Imeglimin is a new oral antidiabetic drug that acts through three main mechanisms: increasing insulin sensitivity, decreasing gluconeogenesis, and improving mitochondrial function. It has shown significant reductions in HbA1c and fasting plasma glucose levels in clinical trials as both monotherapy and add-on therapy to other oral medications or insulin. Imeglimin has a favorable safety profile with few side effects reported. Its unique mechanisms and safety make it a promising potential treatment for type 2 diabetes.
Background
No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters.
Methods
Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1) mean (± standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood glucose level and time, 5) increase in blood glucose level after each meal, 6) area under the curve (AUC) for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7) area over the curve (AOC) for daily blood glucose level <70 mg/dL. Plasma glycosylated hemoglobin (HbA1c), glycoalbumin (GA), 1,5-anhydroglucitol (1,5AG), immunoreactive insulin (IRI), C-peptide immunoreactivity (CPR), brain natriuretic peptide (BNP), and plasminogen activator inhibitor-1 (PAI-1) levels, and urinary CPR levels, were measured.
Results
The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012). In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015), the AUC (≥180 mg/dL) within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 μg/day; p = 0.008) than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin.
Conclusions
CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and sitagliptin
This prsentation explains the use of biomarker with reference to an article: Accelerating Drug Develeopment using Biomarkers-Sitagliptin.
It was presented my my 2 friends and me. Hope it helps you guys.
Imeglimin, What is new?
By Dr. Usama Ragab Youssif
Lecturer of Medicine - Zagazig University
Agenda
Mitochondrial function and dysfunction
Mitochondrial (dys)function in diabetes
Diabetes core defects and Imeglimin
Imeglimin drug development and approval
Imeglimin and Heart
Formulation of an alpha Glucosidase Inhibitors Drug as Mucoadhesive Microsphe...SriramNagarajan19
α- glucosidase inhibitors are oral anti-diabetic drugs. These drugs are competitive inhibitors of the intestinal α- glucosidases and reduce post meal excursions by delaying digestion and absorption of starch and disaccharides. Their mechanism of action being limited to the intestinal brush border membrane, and owing to their structural features, they have limited systemic bioavailability, due to which they have much reduced side-effect profile compared to contemporary anti hyperglycemic drugs. Therefore, in the present investigation, an attempt will be made to develop mucoadhesive microspheres of α-glucosidase inhibitor (Miglitol) to enhance the bio- availability and to further reduce the dose and frequency of administration. Microspheres form an important part of novel drug delivery systems. They have carried applications and are prepared using assorted polymers. However, the success of these microspheres is limited owing to their short residence time at the site of absorption. It would therefore be advantageous to have means for providing an intimate contact of the drug delivery system with the absorbing membranes. This can be achieved by coupling bioadhesion characteristics to microspheres and developing bioadhesive microspheres. Bioadhesive microspheres have advantages such as efficient absorption and enhanced bioavailability of drugs owing to a high surface-to-volume ratio a much more intimate contact with the mucus layer and specific targeting of drugs to the absorption site.
Background
No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters.
Methods
Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1) mean (± standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood glucose level and time, 5) increase in blood glucose level after each meal, 6) area under the curve (AUC) for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7) area over the curve (AOC) for daily blood glucose level <70 mg/dL. Plasma glycosylated hemoglobin (HbA1c), glycoalbumin (GA), 1,5-anhydroglucitol (1,5AG), immunoreactive insulin (IRI), C-peptide immunoreactivity (CPR), brain natriuretic peptide (BNP), and plasminogen activator inhibitor-1 (PAI-1) levels, and urinary CPR levels, were measured.
Results
The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012). In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015), the AUC (≥180 mg/dL) within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 μg/day; p = 0.008) than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin.
Conclusions
CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and sitagliptin
This prsentation explains the use of biomarker with reference to an article: Accelerating Drug Develeopment using Biomarkers-Sitagliptin.
It was presented my my 2 friends and me. Hope it helps you guys.
Imeglimin, What is new?
By Dr. Usama Ragab Youssif
Lecturer of Medicine - Zagazig University
Agenda
Mitochondrial function and dysfunction
Mitochondrial (dys)function in diabetes
Diabetes core defects and Imeglimin
Imeglimin drug development and approval
Imeglimin and Heart
Formulation of an alpha Glucosidase Inhibitors Drug as Mucoadhesive Microsphe...SriramNagarajan19
α- glucosidase inhibitors are oral anti-diabetic drugs. These drugs are competitive inhibitors of the intestinal α- glucosidases and reduce post meal excursions by delaying digestion and absorption of starch and disaccharides. Their mechanism of action being limited to the intestinal brush border membrane, and owing to their structural features, they have limited systemic bioavailability, due to which they have much reduced side-effect profile compared to contemporary anti hyperglycemic drugs. Therefore, in the present investigation, an attempt will be made to develop mucoadhesive microspheres of α-glucosidase inhibitor (Miglitol) to enhance the bio- availability and to further reduce the dose and frequency of administration. Microspheres form an important part of novel drug delivery systems. They have carried applications and are prepared using assorted polymers. However, the success of these microspheres is limited owing to their short residence time at the site of absorption. It would therefore be advantageous to have means for providing an intimate contact of the drug delivery system with the absorbing membranes. This can be achieved by coupling bioadhesion characteristics to microspheres and developing bioadhesive microspheres. Bioadhesive microspheres have advantages such as efficient absorption and enhanced bioavailability of drugs owing to a high surface-to-volume ratio a much more intimate contact with the mucus layer and specific targeting of drugs to the absorption site.
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
This Presentation Give You A brief Information About DPP4 And New Recommendations .This Presentation Guide You How To Treat Patients With Safety.
For Further Contact:03354999496
Anti-diabetic Therapies, Strategies for Diabetes Management, and Advancement ...PriyankaKilaniya
Diabetes Mellitus (DM) stands as a prominent metabolic disorder characterized by impaired insulin activity and/or secretion, leading to various pathological complications such as nephropathy, retinopathy, and cardiovascular issues. This review delves into the intricacies of Diabetes Mellitus (DM), exploring its sub-types, conventional treatment modalities, and the emerging role of nanotechnology in revolutionizing drug delivery for improved therapeutic outcomes. Pathophysiology of Diabetes Mellitus manifests through aberrations in insulin dynamics, leading to hyperglycemia and subsequent tissue damage. Understanding the underlying pathophysiological mechanisms is crucial for devising effective therapeutic strategies. Classification of Diabetes Mellitus is broadly categorized into Type 1 and Type 2, each with distinct etiological factors and treatment approaches. Type 1 DM necessitates insulin replacement therapy, whereas Type 2 DM is primarily managed through oral hypoglycemic agents. Insulin replacement therapy is the cornerstone of treatment for Type 1 DM. It involves administering exogenous insulin to mimic the physiological insulin secretion that is deficient in individuals with T1DM. This aims to maintain blood glucose levels within a normal range to prevent acute as well as long-term complications. Drug therapy for Type 2 Diabetes Mellitus : The pharmacological armamentarium for Type 2 DM includes Insulin Secretagogues, Biguanides, Insulin Sensitizers, α-Glucosidase Inhibitors, Incretin Mimetics, Amylin Antagonists, and SGLT2 Inhibitors. The Complex pathophysiology of DM demands innovatives therapeutic approaches to enhance drug efficacy and patient adherence. Nanotechology offers promising solutions by enabling targeted drug delivery, improved bioavailability, and reduced dosing frequency. Clinical Implications and Future Perspectives Nanotechnology holds immense potential in revolutionizing diabetes management by addressing the limitations of conventional therapies and enhancing therapeutic efficacy. Future research endeavors should focus on translational studies to validate the clinical utility of nanotechnology-based drug delivery systems. In Conclusion, the integration of nanotechnology into Diabetes management offers a paradigm shift in therapeutic approaches, promising targeted drug delivery, improved bioavailability, and enhanced patient outcomes. Continued research and development in this field are imperative to realize the full potential of nanotechnology in combating the global burden of Diabetes Mellitus. In this article, we endeavor to delve into the pathophysiolgy of Diabetes Mellitus (DM), traditional treatment methods for both Type 1 (T1DM) and Type 2 (T2DM) diabetes, alongside innovative drug delivery strategies for managing Diabetes Mellitus.
Newer Anti-Hyperglycemic agents in type 2 Diabetes Mellitus e Expanding the h...Apollo Hospitals
Diabetes mellitus is a common, chronic and progressive disease resulting in micro and macrovascular complications. Many classes of drugs are available for treatment but still the search for newer anti-hyperglycemic agents continues to combat significant adverse effect profile, loss of efficacy, progressive nature of disease and improve patient compliance. New emerging therapies in pipeline include drugs targeting various pathophysiologic mechanisms like incretin based therapies, sodium glucose co-transporter inhibitors, glucokinase inhibitors, 11b hydroxy steroid dehydrogenase inhibitors, drugs modulating fatty acid metabolism, selective PPARg receptor modulators and anti inflammatory agents.
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
This Presentation Give You A brief Information About DPP4 And New Recommendations .This Presentation Guide You How To Treat Patients With Safety.
For Further Contact:03354999496
Anti-diabetic Therapies, Strategies for Diabetes Management, and Advancement ...PriyankaKilaniya
Diabetes Mellitus (DM) stands as a prominent metabolic disorder characterized by impaired insulin activity and/or secretion, leading to various pathological complications such as nephropathy, retinopathy, and cardiovascular issues. This review delves into the intricacies of Diabetes Mellitus (DM), exploring its sub-types, conventional treatment modalities, and the emerging role of nanotechnology in revolutionizing drug delivery for improved therapeutic outcomes. Pathophysiology of Diabetes Mellitus manifests through aberrations in insulin dynamics, leading to hyperglycemia and subsequent tissue damage. Understanding the underlying pathophysiological mechanisms is crucial for devising effective therapeutic strategies. Classification of Diabetes Mellitus is broadly categorized into Type 1 and Type 2, each with distinct etiological factors and treatment approaches. Type 1 DM necessitates insulin replacement therapy, whereas Type 2 DM is primarily managed through oral hypoglycemic agents. Insulin replacement therapy is the cornerstone of treatment for Type 1 DM. It involves administering exogenous insulin to mimic the physiological insulin secretion that is deficient in individuals with T1DM. This aims to maintain blood glucose levels within a normal range to prevent acute as well as long-term complications. Drug therapy for Type 2 Diabetes Mellitus : The pharmacological armamentarium for Type 2 DM includes Insulin Secretagogues, Biguanides, Insulin Sensitizers, α-Glucosidase Inhibitors, Incretin Mimetics, Amylin Antagonists, and SGLT2 Inhibitors. The Complex pathophysiology of DM demands innovatives therapeutic approaches to enhance drug efficacy and patient adherence. Nanotechology offers promising solutions by enabling targeted drug delivery, improved bioavailability, and reduced dosing frequency. Clinical Implications and Future Perspectives Nanotechnology holds immense potential in revolutionizing diabetes management by addressing the limitations of conventional therapies and enhancing therapeutic efficacy. Future research endeavors should focus on translational studies to validate the clinical utility of nanotechnology-based drug delivery systems. In Conclusion, the integration of nanotechnology into Diabetes management offers a paradigm shift in therapeutic approaches, promising targeted drug delivery, improved bioavailability, and enhanced patient outcomes. Continued research and development in this field are imperative to realize the full potential of nanotechnology in combating the global burden of Diabetes Mellitus. In this article, we endeavor to delve into the pathophysiolgy of Diabetes Mellitus (DM), traditional treatment methods for both Type 1 (T1DM) and Type 2 (T2DM) diabetes, alongside innovative drug delivery strategies for managing Diabetes Mellitus.
Newer Anti-Hyperglycemic agents in type 2 Diabetes Mellitus e Expanding the h...Apollo Hospitals
Diabetes mellitus is a common, chronic and progressive disease resulting in micro and macrovascular complications. Many classes of drugs are available for treatment but still the search for newer anti-hyperglycemic agents continues to combat significant adverse effect profile, loss of efficacy, progressive nature of disease and improve patient compliance. New emerging therapies in pipeline include drugs targeting various pathophysiologic mechanisms like incretin based therapies, sodium glucose co-transporter inhibitors, glucokinase inhibitors, 11b hydroxy steroid dehydrogenase inhibitors, drugs modulating fatty acid metabolism, selective PPARg receptor modulators and anti inflammatory agents.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
Follow us on: Pinterest
Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
2. Imeglimin: A new antidiabetic
drug with potential
for the treatment of patients
with type 2 diabetes
ENDOKRYNO POL 2022; 73(2): 361-370
3. AUTHORS AND AFFILIATIONS
MARIUSZ NOWAK AND WLADYSLAW GRZESZCZAK
Pathophysiology Division, Department of Pathophysiology and
Endocrinology, Faculty of Medical Sciences in Zabrze,
Medical University of Silesia in Katowice, Poland
Department of Internal Medicine, Diabetology, and Nephrology, Faculty
of Medical Sciences in Zabrze, Medical University of Silesia in Katowice,
Poland
4. BACKGROUND
According to the International Diabetes Federation (IDF), 10.5% of the adult population (20-
79 years) has diabetes, with almost half unaware that they are living with the condition.
The IDF Diabetes Atlas (2021) reports that approximately 540 million people worldwide
have diabetes.
By 2045, IDF projections show that 1 in 8 adults, approximately 783 million, will be living
with diabetes, an increase of 46%
5. • The essence of diabetes treatment is multidirectional therapeutic
intervention, including both carbohydrate and lipid control and
normalization of blood pressure.
• This strategy has been shown to be beneficial for diabetic patients
and contributes to the reduction of mortality, cardiovascular deaths,
and the risk of microangiopathy
6. IMEGLIMIN
Imeglimin is the first in a new tetrahydrotriazine containing
class of oral antidiabetic agents referred to as “glimins”.
Imeglimin is under investigation with three pivotal Phase III
clinical trials having recently completed in Japan.
Clinical experience with Imeglimin in Japanese and
Caucasian patients with T2DM has shown significant and
durable antihyperglycemic activity, generally favorable
safety and tolerability, and a lack of severe hypoglycemia in
multiple trials
including combinations with metformin, dipeptidyl peptidase
(DPP) 4 inhibitors, insulin and other
8. EFFECTS ON INSULIN SENSIVITY
• EFFECTS ON INSULIN SENSITIVITY( increase)
• Mechanism not well understood
• GLUT 4 , INSULIN RECEPTOR AUTOPHOSPHORYLATION
• Facilitate signal transduction through insulin
• EFFECTS ON GLUCONEOGENESIS( decrease)
• Decreasing PEPCK , G6Pase activity
• EFFECTS ON MITOCHONDRIAL FUNCTION
• IMEG improved mitochondrial function by modulating the activity of
complexes I and III, stimulating mitochondrial fatty acid oxidation, and by
normalizing mitochondrial phospholipid composition
9. • EFFECTS ON PANCREATIC FUNCTION
• ANTIOXIDANT EFFECTS
• Supress MITOCHONDRIAL ROS production and also improves vascular endothelial dysfunction
10. Pharmacokinetics
• Half life : 10-20 hrs
• After oral administration of IMEG, its absorption occurs by both passive
and active transport and lasts up to 6 hours
• The bioavailability after oral administration of IMEG drug ranges from 50 to
20%, and it depends on the dose of the drug administered (100–6000 mg)
–it decreases with the drug dose increasing
• Imeglimin bonds to plasma proteins only to a small extent (1–8%).
• Imeglimin is eliminated from the body in a biphasic manner with an initial
rapid phase followed by a slower elimination phase.
• The hepatic metabolism of IMEG is very low, so it is excreted almost
completely unchanged in urine
11. Clinical evidence for IMEGLIMIN effects
• There is increasing evidence that IMEG
• reduces fasting plasma glucose,
• normalizes HbA1c levels, and
• improves b-cell function in T2DM patients .
• Imeglimin as add-on therapy to METFORMIN or SITAGLIPTIN reduces
HbA1c levels by 4–8 mmol/mol
12. • Pacini et al. In the study group of 33 patients, GSIS was evaluated
using a hyperglycaemic clamp. Total insulin secretory response and
insulin secretion rate calculated and evaluated.
• Treatment with imeglimin IMEG (1500 mg/12 h), for 7 days there was
an improvement in beta-cell function in T2DM patients and increased
insulin secretion in response to glucose stimulation
13. • Pirags et al. published the results of 2 phase II trials conducted for 4
weeks and 8 weeks.
In the first study, 60 T2DM
patients received
IMEG 2000 mg once a day
(OD),
IMEG 1000 mg twice a day
(BID), or
MET 850 mg BID.
Imeglimin BID treatment was shown to be as effective as MET
treatment as assessed by OGTT plasma glucose measurement
Use of IMEG once daily at 2000 mg also reduced incremental AUC in
OGTT but only by 10%, and it was less effective than IMEG and MET
used BID
14. • In the second study on T2DM patients, these authors demonstrated
no increase in insulin secretion after IMEG compared with placebo
and no concomitant change in HbA1c levels.
• IMEG 500 mg BID and placebo showed an unknown increase in
fasting plasma glucose.
15. • Fouqueray et al. conducted 2 studies evaluating the effects of IMEG
on HbA1c levels and FPG
MET treatment in combination with
IMEG at 1500 mg BID or placebo
subjects treated with MET with IMEG
compared to those treated with MET
with placebo achieved HbA1c < 7%
effect of combination treatment of SITA
with IMEG 1500 mg BID and SITA with
placebo given for 12 weeks on HbA1c levels.
SITA-IMEG combination treatment
compared to SITA-placebo treatment
significantly increased the number of
subjects achieving HbA1c levels ≤ 7%
16. • Douborg et al. published the results of a phase II clinical trial
evaluating the efficacy and safety of IMEG monotherapy versus
placebo at 24-week follow-up
placebo 68%
IMEG 500 mg 0.52% 68%
IMEG 1000mg 0.94% 62.2%
IMEG 1500mg 1.00% 73.3%
17. • Fouqueray et al. investigated the effect of IMEG at doses of 500 mg,
1000 mg, 1500 mg, 2000 mg, or placebo BID on HbA1c levels and
change in FPG levels.
• Maximum efficacy for all IMEG drug doses tested was achieved after
18 weeks of treatment.
• After 24 weeks, significantly more subjects treated with IMEG at 1500
mg BID achieved HbA1c levels ≤ 7% (33.3%) compared with the
placebo group (12.5%) .
• Fasting plasma glucose reductions were also the greatest with the
treatment with IMEG at 1500 mg BID
18. • The phase III TIMES (Trials of Imeglimin for Efficacy and Safety) study
has recently been completed in Japan and consists of 3 separate
studies (TIMES 1–3) involving a total of 1100 study patients with
T2DM receiving IMEG at 1000 mg BID or placebo for 24 weeks.
• The TIMES 1 phase III study included 213 Japanese T2DM patients
aged 20 years or older treated with diet and exercise, with a stable
course for the last 12 weeks before entering the study, with HbA1c
levels between 7.0 and 10.0%
• Treatment in T2DM patients with IMEG resulted in a reduction in
HbA1c as well as FPG
19. • TIMES 2 was a placebo-controlled, multicentre, 52-week study that
evaluated the efficacy and safety of IMEG as monotherapy or in
addition to other hypoglycaemic agents
• The change in HbA1c levels from the baseline ranged from –0.56 ±
0.08 to –0.92 ± 0.11% in patients receiving IMEG in combination with
other oral antidiabetic drugs
• In the TIMES 3 study, 215 T2DM patients with a mean HbA1c level of
73 mmol/mol (8.8%) treated with insulin in monotherapy (81%) or
insulin in combination with an oral antidiabetic drug (19%) were
included in the study. The subjects received either 1000 mg BID or
placebo in addition to their existing treatment with IMEG
20. TOLERABILITY
• Phase I and II clinical trials in T2DM have shown that IMEG is
effective as monotherapy or as add-on therapy and has an adequate
safety and tolerability profile.
• Dose-dependent side effects, mainly headache and gastrointestinal
symptoms, have been demonstrated after IMEG use. No serious
adverse events have been reported
• In the TIMES 1 phase III study with 24 weeks of IMEG monotherapy,
drug tolerability was good and consistent with the results of the
phase II study. Treat ment discontinuation due to adverse events was
reported in 3% of IMEG-treated patient
21. INTERACTIONS
• IMEG to be a substrate of the renal multidrug and toxic extrusion
transporters (MATE): MATE1 and MATE2-K
• IMEG is also a substrate of OCT1 and 2, which are expressed in the
liver and kidney
• IMEG had no clinically relevant effect on the pharmacokinetics of
metformin, which is also a substrate for MATE1, MATE-2K, and OCT2
transporters
• The effects of cimetidine, a reference inhibitor of MATE1, MATE-2K,
OCT1, and OCT2 transporters, on the pharmacokinetics and safety of
IMEG were also investigated. No clinically significant interactions
between IMEG and cimetidine were observed
22. • Chevalier et al. investigated the effect of hepatic impairment on IMEG
pharmacokinetics
• The authors evaluated the pharmacokinetics as well as safety of IMEG
after oral administration of a single 1000 mg dose in subjects with
moderate hepatic impairment and in a control group with normal
liver function.
• There was a 1.3-fold increase in plasma concentration (Cmax) and a
1.5-fold increase in the area under the plasma concentration-time
curve (AUC) in the subjects with moderate hepatic impairment
compared to the control group, but this was not considered clinically
significant.
23. OTHER BENEFITS
• The results of the study suggest that IMEG prevents endothelial cell
apoptosis by inhibiting mitochondrial permeability without inhibiting
mitochondrial respiration, which may reduce the risk of
cardiovascular complications in T2DM
• Imeglimin treatment reduced left ventricular end-diastolic pressure
and LV end-systolic volume, increased LV tissue perfusion, and
reduced LV ROS production.
24.
25.
26. conclusion
• Imeglimin , new oral drug acts on 3 mechanisms. Its unique
mechanism of action and safety profile compared to currently
available antidiabetic therapies potentially fills important gaps in the
current treatment of T2DM