This document summarizes several newer anti-hyperglycemic agents that are expanding treatment options for type 2 diabetes mellitus. It discusses drugs that target the incretin system like DPP-4 inhibitors and GLP-1 agonists. It also covers SGLT2 inhibitors, glucokinase activators, combined PPARα/γ agonists, and selective PPARγ modulators. The document analyzes the mechanisms and potential benefits of these newer classes of drugs, such as lower risks of hypoglycemia, weight neutrality, and potential disease-modifying effects through β-cell protection. It also notes some safety concerns that require further research.
Newer anti-hyperglycemic agents in type 2 diabetes mellitus - 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, 11β hydroxy steroid dehydrogenase inhibitors, drugs modulating fatty acid metabolism, selective PPARγ receptor modulators and anti inflammatory agents. Aim of this review is to describe the emerging therapies for 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.
Prospects of incretin mimetics in therapeuticsDr Sukanta sen
Comparative trials show that there are important differences between
and among the GLP-1 receptor agonists and DPP-4 inhibitors with
respect to glycemic lowering, weight effects, and effects on systolic
blood pressure and the lipid profile.
•Nausea, diarrhea, headaches, and dizziness are common with the
available GLP-1 receptor agonists.
•Upper respiratory tract infections, nasopharyngitis, and headaches
are common with the DPP-4 inhibitors.
•Ongoing safety evaluations should provide a clear picture regarding
long-term safety.
Newer anti-hyperglycemic agents in type 2 diabetes mellitus - 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, 11β hydroxy steroid dehydrogenase inhibitors, drugs modulating fatty acid metabolism, selective PPARγ receptor modulators and anti inflammatory agents. Aim of this review is to describe the emerging therapies for 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.
Prospects of incretin mimetics in therapeuticsDr Sukanta sen
Comparative trials show that there are important differences between
and among the GLP-1 receptor agonists and DPP-4 inhibitors with
respect to glycemic lowering, weight effects, and effects on systolic
blood pressure and the lipid profile.
•Nausea, diarrhea, headaches, and dizziness are common with the
available GLP-1 receptor agonists.
•Upper respiratory tract infections, nasopharyngitis, and headaches
are common with the DPP-4 inhibitors.
•Ongoing safety evaluations should provide a clear picture regarding
long-term safety.
Teneligliptin the next generation gliptinAKSHATA RAO
Teneligliptin , one of the emerging gliptins have established its prowess among the gliptin giants like Sitagliptin Vildagliptin and Linagliptin. Proven to be safe in renally compromised patients, this one is to watch out for.
A Study of Prescription Patterns of DPP-4 inhibitors..Samya Sayantan
Diabetes Mellitus (DM) is a metabolic disorder of which inappropriate hyperglycemia is the hallmark. For this reason, several classes of oral hypoglycemic drugs like Sulfonylurea, Biguanides, Meglitinides, Thiazolidinediones, α-glucosidase inhibitors are prescribed to treat Diabetes Mellitus. But at present Dipeptidyl Peptidase (DPP-4) Inhibitors have attracted attention as oral hypoglycemic agents that recently introduced to Bangladesh. This study aims to evaluate the current prescribing pattern of DPP-4 inhibitors at BIRDEM hospital, Bangldesh.during the survey, 150 prescriptions were collected and investigated where only 49% DPP-4 inhibitors – Sitagliptin, Linagliptin, Vildagliptin are prescribed even along with other conventional oral hypoglycemic drug. According to this survey, it is clear that Dipetidyl Peptidase (DPP-4) inhibitors is becoming more popular day by day in the management of hyperglycemia in Type-2 Diabetes without causing weight gain or hypoglycaemia in Bangladesh.
Teneligliptin the next generation gliptinAKSHATA RAO
Teneligliptin , one of the emerging gliptins have established its prowess among the gliptin giants like Sitagliptin Vildagliptin and Linagliptin. Proven to be safe in renally compromised patients, this one is to watch out for.
A Study of Prescription Patterns of DPP-4 inhibitors..Samya Sayantan
Diabetes Mellitus (DM) is a metabolic disorder of which inappropriate hyperglycemia is the hallmark. For this reason, several classes of oral hypoglycemic drugs like Sulfonylurea, Biguanides, Meglitinides, Thiazolidinediones, α-glucosidase inhibitors are prescribed to treat Diabetes Mellitus. But at present Dipeptidyl Peptidase (DPP-4) Inhibitors have attracted attention as oral hypoglycemic agents that recently introduced to Bangladesh. This study aims to evaluate the current prescribing pattern of DPP-4 inhibitors at BIRDEM hospital, Bangldesh.during the survey, 150 prescriptions were collected and investigated where only 49% DPP-4 inhibitors – Sitagliptin, Linagliptin, Vildagliptin are prescribed even along with other conventional oral hypoglycemic drug. According to this survey, it is clear that Dipetidyl Peptidase (DPP-4) inhibitors is becoming more popular day by day in the management of hyperglycemia in Type-2 Diabetes without causing weight gain or hypoglycaemia in Bangladesh.
O futuro na terapia baseada em incretins.Ruy Pantoja
Neste belo artigo realcei em amarelo as partes que mais me instigaram. Depois traço um paralelismo com a bela conferência do Prof. Buse, realizada em San Diego há um mês.
International Journal of Pharmaceutical Science Invention (IJPSI)inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Obesity context of type 2 diabetes and medication perspectivesApollo Hospitals
Drug therapy of obesity has harsh antecedent that many earlier introduced drugs are withdrawn from market. The drugs in present use lack sufficient long-term efficacy and safety data. The difficulty of reversing changing dietary habits and decline in physical activity, however, offers major scope for anti-obesity therapeutics, implied in managing the epidemic chronic inflammatory maladies and cardiovascular sequel. Metabolic syndrome, pre-diabetes and type 2 diabetes mellitus, commonly associate with obesity. Weight reduction is crucial to prevent and control type 2 diabetes. This emphasizes rational choice of therapeutic regimens that do not themselves cause weight gain, and better promote weight loss. Such an aspect is addressed briefly focusing upon the available newer anti-obesity drug options, in particular.
Manish yadav .M Pharm First year
Pharmacology . Under -guidence of
Professor Dr. Govind Singh .
M.D.University Rohtak
Department Pharmaceutical science
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.
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.
Diabetes, a chronic medical condition affecting millions worldwide, is characterized by elevated blood sugar levels that result from the body's inability to properly produce or use insulin.
Insulin, a hormone produced by the pancreas, plays a crucial role in regulating blood glucose and facilitating its entry into cells for energy.
There are two main types of diabetes: Type 1, where the immune system mistakenly attacks insulin-producing cells, and Type 2, characterized by insulin resistance and inadequate insulin production. Managing diabetes often involves a combination of lifestyle changes, such
as a healthy diet and regular exercise, and medications designed to
regulate blood sugar levels.
In this context, various medications play pivotal roles, from traditional
insulin therapies to a diverse array of oral and injectable options for Type 2
diabetes.
This introduction provides a foundation for exploring the medications
commonly prescribed for diabetes management, offering insights into their
mechanisms of action and the diverse strategies employed to empower
individuals in effectively navigating this complex and chronic condition
Malignant Mixed Mullerian Tumor – Case Reports and Review ArticleApollo Hospitals
Malignant mixed mullerian tumors are very rare genital tumors. They are biphasic neoplasms composed of an admixture of malignant epithelial and mesenchymal elements. In descending order of frequency they originate in the uterus, ovaries, fallopian tubes, cervix and vagina. Also they arise denovo from peritoneum. They are highly aggressive and tend to occur in postmenopausal low parity women. Because of rarity, there is as such no treatment guidelines available. Multimodality treatment in the form of radical surgery followed by adjuvant chemotherapy or radiotherapy or combined chemoradiation gives a better prognosis & outcome. Two case reports of such tumors, one from ovary and other from penitoneum are presented along with the review of literature.
Intra-Fetal Laser Ablation of Umbilical Vessels in Acardiac Twin with Success...Apollo Hospitals
To interrupt blood supply to the acardiac twin in a case of TRAP sequence of monochorionic diamniotic multiple pregnancy to allow for continuation of the normal twin.
Breast Cancer in Young Women and its Impact on Reproductive FunctionApollo Hospitals
Breast cancer is the most common cancer in women in developed countries. Chemotherapy for breast cancer is likely to negatively impact on reproductive function. We review current treatment; effects on reproductive function; breastfeeding and management of menopausal symptoms following breast cancer.
Turner syndrome (gonadal dysgenesis) is one of the most common chromosomal abnormalities occuring 1 in 2500 to 1 in 3000 live-born girls. It is an important cause of short stature in girls and primary amenorrhea in young women that is usually caused by loss of part or all of an X chromosome. This review briefly summarises the current knowledge about the syndrome and the management strategies.
Due to pregnancy thyroid economy is affected with changes in iodine metabolism, TBG and development of maternal goiter. The incidence of hypothyroidism in pregnancy is quite common with autoimmune hypothyroidism being the most important cause. Overt as well as subclinical hypothyroidism has a varied impact on maternal and neonatal outcome. After multiple studies also, routine screening in pregnancy for hypothyroidism can still not be recommended. Management mainly comprises of dosage adjustments as soon as pregnancy is diagnosed based on results of thyroid function tests. The aim should be to keep FT4 at the upper end of normal range.
Growth Hormone Deficiency (GHD) can persist from childhood or be newly acquired. Confirmation through stimulation testing is usually required unless there is a proven genetic/structural lesion persistent from childhood. Growth harmone (GH) therapy offers benefits in body composition, exercise capacity, skeletal integrity, and quality of life measures and is most likely to benefit those patients who have more severe GHD. The risks of GH treatment are low. GH dosing regimens should be individualized. The final decision to treat adults with GHD requires thoughtful clinical judgment with a careful evaluation of the benefits and risks specific to the individual.
Advances in the management of thalassemia have led to marked improvements in the life span and quality of life of children and young adults. This poses new challenges for the treating physicians. There is now increasing recognition that thalassemics have impaired bone health which is multifactorial in etiology. This paper aims to highlight the factors that predispose these patients to osteoporosis and suggests measures to minimise the impact on bone health.
Laparoscopic Excision of Foregut Duplication Cyst of StomachApollo Hospitals
Retroperitoneal gastric duplication cysts lined by ciliated columnar epithelium are extremely rare lesions and its presentation during adulthood is a diagnostic challenge for treating clinicians. This entity often resembles cystic pancreatic neoplasm, retroperitoneal cystic lesions and sometimes as an adrenal cystic neoplasm. Correct diagnosis on the basis of radiological investigation is difficult and histopathologic analysis. We report a case of gastric duplication cyst in a 16year old girl that mimicked as a retroperitoneal /pancreatic /adrenal cystic lesion and was successfully managed by laparoscopy.
Occupational Blood Borne Infections: Prevention is Better than CureApollo Hospitals
Viral infections like HIV, hepatitis Band C virus pose a big risk to the contacts of individuals with high risk behaviour as well as to the attending health care workers. Blood, semen, vaginal and other potentially infectious materials can transmit the infection to the susceptible contacts. Universal precautions should be strictly implemented during clinical examination, laboratory work and surgical procedures to prevent transmission to the health care providers. Health care workers should receive vaccination for hepatitis B infection. An inadvertent exposure should be managed with proper first aid and infectivity of the source and severity of exposure should be assessed. Severity of exposure is based on the nature and area of exposed surface, mode of injury and volume of infective material. Post-exposure prophylaxis (PEP) should be started as soon as possible after a proper counseling about the effectiveness of post-exposure prophylaxis, side effects and risk of carrying the infection to his familial contacts and its prevention.
Evaluation of Red Cell Hemolysis in Packed Red Cells During Processing and St...Apollo Hospitals
Storage of red cells causes a progressive increase in hemolysis. Inspite of the use of additive solutions for storage and filters for leucoreduction some amount of hemolysis is still inevitable. The extent of hemolysis however should not exceed the permissible threshold for hemolysis even on the 42nd day of storage.
Efficacy and safety of dexamethasone cyclophosphamide pulse therapy in the tr...Apollo Hospitals
Various drugs used to treat pemphigus can cause remission, but none can provide permanent remission as relapses are common. With the introduction of DCP in pemphigus in 1984, patients started being in prolonged/permanent remission. This study was done to compare the efficacy of DCP to oral corticosteroids and cyclophosphamide in combination.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)Apollo Hospitals
Severe skin adverse drug reactions can result in death. Toxic epidermal necrolysis (TEN) has the highest mortality (30–35%); Stevens-Johnson syndrome and transitional forms correspond to the same syndrome, but with less extensive skin detachment and a lower mortality (5–15%). Hypersensitivity syndrome, sometimes called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), has a mortality rate evaluated at about 10%. It is characterised by fever, rash and internal organ involvement. Prompt diagnosis is vital, along with identification and early withdrawal of suspect medicines and avoidance of re-exposure to the responsible agent is essential. Cross-reactivity to structurally-related syndrome caused by Carbamazepine medicines is common, thus first-degree relatives may be predisposed to developing this syndrome. We report a case of DRESS secondary to use of Carbamazepine.
Difficult Laparoscopic Cholecystectomy-When and Where is the Need to Convert?Apollo Hospitals
Laparoscopic cholecystectomy has now become the treatment of choice for the gall bladder stone. With increasing experience, surgeon has started to take more difficult cases which were considered relative contra indications for laparoscopic removal of gall bladder few years back.
We conducted this study at our hospital and included all laparoscopic cholecystectomy done from May'08 to January'10. Total time taken in surgery, conversion rate and complication rate were analysed. Factors making laparoscopic cholecystectomy difficult were also analysed. We defined difficult laparoscopic cholecystectomy when we found -dense fibrotic adhesions in and around Callot's triangle, gangrenous gall bladder, empyma, large stone impacted at gall bladder neck, contracted gall bladder, Mirrizi's syndrome, h/o biliary pancreatitis, CBD stones, acute cholecystitis of <72 hrs duration.
Out of 206 cases done during above period, 56 cases were considered difficult. Only two cases were converted to open.
With growing experience and technical advancement surgery can be completed in most of the difficult cases. This is important because recently it is shown in literature that laparoscopic cholecystectomy is associated with less morbidity than open method irrespective of duration of the surgery.
Deep vein thrombosis prophylaxis in a tertiary care center: An observational ...Apollo Hospitals
Deep vein thrombosis (DVT) is a major health problem with substantial mortality and morbidity in medically ill patients. Prevention of DVT by risk factor stratification and subsequent antithrombotic prophylaxis in moderate- to severe-risk category patients is the most rational means of reducing morbidity and mortality.
The spread of dengue and dengue haemorrhagic fever is increasing, atypical manifestations are also on the rise, although they may be under reported because of lack of awareness. We report two such cases of dengue hemorrhagic fever with hepatitis, intraocular hemorrhage, ARDS and myocarditis.
A 71-year-old male presented in ENT department with dysphagia for last three weeks, more to solids than liquids. He had a hard bony bulge in the posterior pharyngeal wall on palpation and hence was referred for an Orthopaedic opinion. Lateral radiograph of the cervical spine revealed diffuse ossification of the anterior longitudinal ligament. This ossification was extending almost half the width of the cervical body from its anterior body at C1 and C2 vertebra level.
Pediatric Liver Transplant (LT) is now an established procedure for End Stage Liver Disease (ESLD) with biliary atresia being the commonest indication. Intensive pre-transplant evaluation, nutritional buildup and immunization are the fundamental pre-requisites of a successful LT. With improvement in surgical micro-anastomotic techniques and superior immunosuppressive regimens the success rate of pediatric LT is in excess of 90%. Most of the transplants in our country however are Living related, due to which a fairly large number of children expire awaiting a donor liver. There should be a concerted effort to evolve the cadaveric donation program, so that majority of the children are benefitted.
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We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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
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
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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.
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.
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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
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
2. Review Article
Newer anti-hyperglycemic agents in type 2 diabetes
mellitus e Expanding the horizon
Savita Jain a,
*, Nitin Gupta a
, Radhika Jindal a
, Tuhin Dubey a
, Niti Agarwal b
,
Asim Siddiqui b
, S.K. Wangnoo c
a
DNB Fellow, Department of Endocrinology, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, India
b
Associate Consultant, Department of Endocrinology, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, India
c
Senior Consultant, Department of Endocrinology, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, India
a r t i c l e i n f o
Article history:
Received 5 May 2013
Accepted 16 May 2013
Available online 6 June 2013
Keywords:
Type 2 diabetes mellitus
Newer therapy
Pathophysiology
a b s t r a c t
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 patho-
physiologic 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 in-
flammatory agents. Aim of this review is to describe the emerging therapies for diabetes
mellitus.
Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
1. Introduction
Diabetes mellitus is a chronic disease reaching epidemic
levels in both developed and developing countries. According
to WHO by 2030, there will be 366 million diabetic patients
worldwide and 80 million diabetics only in India. Significant
morbidity, mortality and cost are associated with this disease
due to progressive nature resulting in many micro and mac-
rovascular complications. It requires continuous medical care
and self-management by the patient to prevent both acute
and chronic complications related to uncontrolled glycemic
status. Many classes of drugs are available for treatment of
diabetes mellitus like metformin, sulfonylureas, a-glucosi-
dase inhibitors, glitazones, glinides and insulin. Newer drugs
like DPP4 inhibitors, GLP1 agonists, SGLT2 inhibitors, insulin
analogs have been added to this list during last few years.1
With these, clinical management of diabetes mellitus has
undergone a significant change. Despite availability of
numerous classes of drugs addressing different pathophysi-
ologic mechanisms, search for new drugs continues to combat
adverse drug effects associated with available drugs (weight
gain, hypoglycemia, fluid retention, cardiovascular risk), effi-
cacy, poor adherence due to need of injection or frequent
administration, cost or other factors and most importantly to
combat progressive decline in b cell function. In this review,
we discuss new emerging therapies for treatment of type 2
diabetes and other potential targets for development of new
drugs.
* Corresponding author.
E-mail addresses: dr.jain.savita@gmail.com, savitajain@yahoo.com (S. Jain).
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/apme
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 0 8 e1 1 2
0976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.apme.2013.05.013
3. 2. Pathogenesis
b cells are the seat of pathophysiology of diabetes. b cell
dysfunction is an important pathophysiologic mechanism
underlying development of diabetes mellitus. There are non-
modifiable factors influencing b cell health like age and ge-
netic predisposition. Also there are modifiable factors like
insulin resistance, lipotoxicity, glucotoxicity, incretin defect
and increase in islet amyloid polypeptide (IAPP). Along with b
cell dysfunction, insulin resistance in liver, muscle and adi-
pose tissue accounts for development of impaired glucose
tolerance. There is increased gluconeogenesis from liver due
to hyperglucagonemia with increased sensitivity to glucagon,
lipotoxicity and glucotoxicity. Muscle is another major site for
insulin resistance characterized by multiple intramyocellular
defects like impaired glucose transport, phosphorylation,
glycogenesis and glucose oxidation. Diabetic patients have
increased lipolysis in adipose tissue thus causing release of
excessive free fatty acids into the circulation. These free fatty
acids are responsible for lipotoxicity in b cells, stimulate
gluconeogenesis from liver and cause insulin resistance. Also
there is increase in release of pro-inflammatory cytokines like
leptin and decrease in anti-inflammatory cytokines like adi-
ponectin thus further exacerbating insulin resistance.2
Cen-
tral adiposity with visceral fat deposition confers a higher risk
of developing diabetes mellitus. Drugs used earlier for dia-
betes targeted mainly these mechanisms for control of
hyperglycemia.
Other less important but established pathophysiologic
mechanisms include a cell dysfunction causing increased
glucagon release, enteroendocrine axis causing reduced
glucagon like peptide 1 (GLP1) secretion, kidney dysfunction
causing increased reabsorption of filtered glucose and
dysfunctional hypothalamic centers for appetite regulation in
brain. Newer drugs like DPP4 inhibitors, GLP1 agonists,
bromocriptine & SGLT2 inhibitors target these pathophysio-
logic mechanisms for anti-hyperglycemic effect. All these
features together form ominous octet responsible for the
development of diabetes mellitus.
Recently some other factors have been implicated and
concept of dirty dozen was proposed. Other four factors
include increased dopamine in brain, vitamin D deficiency,
testosterone deficiency and dysfunction of local renin angio-
tensin system in b cells.
Two other factors that have been proposed are increased
iron stores causing insulin resistance and b cell damage and
gut derived serotonin that activates hormone sensitive lipase
and thus increases lipolysis in adipose tissue.2
Many new drugs are under development targeting these
mechanisms.
3. Drugs
3.1. Incretins
3.1.1. DPP4 inhibitors
DPP4 inhibitors are a class of orally active drugs that enhance
incretin system activity by blocking GLP1 degradation. GLP1 is
a major incretin hormone responsible for glucose dependent
increase in insulin secretion after meals, but its duration of
action is shortened by DPP4 (Dipeptidyl peptidase 4) enzyme.
Increased activity of DPP4 has been seen in diabetic patients.
Thus DPP4 inhibitors are an attractive target as anti-
hyperglycemic drug. AnNumber of DPP4 inhibitors have
become available in last decade like sitagliptin, linagliptin,
alogliptin, vildagliptin and saxagliptin. Others that are in
various phases of trial include dutogliptin and gemigliptin.
As a class, DPP4 inhibitors have been shown to reduce
HbA1C by 0.75%. Benefits over older drugs include very low
risk of hypoglycemia, weight neutrality, oral administration,
cardiovascular safety and most importantly improving b cell
health.
Short-term studies have shown good tolerability. Adverse
effects reported in different studies are minor and include
pruritus, diarrhea, nausea, dizziness and diaphoresis.
3.1.2. GLP1 agonists
GLP1 agonists increase insulin secretion in response to oral
glucose ingestion, induce satiety by slowing gastric emptying,
suppresses appetite, inhibit glucagon secretion and also have
been proposed to cause b cell neogenesis and protection from
cytokine and free fatty acid induced injury. Endogenous GLP1
released from intestinal L cells has a short half-life of
4e11 min. To overcome this, GLP1 analogs resistant to
degradation by DPP4 have been devised. Various drugs avail-
able are exanatide and liraglutide. Drugs under development
are albiglutide (awaiting FDA approval), lixisenatide and
semaglutide.
Potential benefits of these agents include control of post-
prandial hyperglycemia, less hypoglycaemia, satiety induc-
tion and thus promoting weight loss and most importantly
disease modifying effect by causing b cell neogenesis. Major
disadvantage is the need of injecting these drugs once or twice
a day. To overcome this, exanatide extended release has
recently been available. It is administered as once a week dose
at any time of the day without regard to meal.
Other minor adverse effects associated with the use of
GLP1 agonists are nausea, fullness, bloating and vomiting (to
overcome these, slow escalation of dose is done), nasophar-
yngitis, headache and extremity pain. Rarely pancreatitis and
hypersensitivity reactions have been reported.
3.1.3. GPR40 agonists
G-protein coupled receptor is present on b cells and are
responsible for increased glucose dependent insulin secre-
tion. It normally gets activated by fatty acids. GPR40 activation
has been shown to be potential therapeutic target to improve
insulin secretion and glucose tolerance.3
A novel GPR40
agonist TAK-875 has recently been shown to produce clinical
and statistically significant improvement in glycemic control
in type 2 diabetic subjects who were not controlled on diet and
exercise alone.4
Efficacy in HbA1C has been shown to be
equivalent to glimepride at higher doses, with lower pro-
pensity to cause hypoglycaemia and overall good tolerability.
Doses tested range from 6.25 mg to 200 mg, >50 mg produce
reduction in HbA1C equivalent to 1 mg glimepride. Adverse
effect attributable to drug was nasopharyngitis, mild hypo-
glycaemic episodes and weight gain (lesser than glimepride).
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4. Another agent JTT-851 is under trial for safety, tolerability and
efficacy.5
3.1.4. GPR119 agonist
GPR119 is a lipid-sensing G protein coupled receptor (GPCR)
present on enteroendocrine cells in the gut that regulate
incretin secretion & have direct effects on insulin secretion in
pancreatic b cells. GPR-119 agonists currently under develop-
ment include SAR-260093/MBX-2982 (Metabolex) in phase 2
trial, GSK-1292263 in phase 2 trial and PSN-821 in phase 2
trials.6
They have been shown to be weight negative and have
less risk of hypoglycemic episodes. Another important
advantage is oral availability. It has been proposed that co-
administration of GPR119 and DPP4 inhibitors (mechanism
to protect secreted GLP-1) may offer dual benefit of providing
improved glycemic control with weight loss (as observed with
GLP-1 mimetics).
3.2. SGLT2 inhibitors
Sodium glucose co-transporters (SGLT) are located in the
proximal tubules of the kidney and are responsible for renal
glucose reabsorption from proximal tubules. SGLT2 accounts
for 90% of this reabsorption. SGLT2 inhibitors are another
novel class of drugs with potential of improving hyperglyce-
mia. These drugs lower glycemia by causing glucosuria and
thus do not require functioning b cells. As a class they have
modest efficacy in lowering HbA1C, do not cause hypoglyce-
mia and have a potential use in type 1 diabetes also. Along
with glycemic control these drugs are weight negative (due to
calorie loss in urine), mild reduction in blood pressure due to
chronic osmotic dieresis and associated with lower risk of
hypoglycemia. Various drugs in this category include Dapa-
gliflozin, Canagliflozin, Remogliflozin, Empagliflozin, Ipragli-
flozin, Luseogliflozin and Topogliflozin. Canagliflozin has
recently been approved for clinical use (though cardiovascu-
lar safety profile still pending). Adverse effects include uri-
nary tract infections (due to glucosuria providing a good
medium for bacterial growth), nausea, constipation, diarrhea,
concern for potential renal toxicity (short term studies have
not shown any renal toxicity) and small risk of bladder and
breast cancer.5,7
These agents do not have any effect on lipid
profile, but long term cardiovascular safety data is still not
available.
3.3. Glucokinase activators
Glucokinase is an enzyme present in b and a cells of pancreas
and plays an important role in glucose homeostasis. Gluco-
kinase activation acts as glucose sensor and affects coupling
factors ATP and ADP thus depolarizing the cell, resulting in
calcium influx and stimulated insulin release. It also activates
the GABA shunt, producing gamma-hydroxybutyrate that
functions as an important paracrine inhibitor of glucagon
secretion. Further insulin itself along with GABA may inhibit
glucose-mediated alpha cell suppression. Glucokinase acti-
vator drugs thus have the potential as an anti-diabetic drugs.8
Glucokinase activation acts as a prominent regulator of he-
patic intermediary and energy metabolic pathways like
glycogen synthesis, amino acid (alanine, aspartate, glutamate,
glycine and serine), lactate and urea production. Potential
detrimental effects include enhanced lipogenesis and associ-
ated hepatosteatosis and hyperlipidemia. Also this class has
propensity to cause hypoglycemia and glucolipotoxicity on b
cell survival and function.5
Trials for two drugs MK0941
(Merck) and piragliatin (Roche) were terminated prematurely.
To avoid hypoglycemia, hepatospecific compound TTP399 has
been devised by modification by introducing charged side
chains changing permeability characteristics. Preclinical trials
have proven efficacy and apparently no hepatotoxicity and
mild hypoglycemic effect, but this drug has not been exten-
sively tested.5
3.4. Combined a and g PPAR agonists (the glitazars)
PPARg receptors are nuclear receptors directly affecting pe-
ripheral insulin resistance and PPAR-a receptors- modulate
lipids especially triglycerides. So compounds having com-
bined PPAR-a &g agonist activity (glitazars) were developed to
incorporate both insulin sensitizing and lipid lowering activ-
ity. These drugs are classified as thiazolidinedione variants
that include DRF-2189 & KRP-297 and nonthiazolidinedione
variants including JTT-501, BMS-298585 (muraglitazar), AZ-
242 (tesaglitazar) and NN-622 (ragaglitazar).1
These drugs
had favorable side effect profile in relation to cardiac hyper-
trophy, less weight gain and beneficial for triglyceride levels
and visceral adiposity. Other advantages found in animal
models were antiproliferative properties, angiotensin 2
antagonism, antioxidant effects, reduction of blood pressure,
correction of endothelial dysfunction and amelioration of
cardiac fibrosis associated with HT & MI. But clinical trials
revealed development of excessive peripheral edema, volume
overload and heart failure. Other detrimental effects were
bone marrow hematopoietic changes, soft tissue neoplasms
in rodents (Ragaglitazar) and hepatotoxicity.
3.5. SPPARM’s
PPARg agonists with partial agonistic activity (SPPARM), also
known as selective PPARg receptor modulators. SPPARM’s
bind to PPARg in a different manner from full agonists and
recruit different coactivators, thus retaining insulin sensi-
tizing effect with little side effects. Compounds under devel-
opment in this class include INT-131, PN2034 (Wellstat) and
mitoglitazone.1
3.6. 11b hydroxy steroid dehydrogenase 1 inhibitors
11b hydroxy steroid dehydrogenase (11b HSD1) catalyses
activation of cortisone to cortisol in liver, adipose tissue,
pancreas and brain. Cortisol acts as an insulin antagonist,
promotes gluconeogenesis and reduces glycogenesis. Com-
pounds in this novel class include INCB-13739, JTT-654,
AZD4017, DIO902 and RG4929.5,9
These agents are undergoing
phase 2 or 1 clinical trials. Preliminary data has shown good
tolerability, HbA1c reduction similar to DPP4 inhibitors,
modest weight loss, reduction in blood pressure & improve-
ment in cholesterol profile without causing hypoglycemia.
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5. 3.7. Protein tyrosine phosphatase 1B inhibitors
Protein tyrosine phosphatase (PTP) is a negative regulator of
insulin signaling via dephosphorylation of insulin receptor
and insulin receptor substrate-1 and leptin signaling by
dephosphorylation of JAK and STAT3 in hypothalamic
neuron. Thus protein tyrosine phosphatase 1B inhibition is
another potential target for anti-hyperglycemic action.10
These agents have dual benefit of control of hyperglycemia
and weight loss. But lack of selectivity over other similar PTPs
and cell permeability are obstacles in development of these
agents. Presently studies are underway for this class of drugs.
3.8. Regulators of fatty acid metabolism
Fatty acid metabolism is an important pathophysiologic link
in development of insulin resistance and glucose intolerance.
Drugs targeting fatty acid metabolic pathways are an attrac-
tive target for development of anti-hyperglycemic drugs.
Steroyl Co-A desaturase (SCD) and diacylglycerol acyl-
transferase (DGAT) are potential targets for drugs under
development. SCD catalyses the rate limiting step in synthesis
of monounsaturated fatty acids. Isoform SCD1 inhibition
(found in liver and adipose tissue) decreases lipogenesis and
increases fatty acid oxidation thus improving multiple meta-
bolic parameters. But SCD1 inhibition is associated with
reduced production of triglycerides, cholesterol and wax es-
ters required for normal function of eyelid and skin also. To
overcome this, liver-targeted approach has been employed by
including acetic or carboxylic acid group in the inhibitors.
DGAT catalyses the final step in triglyceride synthesis. DGAT1
inhibition has been shown in preliminary studies to benefit
diabetes, obesity, dyslipidemia and metabolic syndrome. Po-
tential adverse effect associated is alopecia due to retinoid
toxicity. DGAT1 inhibitors being evaluated are AZD7687,
PF4620110 and LCQ908. AZD7687 has been found to reduce
postprandial triglyceride increase. Adverse effects reported in
preliminary study are nausea, vomiting and diarrhea.11
3.9. Fibroblast growth factor 21 agonist
Fibroblast growth factor 21 is a hormonal regulator with the
potential to treat a variety of metabolic abnormalities like
diabetes mellitus, obesity and cardiovascular disease. It acti-
vates glucose uptake on adipocytes and reduces triglyceride
also. Currently a drug LP10152 is undergoing trial as anti-
hyperglycemic drug.
3.10. Glycogen phosphorylase inhibitor
Glycogen phosphorylase catalyses the breakdown of glycogen
to glucose 1 phosphate in liver. Inhibits breakdown of
glycogen and thus decrease hepatic glucose output. Glycogen
phosphorylase inhibitors thus serve as a promising treatment
strategy for hyperglycemia.12
An agent GSK1362885 is under-
going phase 1 trial presently.5
3.11. Anti-inflammatory therapies
Diabetes is a state of chronic low-grade inflammation. In-
flammatory markers like interleukin-1b (IL-1b), Nuclear factor
kB and chemokines have been implicated in the pathogenesis
of type 2 diabetes. Monoclonal antibodies against IL-1b, ana-
kinra and canakinubab are in clinical phase 2 studies. Re-
combinant IL-1 receptor antagonist Xoma052 is also under
study. Two compounds Triolex and VGX-1027 modulating NF-
kB are in clinical phase 1 studies. Chemokine receptor (CCR2)
antagonists BMS-741672 and CCX-140 are also in clinical
phase 2 studies.5
4. Conclusion
Better understanding of pathophysiologic mechanisms un-
derlying diabetes, has opened gateway for development of
many new drugs for treating hyperglycemia. Many such drugs
are in pipeline, proven to be efficacious in preliminary studies
and may be available in coming few years. It is expected that
availability of new drugs will provide choices for treating
these patients better with lesser adverse effects.
Conflicts of interest
All authors have none to declare.
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