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1.
Fitoterapia ; 174: 105871, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428618

RESUMO

The essential oils of Thymus vulgaris (TVEO) and Thymus serpyllum (TSEO) show different biological activities. The aim of the study was to evaluate the biological activities of TVEO and TSEO from Montenegro. The main components of TVEO were p-cymene (29.52%), thymol (22.8%) and linalool (4.73%) while the main components of TSEO were p-cymene (19.04%), geraniol (11,09%), linalool (9.16%), geranyl acetate (6.49%) and borneol (5.24%). Antioxidant activity determined via DPPH for TVEO was 4.49 and FRAP 1130.27, while for TSEO it was estimated that DPPH was 4.88 µL/mL and FRAP was 701.25 µmol FRAP/L. Both essential oils were active against all tested bacteria, with the highest level of sensitivity of E. coli with MIC of 1.5625 µL/mL. Essential oils showed strong cytotoxic effects on human cancer cell lines, with IC50 values ranging from 0.20 to 0.24 µL/mL for TVEO and from 0.32 to 0.49 µL/mL for TSEO. TVEO caused apoptosis in cervical adenocarcinoma HeLa cells through activation of caspase-3 and caspase-8, while TSEO caused apoptosis through caspase-3. EOs decreased levels of oxidative stress in normal MRC-5 cells. HeLa cells treated with TVEO had reduced MMP2 expression levels, while cells treated with TSEO had lowered MMP2 and MMP9 levels. The treatment of HeLa cells with TVEO increased the levels of miR-16 and miR-34a, indicating potential tumor-suppressive properties. Our findings suggest that Thymus essential oils may be considered as good candidates for further investigation as cancer-chemopreventive and cancer-therapeutic agents.


Assuntos
Monoterpenos Acíclicos , Cimenos , MicroRNAs , Óleos Voláteis , Thymus (Planta) , Humanos , Óleos Voláteis/química , Antioxidantes/farmacologia , Antioxidantes/química , Caspase 3 , Metaloproteinase 2 da Matriz/farmacologia , Escherichia coli , Thymus (Planta)/química , Células HeLa , Montenegro , Estrutura Molecular , Antibacterianos/farmacologia , Antibacterianos/química , Óleos de Plantas/farmacologia , Óleos de Plantas/química
2.
Arch Sex Behav ; 53(4): 1395-1401, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38285295

RESUMO

Penile pearls are artificial implants placed beneath the skin of a penis to provide enhanced sexual experience for the partner or present a stigma of a particular social subgroup (e.g., prisoner, member of a gang). This genital modification is usually encountered in men of low socioeconomic status and prisoners who might (self) implant improvised pearls under poor sanitary conditions. We have only recently started to encounter penile pearls on autopsy, incidentally. The aim of this study was to analyze our autopsy cases with penile pearls to assess the characteristics of these subjects regarding their socioeconomic status, history of imprisonment, substance abuse, as well as the characteristics of implants. Nineteen men were included. Most were born in the 1970s and 1980s, with only elementary/vocational school education (n = 10). Only five men graduated from high school. At least 14 were in prison at some point in life and 13 were unemployed. Ten men were unmarried. In 11 men, regular alcohol consumption was reported. 12 used illicit substances, most with a history of heroin injection. Penile pearls were improvised and made of rigid plastic in 10 men, eight were of soft silicone-like material, and one was of metal. A distinct characteristic was a ribbed contour of some implants. Although this genital modification seems to gain more attention outside of described vulnerable groups, it mostly remains limited to them in our region. It is most likely performed in improvised, non-professional, unsanitary conditions, probably in prisons.


Assuntos
Prisioneiros , Identificação Social , Masculino , Humanos , Patologistas , Pênis , Comportamento Sexual , Prisões
3.
Biofactors ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38284316

RESUMO

In addition to their usual use in the treatment of cardiovascular disease, weak evidence is available for the potential of combined use of neprilysin inhibitor (sacubitril) and AT1 receptor antagonist (valsartan) to promote browning of white adipose tissue (WAT) in rats with metabolic syndrome (MetS). This study involved 32 male Wistar albino rats divided into four groups: CTRL-healthy control rats; ENT-healthy rats treated with sacubitril/valsartan; MS-rats with MetS; MS + ENT-rats with MetS treated with sacubitril/valsartan. After finishing the experimental protocol, different WAT depots were isolated for further analysis of molecular pathways. Molecular docking and molecular dynamics studies were used for in silico assessment of the binding affinity of sacubitril and valsartan towards subunits of mechanistic target of rapamycin complex 1 (mTORC1). Sacubitril/valsartan treatment markedly diminished morphological changes in adipose tissue, resulting in smaller lipid size and multilocular lipid droplet structure in WAT. We showed significantly higher protein expression of uncoupling protein-1 (UCP-1) and mTORC1 in WAT of MS + ENT rats, correlating with increased relative gene expression of browning-related markers in tissue of rats treated with sacubitril/valsartan compared with MS group of rats. In silico analysis showed that sacubitrilat and valsartan exhibited the highest binding affinity against mTOR and mLST8, forming stable complexes with these mTORC1 subunits. The observed results confirmed strong potential of combined sacubitril/valsartan treatment to increase browning markers expression in different WAT depots in MetS condition and to form permanent complexes with mTOR and mLST8 subunits over the time.

4.
Int J Obes (Lond) ; 48(2): 202-208, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37770573

RESUMO

BACKGROUND: It is still unclear whether femoral fracture risk is positively or negatively altered in individuals with overweight. Considering the lack of studies including men with overweight, this study aimed to analyze regional specificities in mechano-structural femoral properties (femoral neck and intertrochanteric region) in adult male cadavers with overweight compared to their normal-weight age-matched counterparts. METHODS: Ex-vivo osteodensitometry, micro-computed tomography, and Vickers micro-indentation testing were performed on femoral samples taken from 30 adult male cadavers, divided into the group with overweight (BMI between 25 and 30 kg/m2; n = 14; age:55 ± 16 years) and control group (BMI between 18.5 and 25 kg/m2; n = 16; age:51 ± 18 years). RESULTS: Better quality of trabecular and cortical microstructure in the inferomedial (higher trabecular bone volume fraction, trabecular thickness, and cortical thickness, coupled with reduced cortical pore diameter, p < 0.05) and superolateral femoral neck (higher trabecular number and tendency to lower cortical porosity, p = 0.043, p = 0.053, respectively) was noted in men with overweight compared to controls. Additionally, the intertrochanteric region of men with overweight had more numerous and denser trabeculae, coupled with a thicker and less porous cortex (p < 0.05). Still, substantial overweight-induced change in femoral osteodensitometry parameters and Vickers micro-hardness was not demonstrated in assessed femoral subregions (p > 0.05). CONCLUSIONS: Despite the absence of significant changes in femoral osteodensitometry, individuals with overweight had better trabecular and cortical femoral micro-architecture implying higher femoral fracture resistance. However, the microhardness was not significantly favorable in the individuals who were overweight, indicating the necessity for further research.


Assuntos
Fraturas do Fêmur , Sobrepeso , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Microtomografia por Raio-X , Colo do Fêmur/diagnóstico por imagem , Cadáver , Densidade Óssea
5.
Antioxidants (Basel) ; 12(11)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-38001790

RESUMO

OBJECTIVE: The aim of this meta-analysis is to explore all the available literature to obtain updated data about the potential use of antioxidants in the treatment of rheumatoid arthritis (RA) and its ability to reduce disease progression and cardiovascular risk. METHODS: This systematic review and meta-analysis was performed strictly in accordance with the PRISMA guidelines. English and Chinese databases were searched with a retrieval time up to March 2023. These databases included the PubMed, Embase, Medline Complete, Web of Sciences and Cochrane Collaboration, Wanfang, China National Knowledge Infrastructure, and VIP databases. This literature search was formulated by the two researchers independently. The search strategy consists of reading, collecting the literature, and conducting the preliminary screening. After that, they provide the final selection of the literature according to the inclusion criteria and data extraction. Also, for all studies, the risk bias was assessed to evaluate the quality of the included references. The content of the risk assessment of bias included the following criteria: random allocation method, allocation plan hiding, blind method, completeness of result data, and selectivity of reporting of results, as well as other biases. The main outcomes were clinical efficiency of antioxidant therapy (C-reactive protein, DAS28 score, HAQ, Number of tender joints, etc.) and oxidative stress indicators (catalase, superoxide dismutase, or total antioxidant capacity). RESULTS: We observed, in most of the studies, the small or moderate effects of antioxidant treatment. The mean effect size is 0.525, and that means that moderate effects were observed in 30 selected RCTs. Also, this effect is confirmed in the 1652 patients with RA with the mean confidence interval of 0.276 (lower limit) and 0.983 (upper limit). Cohen coefficient was calculated at 0.05. CONCLUSION: The existing evidence is that antioxidants can reduce systemic and local oxidative stress and can reduce damage as the main agent involved in autoimmune diseases such as rheumatoid arthritis.

6.
Medicina (Kaunas) ; 59(11)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38004044

RESUMO

Background and Objectives: This study was conducted to examine the influence of different swimming and running protocols as forms of physiological preconditioning on an isolated rat heart's ischemia/reperfusion injury. Materials and Methods: This study was conducted on 60 male Wistar albino rats (6 weeks old, bw: 200 ± 20 g), divided into: CTRL group-a sedentary control group; sAeT-a group that underwent aerobic swimming conditioning using a swimming protocol for 8 weeks; sAnT-a group that underwent anaerobic swimming conditioning; rAeT-a group that underwent aerobic running conditioning; and rAnT-a group that underwent anaerobic running conditioning. After the preconditioning protocols, ex vivo estimating of myocardial function according to the Langendorff technique was performed. Results: The anaerobic running training decreased heart rate and the anaerobic swimming training reduced coronary flow, demonstrating the difference in the physiological heart response of aerobic/anaerobic physical training (p < 0.05). Heart rate was significantly reduced in both training swimming groups after a period of ischemia (p < 0.05). On the other hand, the anaerobic running protocol induced a significantly decreased heart rate in comparison with the aerobic running group and the sedentary group (p < 0.05). Conclusions: The data from this experimental study support many protective training effects, i.e., improved contractility, improved resting heart rate, and increased physical work capacity and exercise tolerance. Physical training in the form of anaerobic running induces greater heart preconditioning for reperfusion injury in comparison with anaerobic swimming training.


Assuntos
Traumatismo por Reperfusão Miocárdica , Corrida , Ratos , Masculino , Animais , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Ratos Wistar , Natação/fisiologia , Isquemia , Modelos Teóricos
7.
Mol Cell Biochem ; 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880442

RESUMO

OBJECTIVE: This study aimed to evaluate the dental pulp responses to recombinant human erythropoietin (rhEPO) and/or mineral trioxide aggregate (MTA) in pulp capping of inflamed dental pulp in vivo. MATERIALS AND METHODS: In accordance with ARRIVE guidelines, pulp inflammation was induced by exposing the maxillary first molars (n = 64) of Wistar rats (n = 32) to the oral environment for two days. The exposed pulps were randomly assigned four groups based on the pulp capping material: rhEPO, MTA, MTA + rhEPO, or an inert membrane. An additional eight rats formed the healthy control group. After four weeks, the animals were euthanized, and histological, qRT-PCR, and spectrophotometric techniques were employed to analyze the left maxillary segments, right first maxillary molars, and blood samples, respectively. Statistical significance was set at p < 0.05 and < 0.001. RESULTS: Pulp capping with rhEPO, MTA, or MTA + rhEPO resulted in lower inflammation and higher mineralization scores compared to untreated control. MTA + rhEPO group exhibited significantly decreased expression of tumor necrosis factor-alpha, and interleukin 1-beta, while MTA group showed substantially reduced expression of interferon-gamma. Both rhEPO and MTA + rhEPO groups presented elevated dentin matrix protein 1 levels compared to untreated control. Furthermore, pulp capping with rhEPO and/or MTA led to increased transforming growth factor-beta 1 expression and reductions of pro-inflammatory/immunoregulatory cytokine ratios and prooxidative markers. Pulp capping with rhEPO also resulted in increase of systemic antioxidative stress markers. CONCLUSION: Capping with rhEPO or MTA + rhEPO resulted in a favorable effect that was similar or even superior to that of MTA.

8.
Animals (Basel) ; 13(18)2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37760247

RESUMO

BACKGROUND: This study explored the effects of hyperbaric oxygen therapy (HBOT) on the cardiovascular system and oxidative stress in streptozotocin-induced diabetic rats. Wistar albino rats were divided into four groups: DM group (diabetic rats), DM+HBOT group (diabetic rats exposed to HBOT for 1 h daily, five days a week, at 2.8 atmosphere absolute (ATA) with 100% oxygen for two weeks), DM+INS group (diabetic rats treated with neutral protamine hagedorn (NPH) insulin at a dosage of 3-5 U/day), and DM+HBOT+INS group (diabetic rats treated with both NPH insulin and HBOT for two weeks). METHODS: Evaluations included glycemic control, oxidative stress parameters, and cardiac function measurements. RESULTS: NPH insulin treatment reduced blood glucose levels, although normoglycemia was not achieved. The DM+HBOT+INS group demonstrated the lowest pro-oxidative marker levels. NPH insulin treatment improved cardiac function, and combination therapy effectively restored cardiac function in diabetic animals. CONCLUSIONS: NPH insulin treatment reduced hyperglycemia and improved cardiac function in diabetic rats. The combined approach of NPH insulin and HBOT resulted in decreased pro-oxidative markers. These findings provide valuable insights for managing cardiovascular complications and oxidative stress in diabetes.

9.
Heliyon ; 9(8): e18725, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37554803

RESUMO

Although scientific evidence has shown that natural mineral waters have potential beneficial metabolic effects, there is still very scarce data on their influence on type 2 diabetes mellitus (T2DM). The study was designed to investigate the effects of low mineral water from the "Sneznik-1/79″ source in Serbia on microbiota, metabolic, and oxidative stress parameters in patients with T2DM. In total, 60 patients with confirmed T2DM were included in the study, and they consumed "Sneznik-1/79″ water for 28 days. To examine the positive effects of "Sneznik-1/79″ water, we compared the results before and after the four weeks of "Sneznik-1/79″ water intake. Standard biochemical analyses were carried out, such as glucose level, lipid profile, and stool tests. The blood samples were collected to evaluate the effects of "Sneznik-1/79″ water on the redox status. At the end of the monitoring period, the total cholesterol concentration significantly dropped compared to the initial value. A significant improvement in intestinal peristalsis was observed, which was reflected in the fact that after four weeks, all patients established regular, daily bowel movements. Moreover, consumption of "Sneznik-1/79″ water eliminated the appearance of dysbiosis in 50% of patients. Additionally, the antioxidant capacity was improved by increasing the concentration of superoxide dismutase and reduced glutathione. The result of our study pointed out that the intake of "Sneznik-1/79″ water could be a promising adjuvant therapy for improving intestinal peristalsis as well as reducing the appearance of dysbiosis in T2DM patients.

10.
Iran J Public Health ; 52(5): 870-879, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37484720

RESUMO

Background: Three selective and most used inhibitors of PDE-5-sildenafil, vardenafil and tadalafil- have been successfully used for the treatment of erectile dysfunction. Erectile dysfunction and cardiovascular diseases might be considered as two dissimilar clinical signs of the identical systemic disease. PDE-5 inhibitors can through different models and mechanisms induce vasodilation, decrease apoptosis and cell proliferation, and they are widely present in various tissues that make them promising targets in a range of cardiovascular diseases. Methods: PubMed was explored to identify papers published from 1990-2019, presenting data for the most used PDE-5 inhibitors (sildenafil, tadalafil or vardenafil) in treatment of cardiovascular diseases. Results: This article analyses the therapeutic potentials of PDE-5 inhibitors in cardiovascular diseases and discusses mechanisms, possible risks and limitations. Comparable to earlier studies, newer studies suggest cardioprotective effects of PDE-5 inhibitors, which include different models and mechanisms and do not indicate an increased rate of significant cardiovascular adverse reactions. Dissimilarity in the pharmacokinetics and pharmacodynamics of PDE-5 inhibitors are significant to their risk- benefit profile and clinical use. Some of the studies suggesting infarct size reduction after PDE-5 inhibition described the especially close dose-effect relation, other studies dosage adaptation in drug- drug interactions. Conclusion: PDE-5 inhibitors indicate the encouraging useful effects by ischemia/reperfusion injury, myocar-dial infarction, cardiac hypertrophy, cardiomyopathy and systolic and diastolic congestive heart failure. Therefore, this and similar reviews can help for additional clinical targeting in the therapy of cardiovascular diseases.

11.
J Pers Med ; 13(7)2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37511663

RESUMO

(1) Background: The aim of our study was to determine the role of oxidative stress (OS) during early evaluation of acute ST-elevated myocardial infarction (STEMI) and non-ST-elevated myocardial infarction (NSTEMI) patients in order to define the role of redox balance in profiling the development of myocardial infarction (MI). (2) Methods: This prospective observational case-control study included 40 consecutive STEMI and 39 NSTEMI patients hospitalized in the coronary care unit of the cardiology clinic at the Kragujevac Clinical Center, Serbia, between 1 January 2016 and 1 January 2017. Blood samples were collected from all patients for measuring cardio-specific enzymes at admission and 12 h after admission to evaluate systemic oxidative stress biomarkers and the activity of antioxidant enzymes. (3) Results: In this study, participants were predominately female (52%), with a mean age of 56.17 ± 1.22 years old in the STEMI group and 69.17 ± 3.65 in the non-STEMI group. According to the Killip classification, the majority of patients (>50%) were at the second and third level. We confirmed the elevation of superoxide anion radicals in the non-STEMI group 6 h after admission in comparison with the STEMI and CTRL groups, but levels had decreased 12 h after admission. Levels of hydrogen peroxide were statistically significantly increased in the NSTEMI group. A positive correlation of superoxide anion radicals and levels of troponin I at admission was observed (r = 0.955; p = 0.045), as well as an inverse correlation between reduced glutathione and levels of NT-pBNP measured 6 h after admission (r = -0.973; p = 0.027). (4) Conclusions: We confirmed that superoxide anion radicals and reduced glutathione observed together with hs-troponin I at admission and NT-pBNP during hospital treatment could be predictors of ST evolution.

12.
Medicina (Kaunas) ; 59(6)2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37374308

RESUMO

Background and Objectives: Polycystic ovary syndrome (PCOS) is a frequent multifactorial endocrinopathy affecting women in the reproductive period, often associated with infertility and metabolic disorders. The use of animal models helps to better understand etiopathogenesis, enabling the examination of the effects of certain drugs in order to discover the best possible therapeutic approach. We tried to investigate the additional effect of estradiol-valerate (EV) and high-fat diet (HFD) in female rats to explore PCOS-related alterations with special focus on oxidative stress. Materials and Methods: Animals were divided into three groups: control group (CTRL, n = 6), estradiol-valerate group (EV, n = 6), and estradiol-valerate group on HFD (EV + HFD, n = 6). PCOS was induced by single subcutaneous injection of long-acting EV in a dose of 4 mg/per rat. We tried to improve the metabolic characteristics of the PCOS animal model by adding HFD, so the CTRL and EV group had a regular diet, while the EV + HFD group had HFD during the induction period of 60 days. Results: We observed alterations of anthropometric parameters and hormonal disturbances, along with estrus cycle impairment reassembly to obese-type PCOS phenotype. Moreover, glucose metabolism was impaired after addition of HFD to EV protocol, contrary to EV administered alone. Histological analysis confirmed more numerous cystic follicles after the combination of EV and HFD protocol. The alterations of oxidative stress markers could be related to and serve as the mechanistic base for development of PCOS-related endocrine, reproductive, and metabolic properties. Conclusions: The additive effect of EV and HFD was obvious in the majority of the parameters observed. Our study strongly demonstrated metabolic as well as reproductive properties of PCOS in rats.


Assuntos
Síndrome do Ovário Policístico , Ratos , Feminino , Animais , Humanos , Síndrome do Ovário Policístico/metabolismo , Dieta Hiperlipídica/efeitos adversos , Estradiol/efeitos adversos , Reprodução , Estresse Oxidativo , Valeratos/efeitos adversos
13.
Pharmaceuticals (Basel) ; 16(6)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37375735

RESUMO

The present study aimed to examine the biological activity and cardioprotective potential of Trametes versicolor heteropolysaccharides (TVH) in a rat model of metabolic syndrome (MetS). This study included 40 Wistar rats divided into 5 groups: CTRL-healthy non-treated rats; MetS-non-treated rats; and H-TV, M-TV and L-TV-rats with MetS treated with either 300, 200 or 100 mg/kg TVH per os for 4 weeks. After finishing the treatment, we conducted an oral glucose tolerance test (OGTT), hemodynamic measurements and the animals were sacrificed, hearts isolated and subjected to the Langendorff technique. Blood samples were used for the determination of oxidative stress parameters, lipid status and insulin levels. We showed that α-amylase inhibition was not the mode of TVH antidiabetic action, while TVH showed a moderate inhibition of pathogenic microorganisms' growth (MIC 8.00 mg·mL-1; MBC/MFC 16.00 mg·mL-1). H-TV and M-TV significantly reduced the level of prooxidants (O2-, H2O2, TBARS; p < 0.05), increased antioxidants activity (SOD, CAT, GSH; p < 0.05), reduced blood pressure (p < 0.05), improved glucose homeostasis in the OGTT test (p < 0.05), and ejection fraction (p < 0.05) and cardiac contractility (p < 0.05) compared to MetS (p < 0.05). Moreover, TVH treatment normalized the lipid status and decreased insulin levels compared to MetS rats (p < 0.05). The obtained results demonstrated that the TVH may be considered a useful agent for cardioprotection in MetS conditions.

14.
Medicina (Kaunas) ; 59(3)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36984459

RESUMO

Background and objectives: Taking into consideration the confirmed role of oxidative stress in ischemia/reperfusion injury and the insufficiency in knowledge regarding the phosphodiesterase 5 (PDE5)-mediated effects on the cardiovascular system, the aim of our study was to investigate the influence of two PDE5 inhibitors, tadalafil and vardenafil, with or without the addition of N(G)-nitro-L-arginine methyl ester (L-NAME), on oxidative stress markers, coronary flow and left ventricular function, both ex vivo and in vivo. Methods: This study included 74 male Wistar albino rats divided into two groups. In the first, 24 male Wistar rats were orally treated with tadalafil or vardenafil for four weeks in order to perform in vivo experiments. In the second, the hearts of 50 male Wistar albino were excised and perfused according to the Langendorff technique in order to perform ex vivo experiments. The hearts were perfused with tadalafil (10, 20, 50 and 200 nM), vardenafil (10, 20, 50 and 200 nM) and a combination of tadalafil/vardenafil and L-NAME (30 µM). The CF and oxidative stress markers, including nitrite bioaviability (NO2-), superoxide anion radical (O2-), and the index of lipid peroxidation, were measured in coronary effluent. Results: The L-arginin/NO system acts as the mediator in the tadalafil-induced effects on the cardiovascular system, while it seems that the vardenafil-induced increase in CF was not primarily induced by the NO system. Although tadalafil induced an increase in O2- in the two lowest doses, the general effects of both of the applied PDE5 inhibitors on oxidative stress were not significant. The ejection function was above 50% in both groups. Conclusions: Our results showed that both tadalafil and vardenafil improved the coronary perfusion of the myocardium and LV function by increasing the EF.


Assuntos
Inibidores da Fosfodiesterase 5 , Função Ventricular Esquerda , Animais , Masculino , Ratos , Modelos Teóricos , NG-Nitroarginina Metil Éster/farmacologia , Estresse Oxidativo , Perfusão , Inibidores da Fosfodiesterase 5/farmacologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Diester Fosfórico Hidrolases/metabolismo , Ratos Wistar , Volume Sistólico , Superóxidos/metabolismo , Tadalafila/farmacologia , Tadalafila/uso terapêutico , Dicloridrato de Vardenafila/farmacologia , Dicloridrato de Vardenafila/uso terapêutico
15.
Mol Cell Biochem ; 478(12): 2645-2656, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36997815

RESUMO

This study evaluated the effect of sacubtril/valsartan on cardiac remodeling, molecular and cellular adaptations in experimental (rat) model of hypertension-induced hypertrophic cardiomyopathy. Thirty Wistar Kyoto rats, 10 healthy (control) and 20 rats with confirmed hypertension-induced hypertrophic cardiomyopathy (HpCM), were used for this study. The HpCM group was further subdivided into untreated and sacubitril/valsartan-treated groups. Myocardial structure and function were assessed using echocardiography, Langendorff's isolated heart experiment, blood sampling and qualitative polymerase chain reaction. Echocardiographic examinations revealed protective effects of sacubitril/valsartan by improving left ventricular internal diameter in systole and diastole and fractional shortening. Additionally, sacubitril/valsartan treatment decreased systolic and diastolic blood pressures in comparison with untreated hypertensive rats. Moreover, sacubitril/valsartan treatment reduced oxidative stress and apoptosis (reduced expression of Bax and Cas9 genes) compared to untreated rats. There was a regular histomorphology of cardiomyocytes, interstitium, and blood vessels in treated rats compared to untreated HpCM rats which expressed hypertrophic cardiomyocytes, with polymorphic nuclei, prominent nucleoli and moderately dilated interstitium. In experimental model of hypertension-induced hypertrophic cardiomyopathy, sacubitril/valsartan treatment led to improved cardiac structure, haemodynamic performance, and reduced oxidative stress and apoptosis. Sacubitril/valsartan thus presents as a potential therapeutic strategy resulted in hypertension-induced hypertrophic cardiomyopathy.


Assuntos
Cardiomiopatia Hipertrófica , Hipertensão , Ratos , Animais , Tetrazóis/farmacologia , Tetrazóis/metabolismo , Tetrazóis/uso terapêutico , Valsartana/farmacologia , Valsartana/metabolismo , Valsartana/uso terapêutico , Miócitos Cardíacos/metabolismo , Cardiomiopatia Hipertrófica/tratamento farmacológico , Ratos Endogâmicos WKY , Modelos Teóricos
16.
BMC Complement Med Ther ; 23(1): 78, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36899315

RESUMO

This study aimed to examine the effects of dandelion root on rat heart function and oxidative status. At the beginning of the experimental protocol, Wistar albino rats were randomly classified into two groups (10 rats per group): 1. control group - animals that drank tap water; 2. experimental group - animals that drank dandelion root for four weeks. Every morning for four weeks, the animals received freshly boiled dandelion root in a volume of 250 ml. At the end of the dandelion administration, animals were sacrificed, and their hearts were isolated and retrogradely perfused according to the Langendorff technique at a gradually increasing perfusion pressure between 40 - 120 cm H2O. The following myocardial function parameters were measured: maximum rate of left ventricular pressure development (dp/dt max), minimum rate of left ventricular pressure development (dp/dt min), systolic left ventricular pressure (SLVP), diastolic left ventricular pressure (DLVP), heart rate (HR). In addition, the coronary flow (CF) was measured flowmetrically. Finally, blood samples were collected after sacrificing to determine oxidative stress biomarkers: nitrite (NO2-), superoxide anion radical (O2-), hydrogen peroxide (H2O2), the index of lipid peroxidation (TBARS), reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD). The present pioneer results indicated that dandelion root did not manifest a negative impact on functional aspects of isolated rat heart. In addition, dandelion consumption was not associated with promising results in terms of maintaining systemic redox balance.


Assuntos
Taraxacum , Animais , Ratos , Peróxido de Hidrogênio/farmacologia , Ratos Wistar , Estresse Oxidativo , Oxirredução , Superóxidos/farmacologia
17.
J Forensic Leg Med ; 95: 102506, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36868098

RESUMO

This case represents a 27-year-old man, who was found dead in a truckload, trapped between several coils of steel wire, each weighing 500 kg. The autopsy was remarkable for subendocardial hemorrhages in addition to Perthes' syndrome and florid internal findings: congestion/cyanosis of the cervical organs, intrathyroidal and submucosal bleedings. All this implies that compression significantly raised intrathoracic pressure. This might have reached a point that obstructed venous blood return and restricted filling of the right heart during diastole, while simultaneously preserving the function of a left ventricle for some time. A precipitous fall of the blood pressure and consequent decrease in the left ventricle filling, with a pressure gradient between the ventricular lumen and higher-pressured heart vessels could have resulted in myocardial vessel rupture - the same pathophysiologic mechanism that underlies the appearance of subendocardial hemorrhages. If this man was conscious and aware for some time prior and upon initial compression, the fight or flight response could have resulted in a sudden surge of circulating catecholamine levels - which is the second described mechanism of subendocardial hemorrhage development. However, we believe that autopsy findings favor the firstly described scenario. Nevertheless, subendocardial hemorrhages are out of the common finding in crush asphyxia.


Assuntos
Cardiopatias , Doenças Vasculares , Masculino , Humanos , Adulto , Asfixia/etiologia , Hemorragia/etiologia , Autopsia
18.
Forensic Sci Int ; 345: 111618, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36870179

RESUMO

INTRODUCTION: The Burn Index (BI) is a significant clinical prognostic parameter for patients with burns. It simultaneously considers major mortality risk factors: age and burns extensivity. Despite the inability to distinguish between ante- and post-mortem burns, their characteristics on autopsy might indicate if a significant thermal injury occurred before the onset of death. We investigated whether autopsy BI, burn extensivity, and severity could tell whether burns were the concurrent cause of fire-related death (FRD), even if the body remained in a fire. MATERIAL AND METHODS: Ten-year retrospective study analyzed FRD that occurred at the scene in a confined space. Soot aspiration was the main inclusion criterion. Autopsy reports were reviewed for demographic data, burn characteristics (degree, Total Body Surface Area burned- TBSA), coronary artery disease, and blood ethanol. We calculated the BI as a sum of the victim's age and percentage of TBSA affected by 2nd, 3rd and 4th-degree burns. Cases were divided into two groups: those with COHb≤ 30% and with COHb> 30%. Subjects with burned TBSA≤ 40% were analyzed separately afterward. RESULTS: The study included 53 males (71.6%) and 21 females (28.4%). No significant difference in age was observed between groups (p > 0.05). COHb≤ 30% had 33, and COHb> 30% had 41 victims. BI and burns extensivity (TBSA) had significant negative correlation with COHb values (ρ = -0.581, p < 0.01 and ρ = -0.439, p < 0.01, respectively). Both were significantly higher in subjects with COHb≤ 30% compared to those with COHb> 30% (140.7 ± 29.57 vs. 95.49 ± 38.49, p < 0.01 and 98 (13-100) vs. 30 (0-100), p < 0.01, BI and TBSA respectively). BI had excellent and TBSA fair performance for detection of subjects with COHb≤ 30% on ROC curve analysis (AUCs 0.821, p < 0.001 and 0.765, p < 0.001), with optimal cut-off values: BI≥ 107 (sensitivity 81.3%, specificity 70.7%) and TBSA≥ 45 (sensitivity 84.8%, specificity 70.7%). On logistic regression analysis BI≥ 107 was independently associated with COHb≤ 30% values (aOR 6; 95%CI 1.55-23.37). The same holds for the presence of 3rd-degree burns (aOR 5.9; 95%CI 1.45-23.99). In the subgroup of subjects with TBSA≤ 40% burned, those with COHb≤ 50% were significantly older than victims with COHb> 50% (p < 0.05). Here BI≥ 85 was a particularly good predictor for detection of subjects with COHb≤ 50% (AUC=0.913, p < 0.001, 95% CI 0.813-1.00; sensitivity 90.9%, specificity 81%). CONCLUSION: The BI≥ 107, TBSA≥ 45% burned, and 3rd-degree burns observed on autopsy point to a significantly higher odds that limited CO intoxication occurred, and burns should be considered a concurrent cause of indoor FRD. When less than 40% of TBSA was affected, BI≥ 85 indicated sub-lethal CO poisoning.


Assuntos
Queimaduras , Incêndios , Masculino , Feminino , Humanos , Carboxihemoglobina/análise , Estudos Retrospectivos , Autopsia
19.
Forensic Sci Med Pathol ; 19(1): 117-120, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35849278

RESUMO

We present fatal extensive soft tissue infections, a consequence of groin heroin injection, in three subjects, who were 27, 34, and 39 years old and had a history of over 10-, 15-, and 5-years of heroin injection (cases 1, 2, and 3, respectively). In all cases, the first symptoms of the infection appeared at least a week prior, with rapid deterioration on the last day. The hallmark was a disproportion between external and internal findings in the affected thighs. The latter presented as extensively spread suppurative inflammation with soft tissue necrosis. In case 1, subtle skin erythema was present in the left groin, with a wound suggestive of a recent abscess incision and injection-related scarring. However, dissection revealed that inguinal regions and deep soft tissue (including the muscle sheets) of the left thigh, gluteal region, and lower third of the anterior abdominal wall were inflamed with pus, alongside fibrinopurulent peritonitis. Case 2 had pronounced erythema and swelling of the thigh and knee. Diffuse suppuration was observed upon dissection in the inguinal regions, which extended into the iliopsoas muscles, with soft tissue and muscle necrosis. In the abdominal cavity, we detected 150 mL of serofibrinous exudate. Only case 3 had a prominent, 4 × 3.5-cm necrotic skin defect through which pus spontaneously drained. In contrast to the other two, although extensive pus collection within predominantly necrotic thigh's soft tissue was present, the inflammation did not expand above the inguinal ligament, and peritonitis was not observed. Toxicology analysis excluded acute heroin intoxications.


Assuntos
Virilha , Infecções dos Tecidos Moles , Humanos , Virilha/cirurgia , Heroína , Abscesso , Necrose
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