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.
Sitagliptin an oral anti-diabetic agentAmruta Vaidya
A concise presentation on the DPP-IV inhibitor Sitagliptin an oral anti-diabetic agent. Its general mechanism of action, pharmacokinetics, safety is included.
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
Sitagliptin an oral anti-diabetic agentAmruta Vaidya
A concise presentation on the DPP-IV inhibitor Sitagliptin an oral anti-diabetic agent. Its general mechanism of action, pharmacokinetics, safety is included.
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
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.
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.
Low beneficial effects of short term antidiabetic diet treatment in streptozo...iosrphr_editor
Oxidative stress is currently suggested to play a role in the pathogenesis of Diabetes mellitus. The role of dietary management in diabetes mellitus is to provide a proper balance of total nutrients while meeting the special dietary needs of the patient. The present study was designated to evaluate the effect of special antidiabetic diet treatment upon oxidative stress parameters in the initial stages of the development of diabetes. Male Wistar strain rats were used as an experimental model, divided into five groups. A significant decrease in superoxide dismutase and total glutathione activities were observed in the liver of diabetic rats when compared with control animals. The plasma level of aminotransferases, creatine kinase, lactate dehydrogenase and urea were significantly increased after induction of diabetes, in all groups under treatment. In contrast, rats fed special diet food, have shown slight different, but not significant changes. The findings of the present study suggest that special diet formula useful for prevention of progressive hyperglycaemia in age induced diabetes in dogs, could not restore the imbalance of cellular defence mechanism provoked by streptozotocin.
Effect of emulin on blood glucose in type 2 diabetics - https://emulincanada.comAj Martirano
Effect of Emulin on Blood Glucose in Type 2 Diabetics https://emulincanada.com
,effect of emulin on blood glucose in type 2 diabet ,emulin diabetes ,igalen emulin diabetes ,emulin type 2 diabetes
In vitro antidiabetic activity like
Inhibition of Polysaccharide-Degrading Enzymes
Assay for α-Amylase
Assay for α-Glucosidase
Everted Sac Technique for Assaying α-Glucosidase
Assays forGLUT2TransportActivity
Perfusion of Jejunal Loops
Transport Activity of Brush Border Membrane Vesicles
Apical Expression of GLUT2
Evaluation of Glucose Absorption InVivo
Glp 1-based therapies for treatment of type 2 diabetes update on the benefit...Abdulameer Alashbal
GLP-1R agonists lower glycated haemoglobin by about 0.6–1% and induce weight loss. DPP-4 inhibitors reduce glycated haemoglobin by 0.5–0.6% and have no effect on weight. The GLP-1–related drugs arrived in clinical practice with much fanfare and anticipation. DPP- 4 enzyme is a ubiquitous cell-membrane protein, expressed in many tissues, including lymphocytes, which has raised some concerns about the long-term effects of DPP-4 inhibitors, especially on immune function. Data consistent with case reports and animal studies indicate an increased risk for pancreatitis with GLP-1-based therapy and also raise caution about the potential long-term actions of these drugs to promote pancreatic and thyroid cancers. This lecture will review the incretin-based therapies with focus on their benefits and their potential transient and serious side effects.
Transglucosidase improves the gut microbiota profile of type 2 diabetes melli...Enrique Moreno Gonzalez
Recently, the relationship between gut microbiota and obesity has been highlighted. The
present randomized, double-blind, placebo-controlled study aimed to evaluate the efficacy of
transglucosidase (TGD) in modulating blood glucose levels and body weight gain in patients
with type 2 diabetes mellitus (T2DM) and to clarify the underlying mechanism by analyzing
the gut microbiota of T2DM patients.
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.
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 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.
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.
Low beneficial effects of short term antidiabetic diet treatment in streptozo...iosrphr_editor
Oxidative stress is currently suggested to play a role in the pathogenesis of Diabetes mellitus. The role of dietary management in diabetes mellitus is to provide a proper balance of total nutrients while meeting the special dietary needs of the patient. The present study was designated to evaluate the effect of special antidiabetic diet treatment upon oxidative stress parameters in the initial stages of the development of diabetes. Male Wistar strain rats were used as an experimental model, divided into five groups. A significant decrease in superoxide dismutase and total glutathione activities were observed in the liver of diabetic rats when compared with control animals. The plasma level of aminotransferases, creatine kinase, lactate dehydrogenase and urea were significantly increased after induction of diabetes, in all groups under treatment. In contrast, rats fed special diet food, have shown slight different, but not significant changes. The findings of the present study suggest that special diet formula useful for prevention of progressive hyperglycaemia in age induced diabetes in dogs, could not restore the imbalance of cellular defence mechanism provoked by streptozotocin.
Effect of emulin on blood glucose in type 2 diabetics - https://emulincanada.comAj Martirano
Effect of Emulin on Blood Glucose in Type 2 Diabetics https://emulincanada.com
,effect of emulin on blood glucose in type 2 diabet ,emulin diabetes ,igalen emulin diabetes ,emulin type 2 diabetes
In vitro antidiabetic activity like
Inhibition of Polysaccharide-Degrading Enzymes
Assay for α-Amylase
Assay for α-Glucosidase
Everted Sac Technique for Assaying α-Glucosidase
Assays forGLUT2TransportActivity
Perfusion of Jejunal Loops
Transport Activity of Brush Border Membrane Vesicles
Apical Expression of GLUT2
Evaluation of Glucose Absorption InVivo
Glp 1-based therapies for treatment of type 2 diabetes update on the benefit...Abdulameer Alashbal
GLP-1R agonists lower glycated haemoglobin by about 0.6–1% and induce weight loss. DPP-4 inhibitors reduce glycated haemoglobin by 0.5–0.6% and have no effect on weight. The GLP-1–related drugs arrived in clinical practice with much fanfare and anticipation. DPP- 4 enzyme is a ubiquitous cell-membrane protein, expressed in many tissues, including lymphocytes, which has raised some concerns about the long-term effects of DPP-4 inhibitors, especially on immune function. Data consistent with case reports and animal studies indicate an increased risk for pancreatitis with GLP-1-based therapy and also raise caution about the potential long-term actions of these drugs to promote pancreatic and thyroid cancers. This lecture will review the incretin-based therapies with focus on their benefits and their potential transient and serious side effects.
Transglucosidase improves the gut microbiota profile of type 2 diabetes melli...Enrique Moreno Gonzalez
Recently, the relationship between gut microbiota and obesity has been highlighted. The
present randomized, double-blind, placebo-controlled study aimed to evaluate the efficacy of
transglucosidase (TGD) in modulating blood glucose levels and body weight gain in patients
with type 2 diabetes mellitus (T2DM) and to clarify the underlying mechanism by analyzing
the gut microbiota of T2DM patients.
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.
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.
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.
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.
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.
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.
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.
Antihyperlipidemic Activity of Torbangun Extract (Coleus amboinicus Lour) on ...iosrphr_editor
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).
Antihyperglycemic and Anti-hyperlipidemic Effect of Herbamed, A Herbal Formul...CrimsonPublishersIOD
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia and its occurrence is increasing fast in most of the countries. Herbal medicine derived from plant extracts have been utilized increasingly for the treatment of various disorders like diabetes mellitus. The present study was designed to evaluate the anti diabetic activity of ‘Herbamed’, a herbal formulation composed of Vernonia amygdalina, Ocimum gratissimum, Zingiber officinale and Allium sativum in alloxan-induced diabetic rats model.
Congenital Agenesis Of The Corpus Callosum With Intracerebral Lipoma And Fron...iosrphr_editor
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).
“Hemodynamic and recovery profile with Dexmedetomidine and Fentanyl in intrac...iosrphr_editor
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).
Correlation of Estrogen and Progesterone Receptor expression in Breast Canceriosrphr_editor
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).
Analytical Study of Urine Samples for Epidemiology of Urinary Tract Infection...iosrphr_editor
The current study was carried out in District Abbottabad aimed to determine the common urinary
tract infections in local community to determine the epidemiology of significant diseases in asymptomatic patients
of renal disorder. In this study a total of 1000 urine samples were examined during 3rd February to 1st April 2015
from patients attending Ayub Teaching Hospital Abbottabad by using dipstick and microscopic analysis of urine.
There were 638 females and 362 males patients examined during this period. The range of age groups is between
1.5 years to 80 years. Results of this study was reported as Pyuria 11%, Proteinuria 21.1%, Hematuria 10.4%,
Epithelial Cells 8.2%, pH 7.8 %, Granular casts 7.3%, Triple phosphate 6.6%, Calcium oxalate 6.4%, Glycosuria
6.3%, Bacteria 6.2% and mucous 4.1%. This study concludes that routing urinalysis should be performed for all
individuals to diagnose the asymptomatic diseases that will help in simple therapeutic measurements as urinalysis
is a simple step to determine the root of Urinary tract disorders.
Chest sonography images in neonatal r.d.s. And proposed gradingiosrphr_editor
BACKGROUND : Lung sonography has been used to monitor the patients of R.D.S. in
N.I.C.U. in recent times.
AIMS : To Describe and Grade the changes of R.D.S. by lung sonography.
SETTING & DESIGN : Tertiary care institutional set up in a rural medical college.
STUDY DURATION : September 2014 to May 2015. Follow-up variable, upto 2 weeks.
PROSPECTIVE, ANALYTICAL STUDY.
MATERIALS AND METHODS -This was a single institute study approved by the institutional ethics
committee. Prior informed consent was obtained from the parents. 100 consecutive patients admitted in
N.I.C.U. WITH gestational age < 36 weeks with respiratory complaints were enrolled. Chest x-ray was
obtained within few hours of admission and lung sonography was performed within 24 hours. Follow – up
sonography was performed as and when necessary. Sonography image was graded and correlated with chest
xray and clinical picture
The Comprehensive Review on Fat Soluble Vitaminsiosrphr_editor
This review article deals with brief description of fat soluble vitamins with figures and tables
showing statistical analytical data duly quoting the references wherever necessary. The word “soluble” actually
means “able to be dissolved.” Whether a vitamin is classified as 'fat-soluble' or 'water-soluble' has to do with
how the vitamin is absorbed, stored and removed from the body. Vitamins are tiny organic compounds with a
huge impact on the health and well-being of the body. The body needs a small amount of fat soluble vitamins in
order to stay in optimal health. Fat soluble vitamins play an important role in keeping the body healthy and
functioning from immune system and muscle and heart function, easy flow and clotting of blood as well as eye
health. They are critical to health and wellness–particularly reproductive health and wellness. Low-fat, no-fat
and vegan diets are woefully lacking in fat soluble vitamins. However a diet based on traditional foods can
naturally provide these vitamins. Science is still learning about many of the functions of vitamins. "Too much
vitamin A, D, or K can lead to increased levels that are unhealthy and can cause serious health consequences.
Diseased conditions leading to decreased fat absorption leads to decreased absorption of vitamins. The fatsoluble
vitamins work most safely and effectively when obtained them from natural foods within the context of a
diet rich in all their synergistic partners. If fat soluble vitamins are stored for lengthy time they generate threat
for toxicity than water soluble vitamins and such situation even aggravated, provided they are consumed in
excess. Vitamin products, above the legal limits are not considered food supplements and must be registered as
prescription or non-prescription (over-the-counter drugs) due to their potential side effects. Vitamin A and E
supplements do not provide health benefits for healthy individuals, instead they may enhance mortality, and it is
held proved that beta-carotene supplements can be harmful to smokers
Sulphasalazine Induced Toxic Epidermal Necrolysis A Case Reportiosrphr_editor
Toxic Epidermal Necrolysis (TEN) is a rare and life threatening mucocutaneous reaction
characterized by extensive necrosis and detachment of epidermis. The Worldwide incidence of TEN is 0.9 to 1.4
per million populations per year [1]. Here we have discussed a case of Toxic Epidermal Necrolysis secondary
to Sulfasalazine managed with fluid replacement, analgesics, anti-infective therapy aggressive nutritional
support and intravenous high dose steroid therapy.
Keywords- Toxic Epidermal Necrolysis, Sulfasalazine
Evaluation the efficacy of IVIgG in treatment of Hemolytic Disease of Newborniosrphr_editor
Hemolytic disease of newborn (HDN) is an important cause of hyperbilirubinemia in the
neonatal period,and delayed diagnosis and treatment may lead to permanent brain damage. Traditional
neonatal treatment of HDN is intensive phototherapy and exchange transfusion.Intravenous
immunoglobulin(IVIgG) has been introduced as an alternative therapy to exchange transfusion. This study was
conducted to assess the effect of IVIG in HDN .
FIBROLIPOMATOUS HAMARTOMA OF ULNAR NERVE: A RARE CASE REPORT.iosrphr_editor
Nervous fibrolipomatous hamartoma is said to be a rare tumor-like condition involving the peripheral
nerves,in which the epineurium and perineurium are enlarged and distorted by excess of fatty and fibrous tissue
s that infiltrate between and around nerve boundaries. The median nerve is more likely to develop a hamartoma
than other nerves with a predilection for the carpal tunnel.
A fibrolipomatous hamartoma – is a rare, benign, congenital lesion most commonly found in the median nerve,
usually at the level of the wrist or hand.
We report a case of this rare condition in ulnar nerve.
SELF MEDICATION PRACTICES FOR ORAL HEALTH PROBLEMS AMONG DENTAL PATIENTS IN B...iosrphr_editor
Introduction: Self‑ medication is commonly practiced all over the world. Self-medication is defined as the use
of medication by a patient on his own initiative or on the advice of a pharmacist or a lay person instead of
consulting a medical practitioner. The present study was aimed to estimate the prevalence of self-medication for
oral health problems among dental patients in Bengaluru city; to identify triggering factors that could influence
self-medication practices; to identify sources of medications used; to identify sources of information about
medications used; and to identify reasons for self-medication.Study Design: A Cross sectional Study.Methods:A
survey was conducted among 175 subjects among dental patients in Bengaluru city. Data were collected
through a specially designed proforma using a closed‑ ended, self‑ administered questionnaire containing 15
questions, in five sections.
Results: The prevalence of
Clinico-haematological Profile of Falciparum Malaria in a Rural Hospital of T...iosrphr_editor
Aim: To study the clinico-haematological profile malaria in a rural hospital of Tripura.
Material and methods: A cross-sectional hospital-based study was done from at Kulai District
Hospital,Tripura. This hospital based cross sectional study was done on 60 confirmed cases of falciparum
malaria (either by peripheral smear or rapid diagnostic test) admitted in Kulai District Hospital. A case sheet
proforma was prepared and data (demographic profile,clinical feature, investigation, treatment, and
complication) from all indoor patients was collected and analyzed.
Result: Out of 60 patients, 40(66.6%) were males and 20 (33.4%) were females. Most of the patients were
between the age group 21-40 years with the highest prevalence between the age group of 21-30. Fever was the
most common symptom. Anemia was present in 42(70%) patients, out of which 6(10%) patients had severe
anemia. Thrombocytopenia was present in 36(60%) patients.Abnormal liver function tests were observed in
26(43.3%) subjects while abnormal kidney function tests were observed in16(26.6%) patients. All the 60
patients received Artemisinin based antimalarial drugs.
Conclusion: Early detection, prompt management, and adequate supportive therapy may reduce mortality due
to falciparum cerebral malaria.
Indonesian Wild Ginger (Zingiber sp) Extract: Antibacterial Activity against ...iosrphr_editor
Lempuyang gajah (Zingiber zerumbet (L.) Smith), lempuyang pahit (Zingiber amaricans BL.), and
lempuyang wangi (Zingiber aromaticum Vahl.) are used as traditional medicine (jamu) in Indonesia. It is also
used for treatment of microbial infections, helps to increase appetite and stimulate digestion in chickens.
Information on their uses are available, but only limited in the scientific data on their bioactivity. The study was
conducted on the antibacterial effect of organic extracts of these plants with Mycoplasma gallisepticum as the
agent of chronic respiratory disease in chickens. Juice and extracts of fresh and dried rhizome are evaluated
through the disc diffusion assay and minimum inhibitory concentration. Oxytetracyclin (30 µg) are used as
standards. All extracts are individually exhibited as antibacterial activity against Mycoplasma gallisepticum (7
± 0.11 mm to 21 ± 0.86 mm). The minimum inhibitory concentration (MIC) determination of plants extracts are
ranged from 7.8 mg/ml to 31.2 mg/ml. The preliminary results suggested promising antibacterial properties of
wild ginger from Indonesia, and probably could be used in management of chronic respiratory disease in
chickens.
A case of allergy and food sensitivity: the nasunin, natural color of eggplantiosrphr_editor
Abstract: Allergies and food sensitivities can both be considered as "adverse reactions individualistic" to food.
Are pathological and individual forms because they affect a few individuals in way rather serious; immediate
or delayed reactions occur instead with simple effects histamine, or, in severe cases with respiratory and
anaphylactic shock
The eggplant (Solanum melongena L.) is known to cause food allergies in some Asian countries, but detailed
studies on allergies caused by eggplant are lacking, however, it was highlighted the presence of allergens in
edible parts of eggplant with preponderance in the peel .
The purpose of this study was to propose an extraction method rapid, efficient and cost of natural dye from
waste products from the food industry, such as the peels of eggplant, from which it was extracted, isolated and
purified the nasunin,a colored molecule in red-fuchsia.
Nasusin was tested on 58 patients to evaluate the potential sensitizing effect on the skin. The results demonstrate
that allergenic effects are negligible and therefore the nasunin can be used as a colorant in various industrial
sectors with a certain safety margin
Complete NMR Assignment of MogrosidesII A2, II E andIII A1Isolated from Luo H...iosrphr_editor
NMR analysis allowed complete assignments of three known mogrol glycosides, Mogroside IIA2 (1),
II E (2)and IIIA1 (3), isolated from the extracts of Luo Han Guo. Herein, complete 1H and 13C NMR
assignmentsof all threemogrosidesare described based on NMR experiments (1H NMR, 13C NMR, COSY,
HSQC-DEPT, HMBC, NOESY and 1DTOCSY) and mass spectral data.
Nanoemulsion and Nanoemulgel as a Topical Formulationiosrphr_editor
: Nanoemulsion is referred type of emulsion with uniform and extremely small droplet size in the range
of 20-200 nm. Nanoemulsion provides numerous advantages over other carrier such as polymeric nanoparticle
and liposomes, including low cost preparation procedure, high hydrophilic and lipophilic drug loading system
to enhance the longer shelf live upon preserving the therapeutic agents. Incorporating the preparation of
nanoemulsion with hydrogel matrix to produce nanoemulgel exhibited by the two separate systems that forming
it. Nanoemulgel possesses the properties of thixotropic, non-greasy, effortlessly spreadable, easily be removed,
emollient, not staining, soluble in water, longer shelf life, bio-friendly, translucent and agreeable appearance.
Pharmacokinetics of High-Dose Methotrexate in Egyptian Children with Acute Ly...iosrphr_editor
Aim:Since several factors have been shown to influence the clearance of methotrexate, the purpose of this study
was to identify potential relationships between patient covariates and the methotrexate clearance estimates and
deduce a pharmacokinetic model for the estimation of methotrexate clearance in Egyptian pediatric ALL
patients that may help dosage adjustment and achieve target steady-state plasma concentrations in a similar
sittings.
Patients and methods: A total of 94 pediatric patients with B-cell ALL, of whom 70 were the studied population
and 24 were the test population, were treated with four courses of HDMTX doses 2.5 gm/m2
(low-risk arm) or 5
gm/m2
(standard-/high-risk arm) given every other week by intermittent intravenous infusions over 24 hours as
a part of their treatment protocol. Patients were monitored for the 24 hour MTX concentration and the systemic
methotrexate clearance was calculated for each methotrexate dose
Epidemiology of Tuberculosis (TB) in Albania 1998-2009iosrphr_editor
Abstract : In Albania, many people erroneously think that tuberculosis (TB) is a disease of the past-an illness
that no longer constitutes a public health threat. Surveillance is an integral part of tuberculosis (TB) control.
Albania has a highTB notification rate and there are doubts about underreporting. The evolution of the
incidence of tuberculosis is presented, together with more detailed figures over the period 1998-2009. These
figures were obtained by the monthly forms (called 14/Sh) compared with the individual notification data.
Objective: To examine the distribution and sources of increased tuberculosis (TB) morbidity and reporting
system deficiencies in the Albania from 1998 through 2009. Metodology: The study is descriptive one conductet
during the period 1998-2009. The statistical analysis is based on data reported from regional level (regional
epidemiological departments) to the central level (Public Health Institute). Results: The main findings were:
discordance between the collected data (individual form) and reported data (monthly form); tuberculosis
incidence rate shows little oscillations which ranges from 6.67 to 9.2 cases/100.000 population; 50% of the
regions show a lack of information on the confirmation of diagnosis and laboratory examination type used for
confirmation. Conclusion: TB disease in high-risk populations where it is difficult to detect, diagnose, and treat;
limitations of current control measures and the need for new tests and treatments, including an effective
vaccine; improving information system, regulation of individual form and personnel training.
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1. IOSR Journal Of Pharmacy
(e)-ISSN: 2250-3013, (p)-ISSN: 2319-4219
Www.Iosrphr.Org Volume 3, Issue 9 (October 2013), Pp 72-80
Effect of Sitagliptin in Combination with Glimepiride on
Glycemic Control and Islet Cell Diameter/Proliferation in A
Model of Type 2 Diabetic Rats
Noha A. Mohamed1, Sawsan A. Zaitone2, Yasser M. Moustafa2
1
2
(Forensic Medicine Authority, Ministry of Justice, Ismailia, Egypt)
(Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522,
Egypt)
ABSTRACT: The aim of the present study was to investigate the effect of monotherapy with sitagliptin, or its
combination with glimepiride in glycemic control, islet cell diameter and its proliferation in type 2 diabetic rats.
Rats were fed with a high fat diet followed by injection with a low dose of streptozotocin to induce type 2
diabetes. Then, rats were switched to normal diet and for other 28 days. Monotherapy with sitagliptin did not
affect the body weight, while its combination with glimepiride did not induce a significant change. The
combination increased the % change in body weight compared to sitagliptin alone. All the treatment regiment
enhanced glucose clearance as indicated by a reduction in the area under the curve. Pancreatic
immunohistochemistry and morphometric analysis were performed to measure the diameter of islet cells,
insulin-positive area and the number of Ki-67 positive nuclei. In sitagliptin group, diameter of large-sized islets
was 2-fold greater than those observed in diabetic group. The monotherapy with glimepiride did not change the
islet-cell diameter. Further, the combination group showed better glycemic control and greater cell proliferation
compared to monotherapies. Consequently, we conclude that the combination therapy of sitagliptin/glimepiride
has synergistic effect.
KEY WORDS: beta cell, diabetes, glimepiride, sitagliptin, rats.
I.
INTRODUCTION
In the natural history of type 2 diabetes, the development of insulin resistance, impaired glucose
tolerance and finally type 2 diabetes occurs gradually over many years. As the disease develops, however, there
is a progressive loss of beta-cell function. As type 2 diabetes is a progressive disease, intensification of therapy
is normally required over time. Current therapies may also be associated with an increased risk of
hypoglycaemia (sulphonylureas and insulin), weight gain (sulphonylureas, thiazolidinediones and insulin), and
gastrointestinal intolerance (metformin), which represent major barriers to optimal glycemic control
[1].Treatment with a single antihyperglycemic agent is often unsuccessful in achieving and/or maintaining
glycemic control in patients with type 2diabetes, and many patients require combinations of antihyperglycemic
agents [2].Beside the gene background, unhealthy life style such as high-energy intake is correlated with type 2
diabetes. Thus, scientists try to obtain a type 2 diabetes animal model following the real course. The general
strategy is using high-energy diet feeding for a period with the purpose to induce mild insulin resistance at first,
and then an injection of a low dose of STZ to make partial dysfunction of beta cell for suppressing the insulin
secretion, which works as a compensation to insulin resistance with the result of persistent hyperglycemia.
Recently, there is a considerable interest in the therapy of type 2 diabetes, with a focus on the development and
use of new agents that exhibit improved efficacy and safety relative to current available medicines. Incretion
hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) can
act as growth and differentiating factors for pancreatic beta cells [3]. Promising pharmacological approaches
recently approved for the treatment of type 2 diabetes include two incretin-based therapies, the glucagon-like
peptide-1 receptor (GLP-1R) agonists or molecules that inhibition the breakdown of incretin hormones (i.e.
DPP-4 inhibitors)[4].
The new treatment strategy is the use of GLP-1 or other incretin mimetic. This has been shown to
increase beta cell mass by decreasing apoptosis and increasing cell replication or neogenesis [5].Using GLP-1 as
a therapeutic agent has some drawbacks due to its short half-life as a result of inactivation by the enzyme DPP-4
[6]. Therefore, the use of DPP-4 inhibitors which enhance the circulating levels of endogenous GLP-1 and
improve glycemia are more preferred. Gliptins are a novel class of oral anti-diabetic agent that enhance and
prolong the physiological actions of incretin hormones by competitively antagonizing the enzyme DPP-IV.
Animal studies demonstrate the anti-diabetic properties of DPP-IV inhibitors, with a delay of progression from
72
2. Effect Of Sitagliptin In Combination With Glimepiride…
impaired glucose tolerance to type 2 diabetes [7], an improvement in glucose tolerance and insulin secretion
[8,9] as well as an improvement in beta-cell function and an increase in hepatic and peripheral insulin sensitivity
[10]. One of the most recent DPP-4 inhibitor drugs is sitagliptin [11].Sitagliptin, an organic molecule, appears to
be selective for DPP-4 enzyme [12]. Sitagliptin is rapidly absorbed; achieving peak plasma levels 1–6 h after
dosing. Its half-life is 8–14 h with bioavailability of 87%, with or without food [13, 14]. About 80% of the dose
is excreted unchanged by the kidney, with 15% of the bioavailability drug metabolized by CYP3A4 and
CYP2C8 in the liver [13, 15].Glimepiride stimulates the pancreas to release more insulin, both right after a meal
and then over several hours so it taken with meals, on the other hand it have some adverse
effects(hypoglycemia, occasional skin rash, irritability, upset stomach).The synergistic action of using
combination of sitagliptin and traditional antidiabetic agent regards to the action of sitagliptin which increase
of the beta cell mass through its replication which lead to increase the effect of this traditional agents
(glimepiride). The objective of the current study was to evaluate the effect of the DPP-4 inhibitor, sitagliptin, in
combination with glimepiride in modifying the progression of islet dysfunction and loss of islet cell
replication/proliferation in a rodent model of type 2 diabetes induced by feeding of HFD followed by injection
of a low dose of STZ.
II.
MATERIALS AND METHODS
2.1. Drugs and chemicals
Streptozotocin (STZ) was purchased from Sigma-Aldrich (MO, USA). Sitagliptin (Januvia® tablet)
was obtained from Merck Sharp & Dohme Ltd (Pavia, Italy).Glimepiride was a gift from Medical Union
Pharmaceuticals (Abu-Sultan, Ismailia, Egypt). All other chemicals and solvents were of highest analytical
grade. The feed ingredients such as lard and sucrose were procured from the commercial sources. Citric acid,
sodium citrate and sodium carboxymethyl cellulose (Na-CMC) were also obtained from ADWIC CO. (Cairo,
Egypt).
2.2. Experimental animal and diet
Male Wistar rats weighing 220–270 g were obtained from the National Center of Research (Cairo,
Egypt). Rats were housed in stainless steel cages in a normal light–dark cycle at around 22 °C. Rats were fed
with a high-fat diet (HFD) for four weeks, which was prepared by mixing 20% sucrose (w/w) and 10% lard
(w/w) into basal diet and water ad libitum. Normal control rats were fed with basal diet. Food was replaced
daily and any uneaten portions were discarded. Body weights of rats were recorded weekly. All experiment
protocols followed the guidelines of the Institutional Animal Care and Use Committee at the Faculty of
Pharmacy, Suez Canal University, Ismailia, Egypt.
2.3. Induction of diabetes
Rats were fed with HFD for four weeks. Fasting blood glucose level was recorded every three days.
After these four weeks, the rats were fasted overnight then received single intraperitoneal injection of freshly
prepared STZ (30 mg/kg) in citrate buffer (0.1 M, pH = 4.5) in a volume of 2 ml/kg. Three days after STZ
administration, fasting blood glucose level of each rat was recorded. Rats with fasting blood glucose level more
than 135 mg/dl were considered diabetic and included in the experiment. The control rats were fed with a basal
diet and received the vehicle (citrate buffer) parallel to STZ. Treatment with drugs and there combinations
started on the third day after STZ injection (i.e. after the estimation of blood glucose).
2.4. Experimental design
Forty rats were used in the present study and divided into five groups, eight rats each. Group 1: Normal
control rats, received citrate buffer (pH=4.5, 1 ml/kg), Group 2-7: rats were fed with the HFD for four weeks
followed by a single injection of streptozotocin (30 mg/kg, i.p.). Group 2: rats received Na-CMC solution (2
ml/kg, p.o.). Group 3: rats were treated with sitagliptin (10 mg/kg/day, p.o.). Group 4: rats were treated with
glimepiride (0.5mg/kg/day, p.o.); Group 5: rats were treated with a combination of both drugs in the same
aforementioned doses. In general, drugs were administered orally as a suspension in 1% sodium carboxymethyl
cellulose (Na-CMC) solution and continued for a period of 28 days.
2.5. Oral glucose tolerance test
At the end of experiment, animals were fasted overnight andadministered5 ml of glucose solution
(2g/kg body weight) orally. Glucose disposal was analyzed by measuring random blood glucose rat at different
time point 0, 30, 60, 90 and 120 min. Blood samples were obtained by tail prick and glucose was measured by
Accu-check go blood glucose meter (Roche Diagnostic®, Germany).The body weights of all the experimental
rats were monitored every week.
73
3. Effect Of Sitagliptin In Combination With Glimepiride…
2.6. Biochemical assays
Blood samples were collected through the orbital sinus, under light ether anesthesia; centrifuged at
1000 x g for 15 min, serum samples were separated and stored at -20°C for the estimation of various
biochemical parameters. After that, rats were sacrificed by cervical decapitation. The pancreas was rapidly
dissected and stored in 4% phosphate-buffered formalin for histological examination.
2.7. Histopathology and immunohistochemistry
After excision, the whole pancreas from each rat was immediately weighed and kept in 4% phosphatebuffered formalin, fixed and subsequently sectioned (5-μm thick) throughout its length and 5 sections were
taken at regular intervals for insulin immunostaining. Paraffin-embedded pancreatic sections were stained first
for hematoxylin/eosin so as to record the diameter of islet cells. Then other two sections were immunostained
for insulin and Ki-67 (a marker for cell proliferation).Immunohistochemistry for insulin staining in pancreatic
tissues were performed using primary antibody (mouse anti-insulin, NeoMarkers, CA, USA) followed by a
reaction with secondary antibody (goat polyclonal secondary antibodies against mouse IgG, Abcam®,
Cambridge, UK).Immunohistochemistry for ki-67was performed using rabbit polyclonal primary antibodies
against Ki-67(1:50;Abcam, Cambridge, UK) followed by a reaction with secondary antibody (biotinylated goat
anti-rabbit antibodies, Abcam®, Cambridge, UK).After conjugation with streptavidin–biotin–peroxidase
complex(Broad spectrum LAB-SA detection system, Invitrogen),3,3-diaminobenzidine (DAB, Sigma–Aldrich®,
MO, USA) was used as a chromogen, and Mayer’s hematoxylin was used as a counterstain.
2.8. Pancreatic immunohistochemistry–morphometric analysis
All analyses were performed in a blinded fashion where the investigator was not aware of the treatment
groups. The morphometric analysis were done manually by a stereological method with mathematical support
using an image analysis system ‘‘Image J 1.45 F’’ (National Institute of Health, USA) to measure the diameter
of the islet, the optical density of insulin-positive area and the number of ki-67 positive nuclei at 400x
magnification. These cells which present in the endocrine and the exocrine pancreatic parenchyma, therefore,
number of immunpositive nuclei were measured after identification of endocrine pancreatic beta cell from the
insulin immunslides.
2.9. Statistical analysis
All data were collected, tabulated and expressed as mean±SEM. Quantitative parametric variables
were analyzed using one-way analysis of variance (ANOVA) followed by Bonferroni's post-hoc test. The
Statistical Package of Social Science (SPSS) program version 17, (Chicago, IL, USA) was used for the
statistical analysis. A P value < 0.05 was considered to be statistically significant.
III.
RESULT
3.1. Percentage mortality and percentage change in body weight
At the end of the study, the normal and diabetic groups showed 0% mortality whereas; monotherapies
with either sitagliptin or glimepiride produced 12.5 % mortality. The combination group showed significantly
higher mortality (37.5 %) compared to diabetic rats. Diabetic rats showed a lower % change in body weight
compared to normal rats (3.54 ± 1.25 vs. 25.72 ± 2.15, P ≤ 0.05, Table 1). Monotherapy with sitagliptin
significantly reduced the % change in body weight compared to the diabetic rats. However; monotherapy with
glimepiride did not induce a significant change in percent change in body weight. The combination of both
drugs produced greater % change in body weight compared to monotherapy with sitagliptin (Table 1).
74
4. Effect Of Sitagliptin In Combination With Glimepiride…
Table 1: Effect of sitagliptin (10mg/kg/day/28day) , glimepiride (0.5mg/kg/day/28day) and their
combination (with same dose) on percent change in body weight and percent mortality . BWt : body weight.
Values are expressed as mean S.E.M. and analyzed using one-way ANOVA followed by Bonferroni's
multiple comparisons test. *Compared to normal group at P < 0.05. †Compared to diabetic group at P < 0.05.
‡
Compared to sitagliptin group at P < 0.05. $Compared to glimepiride group at P < 0.05, n = 4-8.
Group
%
mortality
Normal
0
232.2 ± 15.7
Diabetic
0
240 ± 6.3
264 ± 6.5
Sitaglipti
n
Glimepiri
de
12.5†
226.2 ± 9.4
205 ± 18.3
12.5†
234.2 ± 9.7
249.8 ± 16
Sitaglipti
n + glimepiride
37.5†
‡
Baseline
BWt (g)
Final
BWt (g)
291.8 ±
20.02
264.5 ±
12.6
242.2 ± 17
% change
in BWt
25.72 ±
2.15
3.54 ±
1.25*
-9.97 ±
3.53†
6.55 ±
2.68‡
8.20
±8.14‡
3.2. Oral glucose tolerance test
In the present study, diabetic rats showed greater area under the curve (AUC) compared to normal rats.
Treatment with sitagliptin (10 mg/kg), glimepiride (0.5 mg/kg) or their combination reduced the AUC
compared to the diabetic rats (Fig 1A&B). The AUC in the combination group was smaller than that calculated
in sitagliptin group.
75
5. Effect Of Sitagliptin In Combination With Glimepiride…
Figure 1: Oral glucose tolerance test in the experimental groups. A) Effect of the combination of sitagliptin and
glimepiride on blood glucose level compared to their monotherapies. B) Area under the curve estimated from
the oral glucose tolerance test. Data are presented as mean ± SEM and analyzed using one-way ANOVA
followed by Bonferroni’s multiple comparisons test. *Compared to normal group at P †Compared to diabetic
group at P ‡Compared to sitagliptin group at P $Compared to glimepride group at P < n = 4-8.
3.3. Biochemical assays
Liver enzyme activities (GOT and GPT) were higher in the diabetic group compared to the normal
group. Glimepiride was the sole treatment that reduced serum GOT compared to diabetic group. On the other
hand, all the treatment regimens reduced serum GPT compared to diabetic group. Analysis of serum lipids
indicated that the diabetic group showed high serum total cholesterol, triglyceride and LDL but lower HDL in
comparison to the normal group. Monotherapy with sitagliptin, glimepiride or their combination reduced the
serum triglyceride and LDL while increased HDL compared to the diabetic group (Table 2). Further, the
combination of sitagliptin plus glimepiride improved these three parameters compared to monotherapy with
sitagliptin.
3.4. Islet cell morphology
Histopathological examination revealed that diabetic rats showed a reduction in the size of the islets
and shrinking as well as spread of vacuoles (Fig. 2A). Monotherapy with sitagliptin produced a marked increase
in the diameter of the islets of pancreatic beta cells compared to the diabetic group beside the absence of
vacuoles and saving its shape uniform. The largest size islet in the diabetic group equaled 8,500 µm² while the
largest size islet in sitagliptin group equaled 13,480 µm². Monotherapy with glimepiride did not produce a
change in the islet diameter compared to the diabetic group. In contrast, the combination of sitagliptin and
glimepiride showed larger islet diameter compared to monotherapy with sitagliptin. The largest size islet in the
combination group equaled 17,790 µm² (Fig 2A&B).
76
6. Effect Of Sitagliptin In Combination With Glimepiride…
Figure 2: A) Histopathological pictures of the pancreatic islets of the experimental groups (hematoxylin & eosin,
immunostaining for insulin and Ki- at 40 x magnification). The diameter (B), optical density of immunreaction.
Data are presented as mean ± SEM and analyzed using one-way ANOVA followed by Bonferroni’s multiplecomparison test at P < 0.05. *Compared to normal group. †Compared to diabetic group. ‡Compared to
sitagliptin group. $Compared to glimepiride group, #Compared to pioglitazone group, n = 4-8.
3.5. Immunohistochemistry for insulin and Ki-67
Immunohistochemical staining for insulin showed lower optical density for immunpositive pancreatic
islet cells in the diabetic rats compared to the normal rats. Treatment with sitagliptin, glimepiride or their
combination increased the optical density for insulin immunostaining compared to the diabetic group (P< 0.05,
Fig 3A).Immunostaining for Ki-67 highlighted the presence of actively dividing cells in the normal group. The
number of Ki-67 immunpositive nuclei was lower in diabetic rats compared to normal. Monotherapy with
sitagliptin or all the sitagliptin combinations with glimepiride significantly increased the number of Ki-67
immunpositive nuclei compared to diabetic rats. However, monotherapy with glimepiride failed to produce a
similar effect (Fig. 3B).
77
7. Effect Of Sitagliptin In Combination With Glimepiride…
(A)
(B)
Figure 3: A) Histopathological pictures of the pancreatic islet of the experimental groups (hematoxylin & eosin,
immunostaining for insulin and Ki- at x magnification). Optical density of immunreaction and number of
immunpositive nuclei (B) in the pancreatic islet cell. Data are presented as mean ± SEM and analyzed using
one-way ANOVA followed by Bonferroni’s multiple-comparison test at P < 0.05. *Compared to normal group.
†Compared to diabetic group. ‡Compared to sitagliptin group. $Compared to glimepiride group, #Compared to
pioglitazone group, n = 4- 8.
IV.
DISCUSSION
The current study was designed to explore the effect of sitagliptin alone and in combination with
glimepiride on glycemic control and islet morphology in type 2 diabetic rats. Rats were fed with a HFD for four
weeks followed with injection of with a low dose of STZ (30 mg/kg) to induce type 2 diabetes. Wang et al. [16]
reported that the injection of a low dose of STZ (30 mg/kg) after a four-week feeding period of a HFD induced
symptoms of human diabetes by markedly elevating serum glucose, total cholesterol and LDL levels. The new
agents of DPP-4 inhibitors act through their effect on incretin hormones. Incretin hormones is represented
mostly by two main types (GLP-1, GIP), which secreted from endocrine cells in the gastrointestinal tract, in
response to ingestion of food. In the present study, monotherapy with sitagliptin decreased the percent change
in body weight although its combination with glimepiride showed an increase. Differently, sitagliptin was found
to be weight neutral, with weight changes similar to those for patients taking placebo. Karasik et al. [17]
Further, Ahren et al. [18] reported anon significant decrease in body weight with the DPP-4 inhibitors in type 2
diabetic patients either as monotherapy or as combination therapy with metformin. These agents may also either
induce weight loss (GLP-1R agonists) or are not associated with weight gain (DPP-4 inhibitors), in contrast to
findings with other presently available treatments for type 2 diabetes [19]
In the current study, monotherapy with sitagliptin, glimepiride and their combination improved glucose
tolerance as indicated by oral glucose tolerance test. It has been demonstrated that treatment with sitagliptin
produced a low incidence of hypoglycemia (0–4%) compared with glipizide (17%) and placebo (2.4%) in
patients with type 2 diabetes. The Authors highlighted that sitagliptin, unlike glipizide, did not increase body
weight compared to control patients Scott et al. [20]. Similarly, sitagliptin was compared to sulfonylurea
(glimepiride) or thiazolidinediones (pioglitazone), it had the advantages of not producing weight gain or
hypoglycemia. Mary et al. [21] concluded that sitagliptin could be an alternative therapy for adult patients who
cannot tolerate other antidiabetic agents. Further, sitagliptin was reported to be well tolerated, causing no
hypoglycaemia or weight gain in patient with type 2 diabetes with Roger et al. [22]. In current study, all the
treatment regimens had favorable effects on serum lipid profile and liver enzymes; this agreed with the data
obtained previously Pospisilik et al. [23]. The authors showed that long-term DPP-4 inhibition improved
glucose tolerance, hyperinsulinemia, and beta-cell function in the VDF Zucker rat; these findings highlighted the
potential utility of these compounds in diabetes therapy. Data from the same study indicated that OGTT and an
in vitro determination of insulin-stimulated glucose uptake in isolated muscle provided an indirect evidence for
a treatment-induced improvement in insulin sensitivity. In conclusion, the addition of improved hepatic and
peripheral insulin sensitivity to the list of beneficial metabolic effects of long-term DPP-IV inhibitor therapy
provides strong support for the use of these compounds in the treatment of diabetes.
78
8. Effect Of Sitagliptin In Combination With Glimepiride…
In addition, Drucker et al. [19] found that GLP-1 regulates glucose homeostasis in the postprandial
period by a number of mechanisms, including stimulation of insulin synthesis, inhibition of glucagon secretion,
delay in gastric emptying, and promotion of satiety Sustained treatment with exogenous GLP-1 is suggested to
impact beta cell regulation which is mostly compatible with the current study, which acts by inhibiting DPP-4
enzyme by sitagliptin so it increased the level of endogenous GLP-1 to affect beta cell proliferation. However,
administration of exogenous GLP-1 is problematic as it is rapidly inactivated by the proteolytic enzyme DPP-4
within minutes of release. Therefore, it is better to use DPP-4 inhibitors which lead to inhibition of degradation
of endogenous GLP-1 enhancing the incretin effect James et al. [24].
The present results demonstrated that monotherapy with sitagliptin and its combination with
glimepiride increased the diameter of islets and keep it regular without vacuoles rather than in diabetic group.
The proliferation marker, Ki-67 antigen, was used in our study to record the cell proliferation. Monotherapy
with sitagliptin and its combination with glimepiride showed greater cell proliferation indicating the presence of
actively dividing cells; this might explain the larger diameter of the pancreatic islets measured in H&E stained
sections.GLP-1 agonists have been reported to stimulate the growth and differentiation of pancreatic beta cell, as
well as to exert cytoprotective and anti-apoptotic effects on beta-cell James et al. [24] . Thus, GLP-1 may be a
means by which to create beta-cell ex vivo for transplantation into patients with insulinopenic type 1diabetes
and severe forms of type 2 diabetes. In addition, long-term DPP-4 inhibitor therapy preserved and increased beta
cell number through an apparent stimulation of islet neogenesis, beta cell regeneration (differentiation from
precursor cells) as well as improved insulin biosynthesis in rat [23]
In this study, histological examination of the pancreas following DPP-4 inhibitor administration produced
an increase in the diameter of pancreatic islets in type 2 diabetic rats. Preservation, neogenesis, or restoration of
beta cell function is essential to alter or reverse the progression of the insulin secretory defect. Given the
observations that GLP-1 stimulates proliferation of beta cell in rodents, and it may promote the differentiation of
beta cell from human precursor cells. It seems reasonable to predict that DPP-4 inhibition, leading to increased
levels of GLP-1, might also produce beneficial effects on beta cell diameter. Glucagon-like peptide-1 has been
reported to reverse the loss of beta cell mass by both increasing new β-cell formation and decreasing β-cell
apoptosis [25, 26]. The DPP-4 inhibitor (sitagliptin) increased GLP-1 concentrations [27] and modestly lowers
glucose levels when used alone in type 2 diabetes Maedler et al. [28] with an additive effect in combination with
other traditional antidiabetic drugs as shown through UK Prospective Diabetes Study (UKPDS) Group [29] such
as sulphonylureas (glimepiride). In conclusion, this study provided evidence that daily treatment with sitagliptin
in combination with glimepiride significantly enhanced glycemic control and preserved beta cell compared to
monotherapies in type diabetic rats.
V.
CONCLUSIONS
We can conclude that upon using a model of obese T2DM, the chronic treatment with inhibition of DPPIV by sitagliptin can correct the plasma glucose level and body weight loss and it's better to use its combination
with glimepiride. This will have favorable effect on pancreatic islet proliferation which will produce a good
glycemic control and will serve the pancreatic islet from loss by increase in its number so avoiding the great
complications of diabetes.
ACKBOWLEDGMENTS
Authors wish to acknowledge Medical Union Pharmaceuticals (MUP, Ismailia, Egypt) for the generous
gift of glimepiride.
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