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1.
Materials (Basel) ; 17(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38473584

RESUMO

Nanocomposites based on silver nanoparticles and chitosan present important advantages for medical applications, showing over time their role in antibacterial evaluation. This work presents the comparative study of two chemical synthesis procedures of nanocomposites, based on trisodium citrate dihydrate and sodium hydroxide, using various chitosan concentrations for a complex investigation. The nanocomposites were characterized by AFM and DLS regarding their dimensions, while FT-IR and UV-VIS spectrometry were used for the optical properties and to reveal the binding of silver nanoparticles with chitosan. Their antibacterial effect was determined using a disk diffusion method on two bacteria strains, E. coli and S. aureus. The results indicate that, when using both methods, the nanocomposites obtained were below 100 nm, yet the antibacterial effect proved to be stronger for the nanocomposites obtained using sodium hydroxide. Furthermore, the antibacterial effect can be related to the nanocomposites' sizes, since the smallest dimension nanocomposites exhibited the best bacterial growth inhibition on both bacteria strains we tested and for both types of silver nanocomposites.

2.
J Clin Med ; 12(19)2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37834966

RESUMO

BACKGROUND: As the COVID-19 pandemic evolved, concerns grew about its impact on pregnant women. This study aimed to determine how SARS-CoV-2 affects pregnancy, birth, and newborns, in order to identify vulnerable individuals and provide proper care. METHODS: This is a retrospective case-control study of 398 pregnant women who delivered at the Emergency Clinical County Hospital in Sibiu, Romania from 1 February 2020 to 31 March 2022. Patients were initially grouped and compared based on their RT-PCR SARS-CoV-2 test results into the COVID group (cases) (N = 199) and non-COVID group (control) (N = 199). The COVID cases were further divided and compared according to the pre-Delta (N = 105) and Delta/Omicron (N = 94) SARS-CoV-2 variants. COVID cases and control groups were compared to identify correlations between sociodemographic factors, pregnancy outcomes, and SARS-CoV-2 infection. The same comparisons were performed between pre-Delta and Delta/Omicron groups. RESULTS: There were no significant differences concerning maternal residence, while educational level and employment proportion were higher among the positively tested patients. No significant differences were found for neonatal and pregnancy complications between COVID cases and control groups. Except for a lower mean gestational age, no significant differences were found between pre-Delta and Delta/Omicron periods. The maternal mortality in the infected group was 0.5% (1 case). CONCLUSIONS: Our study showed that SARS-CoV-2 infection at birth did not significantly affect maternal and neonatal outcomes, not even considering the SARS-CoV-2 strain.

3.
Materials (Basel) ; 16(15)2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37569948

RESUMO

The size of silver nanoparticles plays a crucial role in their ultimate application in the medical and industrial fields, as their efficacy is enhanced by decreasing dimensions. This study presents two chemical synthesis procedures for obtaining silver particles and compares the results to a commercially available Ag-based product. The first procedure involves laboratory-based chemical reduction using D-glucose (C6H12O6) and NaOH as reducing agents, while the second approach utilizes trisodium citrate dehydrate (C6H5Na3O7·2H2O, TSC). The Ag nanoparticle suspensions were examined using FT-IR and UV-VIS spectroscopy, which indicated the formation of Ag particles. The dimensional properties were investigated using Atomic Force Microscopy (AFM) and confirmed by Dynamic Light Scattering (DLS). The results showed particle size from microparticles to nanoparticles, with a particle size of approximately 60 nm observed for the laboratory-based TSC synthesis approach.

4.
In Vivo ; 37(4): 1914-1919, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37369472

RESUMO

BACKGROUND/AIM: Catastrophic antiphospholipid syndrome (CAPS) may be the first manifestation ("de novo") of antiphospholipid syndrome (APS) or a complication in the clinical course of patients known to have this syndrome. Approximately 40% of patients had an associated autoimmune disease, mainly, systemic lupus erythematosus (SLE). The trigger can be one of the following: infections, surgical interventions, neoplasms, pregnancy, discontinuation of anticoagulant treatment, and others. CAPS is a medical emergency in which early identification and prompt initiation of aggressive therapy is extremely important. According to the Guidelines for the use of Therapeutic Apheresis in Clinical Practice developed by the American Society for Apheresis (ASFA), last updated in April 2023, in CAPS, the indication for therapeutic plasma exchange (TPE) is category I, grade 2C. CASE REPORT: We present a case of probable CAPS secondary to systemic lupus erythematosus (SLE) in an elderly patient in whom clinical and biological improvement was achieved through a multidisciplinary approach and prompt initiation of TPE. Because TPE is considered first-line therapy in CAPS, we initiated the procedure as soon as the attending rheumatologist raised this suspicion. Four plasmapheresis sessions were performed in the Intensive Care Unit. We used TPE by membrane filtration. Following the therapeutic intervention with TPE, corticotherapy (Solumedrol in puls-therapy), cyclophosphamide and anticoagulant treatment, the evolution was favourable, with clinical and biological improvement. CONCLUSION: The prompt initiation of TPE, because of the suspicion of CAPS, increases the chances of a favourable evolution.


Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Humanos , Idoso , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Síndrome Antifosfolipídica/complicações , Troca Plasmática , Doença Catastrófica/terapia , Plasmaferese , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia , Anticoagulantes/uso terapêutico
5.
Molecules ; 28(5)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36903462

RESUMO

Hundreds of the plants have been explored and evaluated for antioxidant and anti-amnesic activities, so far. This study was designed to report the biomolecules of Pimpinella anisum L. for the said activities. The aqueous extract of dried P. anisum seeds was fractionated via column chromatography and the fractions so obtained were assessed for the inhibition of acetylcholinesterase (AChE) via in vitro analysis. The fraction which best inhibited AChE was so named as the P. anisum active fraction (P.aAF). The P.aAF was then chemically analyzed via GCMS, which indicated that oxadiazole compounds were present in it. The P.aAF was then administered to albino mice to conduct the in vivo (behavioral and biochemical) studies. The results of the behavioral studies indicated the significant (p < 0.001) increase in inflexion ratio, by the number of hole-pokings through holes and time spent in a dark area by P.aAF treated mice. Biochemical studies demonstrated that the oxadiazole present in P.aAF on one hand presented a noteworthy reduction in MDA and the AChE level and on the other hand promoted the levels of CAT, SOD and GSH in mice brain. The LD50 for P.aAF was calculated as 95 mg/Kg/p.o. The findings thus supported that the antioxidant and anticholinesterase activities of P. anisum are due to its oxadiazole compounds.


Assuntos
Inibidores da Colinesterase , Pimpinella , Camundongos , Animais , Inibidores da Colinesterase/farmacologia , Antioxidantes/farmacologia , Pimpinella/química , Acetilcolinesterase/metabolismo , Extratos Vegetais/farmacologia , Encéfalo/metabolismo
6.
Int J Mol Sci ; 23(10)2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35628585

RESUMO

Silver nanoparticles have been intensively studied over a long period of time because they exhibit antibacterial properties in infection treatments, wound healing, or drug delivery systems. The advantages that silver nanoparticles offer regarding the functionalization confer prolonged stability and make them suitable for biomedical applications. Apart from functionalization, silver nanoparticles exhibit various shapes and sizes depending on the conditions used through their fabrications and depending on their final purpose. This paper presents a review of silver nanoparticles with respect to synthesis procedures, including the polluting green synthesis. Currently, the most commonly used characterization techniques required for nanoparticles investigation in antibacterial treatments are described briefly, since silver nanoparticles possess differences in their structure or morphology.


Assuntos
Nanopartículas Metálicas , Prata , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Extratos Vegetais/química , Prata/química , Cicatrização
7.
Phytomedicine ; 100: 154069, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35364560

RESUMO

BACKGROUND: Cardiovascular diseases (CVDs) are a significant cause of morbidity and death in the current world, posing a challenge to both developing and industrialized nation's health systems. Citrullus lanatus (Thunb.) Matsum. & Nakai. seeds have long been utilized to supplement and enhance health and treat cardiovascular illnesses. However, its treatments for CVDs are still unknown. More research is required to fully comprehend the impact of C. lanatus seeds on vasorelaxation and myocardial infractions. PURPOSE: Therefore, an integrated metabolomics profiling technique was used to investigate possible pathways of C. lanatus in isoproterenol (ISO)-induced myocardial infarction (MI). Isoproterenol causes long-term cardiac hypertrophy by causing cardiomyocyte compensatory loss, eventually leading to heart failure. METHODS: In vitro models of vasoconstriction, atrium, and in vivo models of invasive blood pressure measurement and isoproterenol (ISO) induced cardiac hypertrophy in rats were used to understand underlying mechanistic by LC-MS/MS based dynamic metabolomics analysis of the serum and heart samples to be investigated the effect of ethanolic extract of C. lanatus (Cl.EtOH). RESULTS: Cl.EtOH exhibited vasorelaxant, negative chronotropic, and inotropic effects in in-vitro models whereas, a potent hypotensive effect was observed in normotensive rats. The Cl.EtOH protected the animals from ISO-induced myocardial infarction (MI) with therapeutic interventions in left ventricular thickness, cardiomyocyte hypertrophy, mRNA gene expression, biochemical assays, and metabolomic profiling of serum and heart tissues. CONCLUSIONS: For the first time, our study confirmed that C. lanatus seeds (Cl.EtOH) possess significant antihypertensive and prevent ISO-induced myocardial infarction. These findings comprehensively demonstrated mechanistic insights of Cl.EtOH in vasorelaxation and myocardial infarction. The current study provides evidence for further mechanistic studies and the development of C. lanatus seeds as a potential therapeutic intervention for patients with cardiovascular disorders.


Assuntos
Citrullus , Infarto do Miocárdio , Animais , Cardiomegalia/tratamento farmacológico , Cromatografia Líquida , Etanol/efeitos adversos , Humanos , Isoproterenol/toxicidade , Metabolômica , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológico , Miócitos Cardíacos , Extratos Vegetais/uso terapêutico , Ratos , Sementes , Espectrometria de Massas em Tandem , Vasodilatadores/uso terapêutico
8.
Dose Response ; 20(1): 15593258221079592, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360455

RESUMO

Panicum miliaceum L. is a medicinally effective plant used in indigenous system of medicine for a variety of ailments. However, there is no comprehensive study explaining its effectiveness in gastrointestinal tract, respiratory, and cardiovascular system ailments. This study was designed to validate the pharmacological basis for the folkloric use of Panicum miliaceum L. in diarrhea, asthma, and hypertension. Panicum miliaceum extract was analyzed to detect the presence of bioactive compounds by HPLC. The isolated rabbit jejunum, trachea, and aorta were used for in vitro experiments using tissue bath assembly coupled with Power Lab data acquisition system to explore their relative effects. In-vivo experiments were performed for anti-diarrheal activity. HPLC analysis revealed the presence of gallic acid, butylated hydroxytoluene, catechin, and quercetin. Concentration dependent activities were observed by relaxing K+ (low) induced contractions having spasmolytic effect with EC50 = .358 ± .052, bronchodilator (EC50 = 2.483 ± .05793), and vasorelaxant (EC50 = .383 ± .063), probably due to the ATP dependent potassium channel activation. It was confirmed through pre-exposure of glibenclamide (specific ATP-dependent K+ channel blocker) having similarities with cromakalim. Pm.Cr revealed its antidiarrheal via in vivo experiments on rats. This study indicates that Panicum miliaceum has antidiarrheal, spasmolytic, bronchodilator, and vasorelaxant activities probably due to the ATP dependent K+ channel activation.

9.
Biomed Pharmacother ; 148: 112704, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35180666

RESUMO

Cucumis sativus L., widely cultivated as an edible vegetable. Its seeds are well reputed for cardiovascular preventive properties. However, the mechanisms underlying for cardiovascular protection of C. sativus are still unidentified. Therefore, this study utilized a metabolomics approach to investigate putative mechanisms of C. sativus seeds in myocardial infarction (MI) and in vitro models of vasoconstriction, atrium, and invasive blood pressure measurement. Results showed that Cu.EtOH extract showed a vasorelaxant response with potent hypotensive effect in normotensive rats and L-NAME induced hypertension. Cu.EtOH caused a negative inotropic and positive chronotropic effect on the atrium. Cu.EtOH protected the animals from ISO-induced myocardial infarction (MI) interventions in left ventricular thickness, cardiomyocyte hypertrophy, mRNA gene expression, and biochemical assays. The metabolomics data suggested that Cu.EtOH mainly affected amino acid metabolism, BCAA degradation, ketone bodies degradation, and oxidative stress. Our study showed that Cu.EtOH suppressed inflammation with a strong anti-myocardial infarction impact. Additionally, our findings indicated Cu.EtOH reverted the amino acid metabolism, BCAA, and ketone bodies degradation. The findings show the antihypertensive mechanism of Cu.EtOH may include the modulation of endothelium-derived relaxing factor (EDRF) produced from nitric oxide (NO) and is connected with vascular endothelial function. C. sativus seeds, in particular, played a pivotal role in the treatment of myocardial and vascular disorders by enhancing the EDRF mechanism, energy generation, and antioxidant capacity. In summary, our findings showed the mechanistic insights on the therapeutic potential of C. sativus seeds for cardiovascular disorders.


Assuntos
Cucumis sativus , Hipertensão , Infarto do Miocárdio , Animais , Hipertensão/induzido quimicamente , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Isoproterenol/efeitos adversos , Metabolômica , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Sementes
10.
Sensors (Basel) ; 21(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34372352

RESUMO

Dynamic Light Scattering is a technique currently used to assess the particle size and size distribution by processing the scattered light intensity. Typically, the particles to be investigated are suspended in a liquid solvent. An analysis of the particular conditions required to perform a light scattering experiment on particles in air is presented in detail, together with a simple experimental setup and the data processing procedure. The results reveal that such an experiment is possible and using the setup and the procedure, both simplified to extreme, enables the design of an advanced sensor for particles and fumes that can output the average size of the particles in air.

11.
Medicine (Baltimore) ; 100(18): e25832, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950993

RESUMO

ABSTRACT: Tocilizumab (TCZ), a monoclonal recombinant antibody against IL-6 receptor, is currently used in managing the cytokine release syndrome (CRS) that occurred in coronavirus disease 2019 (COVID-19) selected cases. The primary objective of our study was to establish the effectiveness of TCZ in patients with severe or critical severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pneumonia.We retrospectively analyzed 25 consecutive patients, admitted in the Academic Emergency Hospital Sibiu, Romania from April 1, 2020 until May 25, 2020, all with confirmed SARS-CoV-2 infection and severe pneumonia. All patients were treated off-label with TCZ, beside their standard care. Adjuvant iron chelator was associated in 11 patients.Six female and 19 male patients admitted in our hospital all with confirmed SARS-CoV-2 infection and severe pneumonia as defined by Chinese Centers for Disease Control and Prevention were enrolled in this study. Seventeen of the 25 enrolled patients (68%) were seriously ill requiring noninvasive ventilation or oxygen mask, and 8 cases (32%) were critically ill requiring invasive mechanical ventilation. All patients received TCZ, and also received hydroxychloroquine, and lopinavir/ritonavir 200/50 mg for 10 days. Adjuvant iron chelator (deferasirox - marketed as Exjade) was associated in 11 patients who had ferritin serum levels above 1000 ng/mL. No side effects were encountered during infusions or after TCZ. We observed a rapid increase in arterial oxygen saturation for 20 of the 25 cases (80%) with a favorable evolution toward healing. Survivors were younger than 60 years old (80%), had less comorbidities (10% no comorbidities, 70% with 1 or 2 comorbidities), lower serum ferritin levels (30% under 1000 ng/mL), and 50% had no serum glucose elevation. Our patients with CRS had no response to corticosteroid therapy. Five out of the 25 patients had an unfavorable evolution to death. The off-label use of TCZ in patients with severe or critically ill form of SARS-CoV-2 infection had good results in our study.Off-label use of TCZ in severe and critical cases of COVID-19 pneumonia is effective in managing the "cytokine storm." Better outcomes were noted in younger patients. Associated adjuvant iron chelators may contribute to a good outcome and needs to be confirmed in larger studies.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Tratamento Farmacológico da COVID-19 , Síndrome da Liberação de Citocina/tratamento farmacológico , Deferasirox/uso terapêutico , Quelantes de Ferro/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Uso Off-Label , Pneumonia Viral/virologia , Respiração Artificial , Estudos Retrospectivos , Romênia , SARS-CoV-2
12.
Molecules ; 25(15)2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32751601

RESUMO

Anogeissus acuminata (Roxb. ex DC.) is a folkloric medicinal plant in Asia; including Pakistan; used as a traditional remedy for cardiovascular disorders. This study was planned to establish a pharmacological basis for the trivial uses of Anogeissus acuminata in certain medical conditions related to cardiovascular systems and to explore the underlying mechanisms. Mechanistic studies suggested that crude extract of Anogeissus acuminata (Aa.Cr) produced in vitro cardio-relaxant and vasorelaxant effects in isolated paired atria and aorta coupled with in vivo decrease in blood pressure by invasive method; using pressure and force transducers connected to Power Lab Data Acquisition System. Moreover; Aa.Cr showed positive effects in left ventricular hypertrophy in Sprague Dawley rats observed hemodynamically by a decrease in cardiac cell size and fibrosis; along with absence of inflammatory cells; coupled with reduced levels of angiotensin converting enzyme (ACE) and renin concentration along with increased concentrations of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). In Acute Myocardial Infarction (AMI) model; creatine kinase (CK), creatine kinase-MB (CK-MB) and lactic acid dehydrogenase (LDH levels) were found to be decreased; along with decreased necrosis; edema and recruitment of inflammatory cells histologically. In vivo and ex vivo studies of Anogeissus acuminata provided evidence of vasorelaxant; hypotensive and cardioprotective properties facilitated through blockage of voltage-gated Ca++ ion channel; validating its use in cardiovascular diseases.


Assuntos
Anti-Hipertensivos/farmacologia , Cardiotônicos/farmacologia , Combretaceae/química , Extratos Vegetais/farmacologia , Animais , Anti-Hipertensivos/isolamento & purificação , Pressão Sanguínea/efeitos dos fármacos , Cardiotônicos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Átrios do Coração/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Hipertensão/patologia , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/patologia , Masculino , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Fitoterapia/métodos , Extratos Vegetais/isolamento & purificação , Coelhos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Roedores , Transdução de Sinais/efeitos dos fármacos , Vasodilatadores/farmacologia
13.
Int J Mol Sci ; 21(5)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143439

RESUMO

BACKGROUND: Early and accurate diagnosis of endometriosis is crucial for the management of this benign, yet debilitating pathology. Despite the advances of modern medicine, there is no common ground regarding the pathophysiology of this disease as it continues to affect the quality of life of millions of women of reproductive age. The lack of specific symptoms often determines a belated diagnosis. The gold standard remains invasive, surgery followed by a histopathological exam. A biomarker or a panel of biomarkers is easy to measure, usually noninvasive, and could benefit the clinician in both diagnosing and monitoring the treatment response. Several studies have advanced the idea of biomarkers for endometriosis, thereby circumventing unnecessary invasive techniques. Our paper aims at harmonizing the results of these studies in the search of promising perspectives on early diagnosis. METHODS: We selected the papers from Google Academic, PubMed, and CrossRef and reviewed recent articles from the literature, aiming to evaluate the effectiveness of various putative serum and urinary biomarkers for endometriosis. RESULTS: The majority of studies focused on a panel of biomarkers, rather than a single biomarker and were unable to identify a single biomolecule or a panel of biomarkers with sufficient specificity and sensitivity in endometriosis. CONCLUSION: Noninvasive biomarkers, proteomics, genomics, and miRNA microarray may aid the diagnosis, but further research on larger datasets along with a better understanding of the pathophysiologic mechanisms are needed.


Assuntos
Biomarcadores/sangue , Biomarcadores/urina , Endometriose/diagnóstico , Autoanticorpos/química , Citocinas/metabolismo , Endometriose/sangue , Endometriose/urina , Endométrio/patologia , Feminino , Genômica , Humanos , Inflamação , Metabolômica , MicroRNAs/metabolismo , Neovascularização Patológica , Análise de Sequência com Séries de Oligonucleotídeos , Estresse Oxidativo , Peptídeos/química , Proteômica
14.
Endocr Pract ; 16(1): 64-70, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19833587

RESUMO

OBJECTIVE: To analyze the interpretation of the 1-microg low-dose adrenocorticotropic hormone (ACTH) test (LDT) for assessment of the presence of adrenal insufficiency (AI) in comparison with the 250-microg or standard high-dose ACTH test (HDT), which uses the same cutoff cortisol value of 18 microg/dL (500 nmol/L) as the lower limit of normal. METHODS: We present a retrospective review of 26 patients referred to the Pituitary Clinic who underwent both the LDT and the HDT for evaluation of the function of the hypothalamic-pituitary-adrenal axis. RESULTS: Of the 26 study patients, 23 had discordant findings--abnormal LDT and normal HDT results with use of the empiric cortisol cutoff of 18 microg/dL at 30 minutes in response to the ACTH dose. Glucocorticoid replacement therapy was stopped or not started in these patients, and no clinical symptoms of AI developed during a follow-up period ranging from 19 to 24 months. CONCLUSION: Our retrospective review of patients' discordant LDT and HDT results questions the reliability of the LDT as a screening test for AI, as currently interpreted. Our data suggest that abnormal results should be evaluated in the context of the clinical picture and that additional testing may be indicated to prevent unwarranted treatment with glucocorticoids. Further studies are needed to establish a safe, sensitive, and specific test for the diagnosis of AI.


Assuntos
Insuficiência Adrenal/diagnóstico , Cosintropina/metabolismo , Cosintropina/farmacologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Insuficiência Adrenal/metabolismo , Adulto , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Estudos Retrospectivos , Adulto Jovem
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