Study of physical-chemical properties for 2nd generation ethanol-blended diesel fuel in India

The present study pertains to glorify the significance of physical and chemical properties of blended diesel fuel with 2nd generation ethanol when applied to compression ignition engine. The assessed fuel properties are density, kinematic viscosity, Cetane number, calorific value, sulfur content and flash point for the prepared blends with respect to fuel quality standards. The results are examined based on present stipulations set for fuel quality rendering Bharat Stage VI standard norms in India. Fuel density and viscosity got slightly decreased with the aggregate of 2nd generation ethanol concentration, at the same time sulfur content also witnessed a similar trend. Cetane number also decreased considerably with the inclusion of 2nd generation ethanol content in diesel fuel. Use of 2nd generation ethanol in diesel fuel will expand markets for agricultural commodities and generate extra revenue from 2nd generation ethanol which is produced from waste residuals of the crops. To achieve stringent emissions regulations and government declarations of increasing biofuel usage can be succeeded by adopting 2nd generation ethanol-blended diesel as a commercial fuel in India. Tested 2nd generation ethanol-blended diesel fuel displayed comparable properties values to those of pure diesel fuel. All verified properties were within the standard limits of diesel fuel. It includes an incisive discussion on the feasible effects of fuel property variation with 2nd generation ethanol-blended diesel fuel concentration. The extreme concentration of 2nd generation ethanol in diesel fuel that can meet the essential characteristics within the range for diesel engine application has been being assessed here.     

Phospholipase C and Src Tyrosine Kinases Mediate Neurotensin-Stimulated Cl− Secretion in Rabbit Proximal Colon

Calcium-dependent secretagogues, such as neurotensin, stimulate age-dependent chloride transport in rabbit distal colonocytes, but their action in the proximal colon is unknown. This study examines the effect of neurotensin on chloride transport and its mechanism of action in rabbit proximal colonocytes. Our results show that neurotensin stimulates chloride transport only in adult, and not weanling or newborn, colonocytes. The calcium ionophore A23187 shows similar age dependence, while PGE2, which acts via cAMP, stimulates transport in all ages. The roles of phospholipase C, tyrosine kinases, and src tyrosine kinases were examined using specific inhibitors, i.e., U73122, genistein, and PP2, respectively. All three agents significantly inhibit neurotensin-stimulated chloride transport in adult colonocytes. In conclusion, this study reports for the first time that neurotensin stimulates chloride secretion in rabbit proximal colonocytes. This is also the first demonstration that neurotensin action exhibits age dependence and is dependent on phospholipase C and src tyrosine kinase activity.     

Tethered spinal cord and lipoma. Contribution of magnetic resonance imaging

A 12 year-old boy was investigated for progressive deformity of the left foot developing over 2 years. The foot was hollow with equinus varus and claw toes. Signs of a lesion of left L5 and S1 roots were present and spina bifida at L5 was noted on X-rays. Magnetic resonance imaging (MRI) showed a tethered spinal cord associated with a lipoma at the level of the S1 vertebra. Modes of presentation and physiopathology of disorders related to tethered cords are reviewed and the diagnostic value of MRI is emphasized.     

A phase I study of 17-allylamino-17-demethoxygeldanamycin combined with paclitaxel in patients with advanced solid malignancies.

BACKGROUND: 17-Allylamino-17-demethoxygeldanamycin (17-AAG) inhibits heat shock protein 90, promotes degradation of oncoproteins, and exhibits synergy with paclitaxel in vitro. We conducted a phase I study in patients with advanced malignancies to determine the recommended phase II dose of the combination of 17-AAG and paclitaxel. METHODS: Patients with advanced solid malignancies that were refractory to proven therapy or without any standard treatment were included. 17-AAG (80-225 mg/m2) was given on days 1, 4, 8, 11, 15, and 18 of each 4-week cycle to sequential cohorts of patients. Paclitaxel (80-100 mg/m2) was administered on days 1, 8, and 15. Pharmacokinetic studies were conducted during cycle 1. RESULTS: Twenty-five patients were accrued to five dose levels. The median number of cycles was 2. Chest pain (grade 3), myalgia (grade 3), and fatigue (grade 3) were dose-limiting toxicities at dose level 4 (225 mg/m2 17-AAG and 80 mg/m2 paclitaxel). None of the six patients treated at dose level 3 with 17-AAG (175 mg/m2) and paclitaxel (80 mg/m2) experienced dose-limiting toxicity. Disease stabilization was noted in six patients, but there were no partial or complete responses. The ratio of paclitaxel area under the concentration to time curve when given alone versus in combination with 17-AAG was 0.97 +/- 0.20. The ratio of end-of-infusion concentration of 17-AAG (alone versus in combination with paclitaxel) was 1.14 +/- 0.51. CONCLUSIONS: The recommended phase II dose of twice-weekly 17-AAG (175 mg/m2) and weekly paclitaxel (80 mg/m2/wk) was tolerated well. There was no evidence of drug-drug pharmacokinetic interactions.     

Adjunctive ablation strategies improve the efficacy of pulmonary vein isolation in non-paroxysmal atrial fibrillation: a systematic review and meta-analysis

Background: Pulmonary vein (PV) isolation (PVI) has suboptimal outcomes in patients with non-paroxysmal atrial fibrillation (AF). Adjunctive strategies employed to ablate non-PV triggers have shown favorable outcomes.

Aims: To delineate the incremental benefit of adjunctive ablation in patients with non-paroxysmal AF through a meta-analysis.

Methods and results: Database searches through August 2016 identified five non-randomized and seven randomized controlled trials (enrolling 1694 patients). The adjunctive strategies employed for non-PV ablation included focal impulse and rotor modulation; empirical linear lines, ablation of complex fractionated atrial electrograms and ganglionated plexi. The risk ratio (RR) for AF recurrence, calculated with random effects meta-analysis showed a 36% reduction of AF recurrence at a median follow up of 12 months (RR: 0.64, 95% Confidence interval: 0.48 to 0.85; p = 0.003). The benefits persisted during longer follow up when assessed in subgroup analysis.

Conclusions: Addition of adjunctive ablation to PVI improves outcomes.     

Oral Fenretinide in Biochemically Recurrent Prostate Cancer: A California Cancer Consortium Phase II Trial

Background

Fenretinide is a synthetic retinoid that is cytotoxic to a variety of cancers. We conducted a phase II trial of oral fenretinide in patients with biochemically recurrent prostate cancer.

Patients and Methods

Eligible patients had histologically confirmed prostate cancer and a confirmed rising prostate-specific antigen (PSA) ≤ 2 ng/mL following either radical prostatectomy and/or pelvic radiation therapy, without clinical or radiographic evidence of metastasis. The primary endpoint was PSA response, which was defined as a confirmed decrease by ≤50%, and ≤5 ng/mL, from the pretreatment value. Treatment comprised oral fenretinide 900 mg/m² twice daily for 1 week, every 3 weeks, for 1 year.

Results

After a median follow-up of 17.7 months, out of 23 patients, 7 (30%) patients had PSA stable disease (SD), 11 (48%) patients had PSA progression within 3 months, 4 patients had minimal increases over 3 months that did not qualify as SD or progression (17%), and one patient (4%) was not evaluable. Median time to PSA progression was 4.6 months (95% CI, 3.2-8.2 months). Observed grade 3 toxicities included fatigue, pain, hypermagnesemia, a rise in lipase, and nyctalopia.

Conclusion

Although well-tolerated, oral fenretinide did not meet prespecified PSA criteria for response in biochemically recurrent prostate cancer; however, 30% of patients had SD, which suggests modest single-agent clinical activity. The role of different formulations of fenretinide, which might allow for higher serum concentrations of the drug, is currently under investigation.     

Aging and the dendritic cell system: implications for cancer

The immune system shows a decline in responsiveness to antigens both with aging, as well as in the presence of tumors. The malfunction of the immune system with age can be attributed to developmental and functional alterations in several cell populations. Previous studies have shown defects in humoral responses and abnormalities in T cell function in aged individuals, but have not distinguished between abnormalities in antigen presentation and intrinsic T cell or B cell defects in aged individuals. Dendritic cells (DC) play a pivotal role in regulating immune responses by presenting antigens to na?ve T lymphocytes, modulating Th1/Th2/Th3/Treg balance, producing numerous regulatory cytokines and chemokines, and modifying survival of immune effectors. DC are receiving increased attention due to their involvement in the immunobiology of tolerance and autoimmunity, as well as their potential role as biological adjuvants in tumor vaccines. Recent advances in the molecular and cell biology of different DC populations allow for addressing the issue of DC and aging both in rodents and humans. Since DC play a crucial role in initiating and regulating immune responses, it is reasonable to hypothesize that they are directly involved in altered antitumor immunity in aging. However, the results of studies focusing on DC in the elderly are conflicting. The present review summarizes the available human and experimental animal data on quantitative and qualitative alterations of DC in aging and discusses the potential role of the DC system in the increased incidence of cancer in the elderly.