RESUMEN
Sterility in male NHP has long been achieved through surgical castration or vasectomy. However, these techniques are irreversible, require a surgical procedure, and have potential consequences such as sperm granulomas and long recovery time. Deslorelin is a gonadotropin-releasing hormone agonist that temporarily and reversibly suppresses sex hormone secretion. Our goal in this study was to investigate the effects of deslorelin on testosterone secretion and testicular volume in male rhesus macaques (Macaca mulatta). Male macaques (n = 4) each received two, 4.7-mg deslorelin implants subcutaneously in the interscapular region. Serum testosterone and testicular volume were then monitored at specific time points until 10 mo after treatment. Testosterone suppression was defined as testosterone levels lower than 0.6 ng/mL for a sustained period of at least 30 d. After implantation, mean testicular volume was significantly reduced by day 121. Testosterone suppression was observed in all subjects. However, the time from implantation to testosterone suppression and duration of suppression varied. Two macaques were hormonally suppressed by day 26 after implantation and remained suppressed for at least 6 mo. The other 2 macaques were hormonally suppressed by 2 mo after implantation; of these two, one remained suppressed for 70 days while the other was suppressed for at least 245 days. We conclude that deslorelin can safely suppress testosterone secretion in male rhesus macaques, but individual variation in onset and duration of action should be considered when establishing reimplantation time points and potential return to reproductive activity.
Asunto(s)
Hormona Liberadora de Gonadotropina , Testículo , Pamoato de Triptorelina/análogos & derivados , Masculino , Animales , Hormona Liberadora de Gonadotropina/farmacología , Macaca mulatta , Testosterona , Semen , Implantes de Medicamentos/farmacologíaRESUMEN
Driving under the influence of drug (DUID) cases continue to challenge forensic toxicologists as both the volume and complexity of casework increases. Comprehensive DUID testing should also meet the drafted Academy Standards Board (ASB)/ American National Standard Institute (ANSI) standard and the National Safety Council's Alcohol, Drugs and Impairment Division (NSC-ADID) recommendations. A simple method using protein precipitation followed by filtration extraction with an 8 minute run time by liquid chromatography-tandem mass spectrometry (LC-MS-MS) was developed, and a comprehensive ASB/ANSI validation was performed. Target drugs and metabolites were quantitatively assessed in blood and qualitatively assessed in urine. Included were 127 target analytes including cannabinoids (12), amphetamines (11), cocaine and metabolites (6), benzodiazepines (36), Z-drugs (5), opioids (27), anticonvulsants (3), first-generation antihistamines (6), muscle relaxants (2), dissociatives and hallucinogens (6), barbiturates (10), and miscellaneous substances (3). Limits of detection are appropriate for DUID and other forensic casework such as drug-facilitated crime (DFC) and postmortem investigations. To demonstrate applicability, 78 proficiency test blood and urine samples and 1,645 blood and urine samples from authentic cases samples demonstrated effective detection of target analytes in forensic casework. By increasing the analytical scope of multiple drug classes via a single method, this technique detects drugs that may have previously gone undetected, such as flualprazolam, etizolam, mitragynine, gamma-hydroxybutyric acid and psilocin and improves laboratory efficiency by reducing the number of tests required. The described method is, to the authors' best knowledge, the only published single procedure to meet all drugs listed in the drafted ASB/ANSI standard and recommended Tier 1 and traditional drugs from Tier 2 for DUID screening, while also achieving many drug scope and sensitivity recommendations for DFC and postmortem testing.
Asunto(s)
Cannabinoides , Espectrometría de Masas en Tándem , Anfetaminas , Cromatografía Liquida/métodos , Toxicología Forense/métodos , Detección de Abuso de Sustancias/métodos , Espectrometría de Masas en Tándem/métodosRESUMEN
Using analytical chemistry techniques such as nuclear magnetic resonance (NMR) spectroscopy and liquid or gas chromatography-mass spectrometry (LC/GC-MS), metabolomics allows detection of most endogenous and exogenous metabolites in a biological sample. Metabolomics has a wide range of applications, and has been employed in nutrition science, toxicology, environmental studies, and systems biology. Metabolomics is particularly useful in biomedical science, and has been used for diagnostic laboratory testing, identifying targets for drug development, and monitoring drug metabolism, mode of action, and toxicity. Despite its immense potential, metabolomics remains underutilized in the study of spontaneous animal diseases. Our aim was to comprehensively review the existing literature on the use of metabolomics in spontaneous veterinary diseases. Three databases were used to find journal articles that applied metabolomics in veterinary medicine. A screening process was then conducted to eliminate references that did not meet the eligibility criteria; only primary research studies investigating spontaneous animal disease were included; 38 studies met the inclusion criteria. The main techniques used were NMR and MS. All studies detected metabolite alterations in diseased animals compared with non-diseased animals. Metabolomics was mainly used to study diseases of the digestive, reproductive, and musculoskeletal systems. Inflammatory conditions made up the largest proportion of studies when articles were categorized by disease process. Following a comprehensive analysis of the literature on metabolomics in spontaneous veterinary diseases, we concluded that metabolomics, although in its early stages in veterinary research, is a promising tool regarding diagnosis, biomarker discovery, and in uncovering new insights into disease pathophysiology.