Contraceptive Drugs Research Articles

Mifepristone increases AQP1 mRNA expression, angiogenesis, and cell permeability through the ERK MAPK pathway.

The purpose of this study was to investigate the mechanism of mifepristone serves as an anti-implantation contraceptive drug on aquaporins 1 (AQP1) expression. Human umbilical vein endothelial cells (HUVECs) were used to detect the effects of different concentrations of mifepristone (0, 0.065, 0.2, and 1μmol/L) on the activity of angiogenesis and AQP1 expression. The expression of AQP1 was tested by the real-time PCR. The angiogenesis and penetration function of HUVECs was investigated by Matrigel lumen formation and trans-well assay, respectively. The expression of AQP1, angiogenesis and cell permeability were significantly higher than control groups in HUVECs treatment with mifepristone at 1μmol/L for 12h. Estrogen and progesterone decreased the up-regulation of AQP1 and cell permeability, not angiogenesis, induced by mifepristone. Mifepristone increased protein levels of p-ERK, not p-p38 or p-JNK, and pre-treatment with ERK MAPK-specific inhibitor significantly inhibited the up-regulation of AQP1 mRNA expression, angiogenesis and cell permeability induced by mifepristone. si-AQP1 significantly reduced the up-regulation of angiogenesis, cell permeability and p-ERK/ERK ratio expression induced by mifepristone treatment. Overexpression of AQP1 enhanced the increase of expression ratio of p-ERK/ERK induced by mifepristone. Low-dose mifepristone increased cell permeability, angiogenesis and AQP1 expression, which was involved in MAPK pathways. This provides new insights into the molecular mechanism of mifepristone serves as an anti-implantation contraceptive drug.

Advancing ASMS with LC-MS/MS for the discovery of novel PDCL2 ligands from DNA-encoded chemical library selections.

A safe, effective, and reversible nonhormonal male contraceptive drug is greatly needed for male contraception as well as for circumventing the side effects of female hormonal contraceptives. Phosducin-like 2 (PDCL2) is a testis-specific phosphoprotein in mice and humans. We recently found that male PDCL2 knockout mice are sterile due to globozoospermia caused by impaired sperm head formation, indicating that PDCL2 is a potential target for male contraception. Herein, our study for the first time developed a biophysical assay for PDCL2 allowing us to screen a series of small molecules, to study structure-activity relationships, and to discover two PDCL2 binders with novel chemical structure. To identify a PDCL2 ligand for therapeutic male contraception, we performed DNA-encoded chemical library (DECL) screening and off-DNA hit validation using a unique affinity selection mass spectrometry (ASMS) biophysical profiling strategy. We employed the screening process of DECL, which contains billions of chemically unique DNA-barcoded compounds generated through individual sequences of reactions and different combinations of functionalized building blocks. The structures of the PDCL2 binders are proposed based on the sequencing analysis of the DNA barcode attached to each individual DECL compound. The proposed structure is synthesized through multistep reactions. To confirm and determine binding affinity between the DECL identified molecules and PDCL2, we developed an ASMS assay that incorporates liquid chromatography with tandem mass spectrometry (LC-MS/MS). After a screening process of PDCL2 with DECLs containing>440 billion compounds, we identified a series of hits. The selected compounds were synthesized as off-DNA small molecules, characterized by spectroscopy data, and subjected to our ASMS/LC-MS/MS binding assay. By this assay, we discovered two novel compounds, which showed good binding affinity for PDCL2 in comparison to other molecules generated in our laboratory andwhich were further confirmed by a thermal shift assay. With the ASMS/LC-MS/MS assay developed in this paper, we successfully discovered a PDCL2 ligand that warrants further development as a male contraceptive.

How do new therapeutic strategies for PCOS management influence the health of the affected individuals? The narrative review

Introduction and purpose: Management of polycystic ovary syndrome (PCOS) is difficult since the exact pathogenic mechanism has not been established yet. Due to that fact, the substances registered to treat PCOS are still lacking efficacy and are associated with a number of adverse effects. The aim of this study is to review new possible treatment approaches.
 
 State of knowledge: Inositol administered alone or combined with oral contraceptive drugs improves patients’ hormonal status and alleviates the weight increase in comparison to oral contraceptive drugs on their own. Berberine reduces insulin resistance, improves lipid metabolism, and reduces inflammatory reactions. Glucagon-like peptide-1 receptor agonists have a better weight loss effect and less severe adverse reactions than metformin. Thiazolidinediones combined with metformin improve ovulation rate, acne and increase SHGB levels. Thiazolidinediones have also less severe adverse reactions than metformin and can be useful in patients who are not able to tolerate metformin.
 
 Summary: The review has shown that inositol, berberine, glucagon-like peptide-1 receptor agonists andthiazolidinediones have promising therapeutic effects in terms of PCOS treatment, however, more research is needed to establish safety and efficacy of those agents. Nonetheless, results of this study may be utilized in the education of health specialists in endocrinology departments.

Symptom: Runny Nose Six Years After Acoustic Neuroma Surgery

Symptom: Runny Nose Six Years After Acoustic Neuroma Surgery

The diagnosis and treatment of primary dysmenorrhea

Primary dysmenorrhea is defined as pain in the pelvic area that occurs for no specific reason during menstrual cycle. Dysmenorrhea occurs in 50% to 90% of adolescent girls and women of reproductive age which makes it one of the most common causes of pelvic pain in women. The mechanism of this condition is overproduction of prostaglandins by the endometrium, causing uterine hypercontractility, thereby leading to uterine muscle ischemia, hypoxia and pain. Dysmenorrhea significantly reduces the quality of women life, often making it impossible to perform daily activities and, in addition, it may cause a mental stress that makes both professional and school life difficult. Despite this, females often consider these symptoms as a normal part of their menstrual cycle, which makes this disease underrated and untreated. Dysmenorrhea can be treated in a various ways such as non-pharmacological, pharmacological and surgical. However, women with a typical history of primary dysmenorrhea can commence empirical therapy without any additional tests. Hormonal contraception and nonsteroidal antiinflammatory drugs have proved to be effective in this treatment. However, if conventional treatment is contraindicated, alternative treatments such as topical heat, lifestyle modification, transcutaneous electrical nerve stimulation, dietary supplements, acupuncture, and acupressure may be used. Surgical treatment is possible, but it is used rarely and only in severe cases of treatment-resistant dysmenorrhea. However, it should be emphasized how important it is to exclude secondary causes of dysmenorrhea.

Unanticipated Consequences of Switching to Sugammadex: Anesthesia Provider Survey on the Hormone Contraceptive Drug Interaction

(Anesth Analg. 2021;133:958–966) Sugammadex is thought to reduce the efficacy of hormonal contraceptive (HC) due to its ability to bind progesterone. In February 2017, a large, tertiary-care medical center switched from neostigmine to sugammadex as the neuromuscular blockade (NMB) drug of choice. Care should be taken by anesthesiologists to recommend alternative contraceptive methods for patients exposed to sugammadex to avoid unintentional pregnancy. This study, conducted 2 years following the switch to sugammadex, aims to assess the institution’s anesthesiologist provider management of the drug and any knowledge gaps present.

DETERMINATION OF VULVOVAGINAL CANDIDIASIS IN TERTIARY CARE HOSPITAL

Objectives: Infections of vulva and vagina are commonly encountered in gynecology practice. These infections are predominant in the women of reproductive age group so, this study was done to determine the prevalence of vaginal candidiasis and identify, differentiate Candida species isolated from the patients. Three high vaginal swabs per patients were collected using sterile cotton-tipped swabs from Gynecology Department and processed in Department of Microbiology, MLBMC, India. Candida was identified using standard guidelines. The study was done on 350 women in reproductive age group (18–49 years), 63.4% were non-pregnant and 36.5% pregnant. One hundred and sixteen/350 (33.1%) samples showed pure growth of Candida species. Candida positivity among pregnant women (42.9%) was higher than in non-pregnant women (27.1%). Isolation of non-albican Candida was higher (26.7%) than Candida albicans, this difference was statistically significant (p<0.05) The most common isolated species by conventional methods was C. albicans (36.3%) followed by Candida glabrata (24.1%), Candida tropicalis (22.5%), Candida krusei (10.3), and Candida parapsilosis (7.7%). In case of C. albicans, Fluconazole and Amphotericin B were found to be most sensitive drugs followed by Nystatin, voriconazole and ketoconazole and among non-albicans candida, Nystatin was the highly sensitive drug. Vulvovaginal candidiasis (VCC) is the most common infection in the women reproductive age group. Several predisposing factors such as HIV, diabetes mellitus, oral contraceptive, IUCD usage, antibiotics, and immunosuppressive drug increase the VCC, C. albicans was the most prevalent species followed by C. glabrata and C. tropicalis.

Alveolar osteitis: the current state of knowledge

Introduction and purpose:
 Alveolar osteitis, also known as dry socket is a common complication after tooth extraction, especially third molar extraction. Taking into consideration only third molar extractions, the prevalence of dry socket reaches even 45%. The aim of this literature review was to describe current knowledge about etiology, risk factors, treatment, and prevention of dry socket.
 State of knowledge:
 The symptoms of alveolar osteitis most frequently are reported between the first and third post-extraction days and they include discomfort, lancing, and intense pain which radiates to the neck and ear. The etiopathogenesis of dry socket remains unclear. However, the currently accepted hypothesis describes a loss of formed after an extraction blood clot from the alveolar socket as the main cause of this pathology. Several factors may increase the risk of dry socket and include smoking, oral hygiene, female gender, oral contraceptive drugs, and anesthesia. In the treatment of alveolar osteitis, irrigation of the socket with chlorhexidine gluconate, iodopovidone, or physiological saline followed by filling the socket with intra-alveolar dressing constitute a current fundamental procedure. Plenty of substances are currently used as an intra-alveolar dressing. Part of them exhibits only pain-decreasing features, whereas some drugs can also stimulate the regeneration of treated tissue. In the prevention, the use of alveolar osteitis warm saline, antibiotics, chlorhexidine, ozone gas, or autologous platelet therapy may be useful maneuvers.
 Conclusion:
 This literature review summarizes the current state of knowledge about causes, risk factors, and therapeutic and preventive methods with regard to alveolar osteitis.

Bivalent BET Bromodomain Inhibitors Confer Increased Potency and Selectivity for BRDT via Protein Conformational Plasticity.

Bromodomain and extraterminal domain (BET) proteins are important regulators of gene transcription and chromatin remodeling. BET family members BRD4 and BRDT are validated targets for cancer and male contraceptive drug development, respectively. Due to the high structural similarity of the acetyl-lysine binding sites, most reported inhibitors lack intra-BET selectivity. We surmised that protein-protein interactions induced by bivalent inhibitors may differ between BRD4 and BRDT, conferring an altered selectivity profile. Starting from nonselective monovalent inhibitors, we developed cell-active bivalent BET inhibitors with increased activity and selectivity for BRDT. X-ray crystallographic and solution studies revealed unique structural states of BRDT and BRD4 upon interaction with bivalent inhibitors. Varying spacer lengths and symmetric vs unsymmetric connections resulted in the same dimeric states, whereas different chemotypes induced different dimers. The findings indicate that the increased intra-BET selectivity of bivalent inhibitors is due to the differential plasticity of BET bromodomains upon inhibitor-induced dimerization.

Development of a Translational Exposure-Bracketing Approach to Streamline the Development of Hormonal Contraceptive Drug Products.

Worldwide, 922 million women of reproductive age (or their partners) use some sort of contraception to prevent pregnancy. Oral combined hormonal contraceptives (CHCs) typically utilize a combination of a progestin and an estrogen. CHCs are potentially at risk to metabolic drug-drug interaction (DDI) via CYP3A4, the main enzyme involved in the oxidative metabolism of ethinyl estradiol and most progestins (e.g., levonorgestrel (LNG) and drospirenone (DRSP)). Recently, the US Food and Drug Administration (FDA) issued a guidance addressing metabolic DDIs in the realm of CHC, establishing an overall class-based recommendation with respect to avoidance of CYP3A4 induction interactions. Given that different progestins have varying magnitudes of fraction metabolized by CYP3A4 (fmCYP3A4 ), it would be of clinical benefit to determine if all progestins are at the same risk to CYP3A4-mediated metabolic DDIs. LNG and DRSP are commonly used progestins that are at the margins of the rifampicin induction effect observed in vivo because they have the relatively lowest and highest fmCYP3A4 among commonly used CHC formulations containing norgestimate, desogestrel, norgestrel, and norethindrone. Therefore, we applied a multi-pronged strategy (i.e., (i) development of the physiologically-based pharmacokinetic models; (ii) comparison of the effect of CYP3A inducers and inhibitors on DRSP vs. LNG; and (iii) providing the clinical-practice context based on real-world data, to explore the difference in DDI risk for oral CHCs.

Self-efficacy of community pharmacists and associated factors in counselling to support self-medication in Japan: A cross-sectional study.

Background:In 2016, the Ministry of Health, Labour and Welfare established the Health Support Pharmacy Certification System. The certification requirements include a track record of counseling regarding the use of over-the-counter drugs (OTC). Therefore, pharmacists must increase their self-efficacy for counseling.Objectives:To determine pharmacists’ self-efficacy for OTC counseling and related factors.Methods:A web-based survey was conducted. Multivariate analysis was conducted to test the relationship among the mean scores of self-efficacy for OTC counselling for 25 symptoms, pharmacist attributes, years of work, psychosocial factor, job satisfaction, and level of trust from the community and patients.Results:We received responses from 250 people. The overall self-efficacy was 5.8 (SD= 2.4) but varied depending on the symptoms. Self-efficacy was relatively high for allergic symptoms (6.9), cold/influenza (6.9), and constipation (7.1), but relatively low for contraceptive drugs (3.8), palpitation/shortness of breath (4.6), and abnormal taste/smell (4.2). In bivariate analysis, items related to self-efficacy included “age” (Spearman correlation= 0.276, P<0.001), “academic background” (-0.208, P=0.001), “number of years of work” (0.267, P<0.001), “level of trust from the community” (0.155, P=0.014), “level of trust from patients” (0.271, P<0.001), “job satisfaction” (0.236, P<0.001), “role clarity” (0.181, P=0.004), and “positive challenge at work” (0.271, P<0.001). Multivariate analysis indicated that the number of years of work (Standardizing Coefficient: 0.22), trust from patients (0.13), and positive challenge at work (0.25) had a positive effect on self-efficacy.Conclusions:Years of work, recognition that they are trusted by patients, and positive challenge at work were important for the counseling self-efficacy of pharmacists. These results provide implications for pharmacy management and lifelong education strategies to promote self-efficacy in pharmacist counseling.

Mini Review: Quality Control Study of Crude Drug of Justicia gendarussa Burm. f. Leaves as Male Contraceptive

Justicia gendarussa Burm. f. (Gendarussa) leaves contain gendarusin A, which is a potential antifertility agent. Preclinical researches (in vitro, in vivo, and toxicity) and clinical trials have been carried out proving that Gendarussa leaves are safe to be used as a male contraceptive. Quality control of medicine must be carried out from the beginning when selecting crude drugs until the production process. Quality control of the crude drug is needed to maintain the quality, safety, and efficacy of its crude drug. That standardization has been done in Kediri, Mojokerto, and Ponorogo. The research output data used were specific and nonspecific parameters (macroscopic and microscopic assay, determination of ash content, compound levels, etc.). The quality of crude drugs is different in each region. Crude drug from Mojokerto is better than crude drug from Kediri and Ponorogo. This is influenced by environmental difference factors on how plants grow. This review describes the differences in the quality control results of crude drug of Gendarussa from several areas. Hence, in the future, the quality of this plant can be guaranteed to be used as a contraceptive drug.

Effects of an Oral Contraceptive on Dynamic Brain States and Network Modularity in a Serial Single-Subject Study.

Hormonal contraceptive drugs are used by adolescent and adult women worldwide. Increasing evidence from human neuroimaging research indicates that oral contraceptives can alter regional functional brain connectivity and brain chemistry. However, questions remain regarding static whole-brain and dynamic network-wise functional connectivity changes. A healthy woman (23 years old) was scanned every day over 30 consecutive days during a naturally occurring menstrual cycle and again a year later while using a combined hormonal contraceptive. Here we calculated graph theory-derived, whole-brain, network-level measures (modularity and system segregation) and global brain connectivity (characteristic path length) as well as dynamic functional brain connectivity using Leading Eigenvector Dynamic Analysis and diametrical clustering. These metrics were calculated for each scan session during the serial sampling periods to compare metrics between the subject’s natural and contraceptive cycles. Modularity, system segregation, and characteristic path length were statistically significantly higher across the natural compared to contraceptive cycle scans. We also observed a shift in the prevalence of two discrete brain states when using the contraceptive. Our results suggest a more network-structured brain connectivity architecture during the natural cycle, whereas oral contraceptive use is associated with a generally increased connectivity structure evidenced by lower characteristic path length. The results of this repeated, single-subject analysis allude to the possible effects of oral contraceptives on brain-wide connectivity, which should be evaluated in a cohort to resolve the extent to which these effects generalize across the population and the possible impact of a year-long period between conditions.

Catholic Hospitals Should Permit Physicians to Provide Emergency Contraception to Rape Victims as an Act of Conscientious Provision.

While many Catholic hospitals permit the prescription of the emergency contraception drug levonorgestrel for rape victims, some continue to prohibit this practice as a matter of institutional conscience. While the standard approach to this issue has been to offer an argument that levonorgestrel either is or is not morally permissible, we have taken a different tack. We begin by briefly describing and acknowledging that reasonable disagreement exists on this question (part one), and then arguing that the reasonable disagreement itself can serve as a compelling basis for Catholic leadership at hospitals that prohibit emergency contraception for rape victims to accommodate physicians who wish to provide levonorgestrel as a matter of conscience (part two). We end by anticipating and responding to some objections.

Association between polycystic ovary and fibrocystic breast by ultrasound

Background: Polycystic ovary syndrome is one of the most gynecologic, endocrine cases affect approximately 5-15%of women during reproductive age. Polycystic ovary syndrome (PCOS) is a multifactorial and polygenic pathology that manifests itself with a wide spectrum of signs and symptoms. The study aims to find out the association between PCOS and fibrocystic disease of the breast according to finding detected by ultrasound. Method: Across sectional study with 140 patients were enrolled in this study collected from the gynecologic and infertility clinic in Al-Imameen Al-Kadhymian Medical City, Iraq, Baghdad during the period from march 2021 to January 2022.Information was taken from patients through interview, inclusion criteria includes female gender, age between 20-50 years old not using oral contraceptive drug, pelvic and breast ultrasound report. SPSS version 24 was used to examine the frequency association between variable. Result: There were 140 female cases of PCOs, fifty-five (39%) were fibrocystic disease of breast. The prevalence of fibrocystic disease of breast in patient with PCOs in current study were fifty-five (39%).there were significant association between fibrocystic disease of breast with age, education level, BMI, age of monarch, hirsutism, history of infertility and history of pain with p value ≤ 0.05.

Molecular spectroscopic and molecular simulation studies on the interaction of oral contraceptive drug Ormeloxifene with CT–DNA

The interaction between oral contraceptive drug Ormeloxifene (ORM) and calf thymus DNA (CT–DNA) was studied using UV–Vis, fluorescence, circular dichroism (CD) and 1H NMR spectral techniques under physiological buffer (pH 7.4). Competitive binding assays with ethidium bromide (EB) and Hoechst 33258, viscosity measurements, KI quenching studies, molecular docking and metadynamics simulation studies were also substantiated the spectroscopic results. ORM is found to binds in the minor groove of CT–DNA as evidenced by: (1) non–displacement of EB from EB/CT–DNA complex; (2) appreciable displacement of Hoechst 33258 from its CT–DNA complex; (3) slight alteration in the CD signal; (4) small shifts (Δδ < 0.033 ppm) without broadening in 1H NMR signals and (5) the nearly equal extent of quenching of fluorescence of ORM by KI in the absence and presence of CT–DNA. Negative values of both enthalpy and entropy changes pointed out that the interaction between ORM and CT–DNA is governed mainly by H–bonding and van der Waals forces. Negative free energy change suggested a spontaneous interaction between ORM and CT–DNA. The free energy landscape of the binding process was computed using metadynamics simulation. The simulation study results disclosed that ORM binds to the minor groove of DNA through H–bonding and π–π stacking interactions. The results of molecular docking and simulation studies corroborate the available experimental data.

Suppression of fertility by &lt;em&gt;Capparis spinosa&lt;/em&gt; root extract through antioxidant alteration in reproductive system of male rats

Aim: To evaluate the suppression of fertility by oral mode of Capparis spinosa root extract through alteration in antioxidant defence of the reproductive system of male albino rats. Methods: The methanol extract of Capparis spinosa root (100mg/kg/day) was fed for 60 days to male, Wistar strain, albino rats. The fertility and testicular functions were assessed by mating tests, antioxidant defence indices, and spermatogenesis, histometry, and biochemical estimations for fertility suppression along with serum biochemistry and hematology for assessment of toxicology. Results: Capparis spinosa root extract administration for a period of 60 days did not cause body weight loss significantly, while the weight of testes, Cauda epididymis, seminal vesicle, and ventral prostate were significantly reduced. The lipid peroxidation and antioxidants levels i.e. superoxide dismutase, catalase, glutathione reduced, glutathione peroxidase, vitamin C, and Vitamin E in testes, Cauda epididymis, seminal vesicle, and ventral prostate were altered significantly (P<0.001) after the 60 days treatment of Capparis spinosa extract when compared to the controls. The root extract feeding caused a marked reduction in the number of primary spermatocytes, secondary spermatocytes, and spermatids however spermatogonia population showed non-significant change. Sertoli cell population was also affected. The number of mature Leydig cells was decreased and degenerating cells increased proportionately. The seminiferous tubule and Leydig cell nuclear area were reduced significantly (P<0.001) when compared to the controls. The protein and sialic acid content of the testes, Cauda epididymis, seminal vesicle, and ventral prostate were significantly (P<0.001) decreased. The glycogen in testes and fructose in seminal vesicle was also significantly reduced, whereas the testicular cholesterol was elevated as compared with the controls. Reduced sperm count and motility resulted in a total suppression of fertility. The RBC and WBC count, hemoglobin, and hematocrit in whole blood whereas marker enzymes and glucose in serum were found to be within the normal range after the 60 days of Capparis spinosa extract treatment. Conclusion: Capparis spinosa root extract may selectively act on developing germ cells mediated via Sertoli cells through increased oxidative stress or impairment of antioxidant defence system in reproductive organs of male rats, leading to suppression of fertility and suggests the feasibility of developing non-toxic, herbal male contraceptive drug.

The Innovation Imperative in Global Health: Gendered Futurity in the Sayana® Press

In this Position Piece, we explore the hegemony of innovation and the construction of gendered futures in global health through the Sayana® Press, a device that delivers a version of the contraceptive drug commonly known as Depo-Provera. The device has generated tremendous enthusiasm amongst global family planning advocates for its effectiveness and ease of use, including administration by community level providers and self-injection. Claims about its potential are compelling: advocates hope it will dramatically increase access to contraceptives, and thereby unlock the social and material emancipatory promise of family planning. We offer preliminary observations about Sayana Press as an ethnographic and discursive object and further the scholarly conversation on humanitarian design by considering the gendered dimensions of global health technologies. The advent of Sayana Press reflects several significant trends in global health including the intensification of the innovation imperative and the bypassing of investments in infrastructure—both bolstered by the recent rise of the ‘self-care agenda’. Further, we suggest that global health technologies are also techniques in the Foucauldian sense—scripting new subjectivities and bodily norms towards gendered futurities. Finally, we note the dual role of the state in sexual and reproductive health as both source and object of reproductive governance.

Contraceptive drug, Nestorone, enhances stem cell-mediated remodeling of the stroke brain by dampening inflammation and rescuing mitochondria

Ischemic stroke remains a significant unmet need causing massive mortality and morbidity due to few treatment options with limited therapeutic window. The progestin Nestorone® (segesterone acetate) displays high affinity for the progesterone receptor in exerting its potent birth control and hormone replacement therapy. Accumulating evidence implicates a new utility of Nestorone in affording neuroprotection in a variety of central nervous system diseases, including stroke. However, the mechanism of action mediating Nestorone's neuroprotection in stroke remains unknown. Here, we showed that stand-alone treatments of Nestorone or human amniotic fluid-derived stem cells (hAFSc), but more pronounced with their combined treatment, led to significant improvements in behavioral function and reductions in infarction and peri-infarct cell loss in adult rats with ischemic stroke. We detected significantly lower levels of pro-inflammatory signals (OX6 and IBA1) coupled with enhanced levels of stem cell proliferation (Ki67) and differentiation (DCX and MAP2) in both brain and spleen of stroke rats that received stand-alone or combined treatments of Nestorone and hAFSc. In concert, the in vitro oxygen-glucose deprivation stroke model revealed that neural stem cells treated with Nestorone exhibited increased stem cell proliferation and differentiation that was accompanied by rescue of the mitochondrial respiratory activity characterized by reduced mitochondrial reactive oxygen species, increased ATP, elevated mitochondrial deacetylase Sirtuin 3 (SIRT3), and a normalized ratio of acetyl-superoxide dismutase 2 (Ac-SOD2)/SOD2, suggesting the key role of mitochondrial metabolism and oxidative protection in Nestorone's therapeutic effects in stroke.

BMI and Contraceptives Affect New Age-, Sex-, and Puberty-adjusted IGF-I and IGFBP-3 Reference Ranges Across Life Span.

Various clinical factors influencing serum levels of insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) are not entirely consistently described. We asked whether body mass index (BMI), contraceptive drugs (CDs), and hormone replacement therapy (HRT) have potential effects on data for interpreting new age-, sex-, and puberty-adjusted reference ranges for IGF-I and IGFBP-3 serum levels. Subjects were mainly participants from 2 population-based cohort studies: the LIFE Child study of children and adolescents and the LIFE Adult study. We investigated 9400 serum samples from more than 7000 healthy and 1278 obese subjects between 3 months and 81 years old. Associations between IGF-I or IGFBP-3, measured with a new electrochemiluminescence immunoassay, and the predictors BMI and CDs were estimated using hierarchical linear modeling. During infancy, obese children had up to 1 SD score (SDS) higher mean predicted IGF-I values, converging with levels of normal-weight subjects up to 13 years old. Between 20 and 40 years of age, obesity was related to up to -0.5 lower IGF-I SDS values than the predicted values. Obesity had less impact on IGFBP-3. Estrogen- and progestin-based CDs, but not HRT, decreased IGF-I and increased IGFBP-3 (P < 0.01) in adolescents (β IGF-I = -0.45, β IGFBP-3 = 0.94) and adults (β IGF-I = -0.43, β IGFBP-3 = 1.12). Conversely, progestin-based CDs were significantly positive associated with IGF-I (β IGF-I =0.82). BMI and CDs must be considered when assessing and interpreting the clinical relevance of IGF-I and IGFBP-3 measurements.