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.     

Assessment of oxidative stress and effect of antioxidant supplementation during radiotherapy in carcinoma of upper digestive tract

Oxidative stress was studied by estimating plasma levels of malondialdehyde (MDA), beta carotene, vitamin E and erythrocytic superoxide dismutase(E-SOD) activity in 50 cases of carcinoma of upper digestive tract which included carcinoma of oral cavity, pharynx and oesophagus. While plasma MDA level was found to be increased (3.5±1.0 nmole/ml), a significant decrease in beta carotene (81.2±14.5mg%), vitamin E (8.5±1.1 mg/L) level and E-SOD activity (657.0±80.6 U/G Hb) were observed in carcinoma of upper digestive tract. Patients were treated with radiotherapy which itself was toxic enough and produced its deleterious effects by generation of reactive oxygen species (ROS). As antioxdiants can detoxify ROS, beneficial effect if any, of antioxidant administration during radiotherapy was studied in two groups of patients, group A (n=5, supplemented with antioxidants) and group B (n=5, without antioxidant supplementation). Plasma MDA level was found to be elevated in both the groups but the increase in group B was significant, compared to pretreatment level. Further, body weight was found to be significantly decreased in group B patients, which was maintained in group A patients. Moreover, group A patients showed significant elevation in beta carotene concentration, thus showing beneficial effect of administration of antioxidants during radiotherapy without disturbing the desirable therapeutic effect of radiotherapy.     

Social justice and curriculum renewal for Samoan students: an Australian case study

This paper examines the construction of ‘socially just’ curriculum renewal initiatives for Samoan students in a low socio-economic secondary school. Basil Bernstein's concept of recontextualization is used to investigate the implementation of Queensland's Social Justice Strategy at the school level. Interview data provided by the school's first two ‘social justice coordinators’ is analysed, focussing on the categorizations of students and discourses operative within the reform initiatives. Shifts in what counted as socially just curriculum for Samoan students are documented. The focus is on the varying strength of the boundaries of cultural categories (i.e. ‘Samoan’) and on tensions over the emphasis on the cultural knowledge of community representatives and the professional knowledge of school educators. The findings make explicit implications for the distribution of discursive resources to the Samoan students and, hence, life chances in a world in which English is a tool needed by young Australians irrespective of their cultural background.     

Revisiting the occupational aspirations and destinations of Anglo-Australian and Chinese-Australian high school students

Evidence from Australia lends support to the “Asian high achieving syndrome” in Chinese-Australian students and “self-deprivation syndrome” in Anglo-Australian students. Applying ethnographic case studies approach for doctoral thesis the author collected data on a longitudinal basis from homes and school of these students. All of these students attended the same school located in a predominantly middle class suburb of Perth Metropolitan area in Western Australia. Chinese-Australian families had settled in Perth from Malaysia, Singapore and Hong Kong, whereas Anglo-Australian families had been residing in Perth for three generations. Impetus to revisit these students (now young adults with their own families) 10 years later came from an urge to test the validity of the prediction the author had made in the concluding chapter of his doctoral thesis. The author had claimed that “if Anglo-Australian parents keep on dwelling in the era of 1950s and 1960s and do not change their laid-back attitude about education, their children could eventually be under-privileged in their own country”. Ten years later, the author undertook a follow-up study on these young adults from six of the eight original families in order to find out their occupational destinations and future aspirations. Data for the follow-up study were collected from these young adults and their parents. These research cases were interviewed twice, each time approximately for two hours and their parents were interviewed once for two to three hours. The purpose of this paper is to report the findings of the follow-up study which reveals a remarkable relationship between the attitude towards schooling and academic performance with their subsequent occupational destination.     

Breast cancer in developing population: A nutrition caveat

From January 1992-January 1998, 1404 patients attended the “Breast Clinic” of R.N.T. Medical College M.B. Hospital, Udaipur. Out of these, 11% and 81% patients had breast cancer (B.C.) and benign breast cancer (B.B.D.) respectively. The oxidative load in B.C. was 2.32 times higher than controls, but comparable to B.B.D. β-Carotene deficiency was uncommon in patients, whereas vitamin A deficiency was almost equally common in both B.C. and controls. Most of the patients had almost depleted levels of α-tocopherol and ascorbic acid but their TBAR levels were in normal range. The data in the present study when compared with B.B.D. and other local normal subjects point out: a) oxidative burden in B.C. is a consequence and not the cause of the disease, (b) oxidative stress could be one of the etiological factors in tumor expression, which need not to be malignant and c) α-tocopherol and ascorbic acid are not importantly responsible for higher oxidative burden in B.C.     

Teacher support,instructional practices,student motivation,and mathematics achievement in high school

The authors examined the relationships among teacher classroom practices, student motivation, and mathematics achievement in high school. The data for this study was drawn from the base-year data of High School Longitudinal Study of 2009. Structural equation modeling method was used to estimate the relationships among variables. The results indicate that conceptual teaching positively affected student mathematics achievement, whereas procedural emphasis in mathematics instruction had a negative effect. Teacher support influenced student mathematics achievement indirectly through students' mathematics self-efficacy, and also influenced students' interest in mathematics courses. Finally, students with higher levels of family socioeconomic status and prior achievement were more likely to have teachers who use conceptual teaching strategies. Students with higher prior achievement were also more likely to perceive higher levels of teacher support. The findings have theoretical and practical implications.     

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.     

Are we using Thyroid Function Tests Appropriately?

Thyroid function tests are very important for the diagnosis and monitoring of patients with thyroid dysfunction. The guidelines recommend serum thyroid stimulating hormone (TSH) as the single most reliable test to diagnose all common forms of hypothyroidism and hyperthyroidism. The aim of this study was to analyze the ordering pattern for thyroid function tests by physicians and the analysis of results based on the clinical history. The mean age of the patients was 32.5 ± 6.5 years. Majority of samples (87.7% of total) were received from the departments of Medicine and Gynae. Thyroid profiles (47.5%) were ordered more frequently as compared to TSH only (46%). There was no significant difference in the percentage of normal reports for both types of tests. 77.8% of TFT and 76.6% of TSH samples had results within the reference range. The percentage of abnormal results was 13.7% in the patients who were screened for thyroid disorders. There is a need to redefine the case definition for thyroid dysfunction and order the appropriate test in a rational and cost effective manner.     

Hematological Parameters and RBC TBARS Level of Q 10 Supplemented Tribal Sickle Cell Patients: A Hospital Based Study

The study has been undertaken as number of sickle cell patients in Chhattisgarh tribal population is 23.7 %. The Co enzyme Q10 is a strong antioxidant and energy producing compound. The patients were divided into three groups group A homozygous (SS), group B heterozygous (AS) and group C controls for TBARS study. The age group is 10–55 years and 200 mg of CoQ10 was given to A and B groups. The hematological parameters, C reactive protein as well as RBC TBARS level were performed by usual and standard techniques. The results were obtained as 25.37 % increased RBC level in group A and 23.24 % in group B. The increased hemoglobin level was observed as 16.73 % in group A and 10.7 % in group B. In case of WBC it was observed increased 24.38 % in group A and 12.0 % in group B. C-reactive protein was observed 7.8 times decreased in group A and 1.54 times in group B. The RBC TBARS level was also found decreased 48 % in group A and 51 % in group B as compared to group C. During the supplementation of coenzyme Q10 the pain caused by vaso-occlusive events has reduced. This significant increase in hematological parameters as well as decreased C-reactive protein and TBARS level suggest that the Q10 should be included in the diet of sickle cell patients.