<Emphasis Type="Bold">9</Emphasis><Superscript><Emphasis Type="Bold">th</Emphasis></Superscript><Emphasis Type="Bold">International Conference On Homocysteine and One-Carbon Metabolism - HCY2013</Emphasis>

Canavan disease (CD) is a fatal neurological disorder caused by defects in the gene that encodes for a critical metabolic enzyme. The enzyme aspartoacylase catalyzes the deacetylation of N-acetylaspartate to produce acetate required for fatty acid biosynthesis in the brain. The loss of aspartoacylase activity leads to the demyelination and disrupted brain development that is found in CD patients. Sixteen different clinical mutants of aspartoacylase have been cloned, expressed and purified to examine their properties and the relationship between enzyme properties and disease phenotype. In contrast to numerous cell culture studies that reported virtually complete loss of function, each of these purified mutant enzymes was found to have measureable catalytic activity. However, the activities of these mutants are diminished, by as little as three-fold to greater than 100-fold when compared to the native enzyme. Many of these mutated enzyme forms show decreased thermal stability and an increased propensity for denaturation upon exposure to urea, but only four of the 16 mutants examined showed both diminished thermal and diminished conformational stability. Significantly, each of these lower stability mutants are responsible for the more severe phenotypes of CD, while patients with milder forms of CD have aspartoacylase mutants with generally high catalytic activity and with either good thermal or good conformational stability. These results suggest that the loss of catalytic function and the accumulation of N-acetylaspartate in Canavan disease is at least partially a consequence of the decreased protein stability caused by these mutations.     

Newborn care practices and health seeking behavior in urban slums and villages of Anand, Gujarat

Health status of neonates in urban slums has not been studied in smaller towns. A questionnaire was administered to 154 families of 10 urban slums of Anand (population — 197351) and 160 families from 6 villages of Anand district. The socioeconomic and education status of the slum dwellers versus rural participants were significantly lower (P<0.001). Antenatal care (79.9 vs 94.4%, P<0.001), hospital delivery (82.5 vs 93.8%, P=0.002), neonatal follow-up (27.9 vs 78.8%, P<0.001), health seeking (56.5 vs 91.3%, P<0.001), essential newborn care and exclusive breastfeeding (6.5 vs 85.6%, P<0.001) were also lower in urban slums, as compared to villages, Care seeking was low in urban slums, Hindus and illiterate mothers. Health care and socioeconomic status of neonates in slums of smaller cities is poorer than in surrounding villages.     

Differential Effects of Wine Consumption on Colorectal Cancer Outcomes Based on Family History of the Disease

Potentially favorable effects of wine consumption on colorectal cancer (CRC) incidence have been reported, but effects on clinical outcomes are unknown. This case-only analysis was designed to investigate outcomes among familial (n = 141) and sporadic (n = 358) CRC patients enrolled in the University of California Irvine CRC gene-environment study during 1994–1996 based on their reported frequency of wine consumption in the year prior to diagnosis. Cases were categorized as either regular or infrequent wine consumers. Univariate survival rate analyses were estimated using the Kaplan and Meier method and log-rank test. Multivariate survival analyses were performed using Cox proportionalhazards ratios (HRs). Earlier stage at presentation (P = 0.034) was noted for familial (but not sporadic) CRC cases reporting regular wine consumption. An overall survival (OS) benefit was observed for familial (but not sporadic) CRC cases that were regular (10-yr OS = 75%) versus infrequent wine consumers (10-yr OS = 47%; P = 0.002). This survival improvement for familial CRC cases remained after adjustment for age, stage, treatment, and other clinically relevant factors (HR = 0.50, 95% confidence interval = 0.25–0.99). Our findings implicate favorable effects of wine consumption on stage at presentation and survival in CRC, selectively among familial CRC cases.     

Comparison of efficacy and safety of intralesional triamcinolone and combination of triamcinolone with 5-fluorouracil in the treatment of keloids and hypertrophic scars: Randomised control trial

The treatment of keloid and hypertrophic scar is challenging with no universally accepted mode for permanent ablation. Conventional therapies yield unpredictable results, significant complications and require elaborate hardware.

Diabetic peripheral neuropathy in people with type 2 diabetes: too little too late

Diabetic peripheral neuropathy in people with type 2 diabetes is poorly managed because of its insidious onset, delayed diagnosis and more complex aetiology resulting from the contribution of not only hyperglycaemia, but also ageing, hyperlipidaemia, hypertension and obesity. Because there is no US Food and Drug Adminstration-approved disease-modifying therapy for diabetic peripheral neuropathy, the key to ameliorating it in type 2 diabetes has to be through earlier diagnosis and timely multi-factorial risk factor reduction. The management of painful diabetic peripheral neuropathy also requires a detailed appraisal of the choice of therapy, taking into account efficacy, patient wishes, comorbidities, side effect profile and potential for abuse.     

Bispecific antibody based therapeutics: Strengths and challenges

Monoclonal antibody-based targeted therapy has greatly improved treatment options for patients. However, long-term efficacy of such antibodies is limited by resistance mechanisms. New insights into the mechanisms by which tumors evade immune control have driven innovative therapeutic strategies to eliminate cancer by re-directing immune cells to tumors. Advances in protein engineering technology have generated multiple bispecific antibody (BsAb) formats capable of targeting multiple antigens as a single agent. Approval of two BsAb and three check point blocking mAbs represent a paradigm shift in the use of antibody constructs. Since BsAbs can directly target immune cells to tumors, drug resistance and severe adverse effects are much reduced. The wave of next generation “bispecific or multispecific antibodies” has advanced multiple candidates into ongoing clinical trials. In this review, we focus on preclinical and clinical studies in hematological malignancies as well as discuss reasons for the limited success of BsAbs against solid tumors.