Open Access Short Research Article

Effect of Oral Administration of Ibuprofen on Prothrombin Time, Activated Partial Thromboplastin and Platelet Count in Wistar Albino Rats

Jonathan Esima, Abraham Zorte, O. Onwuli, Donatus, Waribo, Helen Anthony

Journal of Pharmaceutical Research International, Page 45-50
DOI: 10.9734/jpri/2020/v32i630445

Aim: Ibuprofen is analgesic, antipyretic and anti-inflammatory drug, which is widely used as a cheap over- the counter drug (OTC); however, this drug accompanies anti coagulation/anti platelets effects which sometimes might illicit adverse effects. In this study, we investigated effect of ibuprofen on prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet count using wistar albino rats.

Methods: A total of 21 rats grouped into 3(control, acute and chronic exposure groups, with all consisting of 7 rats each) was used. The acute and chronic exposure group were given 0.7 mg of ibuprofen orally for 1 and 21 days, respectively. Blood sample was collected via cardiac puncture then analyzed.

Results: PT was significantly higher in both group 2 and 3 (acute and chronic exposure, respectively) than that of the control. Acute exposure group showed the highest PT rise. A PTT was not significantly different between group 2 and 3 versus the control group. Platelet count was significantly lower in both group 2 and 3than that in the control group (p<0.05). Group 3 (chronic exposure) showed the lowest platelet count.

Conclusion: Oral administration of ibuprofen affected coagulation parameters and a longer exposure reduce platelets count. A strictly prescription for this drug may be needed to prevent its indiscriminate use.

Open Access Original Research Article

Knowledge of Root Canal Treatment and Its Association with Patients’ Demographics – A Cross-Sectional Insight

Muhammad Zahid Iqbal, Fahad I. Al-Saikhan, Sawri Rajan, Muhammad Shahid Iqbal

Journal of Pharmaceutical Research International, Page 1-8
DOI: 10.9734/jpri/2020/v32i630440

Introduction: Endodontics is the division of dentistry that mainly dealt with the physiology, pathophysiology, pathology and morphology of human dental tissues. The study determined the knowledge among patients who underwent root canal treatment (RCT).

Methods: A cross-sectional study was carried among RCT patients visiting various dental clinics. A validated self-administered questionnaire including information related to knowledge about RCT was used to collect required data. Statistical Package for Social Science (SPSS) Version 22.0 was used to analyze the data.

Results: Regarding the RCT knowledge, it was revealed that patients with previous RCT history were having better knowledge than patients without RCT history or those who were planning to undergo for RCT procedure (p= <0.001). Differences between smoking status and RCT knowledge were also statistically significant (p=0.048).

Conclusion: In conclusion, moderate knowledge was observed among patients who underwent RCT or those who were planning to perform RCT.

Open Access Original Research Article

Toxicity of the Hydroethanolic Leaves Extract of Duranta erecta L. in Rat Models

Shadrack Donkor, Christopher Larbie, Gustav Komlaga, Benjamin Obukowho Emikpe

Journal of Pharmaceutical Research International, Page 9-18
DOI: 10.9734/jpri/2020/v32i630441

Background and Objectives: Duranta erecta is used in folklore medicine for the treatment of myriad of diseases in Africa. The study was carried out to evaluate the safety of hydroethanolic leaves extract of D. erecta in experimental rats in order to ascertain its potential toxic effects. Materials and Methods: The acute toxicity study was performed by fixed dose method at 5000 mg/kg. In the subacute study performed on both male and female rats, group I (control) received 1 mL of freshly distilled water, groups II, III, IV were treated with 100, 250 and 500 mg/kg of freshly prepared extract respectively for 28 days. At the end of the study, haematological and biochemical parameters were determined. Internal organs (kidney, liver, lung, heart, spleen, stomach, testes and uterus) were weighed.

Results: 50% lethal dose (LD50) of the extract was determined to be > 5 g/kg body weight. The subacute toxicity assessment resulted in overall body weight increase, a change in relative organ weight of the liver, lung, stomach, and changes in the haematological indices such as HCT%, LYM%, RDW- SD/fL, MCHC, MCV/fL, P-LCR% and biochemical parameters namely ALT, AST, LDH and creatinine of the tested group relative to the normal. The positive activity of the extract on liver enzymes and LDH is an indication of its good hepatoprotective potential.

Conclusion: The results affirmed that the extract is safe but could cause kidney problems when used for a prolonged period.

Open Access Original Research Article

Quality Use of Medicines among Makkah Residents, Saudi Arabia

Abdul Haseeb, Rozan Radwan, Somaiah Bokhari, Ashwaq Alqurashi, Saly Albaz, Azizah Ali Algarni, Mahmoud E. Elrggal, Mohamed Azmi Hassali, Muhammad Shahid Iqbal

Journal of Pharmaceutical Research International, Page 19-26
DOI: 10.9734/jpri/2020/v32i630442

Introduction: Quality Use of Medicines (QUoM) is of utmost importance regarding the safety and overall healthcare of the consumers/patients. This study aimed to explore the general usage pattern and attitude of the Makkah community about the safe use of medicines i.e. QUoM.

Methods: Face to face interviews were done to administer questionnaires among patients from two hospitals and four primary care centers dealing with patients from rural and urban areas in the Holly Makkah region.

Results: A total of 554 patients were enrolled while the majority of them were lived in urban areas (n=457,82%). Around 419 (76%) responder were females and 531(96%) were living with their family and had up to college education (n=174,31%). We found that most of the respondents were diabetic (185,33%) and hypertensive (n=172,31%). Most of the patients (207,37%) stated that they preferred to get drug information from healthcare professionals.

Conclusion: This periodic mapping of appropriate medication usage among patients/consumers is indeed an important effort to explore issues on QUoM.

Open Access Original Research Article

Retracted: In silico Assessment of Potential Leads Identified from Bauhinia rufescens Lam. as α-Glucosidase and α-Amylase Inhibitors

Wadah Osman, Esraa M. O. A. Ismail, Shaza W. Shantier, Mona S. Mohammed, Ramzi A. Mothana, Abdelkhalig Muddathir, Hassan S. Khalid

Journal of Pharmaceutical Research International, Page 27-38
DOI: 10.9734/jpri/2020/v32i630444

 

This paper has been Retracted.

Retraction Notice: This paper has been retracted from the journal after receipt of written complains. This journal is determined to promote integrity in research publication. This retraction is in spirit of the same. After formal procedures editor(s) and publisher have retracted this paper on 21th  July-2020. Related policy is available here: http://goo.gl/lI77Nn

Open Access Original Research Article

A Point Prevalence Survey of Antimicrobial Usage for Surgical Site Infections- A Pilot Perspective from Holy Makkah, Saudi Arabia

Abdul Haseeb, Hani Saleh Faidah, Manal Al-Gethamy, Saad Alghamdi, Abrar Mohammed Barnawi, Afnan Abid Aljuhani, Haneen Smai Hareedi, Halimah Saeed Basndwah, Randa Talat Malayou, Reham Mohammed Almotairi, Shuruq Sami Elahe, Muhammad Shahid Iqbal

Journal of Pharmaceutical Research International, Page 39-44
DOI: 10.9734/jpri/2020/v32i630443

Introduction: This study aimed to assess the incidence, microbiological features and management of surgical site infections (SSIs).

Methodology: All patients in the surgical ward were followed from admissions until discharge during the study period. Only hospitalized patients with certain SSIs within 30 days of surgeries were included in the study.

Results: A total of 457 patients were followed during the study period. Interestingly, only 9 (1.9 %) of the patients developed SSIs. Most of the patients were males 6 (66.7%) and Saudi nationals 7 (77.8 %). The most common surgical procedures were laparoscopic and orthopedic surgeries with a similar rate of 3 (3.3 %).

Conclusion: This study revealed that the incidence of SSIs was quite lower at the hospital where the study was conducted and different types of antibiotics were used and recommended for prophylaxis.

Open Access Original Research Article

Formulation Development, Characterization and In-vitro Evaluation of Tamoxifen Loaded Liposomes

Md. Mazed Hasan, Md. Hamiduzzaman, Ishrat Jahan, A. H. M. Nazmul Hasan, Md. Asaduzzaman

Journal of Pharmaceutical Research International, Page 64-82
DOI: 10.9734/jpri/2020/v32i630449

Background: The study was aimed to prepare and evaluate tamoxifen loaded controlled release liposomes to reduce the side effects of tamoxifen during cancer treatment. 

Methods: Different tamoxifen loaded liposomes were prepared by modified ether injection (MEIM) and thin film hydration method (TFHM) under prescribed conditions. The prepared liposomes were characterized by using optical microscopy, evaluating encapsulation efficiency, in-vitro and ex-vivo diffusion studies by using dialysis membrane and chicken intestinal sac respectively.

Results: The data revealed that all of the liposomes were spherical in shape and stable under three physical conditions i.e. 4, 25 and 37 ± 2°C temperatures and 60 ±5% relative humidity. Additionally most of the liposomes followed zero order and class II release kinetics. It was also observed that with the increase of phospholipids and cholesterol, entrapment efficiency of liposome vesicles increased thus giving a controlled release drug delivery system but further increase reduced this efficiency at a certain level.

Conclusion: The formulated control release liposomes might be a good drug delivery system for target oriented drug delivery with minimum side effects of tamoxifen during cancer treatment.

Open Access Original Research Article

Date Palm Pollen Grains as a Potential Manager for Male Sub-fertility: A Clinical Trial

Husamuldeen S. M. Saeed, Bashier Osman, Tarig Muhammed H. El-Hadiyah, Mona S. Mohamed, Wadah J. A. Osman, Iman H. Abdoon, Ramzi A. Mothana

Journal of Pharmaceutical Research International, Page 83-95
DOI: 10.9734/jpri/2020/v32i630451

Medicinal plants are identified and used throughout human history; it has a great economic value especially in drugs discovery. Date palm pollen (DPP) is used traditionally in Sudan for treating sub-fertile male patients. Male infertility is heterogeneous group of disorders, most of them are idiopathic. This study is aimed to investigate the role of pharmaceutical preparation of DPP in amelioration of male sub fertility with detection of any possible adverse effects on the major body system functions, through blood picture, liver enzymes and kidney function. This study is a single group pretest-posttest experimental prospective comparative self-control. Sub-fertile men with Idiopathic oligoasthenozoospermia or azoospermia were received 500 mg capsules of  DPP  twice daily for three months after conducting their safety profiles to detect any toxic effects on hematological, hepatological and nephrological functions, Blood samples were taken from the patients for serum level of FSH (for azoospermic patients), FSH and Testosterone (for oligoasthenozoospermic patients). Finally, Semen sample have been obtained for computerized assisted semen analysis (CASA) report I and II. DPP administration induced significant increase (p≤0.001) in testosterone level (in oligoasthenozoospermic patients) and FSH level (in azoospermic patients). DPP induced significant changes (p≤0.001) towards improvement in the total and progressive sperm motility percentages measured in oligoasthenozoospermic patients by CASA dynamic analysis report I and II.  The toxicological studies for DPP approved their safety use in human.

Open Access Original Research Article

Clinico-histopathological Assessment of Patients Undergoing Thyroidectomy

Rasool Bux Behan, Agha Taj Mohammed, Bilal Rasool, Mujeeb-Ur-Rehman Laghari

Journal of Pharmaceutical Research International, Page 96-101
DOI: 10.9734/jpri/2020/v32i630452

Objective: To determine the clinical presentation and histopathological evaluation of patients undergoing thyroidectomies at tertiary care Hospital.

Methodology: This cross-sectional study was done at department of general surgery of LUMHS/Jamshoro. Duration of the study was 1 year from October 2017 to September 2018. All the cases with a diagnosis of thyroid disorder and underwent thyroidectomy were selected and above 25 years of the age were included. All the surgeries were carried out by senior surgeons along with the cooperation of the ENT surgeons. After surgeries specimens of all the cases were sent to the diagnostic laboratory for the histological assessment. Data was collected via self-made proforma.

Results: Of 58 patients majority i.e. 43.10% were found with age group of 35-44 years. Females found in the majority 63.80%. The swelling was noted among all of the cases, followed by pain, difficulty in swallowing, difficulty in breathing and

others 8.62%, 10.34%, 20.68% and 25.68% respectively. Adenomatous goiter was the most common histopathological finding in 82.75% cases, papillary carcinoma was found 8.62%, follicular carcinoma was only in one case and anaplastic carcinoma was also in 1 case.

Conclusion: Swelling, difficulty in swallowing and difficulty in breathing were the most common clinical features. Adenomatous goiter was the most common histological finding and papillary carcinoma was the commonest malignancy.

Open Access Original Research Article

Piper nigrum Derived Phytochemicals against Gonorrhoea

Sharbani Bahali, Debasmita Das, Sunanya Das, Sitaram Swain, G. K. Panigrahi, Dipankar Bhattacharyay

Journal of Pharmaceutical Research International, Page 102-105
DOI: 10.9734/jpri/2020/v32i630500

Phytochemicals from Piper nigrum plant extract are traditionally used to cure Gonorrhoea. It is caused by Neisseria gonnorrhoeae. Molecular docking method applied using “Biovia Discovery Studio”. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that p-cymenecan effectively deactivate the dihydrofolate reductase enzyme thereby interrupting the life cycle of the organism.

Open Access Original Research Article

Santalum album L. Derived Phytochemicals against Jaundice

Sonupriya Sahu, Ashok Kumar Sahoo, Rukmini Mishra, G. K. Panigrahi, Sonali Dash, Dipankar Bhattacharyay

Journal of Pharmaceutical Research International, Page 106-109
DOI: 10.9734/jpri/2020/v32i630501

Phytochemicals are produced by plants as secondary metabolites to protect the plants from predators. When the parts of the plant, which are rich in different phytochemical constituents, are consumed by humans, they can cure different diseases. Phytochemicals from Santalum album plant extract are traditionally used to cure Jaundice. Molecular docking method applied using “Biovia Discovery Studio”. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that Isohamnetin can effectively deactivate the enzyme, thereby interrupting the life cycle of the organism.

Open Access Original Research Article

Myristica fragrans Derived Phytochemicals against Shikimate Dehydrogenase of E. coli Causing Diarrhea

Sunanya Das, Debasmita Das, Ashrumochan Nayak, Sonali Dash, Dipankar Bhattacharyay

Journal of Pharmaceutical Research International, Page 110-112
DOI: 10.9734/jpri/2020/v32i630502

Medicinal plants play a key role in human health care. Phytochemicals can be derived from different parts of plants. Different medicinal plants and their phytoextracts have shown anti-microbial action. Phytochemicals from Myristica fragrans plant extract are traditionally used to cure Diarrhea. Molecular docking method applied using “Biovia Discovery Studio”. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that Eugenol can effectively deactivate the shikimate dehydrogenase enzyme thereby interrupting the life cycle of the organism.

Open Access Original Research Article

Syzygium aromaticum Derived Phytochemicals against Infections in Feet Crack Caused by Trichophyton rubrum

Debasmita Das, Sonu Priya Sahu, Sunanya Das, G. K. Panigrahi, Sitaram Swain, Dipankar Bhattacharyay

Journal of Pharmaceutical Research International, Page 113-116
DOI: 10.9734/jpri/2020/v32i630503

Phytochemicals from Syzygium aromaticum plant extract traditionally used to cure Feet Crack. Molecular docking method applied using “Biovia Discovery Studio”. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that Myricetin can effectively deactivate the dihydrofolate reductase enzyme thereby interrupting the life cycle of the organism.

Open Access Original Research Article

Alpinia galanga Derived Phytochemicals against Shikimate Dehydrogenase Causing Peptic Ulcer

Sonali Parida, Sutapa Nayak, Seema Suvadarshini, G. K. Panigrahi, Sitaram Swain, Dipankar Bhattacharyay

Journal of Pharmaceutical Research International, Page 117-119
DOI: 10.9734/jpri/2020/v32i630504

Phytochemicals can be derived from different parts of plants. Different medicinal plants and their phytoextracts have shown anti-microbial action. These medicinal plants play a key role in human health care. Phytochemicals from Alpinia galanga plant extract are traditionally used to cure Peptic Ulcer. The objective of the study is to identify the phytochemical of Alpinia galanga capable of curing Peptic Ulcer. Molecular docking method applied using “Biovia Discovery Studio”. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that Alpinia galanga derived Phytochemicals cannot act effectively against Peptic Ulcer caused by Helicobacter pylori.

Open Access Original Research Article

Boswellia serrata Derived Phytochemicals against Dysentery

Krutanjali Rout, Chinmayee Naik, Sujata Prusty, G. K. Panigrahi, Sitaram Swain, Dipankar Bhattacharyay

Journal of Pharmaceutical Research International, Page 120-123
DOI: 10.9734/jpri/2020/v32i630505

Dysentery is an intestinal inflammation, primarily of the colon. Nature is a major source of medicines for different diseases like Dysentery. Phytochemicals from Boswellia serrata plant extract can cure Dysentery. This objective of the study is to identify the phytochemical of Boswellia serrata capable of curing Dysentery. Molecular docking method applied using “Biovia Discovery Studio”. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that p-cymene can effectively deactivate the enzyme, thereby interrupting the life cycle of the organism.

Open Access Original Research Article

Buddleja asiatica Derived Phytochemicals against Diarrhea

Dipankar Bhattacharyay

Journal of Pharmaceutical Research International, Page 124-127
DOI: 10.9734/jpri/2020/v32i630506

Plants produce nonnutritive compounds that are often extracted to make herbal medicines. It has been reported that extracts of Buddleja asiatica are effective to treat diarrhea. One of the causes of Diarrhea is an infection by Campylobacter jejuni. The objective of the study is to identify the phytochemical of Buddleja asiatica capable of curing Diarrhea. ATP-phosphoribosyl transferase enzyme plays an important role in Purine Metabolism. Molecular docking method applied using “Biovia Discovery Studio”. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that Lignoceric acid can effectively deactivate the transferase enzyme thereby interrupting the life cycle of the organism.

Open Access Original Research Article

Capsicum Derived Phytochemicals against Shikimate Dehydrogenase of Haemophilus influenza causing Bronchitis

Debesh Kumar Hota, Debadatta Nayak, Sitaram Swain, Dipankar Bhattacharyay

Journal of Pharmaceutical Research International, Page 128-131
DOI: 10.9734/jpri/2020/v32i630507

Phytochemicals from Capsicum plant extract are traditionally used to cure Bronchitis. It is caused by Haemophilus influenzae. Molecular docking method applied using “Biovia Discovery Studio”. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that Apigenin can effectively deactivate the Shikimate dehydrogenase enzyme thereby interrupting the life cycle of the organism.

Open Access Original Research Article

Cardamom Derived Phytochemicals against Mycobacterium tuberculosis Causing Tuberculosis

Bijan Pumar Patra, Bapujee Palai, Sarthak Siddhant Mishra, Sunil Jha, Dipankar Bhattacharyay

Journal of Pharmaceutical Research International, Page 132-135
DOI: 10.9734/jpri/2020/v32i630508

Tuberculosis is a disease caused by severe infections by Mycobacterium tuberculosis, a pathogenic bacteria. These bacteria cause infections in humans and thus lead to an unhealthy life. Phytochemicals from cardamom plant extract are traditionally used to cure Tuberculosis. Molecular docking method applied using “Biovia Discovery Studio”. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that acetic acid can effectively deactivate histidinol dehydrogenase (H37Rv) thereby interrupting the life cycle of the organism.

Open Access Original Research Article

Cardamom Derived Phytochemicals against Mycoplasma pneumonia Causing Bronchitis

Bapujee Palai, Bijan Pumar Patra, Sidhartha Ray, Sitaram Swain, Dipankar Bhattacharyay

Journal of Pharmaceutical Research International, Page 136-139
DOI: 10.9734/jpri/2020/v32i630509

Bronchitis is inflammation of the bronchi in the lungs. Bronchitis is mainly caused by a viral infection and a small number of cases are caused by a bacterial infection like Mycoplasma pneumonia. Cardamom extract is a traditional medicine that is used to treat Bronchitis. The objective of the study is to identify the phytochemical of Cardamom capable of curing pneumonia-like bronchitis Molecular docking method applied using “Biovia Discovery Studio”. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that acetic acid can effectively deactivate glycerophosphodiester phospho diesterase enzyme thereby interrupting the life cycle of the organism.

Open Access Original Research Article

Cardamom Derived Phytochemicals against Bronchitis Caused by Streptococcus pneumoniae

Bijan Pumar Patra, Bapujee Palai, Sidhartha Ray, Sitaram Swain, Dipankar Bhattacharyay

Journal of Pharmaceutical Research International, Page 140-143
DOI: 10.9734/jpri/2020/v32i630510

Phytochemicals from Cardamom plant extract can cure Bronchitis. One of the causes of Bronchitis is an infection of Streptococcus pneumoniae. Molecular docking method applied using “Biovia Discovery Studio”. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that 4-terpineol can effectively deactivate thymidine phosphorylase enzyme thereby interrupting the life cycle of the organism.

Open Access Original Research Article

Michelia champaca Derived Phytochemicals against Skin Disease

Dipankar Bhattacharyay

Journal of Pharmaceutical Research International, Page 144-147
DOI: 10.9734/jpri/2020/v32i630511

Phytochemicals from Michelia champaca plant extract can cure skin disease. Skin disease can be caused by many reasons. Infections due to Staphylococcus aureus is one of the main reasons for skin disease. This objective of the study is to identify the phytochemical of Michelia champaca capable of curing skin diseases. Molecular docking method applied using “Biovia Discovery Studio”. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that Magnoflorine can effectively deactivate thymidylate synthase thereby interrupting the life cycle of the organism.

Open Access Review Article

Glycemic and Non-Glycemic Effects of Teneligliptin

Ranakishor Pelluri, Kongara Srikanth, Jithendra Chimakurthy, Rasheed Ahemad Shaik, R. Lavanya, N. Vanitha Rani

Journal of Pharmaceutical Research International, Page 51-63
DOI: 10.9734/jpri/2020/v32i630446

The gut enzymes are released in response to intake of meal, those are GLP-I (glucagon link peptide-I) & GIP (glucose-dependent insulin tropic polypeptide) along with DPP-4(Dipeptidyl peptidase-4). GLP-I has vital role in control of glucose levels and it may also has capacity reduce body weight and it can manage some micro & macro-vascular complications. Unfortunately it has very shorter half-life 1-2 min, and eventually it was degraded by DPP-4 enzyme.  Therefore GLP-I has ineffective to perform its tasks. To overcome this incidence essential to inhibit DPP-4 enzyme is benefited in diabetics and in non diabetics suffering with micro, macro vascular complications. Ubiquitous Dipeptidyl peptidase (DPP) - 4 has pleiotropic effects because it is widely distributed other than intestine. DPP-4 enzyme inhibition has a promising effect on glycemic control. DPP-4 inhibition is also involved in the improvement of non-glycemic effects as directly or indirectly the DPP-4 enzyme is linked with some pathological conditions of particular organs, such as DPP-4 is linked with the intestinal secretion of triglycerides, and DPP-4 is expressed in the glomerulus in uncontrolled diabetics which in turn leads to nephritis. DPP-4 release strongly correlates with adipocyte size, potentially representing an important source of DPP-4 in obesity. DPP-4 inhibition produces an anti-inflammatory activity because the activity of DPP-4 results in reduced production of cytokines including interleukins and interferon-G. All these anti-inflammatory agents are inhibited by the DPP-4 enzyme which can lead to pathogenesis of cardiovascular diseases and provokes atherosclerosis & psoriasis. Serum sodium and brain natriuretic peptide (BNP) levels are also regulated by inhibition of the DPP-4 enzyme and which can produce vascular protection & regulates blood pressure. Teneligliptin is a recently developed oral DPP-4 inhibitor indicated for the management of T2DM in adults along with diet and exercise. Teneligliptin is recently available in India and is also available in combination with other oral hypoglycemic agents at affordable prices. This review is aimed at exploring the status of teneligliptin with emphasis on its glycemic effects and non-glycemic clinical benefits associated with increasing GLP-1 & GIP.