Effects of chronic estradiol treatment on the thyroid gland structure and function of ovariectomized rats

<p>Abstract</p> <p>Background</p> <p>Estrogen therapy is widely used nowadays in women to treat many postmenopausal symptoms but it may have some undesirable effects due to multiple organs affection. So, the aim of this study was to determine the effects of chronic estradiol treatment on the structure and function of the thyroid gland in ovarictomized rats as a model simulating menopause.</p> <p>Findings</p> <p>Thirty adult female Wistar rats divided into three groups were used in this study; the first group was sham-operated, while the second and third groups were ovariectomized. The first and second groups were injected with olive oil while the third group was injected with estradiol dipropionate daily for three months, after that; hormonal assay for T3, T4, TSH and specimens of the thyroid were taken and processed to be examined by light and electron microscopy. The results of this study revealed that serum levels of T3 and T4 decreased in ovariectomized animals and significantly increased after estradiol treatment, while TSH increased in ovariectomized animals and decreased with estradiol treatment. Histological and morphometric study in ovariectomized group revealed marked accumulation of colloid in follicular lumens with decreased epithelial height in addition to increased connective tissue amount. After estradiol treatment the follicles became smaller in size, having small amount of colloid with increased epithelial height in addition to decreased connective tissue content. Ultrastructural study supported these results in addition to the presence of large amount of intracytoplasmic colloid vesicles after estradiol treatment.</p> <p>Conclusion</p> <p>Low estrogen level may lead to mild thyroidal hypofunction while estradiol treatment may lead to hyperactivity so it should be used very cautiously in the treatment of postmenopausal symptoms to avoid its undesirable stimulatory effect on the thyroid.</p

Molecular Characterization, Developmental Expression and Immunolocalization of Clathrin Heavy Chain in the Ovary of the American Cockroach, Periplaneta Americana During Oogenesis

Clathrin is the principal protein involved in receptor mediate endocytosis and the main component of the coated vesicles. It is composed of three identical clathrin heavy chains (CHC), each with an attached light chain. We characterized the deduced amino acid sequence of the partial cDNA clone of the American cockroach, Periplaneta americana (Pam) CHC. The analysis showed that this sequence is represented as multiple alpha helical repeats occurred in the arm region of the CHC and displayed a high level of identity and similarity to mosquitoes and Drosophila melanogaster CHCs. This is the first report on CHC from a hemimetabolous insect. The amplified CHC probe could hybridize two CHC transcripts in the current preparations, 6.3 kb and 7.3 kb. The Northern blot analysis confirmed that a 6.3 kb transcript is specifically expressed in ovarian tissues at high levels throughout the ovarian development, especially in previtellogenic ovaries (Days 1-4) but dropped during the vitellogenic period (days 5-7) and ultimately no transcript was detected in fully vitellogenic ovaries (days 9-13). Immunoblot analysis detected an ovary specific CHC protein of ~175 kDa that was present in previtellogenic ovaries on the day of female emergence and after initiation of vitellogenesis and onset of Vg uptake. Immunocytochemistry localized CHC protein to germ-line derived cells, oocytes, and revealed that CHC translation begins very early during oocyte differentiation in the germarium. The present work suggested a possible role for clathrin in the early fluid phase endocytosis (pinocytosis) in addition to its role in receptor-mediated endocytosis

Clinical and angiographic outcomes with drug-coated balloons for de novo coronary lesions: A meta-analysis of randomized clinical trials

Background The role of drug-coated balloons (DCBs) in the treatment of de novo coronary lesions is not well established. Methods and Results Electronic databases and major conference proceedings were searched for randomized controlled trials that compared DCBs with stents or angioplasty for de novo coronary lesions. The primary outcome was target lesion revascularization. Summary estimates were conducted using random-effects analysis complemented by several subgroup and sensitivity analyses. A total of 14 randomized controlled trials with 2483 patients were included. At a mean follow up of 12 months, DCBs were associated with no difference in the incidence of target lesion revascularization as compared with alternative strategies (risk ratio [RR], 0.79; 95% CI, 0.35-1.76). There was no difference in treatment effect based on the indication (ie, small-vessel disease, myocardial infarction, bifurcation, or high bleeding risk) (Pinteraction=0.22). DCBs were associated with lower target lesion revascularization compared with bare metal stents and similar target lesion revascularization compared with drug-eluting stents (Pinteraction=0.03). There was no difference between DCBs and control in terms of major adverse cardiac events, vessel thrombosis, or cardiovascular mortality. However, DCBs were associated with a lower incidence of myocardial infarction (RR, 0.48; 95% CI, 0.25-0.90) and all-cause mortality (RR, 0.45; 95% CI, 0.22-0.94). Conclusions In patients with de novo coronary lesions, use of DCBs was associated with comparable clinical outcomes irrespective of the indication or comparator device. DCBs had a similar rate of target lesion revascularization compared with drug-eluting stents. A randomized trial powered for clinical outcomes and evaluating the role of DCBs for all-comers is warranted

Molecular characterization, developmental expression and immunolocalization of clathrin heavy chain in the ovary of the American cockroach, Periplaneta americana during oogenesis

Clathrin is the principal protein involved in receptor mediate endocytosis and the main component of the coated vesicles. It is composed of three identical clathrin heavy chains (CHC), each with an attached light chain. We characterized the deduced amino acid sequence of the partial cDNA clone of the American cockroach, Periplaneta americana (Pam) CHC. The analysis showed that this sequence is represented as multiple alpha helical repeats occurred in the arm region of the CHC and displayed a high level of identity and similarity to mosquitoes and Drosophila melanogaster CHCs. This is the first report on CHC from a hemimetabolous insect. The amplified CHC probe could hybridize two CHC transcripts in the current preparations, 6.3 kb and 7.3 kb. The Northern blot analysis confirmed that a 6.3 kb transcript is specifically expressed in ovarian tissues at high levels throughout the ovarian development, especially in previtellogenic ovaries (Days 1-4) but dropped during the vitellogenic period (days 5-7) and ultimately no transcript was detected in fully vitellogenic ovaries (days 9-13). Immunoblot analysis detected an ovary specific CHC protein of ~175 kDa that was present in previtellogenic ovaries on the day of female emergence and after initiation of vitellogenesis and onset of Vg uptake. Immunocytochemistry localized CHC protein to germ-line derived cells, oocytes, and revealed that CHC translation begins very early during oocyte differentiation in the germarium. The present work suggested a possible role for clathrin in the early fluid phase endocytosis (pinocytosis) in addition to its role in receptor-mediated endocytosis

Ethnic and Gender Disparities in the Uptake of Transcatheter Aortic Valve Replacement in the United States

Introduction: Little is known about ethnic and gender disparities for transcatheter aortic valve replacement (TAVR) procedures in the United States. Methods: We queried the Nationwide Inpatient Sample (NIS) database (2011–2014) to identify patients who underwent TAVR. We described the temporal trends in the uptake of TAVR procedures among various ethnicities and genders. Results: Our analysis identified 39,253 records; 20,497 (52.2%) were men and 18,756 (47.8%) were women. Among all TAVRs, 87.2% were Caucasians, 3.9% were African Americans (AA), 3.7% were Hispanics, and 5.2% were of other ethnicities. We found a significant rise in the trend of TAVRs in all groups: in Caucasian men (coefficient = 0.946, p \u3c 0.001), Caucasian women (coefficient = 0.985, p \u3c 0.001), AA men (coefficient = 0.940, p \u3c 0.001), AA women (coefficient = 0.864, p \u3c 0.001), Hispanic men (coefficient = 0.812, p = 0.001), Hispanic women (coefficient = 0.845, p \u3c 0.001). Hence, the uptrend was most significant among Caucasian women, and relatively least significant among Hispanic men. Multivariate regression analysis was conducted to evaluate in-hospital mortality among different groups after adjusting for demographics and baseline characteristics. After multivariable regression for baseline characteristics overall, the in-hospital mortality per 100 TAVRs was highest among Hispanic men 5.5%, followed by Caucasian women 5.0%, Hispanic women 4.6%, AA women 3.7%, AA men 3.4%, and Caucasian men 3.38% (adjusted p value = 0.004). Conclusions: In this observational study, we demonstrated that there is evidence of ethnic and gender differences in the overall uptake and adjusted mortality of TAVRs in the United States

Ligand-based design, synthesis, computational insights, and in vitro studies of novel N-(5-Nitrothiazol-2-yl)-carboxamido derivatives as potent inhibitors of SARS-CoV-2 main protease

The global outbreak of the COVID-19 pandemic provokes scientists to make a prompt development of new effective therapeutic interventions for the battle against SARS-CoV-2. A new series o

Efficacy and safety of Elagolix in the treatment of endometriosis associated pain: a systematic review and network meta-analysis

Background: Endometriosis commonly presents with dysmenorrhea, non-menstrual pelvic pain, and infertility. Elagolix is an oral, short-acting, gonadotropin-releasing hormone antagonist acting through complete estrogen suppression. Objective: To evaluate the evidence from published randomized controlled trials (RCTs) about the efficacy and safety of Elagolix in the treatment of endometriosis associated pain. Search strategy: Electronic databases containing articles published between January 2000 and February 2020 were searched using the MeSH terms (Elagolix OR gonadotropin-releasing hormone antagonist OR GnRH antagonist OR antigonadotropin) AND (endometriosis) AND (pelvic pain). Selection criteria: All RCTs assessing the efficacy of Elagolix in the treatment of pain associated with endometriosis were considered for this network meta-analysis, where five studies were deemed eligible for this review. Data collection and analysis: The mean difference (MD) and confidence intervals (95% CI) for continuous outcomes including analgesic use, dysmenorrhea, non-menstrual pelvic pain, and quality of life were calculated. Main results: Elagolix 250 mg reduced dysmenorrhea significantly, as compared to placebo, (MD = -0.41, 95% CI [-0.7, -0.13]) at 12 weeks, while Elagolix 200 mg reduced dysmenorrhea significantly (MD= -1.2, 95% CI [-1.9, -0.57]) compared to placebo after 24 weeks of treatment. Conclusions: Elagolix 200 mg seems to be an effective drug with fewer side effects when used to reduce dysmenorrhea and non-menstrual pelvic pain after 24 weeks of treatment in patients with endometriosis

Beneficial Effects of Hesperidin against Cisplatin-Induced Nephrotoxicity and Oxidative Stress in Rats

Abstract: Cisplatin has been frequently used for treatment of wide variety of tumors. The use of cisplatin is associated with severe cytotoxicity such as nephrotoxicity, hepatotoxicity and spermiotoxicity which radically limits its clinical use. The present study aimed to investigate the possible protective effects of multiple doses of hesperidin against cisplatin-induced nephrotoxicity induced by single i.p injection of cisplatin (7.5 mg/kg). Hesperidin was given to rats at two different doses (100 and 200 mg/kg p.o) for 7 days starting one day before cisplatin injection. Blood samples were collected for determination of serum creatinine and Blood Urea Nitrogen (BUN) levels. Kidneys were used for the determination of Malondialdehyde (MDA), Glutathione (GSH) and total nitrate and nitrite contents. Liver samples were also used for histopathological examination. Results showed that hesperidin significantly reduced cisplatin-induced elevations in serum creatinine and BUN levels. It also significantly reduced kidney MDA and NO content and elevated GSH content. In conclusion, hesperidin greatly protected kidney against cisplatin-induced toxicity in a dose-dependent manner

Methodological rigor and temporal trends of cardiovascular medicine meta-analyses in highest-impact journals

Background Well-conducted meta-analyses are considered to be at the top of the evidence-based hierarchy pyramid, with an expansion of these publications within the cardiovascular research arena. There are limited data evaluating the trends and quality of such publications. The objective of this study was to evaluate the methodological rigor and temporal trends of cardiovascular medicine-related meta-analyses published in the highest impact journals. Methods and Results Using the Medline database, we retrieved cardiovascular medicine-related systematic reviews and meta-analyses published i