Antisense therapy specific to mutated K-ras gene in hamster pancreatic cancer model. Can it inhibit the growth of 5-FU and MMC-resistant metastatic and remetastatic cell lines?

K-ras point mutation at codon 12 has a relationship greater than 90% with pancreatic cancer. Cancer therapy should also include the treatment of metastatic disease because it is known that the properties of metastatic cells may vary considerably from those of the primary tumor. AIM: To clarify if the same drugs, which can inhibit the tumor growth in the parental cell line, can inhibit the pancreatic metastatic and remetastatic cell lines at the same concentrations and to compare the inhibition with antisense oligonucleotides mismatched to K-ras gene, in Syrian golden hamsters. MATERIALS AND METHODS: HaP-T1, a BHP-induced hamster pancreatic cancer cell line, MS-PaS-1 (a metastatic cell line established from "return trip" metastases from the liver to the pancreas) and MS-PaS-2 named as a "remetastatic cell line", i.e., metastases from MS-PaS-1 were used. MTT and MTT-agarose assays were performed, using 5-Fluorouracil (5-FU), Mitomycin C (MMC) and antisense oligonucleotide specific to K-ras oncogene. RESULTS: The inhibitory concentration (IC50) of 5-FU, which inhibited HaP-T1, had to be increased by 50-fold to inhibit MS-PaS-1 and 100-fold to inhibit MS-PaS-2. MMC had to be increased by 10-fold to inhibit MS-PaS-1 and 50-fold to inhibit MS-PaS-2. However, IC50 was the same when antisense oligonucleotide was tried in these 3 cell lines. CONCLUSION: Antisense oligonucleotide-targeted K-ras gene may be a good choice for therapy because it could inhibit the growth in metastatic and remetastatic cells as well as in primary tumor cells.     

Impact of a course on human sexuality and adolescence

Obective: This study was conducted as part of a course on Human Sexuarity and Adodescence for school childrenmèt/ to ascertain the prior knowledge of children, source of their knowledge and whether the course was a felt need of the childrenMethod : Students were given a questionnaire before the course. Few selected questions were asked again after the last session. The course was conducted in a private co-educational. English medium school in urban Bangalore involving 392 students 13–15 years of age. The course was designed by the authors and dealt with anatomy, physiology, social and psychological aspects of growing up, HIV and contraception.Results : 55–70% of class VIII; IX and X students had learnt about sex from friends, 30% from movies, 15% from text books and only 10% from parents. Misconceptions about anatomy, childbirth, HIV were common. 90% of tenth class students felt that education in human sexuality was necessary.Conclusion: In spite of chapters on reproduction in textbooks, children turn to peers or media to gather information on sexuality. Education in human sexuality is nequired in our schools, as this need is currently not being addressed adequately in our society.     

Ventricular rate stabilization for the prevention of pause dependent ventricular tachyarrhythmias: results from a prospective study in 309 ICD recipients

Reviews of stored electrograms from ICDs revealed a 5-30% incidence of short-long-short intervals preceding the onset of recurrent ventricular tachyarrhythmias. Rate stabilization by dedicated antibradycardia pacing algorithms has, therefore, been suggested to prevent onset of pause dependent tachyarrhythmias. However, the clinical efficacy of this approach has not been studied systematically. In a prospective multicenter crossover study, patients were randomized to activation or deactivation of an implemented ventricular rate stabilization algorithm (VRS) after first implant of a dual chamber ICD. After 3 months, all patients were crossed over to the alternate programming. The rate of appropriate spontaneous VA episodes was compared between VRS On and VRS Off. Stored electrograms were reviewed for evaluation of the mode of onset of tachyarrhythmias. Overall efficacy analysis was based on 309 patients enrolled in the study. Forty percent (124/309) of the patients experienced 4,973 VA episodes. Based on an intention-to-treat analysis, VRS Off and On arrhythmia incidence was 10.2 and 6.6 normalized to 3 months, respectively (risk reduction 35%; P = 0.18) On an on-treatment basis, a reduction from 9.0 episodes to 8.1 episodes (10% risk reduction, P = 0.24) was seen. In an extended Cox model adjusting for confounding variables, the relative risk for recurrent episodes was 0.92 during VRS On compared to Off (95% CI: 0.58-1.48; P = 0.74). During VRS Off, pause dependent onset was documented in only 36 (8%) of 427 visually analyzed episodes. There was no significant reduction in the incidence of recurrent ventricular tachyarrhythmias with VRS On compared to the Off programming in this prospective study.     

Evidence of prolonged disturbances in the haemostatic,hemorheologic and inflammatory profiles in transmural myocardial infarction survivors

Haemostatic, hemorheologic and inflammatory disturbances have been associated with acute coronary syndromes. Most knowledge is reported in cross sectional studies and are without time dependent evolution of these profiles. The aim of this study was to evaluate, during the first year, the evolution of the haemostatic, hemorheologic and inflammatory profiles determined at hospital discharge in survivors with transmural myocardial infarction (MI). Eighty eight (79 male; 9 female) mean age of 58 +/- 11 years, survivors of a transmural MI were prospectively studied at discharge, 6 months and one year after the event. Haemostatic (protein C, antithrombin III and plasminogen activator inhibitor 1), hemorheologic (blood fluidity and components) and inflammatory profiles (polymorphonuclear elastase and leukocyte count) were determined using standard methodology. The results of the study can be summarized as follows: (1) Protein C decreased (p < 0.05) over time while PAI-1 only varied significantly until 6(th) month. (2) Plasma viscosity and fibrinogen (p < 0.001) decrease over time, while erythrocyte aggregation (p < 0.001) and haematocrit increased. Whole blood viscosity did not vary. (3) Leukocyte decreased (p < 0.001) and elastase did not (4). Those patients with cardiovascular events (n = 7) had higher PAI-1 concentration (p < 0.05) and leukocyte count (p < 0.01), at discharge (5) Left ventricle ejection fraction correlated significantly with plasma viscosity (r = 0.35 p < 0.05). The results of this longitudinal study show dynamic modifications of the haemostatic, hemorheologic and inflammatory profiles during the first year of a transmural myocardial infarction. In addition, there are interrelations between them and the clinical profile that could help to explain the clinical evolution of this group of patients.     

Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity

Current Literature

Gene therapy for hemophilia