RESUMEN
About 60% to 70% of people with dementia have Alzheimer's Disease (AD), a neurodegenerative illness. One reason for this disorder is the misfolding of naturally occurring proteins in the human brain, specifically ß-amyloid (Aß) and tau. Certain diagnostic imaging techniques, such as amyloid PET imaging, tau PET imaging, Magnetic Resonance Imaging (MRI), Computerized Tomography (CT), and others, can detect biomarkers in blood, plasma, and cerebral spinal fluids, like an increased level of ß-amyloid, plaques, and tangles. In order to create new pharmacotherapeutics for Alzheimer's disease, researchers must have a thorough and detailed knowledge of amyloid beta misfolding and other related aspects. Donepezil, rivastigmine, galantamine, and other acetylcholinesterase inhibitors are among the medications now used to treat Alzheimer's disease. Another medication that can temporarily alleviate dementia symptoms is memantine, which blocks the N-methyl-D-aspartate (NMDA) receptor. However, it is not able to halt or reverse the progression of the disease. Medication now on the market can only halt its advancement, not reverse it. Interventions to alleviate behavioral and psychological symptoms, exhibit anti- neuroinflammation and anti-tau effects, induce neurotransmitter alteration and cognitive enhancement, and provide other targets have recently been developed. For some Alzheimer's patients, the FDA-approved monoclonal antibody, aducanumab, is an option; for others, phase 3 clinical studies are underway for drugs, like lecanemab and donanemab, which have demonstrated potential in eliminating amyloid protein. However, additional study is required to identify and address these limitations in order to reduce the likelihood of side effects and maximize the therapeutic efficacy.
Asunto(s)
Enfermedad de Alzheimer , Medicina de Precisión , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/metabolismo , Humanos , Inhibidores de la Colinesterasa/uso terapéutico , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/metabolismoRESUMEN
Background: Anabolic-androgenic steroids (AASs) are often used by men for bodybuilding and to improve sports performance. The use is not limited to professional competitive athletes, but many amateur men. Objective: The objective of this study was to assess and systematically review the effects of AAS on male fertility parameters, spermiogram, testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH) and to review reversibility and other morbidity impacting fertility. Methods: Eligibility criteria - We included studies mentioning data about adult males using supraphysiologic doses of AAS for sports performance or appearance enhancement, with comparison data from general population or matched controls if available reporting fertility parameters and sexual performance. Information sources - A systematic literature search was performed using PubMed, MEDLINE, EMBASE, Google Scholar and World of Science. Controlled clinical trials randomised or nonrandomised (if available), case series with or without matched controls, case reports, cross-sectional surveys, reports on follow-up of subjects caught in doping test and their fertility parameters when reported. Risk of bias/quality assessment - The quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. Results: Included studies - Thirty-two studies were included. There were 12 cohort studies, 5 case-control studies, 9 cross-sectional surveys and 6 case reports. The study population comprised 9371 individuals, of which 2671 were AAS users. Synthesis of results - AAS users had reduced levels of FSH and LH than the naïve population. These levels remained low for 3-6 months after stopping AAS. One year after stopping AAS, the users and naïve population had insignificant differences in FSH and LH values. The total testosterone (TT) levels were comparable in users and naïve populations at baseline, 3 months and 6 months after stopping, but at 1 year, TT values were lower in AAS users. Sperm concentration in AAS users and naïve population was similar, but sperm motility was lower in AAS users. The testicular size was lower in AAS users. The erectile function improved with AAS use, but on withdrawal, there was decreased libido and erectile dysfunction. Most AAS users need additional medications to mitigate detrimental effects on fertility. Description of the effect - AAS use negatively impacted the gonadotrophin levels and had lower sperm motility and testicular size. Strength - Comprehensive review of 32 publications, study population of 9371 individuals, of which 2671 were AAS users, meta-analysis of reproductive hormones, semen parameters and testis size. Limitations: The limitations are small sample size of most of the studies, polypharmacy, lack of information on dosing and high heterogeneity. Interpretation: AAS use is detrimental for sperm motility and has a partially reversible negative impact on male fertility. Users must be cautioned about its negative impact on libido and erectile function.Registration: PROSPERO Registration No. CRD42023411294.
RESUMEN
INTRODUCTION: Recent investigations have raised a doubt regarding the safety of Caudal epidural block (CEB) administered to children with distal hypospadias undergoing tubularised incised plate (TIP) urethroplasty. The primary objective of the study was to investigate whether there is any association between CEB and the occurrence of urethrocutaneous fistula (UCF) in the postoperative period. METHODS: Fifty ASA 1 and 2 children with distal hypospadias aged 0-8 years were randomly allocated to CEB group (GA with CEB, 0.2% ropivacaine 1 ml/kg; n = 25) and Non-CEB group (GA without CEB; n = 25). Penile measurements were taken before and 20 min after administration of CEB to assess penile engorgement. Intraoperative hemodynamics were recorded at 10 min intervals after induction of anaesthesia. Consumption of IV fentanyl intraoperatively and postoperatively in first 24 h was recorded in both the groups. Rescue analgesia was administered for a score >4 on FLACC scale. After surgery children were followed up monthly for first three months and then at 6-months and yearly in paediatric surgery OPD to assess for development of UCF. RESULTS: UCF was found to occur in only two children, one from each group on follow up, with an overall incidence of 4%. There was no difference in the incidence of UCF in the patients with and without CEB. A 26.8% increase in penile volume from baseline was recorded in CEB group (P = 0.000). The intraoperative heart rate and mean arterial pressure was significantly lower in the CEB group as compared to non CEB group at various time intervals. No additional intraoperative IV fentanyl supplementation was required in CEB group. Fentanyl consumption was significantly less in CEB group postoperatively in first 24 h (P = 0.000). DISCUSSION: Administration of CEB was not found to have any impact on UCF formation. No relationship between the increase in penile volume after CEB block and occurrence of UCF was noticed. CONCLUSION: Despite increase in penile volume after CEB, there was no difference between the two groups as regards to the occurrence of post operative UCF. CEB is an effective analgesic modality and can be continued to be used till the results of well powered prospective randomised trials with long follow up are reported.