statistically significant. Results: Plasma total testosterone levels increased by nine-fold in DHEA-treated rats compared to controls (P=0.0001). Administration of DHEA increased Cr and BUN levels and caused severe renal tubular cell injury. In addition, plasma and tissue (kidney and ovary) TAC levels decreased significantly, but TOS levels and OSI values were significantly increased (P=0.019). Significant damage to both glomerular and tubular parts of the kidney and ovarian follicular structure was observed in the DHEA group. Conclusion: Hyperandrogenemia caused systemic abnormalities through OS-related mechanisms and damaged renal and ovarian tissues. DHEA treatment in rat models is recommended to study the mechanisms that mediate PCOS-associated renal injury.
Assuntos
Hiperandrogenismo , Nefropatias , Síndrome do Ovário Policístico , Humanos , Ratos , Feminino , Animais , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Ratos Sprague-Dawley , Hiperandrogenismo/complicações , Hiperandrogenismo/metabolismo , Hiperandrogenismo/patologia , Estresse Oxidativo , Rim , Antioxidantes/metabolismo , Nefropatias/patologia , Testosterona/metabolismo , Desidroepiandrosterona/metabolismoRESUMO
BACKGROUND: Alcohol consumption can cause hepatitis and long-term cirrhosis of the liver. The aim of this study was to evaluate the protective effects of curcumin (CUR) and ursodeoxycholic acid (UDCA) alone and together in the prevention and treatment of liver damage caused by overuse of ethanol. METHODS: Adult Wistar rats were divided into 8 groups of 5, including the control group and various combinations of ethanol, CUR and UDCA groups. Twenty-eight days after the oral treatment, serum levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and Arginase I (ArgI) as well as serum levels of Albumin (Alb), total protein (TP) and Blood Urea Nitrogen (BUN) were measured, and liver tissue was evaluated histopathologically. RESULTS: The solo administration of CUR, UDCA and CUR+UDCA had no effect on the blood parameters and liver tissue compared to the control group (p>0.05). The solo administration of CUR and UDCA in ethanol-treated rats significantly reduced ALT, AST, ALP, GGT, ArgI and BUN levels (p<0.05), while the solo administration increased Alb and TP levels compared to the ethanol group (p<0.05). In these groups, a significant decrease in cell necrosis and local inflammation of hepatocytes was observed, and the liver damage was mild. However, co-administration of ethanol, CUR and UDCA made significantly greater decrease in ALT, AST, ALP, GGT, ArgI and BUN levels (p>0.05), while the co-administration greatly increased Alb and TP levels compared to the ethanol group (p<0.05). Histopathologically, a decrease in structural changes in liver tissue and inflammation was observed, resulting in the improvement of liver tissue. CONCLUSION: The solo administration of CUR and UDCA could reduce ethanol-induced liver damage in rats and improve liver's serum and blood parameters. However, the coadministration of CUR and UDCA has a greater efficacy.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Curcumina , Animais , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Curcumina/farmacologia , Etanol/toxicidade , Ratos , Ratos Wistar , Ácido UrsodesoxicólicoRESUMO
BACKGROUND: There is little descriptive data on Stenotrophomonas maltophilia hospital-acquired pneumonia (HAP) in critically ill patients. The optimal modalities of antimicrobial therapy remain to be determined. Our objective was to describe the epidemiology and prognostic factors associated with S. maltophilia pneumonia, focusing on antimicrobial therapy. METHODS: This nationwide retrospective study included all patients admitted to 25 French mixed intensive care units between 2012 and 2017 with hospital-acquired S. maltophilia HAP during intensive care unit stay. Primary endpoint was time to in-hospital death. Secondary endpoints included microbiologic effectiveness and antimicrobial therapeutic modalities such as delay to appropriate antimicrobial treatment, mono versus combination therapy, and duration of antimicrobial therapy. RESULTS: Of the 282 patients included, 84% were intubated at S. maltophilia HAP diagnosis for duration of 11 [5-18] days. The Simplified Acute Physiology Score II was 47 [36-63], and the in-hospital mortality was 49.7%. Underlying chronic pulmonary comorbidities were present in 14.1% of cases. Empirical antimicrobial therapy was considered effective on S. maltophilia according to susceptibility patterns in only 30% of cases. Delay to appropriate antimicrobial treatment had, however, no significant impact on the primary endpoint. Survival analysis did not show any benefit from combination antimicrobial therapy (HR = 1.27, 95%CI [0.88; 1.83], p = 0.20) or prolonged antimicrobial therapy for more than 7 days (HR = 1.06, 95%CI [0.6; 1.86], p = 0.84). No differences were noted in in-hospital death irrespective of an appropriate and timely empiric antimicrobial therapy between mono- versus polymicrobial S. maltophilia HAP (p = 0.273). The duration of ventilation prior to S. maltophilia HAP diagnosis and ICU length of stay were shorter in patients with monomicrobial S. maltophilia HAP (p = 0.031 and p = 0.034 respectively). CONCLUSIONS: S. maltophilia HAP occurred in severe, long-stay intensive care patients who mainly required prolonged invasive ventilation. Empirical antimicrobial therapy was barely effective while antimicrobial treatment modalities had no significant impact on hospital survival. TRIAL REGISTRATION: clinicaltrials.gov, NCT03506191.
Assuntos
Infecções por Bactérias Gram-Negativas/terapia , Pneumonia Associada a Assistência à Saúde/terapia , Unidades de Terapia Intensiva/tendências , Pneumonia Bacteriana/terapia , Stenotrophomonas maltophilia/isolamento & purificação , Idoso , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Feminino , Seguimentos , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/mortalidade , Pneumonia Associada a Assistência à Saúde/diagnóstico , Pneumonia Associada a Assistência à Saúde/mortalidade , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/mortalidade , Estudos Retrospectivos , Stenotrophomonas maltophilia/efeitos dos fármacos , Resultado do TratamentoRESUMO
OBJECTIVES: This research aims at studying the neuroendocrine effects of music on creating morphine dependence in mice using conditioned place preference (CPP). METHODS: The mice treated with 10 mg/kg morphine subcutaneously, fast music and slow music. Morphine was used to create dependence. In order to recognize the morphine rewarding effects, CPP technique was used. In the conditioning stage that lasted for 8 days, different groups of mice, after receiving the treatment were randomly placed in compartment for 30 minutes. The post-conditioning stage included the fourth day, the ninth day, the 12th day and the 16th day. RESULTS: Comparing place preference between morphine group and the control group, a significant increase (p<0.05) was observed in the place preference of morphine group, while a significant decrease (p<0.05) was demonstrated in the place preferences of morphine + taxi girl music group compared with morphine group alone. In addition morphine + alone in the rain music group demonstrated a significantly increased conditioned place preference (p<0.05) compared with the morphine group. CONCLUSIONS: Alone in the rain music acts as a positive pleasant emotion increasing the dopaminergic activity in the Nucleus Accumbens (NAc) and Ventral Tegmental Area (VTA) and through associated learning mechanisms of reward-related behavior increases morphine addiction. However, taxi girl music may act as unpleasant experiences producing negative emotions and reducing morphine addiction.
Assuntos
Comportamento Animal/efeitos dos fármacos , Condicionamento Psicológico/efeitos dos fármacos , Dependência de Morfina/fisiopatologia , Morfina/farmacologia , Música , Recompensa , Analgésicos Opioides/farmacologia , Animais , Comportamento Animal/fisiologia , Comportamento de Escolha/efeitos dos fármacos , Comportamento de Escolha/fisiologia , Condicionamento Psicológico/fisiologia , Masculino , Camundongos , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/fisiologia , Distribuição Aleatória , Área Tegmentar Ventral/efeitos dos fármacos , Área Tegmentar Ventral/fisiologiaRESUMO
BACKGROUND: In the present study, the oral effect of lead acetate on the parameters related to sexual behavior as well as changes in the level of testosterone hormone in adult male rats have been investigated. MATERIALS AND METHODS: Forty adult male Wistar rats were allocated into five equal groups. The control group received nothing, the sham group received distilled water and the experimental groups received 25, 50 and 100mg/kg lead acetate orally, respectively for 28 days. The changes in testosterone hormone level and following sexual behavior parameters were investigated: mount latency (ML), intromission latency (IL), post ejaculatory interval (PEI), mount frequency (MF), ejaculatory latency (EL), intromission frequency (IF), copulatory efficacy (CE) and intercopulatory interval (ICI). RESULTS: The levels of testosterone hormone in the groups that received 50 and 100 mg/kg lead acetate showed significant decreases in compared to the control group. Additionally, the same doses of lead acetate caused significant increases in ML, IL, PEI and EL compared to the control group. No significant change was observed in MF, but a significant decrease was detected in IF and CE in the experimental group that received 100 mg/kg lead acetate when compared with the control group. ICI showed significant decreases in the experimental groups that received 50 and 100 mg/kg lead acetate compared to the control group. CONCLUSION: It can be concluded that ingestion of lead acetate affects some behavioral activities and the testosterone level of male rats. These effects might be conducted via the alteration of leydig cells following lead acetate poisoning.