Fluoxetine: a case history of its discovery and preclinical development

Introduction: Depression is a multifactorial mood disorder with a high prevalence worldwide. Until now, treatments for depression have focused on the inhibition of monoaminergic reuptake sites, which augment the bioavailability of monoamines in the CNS. Advances in drug discovery have widened the therapeutic options with the synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. Areas covered: The aim of this case history is to describe and discuss the pharmacokinetic and pharmacodynamic profiles of fluoxetine, including its acute effects and the adaptive changes induced after long-term treatment. Furthermore, the authors review the effect of fluoxetine on neuroplasticity and adult neurogenesis. In addition, the article summarises the preclinical behavioural data available on fluoxetine’s effects on depressive-like behaviour, anxiety and cognition as well as its effects on other diseases. Finally, the article describes the seminal studies validating the antidepressant effects of fluoxetine. Expert opinion: Fluoxetine is the first selective SSRI that has a recognised clinical efficacy and safety profile. Since its discovery, other molecules that mimic its mechanism of action have been developed, commencing a new age in the treatment of depression. Fluoxetine has also demonstrated utility in the treatment of other disorders for which its prescription has now been approved

Airborne Mission Concept for Coastal Ocean Color and Ecosystems Research

NASA airborne missions in 2011 and 2013 over Monterey Bay, CA, demonstrated novel above- and in-water calibration and validation measurements supporting a combined airborne sensor approach (imaging spectrometer, microradiometers, and a sun photometer). The resultant airborne data characterize contemporaneous coastal atmospheric and aquatic properties plus sea-truth observations from state-of-the-art instrument systems spanning a next-generation spectral domain (320-875 nm). This airborne instrument suite for calibration, validation, and research flew at the lowest safe altitude (ca. 100 ft or 30 m) as well as higher altitudes (e.g., 6,000 ft or 1,800 m) above the sea surface covering a larger area in a single synoptic sortie than ship-based measurements at a few stations during the same sampling period. Data collection of coincident atmospheric and aquatic properties near the sea surface and at altitude allows the input of relevant variables into atmospheric correction schemes to improve the output of corrected imaging spectrometer data. Specific channels support legacy and next-generation satellite capabilities, and flights are planned to within 30 min of satellite overpass. This concept supports calibration and validation activities of ocean color phenomena (e.g., river plumes, algal blooms) and studies of water quality and coastal ecosystems. The 2011 COAST mission flew at 100 and 6,000 ft on a Twin Otter platform with flight plans accommodating the competing requirements of the sensor suite, which included the Coastal-Airborne In-situ Radiometers (C-AIR) for the first time. C-AIR (Biospherical Instruments Inc.) also flew in the 2013 OCEANIA mission at 100 and 1,000 ft on the Twin Otter below the California airborne simulation of the proposed NASA HyspIRI satellite system comprised of an imaging spectrometer and thermal infrared multispectral imager on the ER-2 at 65,000 ft (20,000 m). For both missions, the Compact-Optical Profiling System (Biospherical Instruments, Inc.), an in-water system with microradiometers matching C-AIR, was deployed to compare sea-truth measurements and low-altitude Twin Otter flights within Monterey Bay red tide events. This novel airborne and in-water sensor capability advances the science of coastal measurements and enables rapid response for coastal events

Project: Center for Diabetes and Metabolism [Centro de Diabetes y Metabolismo: CeDiMet], a collaborative dream comes true

Reynosa urban area has 690,000 inhabitants (384,000 adults \u3e20 years old), 35% moved from other states. The use of cell phones is in 81%, personal computer or laptop with 29%. The prevalence of overweight is 39%, obesity 36%, and T2D 13%. The expected adult population with T2D is 49,900 individuals. The are 5 clinics prepared to attend T2D, and few with specialized personnel. The CeDiMet is a collaborative clinic involving health personnel and researchers from the Universidad Mexico Americana del Norte, Universidad Autonoma de Tamaulipas, Hospital General de Mexico “Dr. Eduardo Liceaga”, University of Texas Rio Grande Valley, and the Texas Diabetes Institute in San Antonio. The funding source comes from private companies in Reynosa. The clinical structure includes physicians, nurses, nutritionists, psychologists, and a section for telemedicine for consulting specialists from USA and Mexico City. Besides clinical attendance, the CeDiMet will conduct educational activities in offices, factories, churches, and schools for prevention of obesity complications (T2D and hypertension), early detection of diabetic foot, fatty liver, and endothelial damage. “Tree of Health in the Family” is a program to encourage youth to know and understand the metabolic problems in their families to focus on prevention. Recently, we obtained a grant from COTACyT to explore the effect of COVID-19 in a cohort of 200 students and their families. The analysis of post-traumatic stress due to confinement and antibodies concentration to detect contacts and its association with metabolic problems is an example of the research we can perform

Motor Decline in Clinically Presymptomatic Spinocerebellar Ataxia Type 2 Gene Carriers

BACKGROUND: Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and their motor learning capabilities. METHODS AND FINDINGS: 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and an equal number of control volunteers matched for age and gender participated in the study. Both groups were tested in a prism adaptation task known to be sensible to both motor performance and visuomotor learning deficits. Our results clearly show that although motor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation of the disease start. CONCLUSIONS: The results show a clear deficit in motor performance that can be detected years before the clinical onset of the disease. This motor performance deficit appears before any motor learning or clinical manifestations of the disease. These observations identify the performance coefficient as an objective and quantitative physiological biomarker that could be useful to assess the efficiency of different therapeutic agents

Neutralizing anti-RBD fraction for SARS-CoV-2 is associated with the interaction waist circumference and sex. An ESFUERSO preliminary report on university students

In a previous study we reported that 25% of college students had a family history of type 2 diabetes (T2D), and 39% of hypertension. Interestingly, between 17 to 47% reported not knowing about T2D or hypertension, neither the existing obesity-metabolic problems (ESFUERSO study). The COVID-19 pandemic forced confinement and modifications in food intake, physical activity, and psychological stress. This study aimed to analyze if the immune Ig-G anti-RBD (protective epitope in S protein) response associated with type of vaccination, metabolic risk, perceived stress, and history of COVID-19 contacts. We included 116 students at the 3th year of follow up in the ESFUERSO cohort at Reynosa. Mean age 21.4 (SD 1.04) years old, BMI 28 (6.6), females 70% (81/116). The serum concentration of Ig-G anti-RGB measured by ELISA adjusted by sex, age, body fat percentage, and BMI was analyzed. Researchers performed a multiple regression analysis with Stata V17.0. We found that 70% of the students had a family history of diabetes, hypertension, and/or obesity at baseline. Only 5 (4%) students did not have any vaccine at the time of the study, 102 (88%) were vaccinated with Moderna or Pfizer and 9 (8%) with other vaccines (Cansino, Sinovac). The prevalence of positive anti-RBD was 91%. The body fat percentage interacted with sex (p=0.034) explaining the serum concentration of anti-RBD decreased as adiposity increases in men, but increased in women. The interaction remained is spite of type of vaccination. We found no differences among metabolic risks for food consumption, distress, uncertainty, lack of sleep, sadness, and anxiety were associated with metabolic problems. Our model predicts neutralizing anti-RBD had multiplicative interaction by sex and body fat percentage (increases in females and decreases in males), with no effects on stress score or food consumption

Looking for Crumbs in the Obesity Forest: Anti-obesity Interventions and Obesity-Associated Cardiometabolic Traits in the Mexican Population. History and Systematic Review With Meta-Analyses

Mexicans and Mexican Americans share culture, genetic background, and predisposition for chronic complications associated with obesity and diabetes making imperative efficacious treatments and prevention. Obesity has been treated for centuries focused-on weight loss while other treatments on associated conditions like gout, diabetes (T2D), and hypertriglyceridemia. To date, there is no systematic review that synthesizes the origin of obesity clinics in Mexico and the efforts to investigate treatments for obesity tested by randomized clinical trials (RCT). We conducted systematic searches in Pubmed, Scopus, and Web of Science to retrieve anti-obesity RCT through 2019 and without an inferior temporal limit. The systematic review included RCT of anti-obesity treatments in the Mexican adult population, covering alternative medicine, pharmacological, nutritional, behavioral, and surgical interventions reporting metabolism-associated traits such as BMI, weight, waist circumference, triglycerides, glucose, among others. Only the studies with at least 3 months of treatment were included in the meta-analyses in order to reduce placebo effects. We found 634 entries, after removal of duplicates and screening the studies based on eligibility criteria, we analyzed 43 national, and 2 multinational-collaborative studies. Most of the national studies had small sample sizes, and the implemented strategies do not have replications in the population. The nutrition/behavioral interventions were difficult to blind, and most studies have medium-to-high risk of bias. Nutritional/behavioral interventions and medications showed effects on BMI, waist circumference, and blood pressure. Simple measures like pure water instead of sweet beverages decrease triglycerides and systolic blood pressure. Dark chocolate showed the highest effect for BMI and high blood pressure, and treatment with insulin increased weight in those with T2D. The study of obesity in Mexico has been on-going for more than four decades, the interest on RCT just increased until this millennium, but with small sample sizes and lack of replication. The interventions affect different cardiometabolic associated traits, which should be analyzed in detail in the population living near the Mexico-U.S. border; therefore, bi-national collaboration is desirable to disentangle the cultural effects on this population\u27s treatment response

Randomized Clinical Trials of obesity treatments in Mexican population. Systematic Review and Meta-Analysis

Background: Mexicans and Mexican Americans share similar culture, genetic background, and predisposition for obesity and diabetes. Randomized clinical trials (RCT) assessing obesity treatments (ObT) are reliable to assess efficacy. To date, there is no systematic review to investigate ObT tested by RCT in Mexican adults. Methods: We conducted systematic searches in Pubmed, Scopus, and Web of Science to retrieve ObT RCT from 1990 to 2019. The ObT included alternative medicine, pharmacological, nutritional, behavioral, and surgical interventions. The analyzed RCT were at least three months of duration, and reported: BMI, weight, waist circumference, triglycerides, glucose and blood pressure. Results: We found 634 entries; after removal of duplicates and exclusions based on eligibility criteria, we analyzed 43 and 2 multinational-collaborative studies. Most of the national studies had small sample sizes, and did not have replications from other studies. The nutrition/behavioral interventions were difficult to blind, and most studies had medium to high risk of bias. Random effects meta-analysis of nutritional/behavioral interventions and medications showed effects on BMI, waist circumference, and blood pressure. Simple measures like plain water instead of sweet beverages decreased triglycerides and systolic blood pressure. Participants with obesity and hypertension had beneficial effects with antioxidants, and the treatment with insulin increased weight in those with T2D. Conclusions: The RCT’s in Mexico reported effects on metabolic components despite small sample sizes and lack of replication. In the future we should analyze ObT in population living on the U.S.-Mexico border; therefore, bi-national collaboration is desirable to disentangle cultural effects on ObT response