A Narrative Review of Potential Future Antidiabetic Drugs: Should We Expect More?

Prevalence of diabetes mellitus, a chronic metabolic disease characterized by hyperglycemia, is growing worldwide. The majority of the cases belong to type 2 diabetes mellitus (T2DM). Globally, India ranks second in terms of diabetes prevalence among adults. Currently available classes of therapeutic agents are used alone or in combinations but seldom achieve treatment targets. Diverse pathophysiology and the need of therapeutic agents with more favourable pharmacokinetic-pharmacodynamics profile make newer drug discoveries in the field of T2DM essential. A large number of molecules, some with novel mechanisms, are in pipeline. The essence of this review is to track and discuss these potential agents, based on their developmental stages, especially those in phase 3 or phase 2. Unique molecules are being developed for existing drug classes like insulins, DPP-4 inhibitors, GLP-1 analogues; and under newer classes like dual/pan PPAR agonists, dual SGLT1/SGLT2 inhibitors, glimins, anti-inflammatory agents, glucokinase activators, G-protein coupled receptor agonists, hybrid peptide agonists, apical sodium-dependent bile acid transporter (ASBT) inhibitors, glucagon receptor antagonists etc. The heterogeneous clinical presentation and therapeutic outcomes in phenotypically similar patients is a clue to think beyond the standard treatment strategy.     

Comparative account of serum lipids,lipoproteins and apolipoprotein-B in patients of coronary artery disease

Serum total lipids (cholesterol and triglyceride), lipoproteins (VLDL, LDL and HDL) and Apolipoprotein-B levels of normal healthy individuals (n=25) and coronary artery disease patients (n=25) were estimated. The objective of the present study was to ascertain the role of apo-B in causation and inheritance of coronary artery disease. It was observed that on an average serum total cholesterol and triglyceride more than 200 mg/dl bring the individuals to a risk of coronary artery disease (CAD) irrespective of the age. CAD patients achieved this value at an early age (35–45 years). Similarly VLDL and LDL levels were found to be significantly raised in CAD patients when compared to that of age matched normal individuals, with patients achieving risk values at an early age. HDL levels were found to be significantly lower in CAD patients as compared to normal individuals. Serum apo-B levels were significantly raised in CAD patients as compared to age matched normal individuals. Patients with positive family history of CAD had raised serum apo-B levels than those having negative family history. A positive coefficient of correlation was observed between serum apo-B and LDL levels suggesting that more the number of Apo-B particles, more will be the synthesis of atherogenic particle (LDL). Patients with negative family history had serum apo-B levels closer to those of normal individuals and in these individuals HDL levels were found to be significantly lowered, suggesting that loss of scavenger role of HDL could be the risk factor responsible for the causation of CAD in these patients, with negative family history of coronary artery disease.     

Effects of roller burnishing process parameters on surface roughness of A356/5%SIC composite using response surface methodology

In this study, a simple roller burnishing tool was made to operate burnishing processes on A356/5%SIC metal matrix composite fabricated by electromagnetic stir casting under different parameters. The effects of burnishing speed, burnishing force and number of burnishing passes on the surface roughness and tribological properties were measured. Scanning electron microscopy （SEM） graphs of the machined surface with PCD （insert-10） tool and roller burnished surface with tungsten carbide （WC） roller were taken into consider- ation to observe the surface finish of metal matrix composites. The mechanical properties （tensile strength, hardness, duc- tility） of A356/5%SIC metal matrix composites were studied for both unburnished samples and burnished samples. The results revealed that the roller burnished samples of A356/ 5%SIC led to the improvement in tensile strength, hardness and ductility. In order to find out the effects of roller bur- nishing process parameters on the surface roughness of A356/ 5%SIC metal matrix composite, response surface methodol- ogy （RSM） （Box-Behnken design） was used and a prediction model was developed relevant to average surface roughness using experimental data. In the range of process parameters, the result shows that roller burnishing speed increases, and surface roughness decreases, but on the other hand roller burnishing force and number of passes increase, and surface roughness increases. Optimum values of burnishing speed （1.5 m/s）, burnishing force （50 N） and number of passes （2） during roller burnishing of A356/5%SIC metal matrix com- posite to minimize the surface roughness （predicted 1.232 μm） have been found out. There was only 5.03% error in the experimental and modeled results of surface roughness.     

Serum apolipoproteins in the patients of myocardial infarction in different age groups

The level of serum cholesterol (Ch), serum-high density lipoprotein cholesterol (HDLc), serum-low density lipoprotein cholesterol (LDLc), serum very low density lipoprotein cholesterol (VLDLc), Triglyceride (Tg), Apolipoprotein A-1, B and ratio of Apolipoprotein A1/B were observed in 151 survivors of myocardial infarction in different age groups. A significant increase was found in the level of triglyceride, LDLc, apolipoprotein-B and a significant decrease in apolipoprotein-A1 and the ratio of apolipoprotein A1/B. No significant alteration was found in serum cholesterol, HDLc except in the age group of 31–40 years and 41–50 years and VLDLc. Thus, serum Apo A-1 and Apo-B may be considerably better markers for coronary artery disease than traditional lipid parameters.     

Serum oestradiol in women with carcinomas of the breast and uterine cervix

Endogenous oestrogens are thought to be involved in breast cancer, but few studies could show the direct relationship between hormones and pathological process of the disease. In the present study, oestradiol was estimated in the serum of pre-and postmenopausal breast cancer patients along with normal healthy controls and patients with carcinoma of the uterine cervix which is not dependent on oestrogens. Premenopausal patients with breast cancer showed higher levels of oestradiol as compared to premenopausal control women as well as cervical cancer patients. Whereas, no statistically significant differences were observed in serum oestradiol levels amongst postmenopausal groups of breast cancer, cervical cancer and normal women. The result of the study reflects the association of oestradiol as well as its difference in the pathological events of pre and postmenopausal breast cancer.     

What is a Species? An endless debate

Everybody is familiar with the ubiquitous term ‘species’. But what is a species? Undeniably, this is one of the most complex dilemmas in the history of biology. There is no other concept in biology as elementary yet controversial as the concept of species. In practice, a species is regarded as the fundamental unit of comparison in all biological disciplines like systematics, evolution, ecology, ethology, physiology, and genetics. However, little agreement exists in the scientific community regarding the nature of species, whether it is a real entity or a cultural artifact, its biological significance or how to delineate a species. This article is a review of the seemingly endless debate on the species concept and its implications.     

Qualitative Differences Between Learning Environments Using Videos in Small Groups and Whole Class Discussions: A Preliminary Study in Physics

Interactivity, group learning and student engagement are accepted as key features of social constructivist learning theories. The challenge is to understand the interplay between such features in different learning environments. This study focused on the qualitative differences between two interventions—small-groups and whole-class discussions. In both interventions, three short video slices on the abstract topic ‘the physics of superconductivity’ were interspersed with the different discussion styles. The video slices are based on the Bruner stages. Twenty-nine first year university physics students completed a pre-test, underwent the intervention and completed a post-test. The remainder of the data were collected from student drawings, video recordings, observer notes and facilitator feedback. Results indicate that the use of the video slices in both interventions were successful in changing students’ understandings of superconductivity. However, the small groups treatment tended to facilitate questioning, meaning-making and subsequent changes of ideas more so than the whole class discussions. Implications for research and practice are discussed.     

Serum lipid profile in diabetics with and without retinopathy

Diabetics showed significantly raised levels of total and LDL cholesterol, (257.0±68.88 mg% 173.5±67.7mg% respectively) compared to controls matched with age, sex and socioeconomic status. No significant difference was observed in these parameters in diabetics with and without retinopathy.     

Oxidative stress in metabolic syndrome

As antioxidants play a protective role in the pathophysiology of diabetes and cardiovascular diseases, understanding the physiological status of antioxidant concentration among people at high risk for developing these conditions, such as Metabolic Syndrome, is of interest. In present study out of 187 first degree non-diabetic relatives and 192 non-diabetic spouses, 33.1% and 19.7% were found to have metabolic syndrome respectively. Subjects with metabolic syndrome (≥3 risk factors) had poor antioxidants status as reflected by significantly low levels of vitamin A, C & E and significantly increased (p<0.01) oxidative stress as compared to those without metabolic syndrome. At the same time serum insulin levels and insulin resistance were found to be significantly high (p<0.001) in metabolic syndrome. A strong positive correlation (r=0.946; p<0.001) between oxidative stress and insulin resistance was observed in metabolic syndrome. Low levels of antioxidants and increased oxidative stress with insulin resistance in metabolic syndrome suggests that besides therapeutic life style changes (TLC) as suggested in ATP III guidelines inclusion of antioxidant vitamins, fruits and vegetable could be beneficial to ward off the consequences of metabolic syndrome.     

Potential Chemoprevention of 7,12-Dimethylbenz[a]anthracene Induced Renal Carcinogenesis by Moringa oleifera Pods and Its Isolated Saponin

Present investigation shows that hydroethanolic extract of Moringa oleifera (MOHE) and its isolated saponin (SM) attenuates DMBA induced renal carcinogenesis in mice. Isolation of SM was achieved by TLC and HPLC and characterization was done using IR and ¹H NMR. Animals were pre-treated with MOHE (200 and 400 mg/kg body weight; p.o), BHA as a standard (0.5 and 1 %) and SM (50 mg/kg body weight) for 21 days prior to the administration of single dose of DMBA (15 mg/kg body weight). Administration of DMBA significantly (p < 0.001) enhanced level of xenobiotic enzymes. It enhanced renal malondialdehyde, with reduction in renal glutathione content, antioxidant enzymes and glutathione-S-transferase. The status of renal aspartate transaminase, alanine transaminase, alkaline phosphatase and total protein content were also found to be decreased along with increase in total cholesterol in DMBA administered mice. Pretreatment with MOHE and SM significantly reversed the DMBA induced alterations in the tissue and effectively suppressed renal oxidative stress and toxicity.