Testosterone Derivatives Research Articles

Understanding the Role of Sex Hormones in Cardiovascular Kidney Metabolic Syndrome: Toward Personalized Therapeutic Approaches.

Cardiovascular kidney metabolic (CKM) syndrome represents a complex interplay of cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic comorbidities, posing a significant public health challenge. Gender exerts a critical influence on CKM syndrome, affecting the disease severity and onset through intricate interactions involving sex hormones and key physiological pathways such as the renin-angiotensin system, oxidative stress, inflammation, vascular disease and insulin resistance. It is widely known that beyond the contribution of traditional risk factors, men and women exhibit significant differences in CKM syndrome and its components, with distinct patterns observed in premenopausal women and postmenopausal women compared to men. Despite women generally experiencing a lower incidence of CVD, their outcomes following cardiovascular events are often worse compared to men. The disparities also extend to the treatment approaches for kidney failure, with a higher prevalence of dialysis among men despite women exhibiting higher rates of CKD. The impact of endogenous sex hormones, the correlations between CKM and its components, as well as the long-term effects of treatment modalities using sex hormones, including hormone replacement therapies and gender-affirming therapies, have drawn attention to this topic. Current research on CKM syndrome is hindered by the scarcity of large-scale studies and insufficient integration of gender-specific considerations into treatment strategies. The underlying mechanisms driving the gender disparities in the pathogenesis of CKM syndrome, including the roles of estrogen, progesterone and testosterone derivatives, remain poorly understood, thus limiting their application in personalized therapeutic interventions. This review synthesizes existing knowledge to clarify the intricate relationship between sex hormones, gender disparities, and the progression of CVD within CKM syndrome. By addressing these knowledge gaps, this study aims to guide future research efforts and promote tailored approaches for effectively managing CKD syndrome.

A Histological Study of the Effects of Administration and Withdrawal of Anabolic Androgenic Steroid (Nandrolone Decanoate) on the Hippocampus and the Prefrontal Cortex in Adult Male Albino Rats

Abstract Background The PFC and the hippocampus are parts of the limbic systems and have a major role in emotion regulation, memory and learning. Anabolic androgenic steroids (AASs) are large groups of synthetic derivatives of testosterone, prescribed for the treatment of male hypogonadism. Common abuse of AASs has spread among the general population and Aim of the Work The aim of the current work was to study the effects of AASs on the PFC and the hippocampus histologically and statistically and to evaluate the reversibility of these effects in these regions after AASs withdrawal. Material and Methods 24 adult male albino rats (3 – 6) months old (weighing 200-225 gm) were used in the current study and divided into 3 groups; according to the procedure and treatment type: control group (I) (12 rats) and AASs treated group (II) (6 rats) and Withdrawal group (III) (6 rats). Fixation for the brain using bouin solution was done first in situ followed by its removal and transfer to a glass bottle containing bouin solution for 24 hours to ensure complete fixation. The PFC and the hippocampi were obtained through parasagittal section. Specimens were processed for preparation of paraffin blocks then stained with H&E stain and immunohistochemically stained for GFAP antibody. Image analysis &morphometry were performed on stained sections for; number of surviving pyramidal neurons and the mean area percentage of GFAP staining. Results On examination of H&E-stained sections of control groups, the PFC was formed of the six- layers, the molecular layer, outer granular layer, outer pyramidal layer, inner granular layer, inner pyramidal layer and the multiform layer. The Hippocampus was formed of two components: the dentate gyrus (DG), the hippocampus proper (Cornu Ammonis, with its four regions: CA1, CA2, CA3 and CA4). The cells forming the hippocampus proper were arranged in three layers; the molecular, the pyramidal and the polymorphic layers. In immunohistochemically stained section, the present work showed minimal apparent immune-reaction in the cytoplasm and processes of astrocytes in the PFC and CA1 region of the hippocampus in the control group. On examination of H&E-stained sections of the AASs treated groups, signs of neuronal damage were observed. The inner pyramidal layer of the PFC and the pyramidal layer of CA1 region of the hippocampus revealed abnormal shrunken pyramidal cells having deeply stained nuclei, peri-cellular spaces and flame like appearance with pointed end. Moreover, these layers demonstrated also normal pyramidal cells showing also large rounded open vesicular nuclei and prominent nucleoli. Immunohistochemically stained sections of the treated group in both regions showed apparent extensive brownish immunostaining of the astrocytes with ramifying processes along the layer. Examination of H&E-stained sections of the withdrawal group revealed the inner pyramidal layer of the PFC and the pyramidal layer of CA1 region of the hippocampus showing normal pyramidal cells having large rounded open vesicular nuclei, prominent nucleoli and apical dendrites. It also showed dark irregular cells having deeply stained nuclei, peri- cellular spaces and flame like appearance with pointed end. Immunohistochemically stained section of the treated group in both regions showed apparent minimal brownish immunostaining of the astrocytes. Conclusion Results of the present experimental study demonstrated that AASs (in the form of ND) administration affecting the PFC and the hippocampus resulted in several histopathological and morphometric harmful effects which regressed to a lesser extent through its withdrawal after 2 weeks.

Do steroid abusers have more temporomandibular joint symptoms? A study with 97 bodybuilders

ABSTRACT Objectives Anabolic androgenic steroids (AAS) are derivatives of testosterone, used to treat gonadal disturbances, performance enhancement, and aesthetic purposes. AAS abuse can lead to side effects, including androgenic, cardiovascular, and liver disturbances, effects on libido, gynecomastia, and behavioral effects. There is a hypothesis that some joint tissues may be targets for sex hormones, and the use of AAS without medical follow-up may exacerbate temporomandibular joint problems in patients seeking performance and aesthetics. Methods In this study, a cross-sectional survey was conducted on AAS abusers who voluntarily presented themselves for clinical evaluation. Patients were subdivided by sex and age group, and the length of AAS use and symptoms such as headache, tinnitus, and temporomandibular joint pain were evaluated. Results It was observed that drug usage is related to symptoms. Conclusion The results suggest that AAS use without medical follow-up may exacerbate temporomandibular joint problems, especially in patients with low estrogen levels.

Novel dummy molecularly imprinted polymer for simultaneous solid-phase extraction of stanozolol metabolites from urine

Stanozolol, a synthetic derivative of testosterone, is one of the common doping drugs among athletes and bodybuilders. It is metabolized to a large extent and metabolites are detected in urine for a longer duration than the parent compound. In this study, a novel dummy molecularly imprinted polymer (DMIP) is developed as a sorbent for solid-phase extraction of stanozolol metabolites from spiked human urine samples. The optimized DMIP is composed of stanozolol as the dummy template, methacrylic acid as the functional monomer, and ethylene glycol dimethacrylate as the cross-linker in a ratio of 1:10:80. The extracted analytes were quantitively determined using a newly developed and validated ultrahigh-performance liquid chromatography tandem mass spectrometry method, where the limits of detection and quantitation were 0.91 and 1.81 ng mL−1, respectively, fulfilling the minimum required performance limit decided on by the World Anti-Doping Agency. The mean percentage extraction recoveries for 3’-hydroxystanozolol, 4β-hydroxystanozolol, and 16β-hydroxystanozolol are 97.80% ± 13.80, 83.16% ± 7.50, and 69.98% ± 2.02, respectively. As such, the developed DMISPE can serve as an efficient cost-effective tool for doping and regulatory agencies for simultaneous clean-up of the stanozolol metabolites prior to their quantification.Graphical abstract

Consequences of Anabolic Androgenic Steroids Abuse in Males, Sexual Hepatic and Metabolic Perspective

Abstract
 Background: anabolic androgenic steroids (AASs) are becoming increasingly popular between bodybuilders and people who want to enhance their physiques. However, according to the rise of the Internet and laws prohibiting sales of these substances without prescription, the route of obtaining and administration practices have become more and more dangerous.
 Objective: Anabolic-androgenic steroids represents a group of synthetic testosterone derivatives its play an important role in clinical treatment. These group of drugs are widely abused among the general public to increase lean body weight and improve athletic performance. It has been reported that AAS use can cause many adverse effects. Although there are many related studies, the current study was to review the effect of AAS on serum levels of LH, FSH, prolactin, free testosterone, ALT, AST, T3, T4, TSH, haemoglobin and platelet in bodybuilders using these hormones and compare the results with control group.
 Method: A 50 body builders were using gym routinely and were using AASs for at least 2 months interviewed and collect blood sample to measure certain lab data and see the effects of AAS on these lab data and compare results with control group who were using gym routinely but never use AAS before.
 Results: The levels of eight parameters were significantly (P-value< 0.05) different according to the participating groups (AAS users vs control): LH, FSH, Prolactin, ALT, T3, TSH, haemoglobin and platelets. Five of the measured parameters were significantly (P-value< 0.05) lower in the group of AAS users compared to the control (non-user) group: LH, FSH, T3, TSH, and platelets. In contrast, the other three parameters (prolactin, ALT and haemoglobin) were significantly (P-value< 0.05) higher in the AAS user group compared to control group.
 Conclusion: the anabolic androgenic steroids had a harmful effect on multi physiological functions leading to hormonal disturbances.

Crystal Structure and Intermolecular Energy for Some Nandrolone Esters.

Nandrolone (Estr-4-en-17β-ol-3-one) is a derivative of testosterone and a naturally occurring anabolic-androgenic agent which belongs to the steroid group. Crystal structures of four short, medium and long esterified forms of nandrolone, including propionate, phenylpropionate, cypionate and undecanoate were determined using single-crystal X-ray diffraction. Crystal packing, supramolecular features and intermolecular interactions were described based on a quantitative and qualitative Hirshfeld surfaces analysis accompanied by evaluation of crystal energies and intermolecular interactions computation. Also, the solubility of the esters was investigated from a pharmaceutical perspective.

A-038 An Improved Multiplexed HTLC-HESI-MSMS Method for the Measurement of Total Testosterone in Serum

Abstract Background Testosterone is an anabolic steroid produced primarily in the testicles of males and mainly in the ovaries of females. Imbalance of testosterone is the primary cause of hypogonadism in males, hirsutism and virilization in females, osteoporosis, and diabetes mellitus. Accurate and fast-turnaround measurement of testosterone is critical for diagnosis, prevention, and treatment of testosterone-related diseases in adults and children. In a previous study, testosterone was derivatized with methoxyamine and hydroxylamine in a multiplexed high turbulence liquid chromatography with heated-electrospray ionization-tandem mass spectrometry (HTLC-HESI-MS/MS) method. Using these reagents, differential mass-tagging of testosterone allowed different specimens to be combined in a single injection to increase assay throughput. However, interference was observed for hydroxylamine-derivatized testosterone in serum collected in serum separator tubes (SST). In the current study, our objectives were to (1) replace hydroxylamine with a new derivatizing agent not subject to interference and (2) develop an improved HTLC-HESI-MS/MS method for multiplexed total testosterone measurement. Methods Healthy male and female donor specimens were collected in SST and red-top tubes. Serum was mixed with stable isotope-labeled testosterone as internal standard (ISTD) prior to protein precipitation. Testosterone in the supernatants was derivatized, enriched by solid phase extraction, dried, and reconstituted. Specimens were injected on the HTLC system for on-line extraction, transferred to analytical columns, and eluted using binary gradient. Testosterone derivatives and ISTDs were detected and analyzed on a Triple Quadrupole Mass Spectrometer (Thermo) equipped with HESI. Ionization and multiple reaction monitoring (MRM) scan parameters were optimized for maximized ion transmission and sensitive, specific, and stable quantitation. MRM transitions were used as quantifiers and qualifiers for both testosterone derivatives. Also assessed were ion suppression using T-column infusion, specimen stability by storage in SST tubes at 4 °C, isobaric interference from dehydroepiandrosterone (DHEA), and carryover. Results Intra- and inter-assay coefficients of variation (CV%) for total testosterone levels were <5% at 12, 80, 250, and 1200 ng/dL for both testosterone derivatives. Limits of quantitation (LOQs) for both derivatives were <1 ng/dL. Calibration linearity was verified across the measurement range of 2.5–2000 ng/dL. Both agents were equivalent in derivatizing and recovering testosterone from serum based on a comparison of their quantitative results (R = 0.991, bias = −3.8 ng/dL). No interference was observed in serum collected in SST. Serum specimens collected in SST and red-top tubes from same donors gave equivalent results (R = 0.991, bias = 0.2 ng/dL). Ion suppression was calculated as less than 20% for both derivatives. CV% of the ion-ratios of both derivatives were less than 15% and were stable across the linear range. Testosterone levels were stable in SST for 72 h (at 4 °C) with the serum not separated from the gel. No isobaric interference and no carry over were observed. Conclusion We have developed and validated an improved multiplexed HTLC-HESI-MS/MS testosterone assay using new derivatizing agents. The current method allowed accurate, rapid, specific, and stable analysis of serum total testosterone. SST is an acceptable specimen type for the current method. Precision, accuracy, linearity, ion suppression, and sample stability in SST were validated.

Androgenic anabolic steroid abuse

Androgen anabolic steroid abuse is a broad term describing the use of structural derivatives of testosterone with the aim to increase body mass and muscle size, or to enhance athletic performance. These drugs are typically used in large doses, much higher than would be prescribed for the treatment of medical conditions. This use of steroids is illegal and can lead to multiple adverse effects including cardiovascular, hepatic, metabolic and psychological issues. Many patients abusing steroids will not typically disclose this information when presenting to their GP. This article aims to help raise awareness of signs and symptoms of abuse, as well as highlight the common long-term risks and discuss a GP’s role in managing these complex scenarios.

Anabolic-androgenic steroids. Mechanism of action and clinical effects

Introduction and aim. Anabolic-androgenic steroids (AAS) are used for the rapid enhancement of muscular mass and optimization of athletic performance. Their administration is frequently linked with a plethora of adverse health implications. The primary objective of this study is to provide a comprehensive analysis of multifaceted impacts of anabolic-androgenic steroids on the human body. Material and methods. A review of literature was performed by searching PubMed and GoogleScholar databases using the following key words: anabolic-androgenic steroids, muscular hypertrophy, female masculinization. Analysis of the literature. Anabolic-androgenic steroids are synthetically manufactured derivatives of testosterone. Given the widespread distribution of the androgen receptor, the effects of these steroids are broad, influencing almost all bodily functions. Their impacts include, promoting muscular hypertrophy including that of the cardiac muscle, premature epiphyseal closure, liver diseases, masculinization in females, feminization in males, and degradation in sperm quality. Conclusion. AAS consumption is a significant public health problem. While they may appeal to users by enhancing their physical attractiveness they carry multiple health consequences. Patients should be educated about the adverse effects of taking AAS so they can make informed decision about starting or stopping their use.

An α, β-unsaturated ketone alkylation and efficient reduction protocol for the synthesis of 3α-hydroxy-3β-methyl-4,4-dimethyl-5α-21-bromo-19-nor-pregnan-20-one

Alkyl-substituted testosterone derivatives are promising platforms for new drug discovery in medicinal chemistry. This approach provides a simple and efficient method for introducing an alkyl substituent to steroids at the C-4 position. In this study, the novel compound 3α-hydroxy-3β-methyl-4,4-dimethyl-5α-21-bromo-19-nor-pregnan-20-one is synthesized from 19-nor-testosterone. The protocol involves methylation of the dienolate, reduction of the alkene, the Grignard reaction of the carbonyl group, a Wittig reaction, hydroboration with BH3, the oxidation and bromination with a 49% overall yield. For the methylation and reduction steps, the effects of the base, solvent, and reactant ratio on the conversion and yield are investigated. The structures of the synthesized compounds are determined by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) (electrospray ionization (ESI)).

Isolation and enrichment of Boldenone and its main metabolite in urinary samples to further determine the 13C/12C ratios by gas chromatography / combustion / isotope ratio mass spectrometry

Gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) can be used to detect the synthetic forms of endogenous anabolic androgenic steroids (EAAS) by comparing the 13C/12C ratios of the endogenous reference compound to that of the target compound. Isolation and enrichment of the target compound from urinary matrices is an essential prerequisite for the GC/C/IRMS confirmation procedure in doping control analysis. Boldenone (Bo) is a natural anabolic androgenic steroid (AAS) and a derivative of testosterone. The GC/C/IRMS confirmation procedure for Bo and its main metabolite 5β-androst-1-en-17β-ol-3-one (BoM) is extremely complicated due to the low concentrations and the enormously complex matrices in urine. The present study demonstrated a sample purification procedure for GC/C/IRMS by using online 2D-HPLC to purify Bo and BoM in urine samples. Bo and BoM with concentrations as low as 2 ng/mL were isolated and enriched with superior purity and selectivity. The validity of the method was verified with the technical document issued by the world anti-doping agency. The online 2D-HPLC purification procedure featured high selectivity for the analytes and no isotopic fractionation in the collection process. The present method can be used as a routine method allowing doping control laboratories to perform Boldenone confirmation.

O-104 The Impact of application of CRISPR /dCas9 systems for increasing the expression of FSH receptor in human granulosa cells

Abstract Study question What are the molecular and physiological effects on human granulosa cells, when CRISPR/dCas9 epigenome edition technology is efficiently used to increase FSH receptor (FSHR) activity? Summary answer The significant increase in expression of FSHR maintained by dCAS9 systems has effects on several fundamental cellular events involving steroidogenic, life-sustaining,cell death related signaling sub-pathways. What is known already Manipulation of the expression of FSHR can result in biological events that include fundamental activities of FSH as regulation of folliculogenesis, production of steroidogenic hormones. FSHR can be activated in vitro by FSH analogues, and signaling networks activate ERK1/2 pathway through p38 mitogen-activated protein kinases. CRISPR/dCAS9 can be used to activate or inhibit gene action without silencing the gene. In spite of being used in many systems, interference of FSHR expression by epigenome edition is very limited as well as the use of in vitro tools to increase FSHR expression for investigating IVM, folliculogenesis, PCOS, FSH hyper/hyposensitivity, cancer biology. Study design, size, duration In-vitro cultured HGrC1 (human granulosa cell line) cells were treated by follitropin-alfa (Gonal-f). The experimental groups were designed in triplicates with cells i. without any genome edition and cells that have i. non-targeting gRNA, ii.dCAS9 activated FSHR, iii. dCAS9 activated FSHR and FSH treatment for 5 min, 15 min, or 1 hr; iv. only FSH treatment for 5 min, 15 min or 1 hr. FSHR related gene and protein expressions and estrogen production were evaluated. Participants/materials, setting, methods For human FSHR gene, two separate gRNAs were designed. Annealing, digestion, ligation, transformation, colony formation, plasmid isolation, Sanger sequencing analysis, MOI were accomplished for dCAS9/SAM system. HGrC1 (immortalized human granulosa cell line) cells were treated with 75 IU/ml Gonal-f in related groups. After treatment, in triplicates, gene/protein expression for MTOR, FSHR, AKT, MAPK8, MAPK1, TP 53, CASP 3, ESR1, CYP 19A1 were evaluated by qPCR, WB and IF. Estradiol was measured by chemiluminescence immunoassay. Main results and the role of chance FSHR has increased significantly in dCas9, dac9 + 5min Gonal-f, dCas9 + 15min Gonal-f, dCas9 + 1h Gonal-f; mostly in 5 min compared to groups without dCas9. The system plasmids did not show any non-specific effects.MAPK1, MAPK8, ESR1, MTOR, AKT, P53 and CASP3 gene expressions showed significant increase in dcas9 system groups compared to control and NT, whereas in all time-dependent treatments, a significant increase was seen in groups that have dcas9+Gonal-f compared to the ones treated with only Gonal-f. As time dependent manner has been investigated, expressions of MAPK1, MAPK8 and ESR1 were highest at min 5, expressions of CASP and AKT were highest at min 15 and the expression of MTOR was highest at hour 1, whereas FSHR and p53were strongly expressed at all time points (p < 0.05 for all mentioned results). Gene expression profiles were also confirmed for P-38 MAPK, AKT, FSHR by WB. IF stainings have revealed higher expression of AKT and MAPK in both dCas9 and dcas9+Gonal-f 5 min compared to the control group, however the intensity of the staining was not satisfactory enough. Interestingly, estrodiol(E2) levels were found to be higher in the 5 minutes only Gonal-f treatment and dcas9 with Gonal-f treatment, while the other groups were similar to control. Limitations, reasons for caution -This study has been conducted in cell line, rather than primary granulosa cells which are not easy targets for epigenome edition. -No testosterone derivatives were used as substrate for aromatase. This has been reflected in the results as significant increase in FSHR and related genes but non-significant increase in E2 production. Wider implications of the findings -dcas9/SAM system can be used efficiently increase other FSH-receptors, which is a potent way to reveal molecular sub-pathways in a temporal manner;eg. in male reproductive system or in other cells of female RS. -FSH related conditions as PCOS can be examined in vitro. -FHSR unresponsive conditions can be modeled in vitro. Trial registration number not applicable

Nutrition, Training, Supplementation, and Performance-Enhancing Drug Practices of Male and Female Physique Athletes Peaking for Competition.

Escalante, G, Barakat, C, Tinsley, GM, and Schoenfeld, BJ. Nutrition, training, supplementation, and performance-enhancing drug practices of male and female physique athletes peaking for competition. J Strength Cond Res 37(8): e444-e454, 2023-The purpose of this descriptive investigation was threefold: (a) to assess the nutrition, training, supplement, and performance-enhancement drug practices of male and female physique competitors 30 days before competition; (b) to examine the specific water and macronutrient manipulation performed by competitors during the last 3 days before competition; and (c) to assess physiological responses to precontest preparation including body composition, body fluids, resting heart rate, and blood pressure. Competitors reported performing moderately high volume, moderate to high repetition, split-body resistance training programs performed on most days of the week; the programs included the use of a variety of advanced training methods. A majority of competitors included cardio to expedite fat loss, and most reported performing cardio in a fasted state despite a lack of objective evidentiary support for the practice. Competitors substantially restricted calories and consumed protein in amounts well above research-based guidelines (>3 g·kg -1 ·d -1 ); carbohydrate and lipid intake were highly variable. Water was substantially reduced in the final 3 days before competition. Competitors used a variety of dietary supplements throughout the study period, many of which are not supported by research. Both male and female competitors reported using performance enhancing drugs (∼48 and ∼38%, respectively) including testosterone derivatives, selective androgen receptor modulators, and human growth hormone. More research is warranted to elucidate safer and more effective peak week practices for physique competitors.

A clinical case of acute anabolic steroid-induced toxic hepatitis

Drug-induced liver injury (DILI) can be considered in cases of acute hepatitis by the exclusion of any disease-related causes. For several decades, anabolic steroids have been considered not only as drugs for treatment of diseases such as hypogonadism, sarcopenia, hypotrophy in cancer patients, aplastic anemia, etc., but also as risk factor for acute liver failure, that can lead to liver cancer, and even sudden death. Anabolic steroids are known to be increasingly used not only for legitimate medical uses, but also for enhance physical performance and promote muscle growth for ideal body shape. The article presents a clinical case of acute drug-induced hepatitis after 2 months of using stanozolol, a synthetic testosterone derivative, in a 25-year-old previously healthy man. Thorough etiological investigations ruled out other causes of DILI. The man was treated at the in-patient department and discharged with improvement, but it took several months for the disappearance of hepatic cytolytic and cholestatic changes. Clinicians should be aware of the risk for toxic drug-induced hepatitis in male bodybuilders and collect a thorough history of the patient’s intake of nutritional supplements that may contain androgen derivatives.

Knowledge and Attitude of Using Anabolic Androgenic Steroids Among Male Bodybuilders in Al-Russafa Baghdad Province

Anabolic androgenic steroids are being more popular between bodybuilders and people who are using gym to enhance their physiques. However, according to the increase of the laws prohibiting sales of these substances without physician prescription, the route of getting and administration practices have become more and more dangerous. Anabolic androgenic steroids include many synthetic derivatives of testosterone its play a significant role in medical treatment. These groups of medications are extensively abused at young ages to rising lean body mass and advance the athletic quality of performance. It has been described that anabolic steroids use can cause many long and short-term side effects, this study intended to assess the level of knowledge about AAS and its effects among gym users. 50 bodybuilders were using gym routinely and were using AASs for at least 2 months and another who were using gym routinely but never use AAS before were interviewed to show their knowledge about short and long term AASs using side effects. Participants used androgenic hormones for three main reasons health, social and personal, vast majority of the participants obtained the required results by using AAS, The majority of participants were going into the gym five to six times weekly for an hour daily. Enanthate was the main steroid abused by the participants and the gym coaches were the major source of selling steroids to the participants. The anabolic androgenic steroids had a harmful effect and abused by large number of young ages.

Rapid 18 F- and 19 F-Difluoromethylation through Desulfurative Fluorination of Transient N-, O-, and C-Linked Dithioles.

The difluoromethyl group plays an important role in modern medicinal and agrochemistry. While several difluoromethylation reagents have been reported, these typically rely on difluoromethyl carbenes or anions, or target specific processes. Here, we describe a conceptually unique and general process for O-H, N-H and C-H difluoromethylation that involves the formation of a transient dithiole followed by facile desulfurative fluorination using silver(I) fluoride. We also introduce the 5,6-dimethoxy-1,3-benzodithiole (DMBDT) function, which undergoes sufficiently rapid desulfurative fluorination to additionally support 18 F-difluoromethylation. This new process is compatible with the wide range of functional groups typically encountered in medicinal chemistry campaigns, and the use of Ag18 F is demonstrated in the production of 18 F-labeled derivatives of testosterone, perphenazine, and melatonin, 58.0±2.2, 20.4±0.3 and 32.2±3.6 MBq μmol-1 , respectively. We expect that the DMBDT group and this 18 F/19 F-difluoromethylation process will inspire and support new efforts in medicinal chemistry, agrochemistry and radiotracer production.

Taxifolin increased semen quality of Duroc boars by improving gut microbes and blood metabolites.

Taxifolin (TAX), as a natural flavonoid, has been widely focused on due to its strong anti-oxidation, anti-inflammation, anti-virus, and even anti-tumor activity. However, the effect of TAX on semen quality was unknown. The purpose of this study was to analyze the beneficial influences of adding feed additive TAX to boar semen in terms of its quality and potential mechanisms. We discovered that TAX increased sperm motility significantly in Duroc boars by the elevation of the protein levels such as ZAG, PKA, CatSper, and p-ERK for sperm quality. TAX increased the blood concentration of testosterone derivatives, antioxidants such as melatonin and betaine, unsaturated fatty acids such as DHA, and beneficial amino acids such as proline. Conversely, TAX decreased 10 different kinds of bile acids in the plasma. Moreover, TAX increased “beneficial” microbes such as Intestinimonas, Coprococcus, Butyrivibrio, and Clostridium_XlVa at the Genus level. However, TAX reduced the “harmful” intestinal bacteria such as Prevotella, Howardella, Mogibacterium, and Enterococcus. There was a very close correlation between fecal microbes, plasma metabolites, and semen parameters by the spearman correlation analysis. Therefore, the data suggest that TAX increases the semen quality of Duroc boars by benefiting the gut microbes and blood metabolites. It is supposed that TAX could be used as a kind of feed additive to increase the semen quality of boars to enhance production performance.

NONISCHEMIC CARDIOMYOPATHY AND CARDIAC ARREST ATTRIBUTABLE TO ANABOLIC-ANDROGENIC STEROIDS

NONISCHEMIC CARDIOMYOPATHY AND CARDIAC ARREST ATTRIBUTABLE TO ANABOLIC-ANDROGENIC STEROIDS

Anabolic Steroids in Fattening Food-Producing Animals-A Review.

Simple SummaryAnabolic steroids significantly affect animal tissues and cause morphological and histological changes, which are often irreversible. This issue is currently a very hot topic, as the answers to the questions concerning the health of endangered animals and humans vary greatly from country to country. There is a need to further investigate whether the use of anabolic steroids in animal fattening threatens consumer health and to develop new tools for the detection of anabolic steroids in meat. One possibility for detection could be to observe histological changes in the tissues, which form a typical pattern of anabolic abuse. This review gathered information on the anabolic steroids most commonly used in animal fattening, the legislation governing this issue, and the main effects of anabolics on animal tissues.Anabolic steroids are chemically synthetic derivatives of the male sex hormone testosterone. They are used in medicine for their ability to support muscle growth and healing and by athletes for esthetic purposes and to increase sports performance, but another major use is in fattening animals to increase meat production. The more people there are on Earth, the greater the need for meat production and anabolic steroids accelerate the growth of animals and, most importantly, increase the amount of muscle mass. Anabolic steroids also have proven side effects that affect all organs and tissues, such as liver and kidney parenchymal damage, heart muscle degeneration, organ growth, coagulation disorders, and increased risk of muscle and tendon rupture. Anabolic steroids also have a number of harmful effects on the developing brain, such as brain atrophy and changes in gene expression with consequent changes in the neural circuits involved in cognitive functions. Behavioral changes such as aggression, irritability, anxiety and depression are related to changes in the brain. In terms of long-term toxicity, the greatest impact is on the reproductive system, i.e., testicular shrinkage and infertility. Therefore, their abuse can be considered a public health problem. In many countries around the world, such as the United States, Canada, China, Argentina, Australia, and other large meat producers, the use of steroids is permitted but in all countries of the European Union there is a strict ban on the use of anabolic steroids in fattening animals. Meat from a lot of countries must be carefully inspected and monitored for steroids before export to Europe. Gas or liquid chromatography methods in combination with mass spectrometry detectors and immunochemical methods are most often used for the analysis of these substances. These methods have been considered the most modern for decades, but can be completely ineffective if they face new synthetic steroid derivatives and want to meet meat safety requirements. The problem of last years is the application of “cocktails” of anabolic substances with very low concentrations, which are difficult to detect and are difficult to quantify using conventional detection methods. This is the reason why scientists are trying to find new methods of detection, mainly based on changes in the structure of tissues and cells and their metabolism. This review gathered this knowledge into a coherent form and its findings could help in finding such a combination of changes in tissues that would form a typical picture for evidence of anabolic misuse.

Anabolic-Androgenic Steroid Use is Associated with Major Depressive Disorder and Suicide Attempt: Analysis of a Multi-National Database

ABSTRACT Introduction Anabolic-androgenic steroids (AAS), synthetic derivatives of the male sex hormone testosterone, are often used to enhance athletic performance and physical appearance. Long term use of AAS can be associated with mood destabilizing effects and psychotic behavior. We hypothesized that AAS use is an independent risk factor for mental health disorders. We investigated AAS use and associations with major depressive disorder (MDD), suicide attempt (SA)/intentional self-harm (ISH), and body dysmorphic disorder (BDD) by querying TriNetX, a global health research network that provides data on large cohort of patients from multiple centers across the United States. Objective To determine the association between AAS use with MDD, SA/ISH, and BDD. Methods To evaluate the psychiatric risk of AAS use two cohorts of adult men, aged 18-50, without history of gender dysphoria (F64, Z87.890) (1) history of documented AAS use, inclusive of testosterone prescriptions (2) history of a visit to a healthcare organization and no history of AAS use. We accounted for confounding variables known to be associated with a risk of mood disorders through propensity score matching by logistic regression for age, race, ethnicity, male hypogonadism (E29.1), history of nicotine dependence (Z87.891), or alcohol-related disorder (F10). We evaluated the association between steroid use and subsequent diagnosis of MDD (F32-33), SA/ISH (T14.91, X71-83, T36-65 and T71 ISH codes), or BDD (F45.22) as a primary outcome through regression analysis with statistical significance assessed at p<.05. Results We identified 159,717 cis-men between age 18-50 who used AAS and following propensity score matching for confounding variables, we compared them to an equal-sized cohort of men without AAS use. AAS use was independently associated with all of the psychiatric outcomes that we studied (MDD OR 2.96 95% CI 2.88-3.04 p<.0001, SA/ISH OR 1.37 95% CI 1.25-1.50 p<.0001, BDD OR 5.37 95% CI 2.82-10.21 p<.0001). Strengths of the study include a large sample size, propensity score matching to adjust for confounding variables, and high strength of association. Limitations include lack of information regarding indication for steroid prescription or details regarding severity, duration, withdrawal, or possible steroid abuse. Conclusions AAS use appears to be an independent risk factor for MDD, BDD, and/or SA/ISH. Future studies are necessary to elucidate whether a dose-response association exists, withdrawal from AAS plays a role, and if patient selection or preventative measures can mitigate the risk. Men with suicide attempt, BDD, or MDD should be investigated for a history of AAS use. Further, men receiving AAS should be counseled on the possible risk of developing MDD in the future. AAS use can lead to profound and complex psychiatric complications which should be discussed in patient counseling. Disclosure No