Management of Type 2 Diabetes: Current Strategies,Unfocussed Aspects,Challenges, and Alternatives

Type 2 diabetes mellitus (T2DM) accounts for >90% of the cases of diabetes in adults. Resistance to insulin action is the major cause that leads to chronic hyperglycemia in diabetic patients. T2DM is the consequence of activation of multiple pathways and factors involved in insulin resistance and β-cell dysfunction. Also, the etiology of T2DM involves the complex interplay between genetics and environmental factors. This interplay can be governed efficiently by lifestyle modifications to achieve better management of diabetes. The present review aims at discussing the major factors involved in the development of T2DM that remain unfocussed during the anti-diabetic therapy. The review also focuses on lifestyle modifications that are warranted for the successful management of T2DM. In addition, it attempts to explain flaws in current strategies to combat diabetes. The employability of phytoconstituents as multitargeting molecules and their potential use as effective therapeutic adjuvants to first line hypoglycemic agents to prevent side effects caused by the synthetic drugs are also discussed.     

Ocular myasthenia gravis: A review

Myasthenia gravis (MG) is a disease that affects the neuro-muscular junction resulting in classical symptoms of variable muscle weakness and fatigability. It is called the great masquerader owing to its varied clinical presentations. Very often, a patient of MG may present to the ophthalmologist given that a large proportion of patients with systemic myasthenia have ocular involvement either at presentation or during the later course of the disease. The treatment of ocular MG involves both the neurologist and ophthalmologist. Thus, the aim of this review was to highlight the current diagnosis, investigations, and treatment of ocular MG.     

Polymorphism in interferon λ3/interleukin-28B gene and risk to noncirrhotic chronic hepatitis C genotype 3 virus infection and its effect on the response to combined daclatasvir and sofosbuvir therapy

Hepatitis C virus (HCV) infection is a considerable public-health problem and an important cause of liver disease with about 71 million people infected worldwide and more than 399 000 people die every year from hepatitis C-related liver diseases. The present study was, therefore, initiated to investigate the association of polymorphism in interferon λ3 (IFNL3) also known as interleukin-28B (IL-28B) gene with chronic HCV infection and association of these polymorphic variants with the combination daclatasvir and sofosbuvir HCV therapy response. Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a total of 250 chronic HCV genotype three patients and 500 number of healthy controls. Our data revealed that the TT (minor) genotype of IFNL3 (rs12979860) and GG (minor) genotype of IFNL3 (rs8099917) exhibited a significant association with chronic HCV genotype 3 infection when compared with controls. The results of treatment response showed that CC (major) genotype of IFNL3 (rs12979860) and TT (major) genotype of IFNL3 (rs8099917) are associated with the likelihood of achieving a higher sustained virological response (SVR), to combined daclatasvir and sofosbuvir therapy, in genotype 3-infected HCV patients, whereas the individuals with TT (minor) genotype of IFNL3 (rs12979860) and GG (minor) genotype of IFNL3 (rs8099917) are more susceptible to chronic HCV infection and treatment relapse, suggesting a role of IFNL3 (rs12979860) and (rs8099917) in the treatment outcome of combined daclatasvir and sofosbuvir therapy in chronic HCV genotype 3 infection.     

Neuroblastoma: Outcome over a 14 year period from a tertiary care referral centre in India

Purpose

To evaluate the outcome of children with neuroblastoma (NB) from a tertiary care referral centre in India.

Method

All children with NB registered from October 1996 through July 2009 were included in the study. INSS was used for staging. All children included in the study received chemotherapy and radiation therapy appropriate for stage. Tumor resection was done when feasible. The final outcome was overall survival and it was categorized as Complete Response (CR), Partial Response (PR); No Response (NR) and Progressive Disease (PD). Analysis of three-year overall survival was done using Kaplan Meier method and Log Rank test of significance. Multivariate analysis for significance of age, site and stage was performed.

Results

144 children in the age range of 1–132 months (median 36) were enrolled. Only 38 (26.4%) children were below 12 months. 112 (77.8%) of the tumors were abdominal and 32 (22.2%) were extra-abdominal. Stage distribution was 1 + 2 in 6 (4.2%); 3 in 58 (40.3%); 4 in 68 (47.2%); 4 s in 12 (8.3%). 83 (57.6%) underwent gross complete resection. At the time of last follow-up, 100 (69.4%) were alive [60 CR (41.7%); 33 PR; 7 PD/NR] and 44 (30.6%) were dead [1CR; 11PR; 32 PD/NR]. The three-year OS was 60.7% [95 CI 50.4–69.5]. The OS was 69.7% for those < 12 months of age [95 CI 51.8–82.0] and CR was achieved in 57.9%, while for those > 12 months the OS was 55.3% [95 CI 42.2–66.6] and CR was achieved in 35.8% (p = 0.73). All 6 (100%) patients with Stage 1 and Stage 2 disease were alive and disease free. The OS was 71.5% for Stage 3[95 CI 55.3–82.7] and CR was achieved in 56.9%, while for Stage 4 the OS was 35.7%[95 CI 19.3–52.4] and CR was achieved in 17.6% (p = 0.001). The OS was 83.3% for 4 s [95 CI 48.2–95.6] and CR was achieved in 75%.

Conclusion

All the six children with Stage 1 & 2 achieved CR and were alive, while 57% of Stage 3 could achieve CR and had an OS of 71.5%. The OS (35.7%) and CR (17.6%) for Stage 4 were significantly less (p = 0.001).     

Single-stage earlobe reconstruction: a simple method with promising results

Various methods have been described in the literature for earlobe reconstruction in one or many stages. Authors describe here a simple, single-stage technique to reconstruct the loss of the earlobe. The technique is clearly illustrated in a step-by-step manner and produces a natural-looking earlobe without an unpleasant secondary deformity with desirable texture and color match. Level of Evidence: Level IV, therapeutic study.     

Geraniol protects hippocampal CA1 neurons and improves functional outcomes in global model of stroke in rats

Geraniol (GE), an acyclic monoterpene, is a chief constituent of essential oils of herbs and fruits. It possesses diverse pharmacological actions like antioxidant, anti-inflammatory, anti-apoptotic, and anti-parkinson. However, its neuroprotective potential in stroke is yet to be explored at large. The present study evaluated the neuroprotective potential of GE against the global model of cerebral ischemia/reperfusion (I/R)-injury in rats. Bilateral common carotid artery (BCCA) occlusion for 30 min followed by 7 days of reperfusion caused varied biochemical/enzymatic alterations viz. increase in levels of lipid peroxidation (LPO), nitric oxide (NO), xanthine oxidase (XO), and decrease in the levels of cerebroprotectives like superoxide dismutase (SOD), catalase (CAT), total thiols, and glutathione (GSH). GE-pretreatment markedly reversed these changes and restored the levels of protective enzymatic and non-enzymatic antioxidants near to normal compared to I/R group. Besides, GE treatment showed marked improvement in anxiety-related behavior and neuronal deficits in animals subjected to I/R injury. Moreover, 2,3,5-triphenyl tetrazolium chloride (TTC)-stained rat brain coronal sections and histopathological studies revealed neuronal protection against I/R-injury, as evidenced by a reduction in infarct area (%) and an increase in hippocampal CA1 neuronal density in the GE-treated groups. The results of this study revealed that GE exhibited potential neuroprotective activity by reducing oxidative stress and infarction area, and protecting hippocampal CA1 neurons against I/R-injury in the global stroke model in rats.     

The role of T regulatory cell-associated markers in monitoring tuberculosis treatment completion and failure

Monitoring tuberculosis (TB) treatment success is crucial for clinical decision-making. The only available tool in this regard is sputum microscopy, but it has demerits. Moreover, in case of smear negatives and extrapulmonary TB, an efficient tool is still sought for. Therefore, we evaluated T regulatory cell (Treg)-associated markers (CD25, CD39, and FoxP3) and cellular subsets in monitoring treatment success in treatment-completed groups. Expression profile of various markers and subsets were compared real time among treatment-naive pulmonary TB patients (TN-PTB), followed-up treatment-completed (TC-fu) cohort, and a not followed-up (TC-nfu) cohort. Peripheral blood mononuclear cells from various groups were incubated overnight and were stained with antibodies for specific markers and studied by flow cytometry. In both the treatment-completed groups, a decline in frequencies of CD25⁺ marker and CD4⁺CD25⁺, CD4⁺CD25⁺FoxP3, CD4⁺CD25⁺CD39⁺ Treg was observed with clearance of infection, indicating their potential in monitoring treatment success. However, in the case of treatment failure patient (Tfp), a drastic increase in frequency of CD4⁺CD25⁺FoxP3⁺ Treg subset was found, indicating its usefulness in predicting treatment failure. Although the investigation unveils markers useful in predicting treatment success or failure, the findings from this study needs to be validated in a larger cohort.