Cardiovascular Activity of the Chemical Constituents of Essential Oils.

Cardiovascular diseases are a leading cause of death in developed and developing countries and decrease the quality of life, which has enormous social and economic consequences for the population. Recent studies on essential oils have attracted attention and encouraged continued research of this group of natural products because of their effects on the cardiovascular system. The pharmacological data indicate a therapeutic potential for essential oils for use in the treatment of cardiovascular diseases. Therefore, this review reports the current studies of essential oils chemical constituents with cardiovascular activity, including a description of their mechanisms of action.

Serca2a and Na(+)/Ca(2+) exchanger are involved in left ventricular function following cardiac remodelling of female rats treated with anabolic androgenic steroid.

UNLABELLED: Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women. AIM: To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats. MAIN METHODS: Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20mg/kg/week for 4weeks); and NDE (trained and treated). The haemodynamic parameters (+dP/dtmax, -dP/dtmin and Tau) were assessed in the left ventricle. The heart was collected for histological analyses and collagen deposition. The gastrocnemius muscle was weighed, and hypertrophy was assessed by the ratio of their weights to gastrocnemius/tibia length. The expression of calcium handling proteins was measured by western blot analysis. RESULTS: ND treatment and physical exercise increased cardiac contractility and relaxation. In addition, ND promoted increases in phospholamban phosphorylated (p-PLB) and isoforms of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, while resistance exercise increased the phosphorylation of PLB and expression of Na(+)/Ca(2+) exchangers (NCX). Cardiac hypertrophy and collagen deposition were observed after ND treatment. CONCLUSION: Regulatory components of cytosolic calcium, such as SERCA2a and p-PLB, play important roles in modulating the contractility and relaxation effects of ND in females.

Relationship between male hormonal status, Bezold-Jarisch reflex function, and ACE activity (cardiac and plasmatic).

The negative relationship between androgens and the Bezold-Jarisch reflex (BJR) has been demonstrated, but no studies evaluated the physiological influence of testosterone on this reflex. We evaluated the influence of male rat castration on the BJR, cardiac morphometric parameters, and the plasmatic and the cardiac angiotensin converting enzyme (ACE) activity. After castration (CAS), the rats were divided into 24 and 72 h (CAS24H, CAS72H), and 7 and 21 days (CAS7D, CAS21D) groups. The BJR was studied by administering increasing doses of phenylbiguanide (PBG; 1.5-24 µg/kg) at different times after castration. Castration results in the following: (i) reduction in testosterone levels (SHAM: 238.7 ± 15.1; CAS24H: 9.0 ± 0.5; CAS72H: 6.7 ± 0.4; CAS7D: 5.2 ± 0.2; and CAS21D: 2.2 ± 0.3 ng/dL; p < 0.05); (ii) no changes in 17ß-estradiol; (iii) a reduced BJR sensitivity (PBG 6 µg/kg; SHAM: 77 ± 7; CAS24H: 63 ± 10; CAS72H: 55 ± 6; CAS7D: 54 ± 4; and CAS21D: 35 ± 2%; p < 0.01); (iv) a decrease in cardiac (SHAM: 107 ± 6; CAS24H: 92 ± 2; CAS72H: 82 ± 3; CAS7D: 54 ± 3; and CAS21D: 43 ± 4%; p < 0.05) and plasmatic (SHAM: 135 ± 8; CAS24H: 102 ± 5; CAS72H: 99 ± 3; CAS7D: 89 ± 4; and CAS21D: 56 ± 6%; p < 0.05) ACE activity. No changes were observed in cardiac morphometry and hemodynamic parameters. Therefore, castration leads to decrease in testosterone levels as early as 24 h, reduction in ACE activity and loss of BJR sensitivity 7 days after castration. The loss of BJR sensitivity was not related to cardiac morphometric changes and cardiovascular hemodynamics.

Cardiopulmonary reflex, cardiac cytokines, and nandrolone decanoate: response to resistance training in rats.

This study evaluated the effects of nandrolone associated with resistance training (RT) on cardiac cytokines, angiotensin-converting enzyme activity (ACEA), and the sensitivity of the Bezold-Jarisch reflex (BJR). Male Wistar rats were divided into 3 groups: CONT (received vehicle, no training); EXERC (RT: after one week of water adaptation, rats were exercised by jumping into water twice a week for 4 weeks), and ND+EXERC (received nandrolone decanoate 10 mg/kg, twice/week, i.m, associated with RT). The BJR was analysed by measuring bradycardic and hypotensive responses elicited by serotonin administration. Myocyte hypertrophy and matrix collagen deposition were determined by morphometric analysis of H&E and picrosirius red-stained samples, respectively. TNF-α and ACEA were also studied. RT promoted physiological myocyte hyrpertrophy but did not cause changes in the other parameters. The association of ND with RT increased myocyte hypertrophy, deposition of matrix type I collagen, TNF-α and ACEA; decreased IL-10, and impairment in the BJR were observed in ND+EXERC compared with CONT and EXERC. ND is associated with alterations in cardiac structure and function as a result of the development of pathological cardiac hypertrophy (cardiac cytokine imbalance, elevation of ACEA) and cardiac injury, even when combined with resistance training.

Antihypertensive effect of Carica papaya via a reduction in ACE activity and improved baroreflex.

The aims of this study were to evaluate the antihypertensive effects of the standardised methanolic extract of Carica papaya, its angiotensin converting enzyme inhibitory effects in vivo, its effect on the baroreflex and serum angiotensin converting enzyme activity, and its chemical composition. The chemical composition of the methanolic extract of C. papaya was evaluated by liquid chromatography-mass/mass and mass/mass spectrometry. The angiotensin converting enzyme inhibitory effect was evaluated in vivo by Ang I administration. The antihypertensive assay was performed in spontaneously hypertensive rats and Wistar rats that were treated with enalapril (10 mg/kg), the methanolic extract of C. papaya (100 mg/kg; twice a day), or vehicle for 30 days. The baroreflex was evaluated through the use of sodium nitroprusside and phenylephrine. Angiotensin converting enzyme activity was measured by ELISA, and cardiac hypertrophy was evaluated by morphometric analysis. The methanolic extract of C. papaya was standardised in ferulic acid (203.41 ± 0.02 µg/g), caffeic acid (172.60 ± 0.02 µg/g), gallic acid (145.70 ± 0.02 µg/g), and quercetin (47.11 ± 0.03 µg/g). The flavonoids quercetin, rutin, nicotiflorin, clitorin, and manghaslin were identified in a fraction of the extract. The methanolic extract of C. papaya elicited angiotensin converting enzyme inhibitory activity. The antihypertensive effects elicited by the methanolic extract of C. papaya were similar to those of enalapril, and the baroreflex sensitivity was normalised in treated spontaneously hypertensive rats. Plasma angiotensin converting enzyme activity and cardiac hypertrophy were also reduced to levels comparable to the enalapril-treated group. These results may be associated with the chemical composition of the methanolic extract of C. papaya, and are the first step into the development of a new phytotherapic product which could be used in the treatment of hypertension.

Probiotics supplementation in the treatment of male infertility: A Systematic Review.

Infertility is a widespread global issue that affects approximately 15% of sexually active and active couples, which contributes to about 50% of cases. Currently, the condition remains prevalent and often inadequately treated. This systematic review aims to evaluate existing studies investigating the effects of probiotic supplementation in men. A comprehensive search was conducted across major databases, including PubMed, Cochrane, Science Direct, and Scielo, using relevant keywords such as 'probiotic' OR 'Lactobacillus' OR 'Bifidobacterium' AND 'Male infertility' OR 'male fertility' OR 'sperm quality' OR 'sperm motility' OR 'oligoasthenoteratozoospermia' and their Portuguese equivalents. Four randomized clinical studies met the inclusion criteria, focusing on men diagnosed with idiopathic male infertility (oligozoospermia, teratozoospermia, and asthenozoospermia). The findings revealed that probiotic administration exhibited promising antioxidant properties by combating reactive oxygen species (ROS), consequently protecting sperm DNA from damage that correlates with declining sperm quality. Significant improvements were observed across all sperm parameters, with notable enhancement in motility. Consequently, probiotic supplementation emerges as a potential therapeutic alternative for men diagnosed with idiopathic infertility, demonstrating positive effects on sperm quality.

Ellagic acid prevents myocardial infarction-induced left ventricular diastolic dysfunction in ovariectomized rats.

Estrogen deficiency is associated with increased oxidative stress, which can contribute to left ventricular diastolic dysfunction (LVDD). We hypothesized that oral treatment with ellagic acid (EA), a potent and natural antioxidant compound, can improve MI-induced LVDD in ovariectomized rats, by reducing the formation of reactive oxygen species. Ovariectomized rats MI-induced LVDD followed by treatment with vehicle (DD) or EA (DD + EA) for 4 weeks. Non-LVDD-induced rats treated with vehicle (S) or EA (S + EA) were used as controls. Left ventricular systolic pressure; left ventricular end-diastolic pressure (LVEDP); maximum rate of pressure rise: +dP/dt and fall: -dP/dt) were evaluated in all animals after treatment. Left ventricle superoxide anion formation was quantified in situ by fluorescence. Phospho-CAMKII, SOD2, catalase, and gp91-phox abundances were evaluated by Western blot analyses. SOD (superoxide dismutase) and catalase activities were measured by spectrophotometry. The results showed that the LVEDP was significantly increased in both DD and DD + EA groups compared to S and S + EA. However, LVEDP in the DD + EA group was significantly decreased compared to DD, indicating an EA-mediated effect. In the DD group, superoxide production and gp91-phox protein abundance were increased while SOD2 abundance was decreased when compared to the S and S + EA groups. An increase in SOD activity was also observed in the DD + EA group. EA treatment reduced CaMKII phosphorylation in the DD + EA group compared to the DD. We concluded that EA treatment attenuated diastolic dysfunction in our experimental model, via reduction of reactive oxygen species and CaMKII activity, indicating EA as a promising natural therapeutic option for cardiac dysfunction.

Long-acting insulin in a public health system: analysis of compliance with clinical protocol in public pharmacies.

Diabetes mellitus (DM) is a chronic disease marked by elevated blood glucose levels. Controlling DM involves adequate diet, physical exercises, medicines and monitoring the blood glucose and glycated hemoglobin (HbA1c) levels. This was a retrospective study of the process of dispensing long-acting insulin analogues to users with diabetes (types 1 and 2) who were registered at high-cost public pharmacies in public health system in a southeast state of Brazil, that sought to evaluate the fulfillment of the criteria of all the clinical protocol to provide these analogs. Of the 987 users registered in the health service, 315 met the inclusion criteria for the study. The evaluation of the dispensing processes of the long-acting insulin analogues revealed that the inclusion, exclusion, and suspension criteria of the protocol related with these insulin analogues were in some extend only partially fulfilled. Additionally, there was no difference between the initial and final fasting glycemic and HbA1c levels. It is concluded that the established criteria for dispensing long-acting insulin analogues were partly fulfilled by pharmacies, compromising the rational use of these analogues. It can directly impact the cost of maintaining the public health service and users' health.

Low and high doses of oxandrolone promote pathological cardiac remodeling in young male rats.

Oxandrolone (OXA) used in clinical practice, however, its misuse is frequent, including by adolescents pursuing an aesthetic goal. However, the impacts of noxious doses on the cardiovascular system remain unknown. AIM: To investigate cardiac effects of OXA in low (LD) and high (HD) doses. METHODS: Male Wistar prepubescent rats were separated into 3 experimental groups: control (CON), LD, and HD. Only the CON group received the carrier (carboxymethylcellulose, 0.5%), while the LD and HD groups received, respectively, 2.5 and 37.5 mg/kg/day of OXA via gavage for 4 weeks. The hemodynamic parameters (+dP/dtmax, -dP/dtmin, and Tau) and cardiac autonomic tonus were assessed. Hearts were retrieved for histological analyses and oxidative stress evaluation. Expression levels of calcium-handling proteins were measured by western blot. RESULTS: The OXA treatment changed neither the cardiac contractility nor the cardiac autonomic tonus. However, cardiac hypertrophy, collagen deposition, and increased angiotensin-converting enzyme (ACE) expression were observed in a dose-dependent way. Also, the p-phospholamban (p-PLB)/PLB ratio was observed to decrease and increase, respectively, in the LD and HD groups; the sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a)/PLB ratio being higher in both groups. OXA increased SOD1 expression and decreased catalase expression only in the LD group, and protein oxidation was increased in HD. CONCLUSION: Both doses of OXA could promote pathological cardiac remodeling, probably via increased ACE, and these effects were exacerbated in the HD treatment, but cardiac contractility was not affected regardless of the dose.

Eight weeks of treatment with nandrolone decanoate in female rats promotes disruption in the redox homeostasis and impaired renal function.

INTRODUCTION: Misuse of AAS is emergent among both genders, however, few studies were performed evaluating AAS effects on female body and none evaluate the impact of nandrolone decanoate (ND) in renal function. AIM: Determine the effects of chronic treatment with ND on kidney function of female rats and evaluate the influence of oxidative stress on it. MATERIAL AND METHODS: Female rats were separated into two groups (n = 8 each), the treated group (DECA), which received ND at a dose of 20 mg/kg/week (i.m), and the control group (C), which was treated with the vehicle (peanut oil, i.m.). All treatments were performed during eight weeks. After this period, 24 h urine, blood and organs (heart, gastrocnemius muscle, liver and kidney) were collected. Organ hypertrophy was calculated, and kidney collagen content was evaluated. AOPP, TBARS, SOD and catalase activity were determined in the kidney. Moreover, proteinuria and creatinine clearance were also investigated. KEY-FINDINGS: Hypertrophy was observed in the liver, gastrocnemius muscle, heart and kidney. Kidney hypertrophy was followed by a reduced organ function and an increase in collagen deposition. Oxidative stress upsurge occurred in both proteins and lipids, followed by a reduction in SOD activity. SIGNIFICANCE: Administration of DN in rats was followed by renal damage and kidney fibrosis due to increased oxidative stress on that organ.

Stanozolol promotes lipid deposition in the aorta through an imbalance in inflammatory cytokines and oxidative status in LDLr knockout mice fed a normal diet.

The aim of the study was to evaluate the effect of an anabolic steroid, stanozolol, in a model of atherosclerosis and to investigate the involvement of the modulation of the inflammatory cytokines and oxidative stress in vascular lipid deposition. Low-density lipid receptor-deficient (LDLr-/-) mice were fed a standard chow diet and were each week injected subcutaneously either saline (control C group) or 20 mg/kg stanozolol (S group). After 8 weeks, the levels of cholesterol, oxidized LDL (OxLDL) and cytokines were measured in plasma, lipid deposition in aorta was evaluated by en face analysis, and thiobarbituric acid-reactive substances and oxidation protein were determined in liver. The S group demonstrated increases in vascular lipid deposition, triglycerides and non-HDL cholesterol levels. Stanozolol increased tumour necrosis factor alpha (TNF-α) and decreased interleukin-10 as well as increased the TNF-α/IL-10 ratio. Furthermore, oxidative stress was observed in the S group, as indicated by an increase in the plasma OxLDL, as well as by lipid peroxidation and oxidation of proteins in the liver. Chronic treatment with stanozolol promoted lipid deposition in the LDLr-/- mice that could be attributed to a modification of the circulating cytokine levels and systemic oxidative stress. Our results suggest that the anabolic steroid stanozolol in the absence of functional LDL receptors by increasing systemic inflammation and oxidative stress may increase the risk of development and progression of atherosclerosis.

[Satisfaction levels of users and verification of the knowledge of pharmacists in public pharmacies in the State of Espírito Santo, Brazil]. / Nível de satisfação dos usuários e verificação do conhecimento dos farmacêuticos em farmácias públicas do Espírito Santo, Brasil.

The scope of this study was to determine the satisfaction levels of users of public pharmacies and verify the knowledge of pharmacists in relation to dispensing of medicines. This is a descriptive study, conducted in municipalities in the State of Espírito Santo, in the period from May to August 2013. Data were collected using a structured questionnaire and SPSS20 software was used for statistical analysis. The Student t or ANOVA test was used for data with normal distribution, while the Mann-Whitney or Kruskal-Wallis test was applied for data without normal distribution. The Spearman correlation was used to evaluate patient satisfaction with the service time and the waiting time. The significance level for the tests was 5%. The main results obtained were the high level of dissatisfaction among users and the correlation with the waiting time to be attended. Apart from this, the knowledge of pharmacists in relation to the medication dispensed was classified as satisfactory/regular. The conclusion drawn is that actions are necessary in the management of pharmaceutical service to address the expectations of users in the dispensation of drugs.

O objetivo do presente estudo foi determinar o nível de satisfação dos usuários de farmácias públicas e verificar o conhecimento dos farmacêuticos com relação à dispensação de medicamentos. Trata-se de um estudo descritivo, realizado em municípios de uma mesma região, no interior do Estado do Espírito Santo, no período de maio a agosto de 2013. Os dados foram coletados por meio de questionário estruturado. Para a análise estatística, foi utilizado o Software SPSS20. Para os dados que apresentaram distribuição normal foram aplicados o teste t student ou ANOVA, enquanto que para os demais foram aplicados os testes Mann-Whitney ou Kruskal -Wallis. A correlação de Spearman foi utilizada para avaliar a satisfação do paciente em relação ao tempo de atendimento e ao tempo de espera. O nível de significância adotado para os testes foi de 5%. Os principais resultados obtidos foram o alto nível de insatisfação por parte dos usuários e a correlação com o tempo de espera até o atendimento. Além disso, o conhecimento dos farmacêuticos em relação à dispensação foi classificado como satisfatório/regular. Conclui-se que são necessárias medidas na gestão de serviços farmacêuticos para atender as expectativas dos usuários na dispensação de medicamentos.

The benefits of soluble non-bacterial fraction of kefir on blood pressure and cardiac hypertrophy in hypertensive rats are mediated by an increase in baroreflex sensitivity and decrease in angiotensin-converting enzyme activity.

OBJECTIVES: We aimed to evaluate whether long-term treatment with the soluble non-bacterial fraction of kefir affects mean arterial pressure (MAP) and cardiac hypertrophy through the modulation of baroreflex sensitivity, ACE activity, and the inflammatory-to-anti-inflammatory cytokine ratio in spontaneously hypertensive rats (SHRs). METHODS: SHRs were treated with the soluble non-bacterial kefir fraction (SHR-kefir) or with kefir vehicle (SHR-soluble fraction of milk). Normotensive control Wistar Kyoto animals received the soluble fraction of milk. All treatments were administered by gavage (0.3 mL/100g/body weight), once daily for eight weeks. At the end, after basal MAP and Heart Rate (HT) measurement, barorreflex sensitivity was evaluated through in bolus administrations of sodium nitroprusside and phenylephrine (AP50 [arterial pressure 50%], the lower plateau, and HR range were measured). ACE activity and cytokines (TNF-α and IL-10) were evaluated by ELISA. Cardiac hypertrophy was analysed morphometrically. RESULTS: Compared to SHR control, SHR-kefir exhibited a significant decrease in both MAP (SHR: 184 ± 5; SHR-Kefir: 142 ± 8 mmHg), and HR (SHR: 360 ± 10; SHR-kefir: 310 ± 14 bpm). The non-bacterial fraction of kefir also reduced cardiac hypertrophy, TNF-α-to-IL10 ratio, and ACE activity in SHRs. SHR-kefir baroreflex sensitivity, resulted in a partial but significant recovery of baroreflex gain, as demonstrated by improvements in AP50, the lower plateau, and HR range. CONCLUSION: In summary, our results indicate that long-term administration of the non-bacterial fraction of kefir promotes a significant decrease in both MAP and HR, by improving baroreflex, and reduces cardiac hypertrophy in SHRs, likely via ACE inhibition, and reduction of the TNF-α-to-IL10 ratio.

Pretreatment with water kefir reduces the development of acidified ethanol-induced gastric ulcers

Abstract To evaluate the gastroprotective and antioxidant effects of pretreatment with water kefir on ulcers induced with HCl/ethanol. All pretreatments lasted 14 days. Male mice were separated into five groups: the control (C) group received vehicle without ulcer induction; the ulcerated (U) group received vehicle; the lansoprazole (L) group received 30 mg/kg/day lansoprazole; the water kefir (WK15 and WK30) groups received WK at a dose of 0.15 or 0.30 ml/kg/day, respectively. Gastroprotection was measured by ulcer area, ulcer index and ulcer reduction percentage. Antioxidant effects were quantified by measuring advanced oxidized protein products (AOPPs), superoxide dismutase (SOD), and catalase activity in the stomach. Pretreatment with WK at both doses promoted gastroprotection against HCl/ethanol-induced ulcers much like the pretreatment with lansoprazole. In addition, WK decreased protein oxidation while increasing SOD and catalase activity. We concluded that pretreatment with water kefir increases the activity of antioxidant enzymes, preventing gastric lesions induced by HCl/ethanol by maintaining the antioxidant performance in gastric tissue.

Pharmaceutical services in primary health care: dissatisfaction among users, managers and pharmacists

Abstract To assess the performance indicators for pharmaceutical services (PS) in primary health care (PHC), the level of satisfaction with pharmacy services among users and managers / pharmacists' impressions in relation to the findings were evaluated. The study used mixed methods, including a retrospective and descriptive study of the performance indicators for PS in PHC, an observational study on the level of satisfaction and a qualitative study of users' perception of pharmacy services at Health Units. Managers and pharmacists' impressions of the study results were also collected. Only 44.4% of pharmacies had a full-time pharmacist. From the establishments visited, 5.3% did not have an air-conditioned environment, and only 33.3% of the items essential to the Good Practices of Storage of Medicines and Supplies criteria were fulfilled. Although 77.9% of the prescribed medicines were dispensed, it did not reach the 80% standard. The satisfaction level of users was 3.2±0.6, indicating dissatisfaction with pharmacies' services. By means of an evaluation of each item within the questionnaire, it was possible to observe that variables related to pharmaceutical care presented low scores in relation to other domains, thus evidencing the fragility of the pharmaceutical- patient relationship in users' perception. Managers and pharmacists suggested that these results were related to the inadequate physical infrastructure of pharmacies, work overload, lack of recognition and undervaluation of pharmacists, lack of interaction within the PHC team, high turnover of pharmacists, and lack of PS prioritization by the administration. PS in PHC has structural and organizational weaknesses that require changes. In general, users are dissatisfied with pharmacies' services, especially with pharmaceutical care.

Long-acting insulin in a public health system: analysis of compliance with clinical protocol in public pharmacies / Insulina de ação prolongada no sistema público de saúde: análise da adesão ao protocolo clínico em farmácias públicas

Abstract Diabetes mellitus (DM) is a chronic disease marked by elevated blood glucose levels. Controlling DM involves adequate diet, physical exercises, medicines and monitoring the blood glucose and glycated hemoglobin (HbA1c) levels. This was a retrospective study of the process of dispensing long-acting insulin analogues to users with diabetes (types 1 and 2) who were registered at high-cost public pharmacies in public health system in a southeast state of Brazil, that sought to evaluate the fulfillment of the criteria of all the clinical protocol to provide these analogs. Of the 987 users registered in the health service, 315 met the inclusion criteria for the study. The evaluation of the dispensing processes of the long-acting insulin analogues revealed that the inclusion, exclusion, and suspension criteria of the protocol related with these insulin analogues were in some extend only partially fulfilled. Additionally, there was no difference between the initial and final fasting glycemic and HbA1c levels. It is concluded that the established criteria for dispensing long-acting insulin analogues were partly fulfilled by pharmacies, compromising the rational use of these analogues. It can directly impact the cost of maintaining the public health service and users' health.

Resumo Diabetes mellitus (DM) é uma doença crônica marcada por níveis sanguíneos elevados de glicose. O controle do DM envolve dieta adequada, exercícios físicos, medicamentos e monitoramento dos níveis sanguíneos de glicose e de hemoglobina glicada (HbA1c). Trata-se de um estudo retrospectivo do processo de dispensação de análogos de insulina de ação prolongada a usuários com diabetes (tipos 1 e 2) cadastrados em farmácias públicas de alto custo do sistema público de saúde de um estado do Sudeste do Brasil, que buscou avaliar o cumprimento dos critérios do protocolo clínico para fornecimento desses análogos. Dos 987 usuários cadastrados no serviço de saúde, 315 preencheram os critérios de inclusão. A avaliação dos processos de dispensação dos análogos de insulina de ação prolongada revelou que os critérios de inclusão, exclusão e suspensão do protocolo dos análogos de insulina eram parcialmente cumpridos. Além disso, não houve diferença entre os níveis inicial e final de glicemia em jejum e HbA1c. Conclui-se que os critérios estabelecidos para dispensação de análogos de insulina de ação prolongada foram parcialmente cumpridos pelas farmácias, comprometendo o uso racional dos análogos. Os achados podem impactar diretamente no custo de manutenção do serviço público de saúde e na saúde do usuário.

Chronic and acute effects of kefir: the role of angiotensin converting enzyme inhibition instead of nitric oxide balance

Probiotic consumption promotes numerous health benefits. The aim of this study is 1) to evaluate the antihypertensive effect of kefir in a hypertension rat model caused by the administration of the nitric oxide synthesis inhibitor, L-NAME, and 2) to evaluate the acute angiotensin converting enzyme (ACE) inhibitory activity of the soluble nonbacterial fraction (SNBF) of kefir. To develop the first aim, male rats were separated into three groups: control group (C) treated with 0.3 mL/100 g of milk; L-NAME group (LN) received 10 mg/kg of said inhibitor; and Kefir group (K) treated with 0.3 mL/100 g of kefir plus L-NAME (10 mg/kg of said inhibitor). The treatments were given by oral gavage twice a day for four weeks. For the second aim"instead additionally, male rats received angiotensin I (in bolus) in three doses (Ang I: 0.03, 3 and 300 µg/kg) and were separated into two groups: a) received captopril (30 mg/kg i.v.) and b)received SNBF of kefir (5 mL/kg i.v.). Blood pressure were evaluated before and after Ang I. After treatment, hemodynamic parameters were evaluated, heart weight was recorded, and body weight gain was calculated. SNBF of kefir did not decrease the blood pressure for L-NAMEtreated animals, and no changes were observed in the cardiac parameters. However, the SNBF of kefir demonstrated acute inhibition of ACE in vivo similar to that of captopril. Thus, our results suggest that kefir may improve human cardiovascular systems by using mechanisms independent of nitric oxide syntheses. Additionally, the renin angiotensin system is probably the most important system involved in kefir effect regarding hypertension.

Finasteride promotes worsening of the cardiac deleterious effects of nandrolone decanoate and protects against genotoxic and cytotoxic damage

Metabolism of anabolic androgenic steroids is important for its physiological effects. The aim was to investigate the effects of finasteride (a 5α-reductase inhibitor - 5αR) on cardiac and mutagenic effects promoted by ND. Male Wistar rats were separated into three groups: CONT, received the vehicles of ND and finasteride (Peanut oil+Saline); DECA group, received ND (20 mg.kg.week-1, i.m.), and DECAF received ND and finasteride (100 µg.kg-1, i.p.), for four weeks. After, hypertrophy, cytokines and Angiotensin Converting Enzyme (ACE) activity was determined in heart. Bone marrow was used for micronucleus evaluation. Treatment with ND promotes increase in cardiac hypertrophy, ACE activity and disbalance among pro- and anti-inflammatory cytokines, and combination with finasteride worsened those effects. Association with finasteride ameliorates the toxic effects of ND on bone marrow cells, as was observed by a normalization of the number of micronucleate polychromatic erythrocytes and the mitotic index. Our data demonstrates that deleterious effects promoted by ND are depend, at least in part, of its metabolization. Also, inhibition of 5αR by finasteride present variated effects dependent on organ studied. It can promote increase on cardiac damage and a reduction on mutagenic effects of ND, which demonstrated that dehydronandrolone has diverse role on ND effects..

Nandrolone decanoate induces cardiac and renal remodeling in female rats, without modification in physiological parameters: The role of ANP system.

UNLABELLED: Anabolic-androgenic steroids are misused, including women, but little is known about the cardiovascular effects of these drugs on females. AIM: Evaluated the effects of nandrolone decanoate (ND), physical exercise and estrogen deficiency on female rats. MAIN METHODS: Female Wistar rats were divided into 8 groups: S and OVX: (SHAM: sham surgery; OVX: ovariectomy, vehicle), SE and OVXE (resistance exercise 5 times a week, vehicle), SD and OVXD (treated with ND, 20 mg/kg/week for 4 weeks); SDE and OVXDE. Treatments were initiated 21 days after surgery. The Bezold­Jarisch reflex was assessed by Phenylbiguanide administration. The right atrium, kidney, and serum were collected for molecular analyses by RT-PCR of atrial natriuretic peptide (ANP), A-type natriuretic peptide receptor (NPR-A) and NPR-C. ELISA assay to estradiol and testosterone concentrations. The gastrocnemius muscle, heart and kidney weights/tibia length were measured.Morphometric analysis of heart was made (H/E) and collagen content of heart and kidney were evaluated using Pirossirius Red. KEY FINDINGS: ND treatment increased ANP expression on atrium and decreased NPR-A expression in kidney. Physical exercise and ovariectomy did not alter this parameter. NPR-C level was reduced in the SDE and OVXDE. Renal and cardiac hypertrophy was observed after ND treatment, with collagen deposition. Plasma estrogen concentrations were reduced and serum testosterone concentrations were increased after ND treatment. SIGNIFICANCE: ANP has an important role in modulating the cardiovascular effects of ND in females. Thismodulating may have occurred by the increasing ANP expression, reducing NPR-A and NPR-C expression levels, and changing sex hormone levels.

Phytochemical and in vitro and in vivo biological investigation on the antihypertensive activity of mango leaves (Mangifera indica L.).

AIMS: The aim of this study was to investigate the antihypertensive effect of leaves Mangifera indica L. using in vitro and in vivo assays. METHODOLOGY: The ethanol extract of leaves of M. indica was fractionated to dichloromethanic, n-butyl alcohol and aqueous fractions. The chemical composition of ethanolic extract and dichloromethanic fraction were evaluated by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Antioxidant activity was evaluated in the DPPH scavenging activity assay. Angiotensin-converting enzyme (ACE) inhibitory activity was investigated using in vitro and in vivo assays. The chronic antihypertensive assay was performed in spontaneously hypertensive rats (SHRs) and Wistar rats treated with enalapril (10 mg/kg), dichloromethanic fraction (100 mg/kg; twice a day) or vehicle control for 30 days. The baroreflex sensitivity was evaluated through the use of sodium nitroprusside and phenylephrine. Cardiac hypertrophy was evaluated by morphometric analysis. RESULTS: The dichloromethanic fraction exhibited the highest flavonoid, total phenolic content and high antioxidant activity. Dichloromethanic fraction elicited ACE inhibitory activity in vitro (99 ± 8%) similar to captopril. LC-MS/MS analysis revealed the presence of ferulic acid (48.3 ± 0.04 µg/g) caffeic acid (159.8 ± 0.02 µg/g), gallic acid (142.5 ± 0.03 µg/g), apigenin (11.0 ± 0.01 µg/g) and quercetin (203.3 ± 0.05 µg/g). The chronic antihypertensive effects elicited by dichloromethanic fraction were similar to those of enalapril, and the baroreflex sensitivity was normalized in SHR. Plasma ACE activity and cardiac hypertrophy were comparable with animals treated with enalapril. CONCLUSIONS: Dichloromethanic fraction of M. indica presented an antihypertensive effect, most likely by ACE inhibition, with benefits in baroreflex sensitivity and cardiac hypertrophy. Altogether, the results of the present study suggest that the dichloromethanic fraction of M. indica leaves may have potential as a promoting antihypertensive agent.