Androgen receptor (AR) gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat (CAG and GGN) length polymorphisms have been an additional subject of interest and controversy among geneticists. The polymorphic variations in triplet repeats have been associated with a number of disorders, but at the same time contradictory findings have also been reported. Further, studies on the same disorder in different populations have generated different results. Therefore, combined analysis or review of the published studies has been of much value to extract information on the significance of variations in the gene in various clinical conditions. AR genetics has been reviewed extensively but until now review articles have focused on individual clinical categories such as androgen insensitivity, male infertility, prostate cancer, and so on. We have made the first effort to review most the aspects of AR genetics. The impact of androgens in various disorders and polymorphic variations in the AR gene is the main focus of this review. Additionally, the correlations observed in various studies have been discussed in the light of in vitro evidences available for the effect of AR gene variations on the action of androgens.
Androgen-Insensitivity Syndrome ; genetics ; physiopathology ; Bone Diseases, Metabolic ; genetics ; physiopathology ; Breast Neoplasms ; genetics ; physiopathology ; Cognition Disorders ; genetics ; physiopathology ; Digestive System Diseases ; genetics ; physiopathology ; Female ; Genital Neoplasms, Female ; genetics ; physiopathology ; Genital Neoplasms, Male ; genetics ; physiopathology ; Humans ; Infertility, Male ; genetics ; Male ; Muscular Atrophy, Spinal ; genetics ; physiopathology ; Phenotype ; Point Mutation ; Polycystic Ovary Syndrome ; genetics ; physiopathology ; Polymorphism, Genetic ; Pre-Eclampsia ; genetics ; physiopathology ; Pregnancy ; Receptors, Androgen ; genetics ; physiology ; Schizophrenia ; genetics ; physiopathology ; Testosterone ; deficiency ; Trinucleotide Repeats

Oxidative stress and sperm DNA fragmentation (SDF) have been linked to idiopathic male infertility (IMI). Various antioxidants have been tried to improve semen parameters and fertility potential in IMI patients, but with inconsistent results. The study aimed to compare the effects of coenzyme Q10 (CoQ10) and Centrum multivitamins on semen parameters, seminal antioxidant capacity, and SDF in infertile men with idiopathic oligoasthenospermia (OA). Methods: This prospective controlled clinical study involved 130 patients with idiopathic OA and 58 fertile controls. The patients were divided randomly into two groups: the first group received CoQ10 (200 mg/day orally) and the second group received Centrum multivitamins (1 tablet/day) for 3 months. Semen parameters, CoQ10 levels, reactive oxygen species (ROS), total antioxidant capacity (TAC), catalase, SDF, and serum hormone levels (follicle-stimulating hormone, luteinizing hormone, testosterone, and prolactin) were compared at baseline and after 3 months. Results: Both CoQ10 and Centrum improved sperm concentration and motility, but the improvement was greater with Centrum therapy (p<0.05). Similarly, both therapies improved antioxidant capacity, but TAC and catalase improvement was greater (p<0.01 and p<0.001 respectively) with CoQ10, whereas ROS (p<0.01) and SDF (p<0.001) improvements were greater with Centrum administration. Centrum therapy was associated with reduced serum testosterone (p<0.05). Conclusion: In conclusion, both CoQ10 and Centrum were effective in improving semen parameters, antioxidant capacity, and SDF, but the improvement was greater with Centrum than with CoQ10. Therefore, Centrum—as a source of combined antioxidants—may provide more effective results than individual antioxidants such as CoQ10 in the treatment of infertile men with idiopathic OA.

AIMTo investigate the role of CAG and GGN repeats as genetic background affecting androgen insensitivity syndrome (AIS) phenotype.

METHODSWe analyzed lengths of androgen receptor (AR)-CAG and GGN repeats in 69 AIS cases, along with 136 unrelated normal male individuals. The lengths of repeats were analyzed using polymerase chain reaction (PCR) amplification followed by allelic genotyping to determine allele length.

RESULTSOur study revealed significantly shorter mean lengths of CAG repeats in patients (mean 18.25 repeats, range 14-26 repeats) in comparison to the controls (mean 22.57 repeats, range 12-39 repeats) (two-tailed P < 0.0001). GGN repeats, however, did not differ significantly between patients (mean 21.48 repeats) and controls (mean 21.21 repeats) (two-tailed P = 0.474). Among patients' groups, the mean number of CAG repeats in partial androgen insensitivity cases (mean 15.83 repeats) was significantly less than in complete androgen insensitivity cases (mean 19.46 repeats) (two-tailed P < 0.0001).

CONCLUSIONThe findings suggest that shorter lengths of repeats in the AR gene might act as low penetrance genetic background in varying manifestation of androgen insensitivity.

Androgen-Insensitivity Syndrome ; genetics ; DNA ; genetics ; Follicle Stimulating Hormone ; blood ; Genetic Predisposition to Disease ; Humans ; Luteinizing Hormone ; blood ; Male ; Phenotype ; Receptors, Androgen ; genetics ; Regression Analysis ; Testosterone ; blood ; Trinucleotide Repeats ; genetics

Male infertility has a complex etiopathology, which mostly remains elusive. Although research has claimed that oxidative stress (OS) is the most likely underlying mechanism of idiopathic male infertility, the specific treatment of OS-mediated male infertility requires further investigation. Coenzyme Q10 (CoQ10), a vitamin-like substance, has been found in measurable levels in human semen. It exhibits essential metabolic and antioxidant functions, as well as playing a vital role in mitochondrial bioenergetics. Thus, CoQ10 may be a key player in the maintenance of biological redox balance. CoQ10 concentrations in seminal plasma directly correlate with semen parameters, especially sperm count and sperm motility. Seminal CoQ10 concentrations have been shown to be altered in various male infertility states, such as varicocele, asthenozoospermia, and medical or surgical regimens used to treat male infertility. These observations imply that CoQ10 plays an important physiological role in the maintenance and amelioration of semen quality. The present article thereby aimed to review the possible mechanisms through which CoQ10 plays a role in the regulation of male reproductive function, and to concisely discuss its efficacy as an ameliorative agent in restoring semen parameters in male infertility, as well as its impact on OS markers, sperm DNA fragmentation, pregnancy, and assisted reproductive technology outcomes.

Male infertility has a complex etiopathology, which mostly remains elusive. Although research has claimed that oxidative stress (OS) is the most likely underlying mechanism of idiopathic male infertility, the specific treatment of OS-mediated male infertility requires further investigation. Coenzyme Q10 (CoQ10), a vitamin-like substance, has been found in measurable levels in human semen. It exhibits essential metabolic and antioxidant functions, as well as playing a vital role in mitochondrial bioenergetics. Thus, CoQ10 may be a key player in the maintenance of biological redox balance. CoQ10 concentrations in seminal plasma directly correlate with semen parameters, especially sperm count and sperm motility. Seminal CoQ10 concentrations have been shown to be altered in various male infertility states, such as varicocele, asthenozoospermia, and medical or surgical regimens used to treat male infertility. These observations imply that CoQ10 plays an important physiological role in the maintenance and amelioration of semen quality. The present article thereby aimed to review the possible mechanisms through which CoQ10 plays a role in the regulation of male reproductive function, and to concisely discuss its efficacy as an ameliorative agent in restoring semen parameters in male infertility, as well as its impact on OS markers, sperm DNA fragmentation, pregnancy, and assisted reproductive technology outcomes.

This study aimed to evaluate whether human chorionic gonadotropin (hCG) therapy is beneficial for improving semen parameters and clinical hypogonadism symptoms in hypogonadic oligozoospermic or severe oligozoospermic men with low or borderline testosterone levels. Methods: A weekly dose of 250 μg (equivalent to approximately 6,500 IU) of hCG was administered subcutaneously for 3–6 months to 56 hypogonadic oligozoospermic or severe oligozoospermic men. Semen, biochemical, and genetic analyses were performed before the start of treatment followed by analyzing semen parameters every 3 months after the start of therapy. We grouped participants into responders and non-responders depending on positive changes in semen parameters. Results: Out of 56 men, 47 (83.93%) responded, while 9 (16.07%) did not. Upon statistical analysis, it was found that age did not affect the overall outcomes (p=0.292); however, men with higher body mass index (BMI; 28.09±3.48 kg/m2 ) showed better outcomes than those with low BMI (25.33±3.06 kg/m2 ) (p=0.042). The duration of therapy (in months) was higher in non-responders than in responders (p=0.020). We found significant improvements in sperm concentration (p=0.006) and count (p=0.005) after 3 months of therapy. Sperm motility and progressive motility were also found to be higher in responders, but did not show statistically significant changes. Conclusion: We conclude that hCG therapy can be beneficial in men with hypogonadic oligozoospermia or severe oligozoospermia.

Of all microorganisms in the human body, the largest and most complex population resides in the gastrointestinal (GI) tract. The gut microbiota continuously adapts to the host environment and serves multiple critical functions for their hosts, including regulating host immunity, procuring energy from food, and preventing the colonization of pathogens. Mounting evidence has suggested gut microbial imbalance (dysbiosis) as a core pathophysiology in the development of GI motility and metabolic disorders, such as irritable bowel syndrome and diabetes. Current research has focused on discovering associations between these disorders and gut microbial dysbiosis; however, whether these associations are a consequence or cause is still mostly unexplored. State-of-the-art studies have investigated how gut microbes communicate with our body systems through microbiota-derived metabolites and how they are able to modulate host physiology. There is now mounting evidence that alterations in the composition of small intestinal microbes have an association with GI dysmotility and metabolic disorders. Although treatment options for gut microbial dysbiosis are currently limited, antibiotics, fecal microbiota transplantation, probiotics, and dietary interventions are currently the best options. However, treatment with broad-spectrum antibiotics has been viewed with skepticism due to the risk of developing antibiotic resistant bacteria. Studies are warranted to elucidate the cellular and molecular pathways underlying gut microbiota-host crosstalk and for the development of a powerful platform for future therapeutic approaches. Here, we review recent literature on gut microbial alterations and/or interactions involved in the pathophysiology of GI dysmotility and metabolic disorders.

No abstract available.
Humans ; Lymphoma, T-Cell* ; T-Lymphocytes* ; Young Adult*

Tuberculosis (TB) occurring after a closed bone fracture in the patient with no history of TB and no evidence of TB infection at the time of initial fracture is a rare entity. We report one such case of a 48-year-old female, who presented in the emergency department with an olecranon fracture which was open reduced and internally fixed with tension band wiring. Patient presented in the outpatient department with serosanguineous discharge at 3 weeks after surgery. The discharge was sent for culture and sensitivity tests, and the patient was managed by antibiotics and daily dressings. There was wound dehiscence and the underlying implant was exposed, which was removed at 12 weeks after surgery. Repeat debridements and dressings continued for 6 months, but the discharge from the wound site continued. X-rays of the elbow performed at 6 months raised the suspicion of TB, which was confirmed by Ziel-Neelsen staining and histopathological examination of the debrided tissue. Following the confirmation, patient was put on antitubercular drugs. The patient responded to antitubercular drug therapy (ATT), the purulent discharge from the wound ceased, and eventually the wound healed after 2 months of starting ATT.
Arthritis, Infectious ; etiology ; Elbow Joint ; Female ; Fracture Fixation, Internal ; Humans ; Middle Aged ; Olecranon Process ; injuries ; Postoperative Complications ; Transforming Growth Factor beta1 ; physiology ; Tuberculosis, Osteoarticular ; etiology

Pulmonary blastoma (PB) is a rare thoracic malignancy and preoperative diagnosis is challenging. A young man presented with dyspnea and chest pain for 3–4 months and chest-computed tomography (CT) revealed large mass in the left lung upper lobe and pleural effusion. Repeated CT-guided fine-needle aspiration cytology from the lesion and pleural fluid aspiration was negative for malignancy. F-18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) revealed heterogeneous tracer avidity in left lung mass with areas of necrosis. Real-time PET-CT-guided biopsy from metabolically active component of the lesion revealed biphasic PB on histopathology.