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This study aimed to evaluate the effect of aqueous extract of Paullinia cupana (AEG) against ketoprofen side effects, through biochemical, hematological, and histological parameters. AEG showed antioxidant activity in the DPPH • scavenging (IC 50  = 17.00 ± 1.00 µg/ml) and HPLC analysis revealed that this extract is constituted by antioxidants (caffeine, catechins, theobromine, and polyphenols). In vivo experiments in female Wistar rats demonstrated that alterations in urea, creatinine, and uric acid levels promoted (p < .05) by ketoprofen were reversed when AEG was co-administered. Ketoprofen significantly decreased the catalase levels of animal tissues (p < .05), which were restored when AEG was co-administered with the mentioned drug. Histological analysis showed that AEG protected tissues from damages caused by ketoprofen. Moreover, AEG reestablished the number of white blood cells, which had decreased when ketoprofen was administered. In conclusion, this study suggested that the association between ketoprofen and AEG may be an alternative to reduce health damages caused by this drug. PRACTICAL APPLICATIONS: Paullinia cupana, popularly known as guaraná, is commonly consumed as a beverage in Brazil and exhibits pharmacological and beneficial effects to humans. Ketoprofen is an efficacious drug employed in the treatment of inflammatory processes. However, this drug can cause several side effects in humans. Thus, the usage of natural products and plant extracts that can reduce such undesirable effects consists in a valuable strategy to be applied in therapeutic interventions., (© 2020 Wiley Periodicals LLC.)

Thyroid diseases are relatively common in women in the reproductive period. It is currently understood that clinically-evident thyroid disorders may impair ovulation and, consequently, fertility. However, to date it has not been proven that high serum levels of thyroid-stimulating hormone and/or positivity for antithyroid antibodies are associated to a reduction in fertility, mainly in the absence of altered thyroxine levels. The present comprehensive review aims to present current data on the association between subclinical hypothyroidism and/or thyroid autoimmunity and reproductive outcomes., Competing Interests: The authors have no conflict of interests to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Competing Interests: None to declare.

Purpose: The aim of this study is to report our results of toric intraocular lens (IOL) implantation in patients with asymmetric astigmatism, its efficacy and safety in reducing the refractive cylinder., Methods: This is a retrospective cohort study. Patients with asymmetric astigmatism and non-progressive corneal ectasia, unable to fit hard contact lenses, with poor-corrected visual acuity or unsatisfactory spectacles-corrected visual acuity, underwent cataract surgery with toric IOL implantation. The choice of lens was individually after optical biometry examination. All surgeries were performed by a single surgeon, with a 2.75-mm clear cornea self-sealing incision at 130° axis, from December 2008 to December 2015., Results: We evaluated 88 eyes of 69 patients with asymmetric astigmatism: primary, secondary to leucoma, post-radial keratectomy, post-lamellar or penetrating keratoplasty, post-LASIK, post-PRK and due to pterygium. Snellen best-corrected spectacles visual acuity increased from 0.39 ± 0.23 preoperative to 0.80 ± 0.23 postoperative. The average refractive cylinder reduced from 2.32 ± 1.78 D preoperatively to 0.87 ± 1.09 D after surgery (P < .001). Sixty-three eyes out of 88 (71%) had residual refractive cylinder ≤ 1.0 D., Conclusion: The favorable efficacy on visual acuity outcomes we have found suggests that toric IOL can be used in cases of asymmetric astigmatism, in order to provide better-corrected vision, less spectacles dependence and an improved quality of vision overall, which is especially important in contact lenses intolerant patients.

Considering that myths and misconceptions regarding natural procreation spread rapidly in the era of easy access to information and to social networks, adequate counseling about natural fertility and spontaneous conception should be encouraged in any kind of health assistance. Despite the fact that there is no strong-powered evidence about any of the aspects related to natural fertility, literature on how to increase the chances of a spontaneous pregnancy is available. In the present article, the Brazilian Federation of Gynecology and Obstetrics Associations (FEBRASGO, in the Portuguese acronym) Committee on Endocrine Gynecology provides suggestions to optimize counseling for non-infertile people attempting spontaneous conception., Competing Interests: The authors have no conflicts of interests to declare., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Background: Medicinal plants are an important source to identify new active pharmaceutical compounds. Traditionally, the sap of Euphorbia umbellata is widely used to treat cancer and inflammatory conditions. These effects have been attributed to the presence of terpenes and phenolic compounds in the extracts of this plant. Euphol, a tetracyclic triterpene alcohol, is one of the major compounds present in Euphorbia species, and some biological activities have been attributed to this compound., Purpose: This study aimed to evaluate the in vitro cytotoxicity of euphol against Jurkat, HL-60, K-562, B16F10, and HRT-18 cells lines, as well as the biological stability, distribution, metabolism properties in vitro, and the determination of the concentration of euphol in the plasma and liver of rats., Methods: The MTT reduction assay was used to evaluate the cytotoxicity of euphol against cancer cell lines, and the selectivity index, the morphology and cell cycle assays to evaluate the death mechanisms in K-562 and B16F10 lineages. UHPLC-MS was applied for the in vivo evaluation of the concentration of euphol in plasma and liver, and in vitro metabolic stability in human liver microsomes and S9 fraction, plasma protein binding, and stability in simulated gastric and intestinal fluids assays., Conclusions: This study demonstrated that euphol exhibited cytotoxic effects against a variety of cancer cells lines, selectivity against leukemia and possibly, the mechanism involved is apoptosis. The evaluation of stability, distribution, and metabolism properties showed that euphol was unstable in gastric and intestinal fluids, presenting moderate plasma protein binding with two hours elimination half-life and possible phase II liver metabolism. All the results suggested that further studies could be developed to prove the viability of euphol as an anticancer agent., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Gender incongruence is defined as a condition in which an individual self-identifies and desires to have physical characteristics and social roles that connote the opposite biological sex. Gender dysphoria is when an individual displays the anxiety and/or depression disorders that result from the incongruity between the gender identity and the biological sex. The gender affirmation process must be performed by a multidisciplinary team. The main goal of the hormone treatment is to start the development of male physical characteristics by means of testosterone administration that may be offered to transgender men who are 18 years old or over. The use of testosterone is usually well tolerated and improves the quality of life. However, there is still lack of evidence regarding the effects and risks of the long-term use of this hormone. Many different pharmacological formulations have been used in the transsexualization process. The most commonly used formulation is the intramuscular testosterone esters in a short-term release injection, followed by testosterone cypionate or testosterone enanthate. In the majority of testosterone therapy protocols, the male physical characteristics can be seen in almost all users after 6 months of therapy, and the maximum virilization effects are usually achieved after 3 to 5 years of regular use of the hormone. To minimize risks, plasmatic testosterone levels should be kept within male physiological ranges (300 to 1,000 ng/dl) during hormonal treatment. It is recommended that transgender men under androgen therapy be monitored every 3 months during the 1st year of treatment and then, every 6 to 12 months., Competing Interests: This revision was elaborated by the Specialized National Committees on Endocrine Gynecology at Federação Brasileira das Associações de Ginecologia e Obstetrícia., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Current data are inconsistent regarding the association between interleukin-6 (IL-6), a marker of acute phase inflammation, and pelvic endometriosis. The aim of the present study was to assess IL-6 levels in serum and peritoneal fluid (PF), as well as IL-6 gene expression in adipose tissue (AT) and endometrial samples in pelvic endometriosis. A total of 30 patients with endometriosis and 18 women with a normal pelvis were enrolled in this case-control study. IL-6 levels in PF and serum were determined using a human enzyme-linked immunosorbent assay and IL-6 gene expression was evaluated using reverse transcription-quantitative polymerase chain reaction. It was observed that IL-6 levels in the PF were higher in patients with endometriosis than in the control group (P=0.047) and patients with stage III/IV endometriosis exhibited higher IL-6 levels in the PF than those with stage I/II endometriosis and the control group (P<0.001). Furthermore, a strong correlation between PF IL-6 levels and the revised American Society for Reproductive Medicine score for endometriosis severity was identified (r=0.77; P<0.001). IL-6 gene expression did not differ significantly between endometriosis and control groups in endometrial samples or in AT of both groups. The results of the current study suggest that there may be an association between IL-6 and the presence and severity of pelvic endometriosis. The source of this higher IL-6 seems not to be specifically related to regional AT.

Septic shock, which is triggered by microbial products, is mainly characterised by inadequate tissue perfusion, which can lead to multiple organ dysfunction and death. An intense release of vasoconstrictors agents occurs in the early stages of shock, which can lead to ischemic injury. In this scenario, cGMP could play a key role in counterbalancing these agents and preventing tissue damage. Sildenafil, which is a phosphodiesterase-5 inhibitor, increases cGMP in smooth muscle cells and promotes vasodilation. Thus, the purpose of this study was to investigate the effect of treatment with sildenafil in the early stages of sepsis. Male rats were submitted to either cecal ligation and puncture (CLP) or a sham procedure. Eight h after the procedure, the CLP and sham groups were randomly assigned to receive sildenafil (10mg/kg, gavage) or vehicle, and twelve or twenty-four h later the inflammatory, biochemical and haemodynamic parameters were evaluated. Sepsis significantly increased levels of plasma nitrate/nitrite (NOx), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, creatine kinase and lactate. Additionally, sepsis led to hypotension, hyporesponsiveness to vasoconstrictor, renal blood flow reduction and also increased lung and kidney myeloperoxidase. Sildenafil increased renal blood flow and reduced the plasma levels of creatinine, lactate and creatine kinase, as well as reducing lung myeloperoxidase. Thus, phosphodiesterase inhibition may be a useful therapeutic strategy if administered at the proper time., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Objective: It has been demonstrated that periodontitis induces systemic inflammation, which may impair endothelial function leading to increased cardiovascular risk. The aim of this study was to evaluate the effect of simvastatin on systemic inflammatory markers and endothelial dysfunction induced by periodontitis., Material and Methods: Wistar rats were subjected to ligature-induced experimental periodontitis. Eight days after the procedure, the ligature and sham groups were randomly assigned to receive simvastatin or vehicle once a day until the 14th day, when the effects of acetylcholine and sodium nitroprusside on blood pressure were evaluated. Blood samples were collected and evaluated for plasma interleukin-6C, -reactive protein and lipids. The maxilla and mandible were removed for bone loss analysis., Results: Simvastatin treatment reduced systemic inflammation and endothelial dysfunction induced by periodontitis. Furthermore, simvastatin improved the blood lipid profile and reduced alveolar bone loss., Conclusion: Simvastatin treatment, in addition to the improvement on serum lipid profile, may reduce other predictors of cardiovascular events associated with periodontitis., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more consecutive pregnancy losses. It is an important reproductive condition with a complex etiology. In approximately 50% of RPL cases an explanation for the cause is not found and they are therefore classified as idiopathic RPL. One of the causes implicated in RPL is thrombophilia, which consists of hemostatic disorders that lead to an increase in thromboembolic processes. The aim of this study was to evaluate polymorphic variants in genes related to thrombophilia as a risk factor in women with RPL. We investigated 145 women with at least two consecutive pregnancy losses and 135 women with at least two children and no history of pregnancy loss. Genotypes for the polymorphisms MTHFR C677T, FVL, FII (prothrombin), eNOS T-786C, and eNOS Glu298Asp were determined using a real-time PCR. Information about the exposure to environmental risk factors was also collected. There was no significant association between the environmental risk factors assessed and the polymorphisms studied. We did not find statistically significant differences in genotypic or allelic frequencies for the polymorphisms studied, in either the women with RPL or in the control group. Such polymorphisms should therefore not be considered as risk factors for this condition in this population.

In this study, leptin/BMI ratio in serum and peritoneal fluid and gene expression of leptin and long form leptin receptor (OB-RL) were assessed in eutopic and ectopic endometria of women with endometriosis and controls. Increased serum leptin/BMI ratio was found in endometriosis patients. Leptin and OB-RL gene expression was significantly higher in ectopic versus eutopic endometrium of patients and controls. A positive, significant correlation was observed between leptin and OB-RL transcripts in ectopic endometria and also in eutopic endometria in endometriosis and control groups. A negative and significant correlation was found between OB-RL mRNA expression and peritoneal fluid leptin/BMI ratio only in endometriosis. These data suggest that, through a modulatory interaction with its active receptor, leptin might play a role in the development of endometrial implants.

Endometriosis is characterized by the presence of endometrial tissue, localized outside the uterine cavity, such as peritoneal surface, ovaries, and rectum-vaginal septum. The prevalence is about 6 to 10%. Concerning the etiopathogenesis, the retrograde menstruation theory is accepted, although disruption in endometrial molecular biology seems to be fundamental to the development of endometriosis ectopic focuses. Women with endometriosis may be asymptomatic or may present complaints of dysmenorrhea, dispareunia, chronic pelvic pain and/or infertility. Although the definitive diagnosis of endometriosis needs a surgical intervention, mainly by laparoscopy, many findings obtained by physicalexamination and imaging and laboratory tests can predict, with a high degree of reliability, that the patient has endometriosis. The most common current treatments include surgery, ovarian suppression therapy or both. Pharmacological treatments that do not inhibit ovarian function are under investigation.

Background and Objectives: Clonidine has been used in anesthesia for its sedative and analgesic properties, and to achieve greater hemodynamic stability with reduction in intra-ocular pressure. This study evaluated the clinical effects of intravenous clonidine (2.5 microg.kg(-1)) on the intra-ocular pressure (IOP), hemodynamic parameters, and post-anesthetic recovery in the surgical treatment of cataract., Methods: This is a randomized, double-blind, placebo-controlled study that included patients undergoing cataract surgery under peribulbar block. After placement of monitoring devices, baseline (M0) values of IOP, mean arterial pressure (MAP), heart rate (HR), SpO2, and the degree of sedation (Ramsay) were determined. Afterwards, placebo (Group P) or clonidine (Group C) was administered intravenously. After 30 minutes, at Moment 1 (M1), measurements were repeated, and once again at the end of the surgery, at Moment 2 (M2)., Results: The change in IOP between M0 and M1 was different for both groups, 14.5% in Group C and 5.25% in Group P (p = 0.01), and the means remained reduced until M2. Mean arterial pressure in Group C showed a 17% reduction from M0 to M1 and increased 3.5% in Group P (p < 0.001) and in Group C it showed a recovery at M2 (p = 0.17). The heart rate decreased 6.4% in Group C and 1% in Group P (p = 0.1) from M0 to M1. There was a greater sedation in Group C when compared with Group P (p < 0.001) but there was no cases of respiratory depression. The relative risk of intraoperative hypertension was 0.657 (CI 95% 0.517 to 0.835) in Group C, p < 0.01. Differences in the incidence of tachycardia, hypoxemia, hypotension, and increased hospital staying were not observed between both groups., Conclusions: Clonidine, under the conditions of the present study, showed to be a safe drug and decreased IOP and the intraoperative risk of hypertension without delaying hospital discharge.

Purpose: To describe 9 eyes in 8 patients who received Dohlman-Doane type 1 keratoprosthesis (KPro) with a mean follow-up of 11.2 months (2 to 25 months)., Methods: A retrospective, non-comparative interventional case series. Previous corneal disease was alcaline burn in 4 eyes, multiple graft failure in 3 eyes, Stevens-Johnson syndrome in 1 eye and thermal injury in 1 eye. Best corrected visual acuity (BCVA) was hand motions or worse in all patients. Glaucoma was present preoperatively in 3 eyes and received Ahmed valve implantation., Results: 88,9% eyes achieved BCVA of better than or equal to 20/100, and 44,4% better than or equal to 20/40. In the postoperative period, 3 eyes developed posterior capsule opacity treated with YAG laser capsulotomy; 3 retroprosthetic membrane treated with tPA injection or steroids; 2 glaucoma in clinical treatment; 1 corneal melting, treated with donor cornea bottom exchange; and 1 fungic endophthalmitis, treated with corneal transplant, anterior vitrectomy, KPro and intraocular lens explantation, and specific intravitreal and endovenous treatment., Conclusion: Dohlman-Doane K-Pro seems to be a good option for cases of corneal blindness with poor prognosis for traditional penetrating keratoplasty. Its main advantage is not requesting systemic immunossuppression. Best results were achieved in non-immune diseases.

The T allele of the C825T polymorphism in the G-protein beta(3) subunit gene (GNB3) is related to the increase of signal transduction by the G-protein. G-proteins are intermediary paths in signal transduction from receptors involved in mood regulation and substance dependence. We studied the C825T polymorphism in individuals with (i) alcohol and nicotine dependence (n = 109), (ii) nicotine dependence only (n = 117) and (iii) non-dependent controls (n = 108). We also tested for possible associations with psychiatric comorbidities among alcohol-dependent individuals. No differences were detected for allele and genotype frequencies in individuals with or without dependencies. Alcohol-dependent individuals with the heterozygous genotype presented more frequently major depressive disorder (chi(2) = 12.34; p = 0.002). These findings, taken together with other studies suggesting an influence of the C825T polymorphism in major depressive disorder, support the hypothesis of the involvement of G-proteins in mood regulation.

The aim of the present study is to test for possible associations between the C-1291G polymorphism in the alpha2A-adrenergic receptor gene (ADRA2A) with tobacco smoking and alcohol dependence. The genotype and allele frequencies were compared in three groups of European-derived Brazilian males: individuals with co-occurrence of tobacco smoking and alcohol dependence (N = 110), with tobacco smoking (N = 121) and controls (N = 114). The frequency of the G allele was higher in the group with both conditions, intermediate among subjects with smoking, and lower among controls (chi(2) = 8.00; p = 0.02). The chi(2) partitioning did not reveal significant differences between the sample with the two conditions and the sample of smokers (chi(2) = 0.82; p = 0.36). Combining both groups, the difference to the non-smoking controls is higher than the one observed in the three-groups analysis (chi(2) = 7.18; p = 0.007). The results suggest a role for the ADRA2A C-1291G polymorphism, notably the G allele, in the predisposition to tobacco smoking. The influence of the ADRA2A gene in nicotine and other substance dependencies should be more extensively assessed in future studies.