Regulation of prostaglandin metabolism by calcitriol attenuates growth stimulation in prostate cancer cells

Calcitriol exhibits antiproliferative and pro-differentiation effects in prostate cancer. Our goal is to further define the mechanisms underlying these actions. We studied established human prostate cancer cell lines and primary prostatic epithelial cells and showed that calcitriol regulated the expression of genes involved in the metabolism of prostaglandins (PGs), known stimulators of prostate cell growth. Calcitriol significantly repressed the mRNA and protein expression of prostaglandin endoperoxide synthase/cyclooxygenase-2 (COX-2), the key PG synthesis enzyme. Calcitriol also up-regulated the expression of 15-hydroxyprostaglandin dehydrogenase, the enzyme initiating PG catabolism. This dual action was associated with decreased prostaglandin E2 secretion into the conditioned media of prostate cancer cells exposed to calcitriol. Calcitriol also repressed the mRNA expression of the PG receptors EP2 and FP, providing a potential additional mechanism of suppression of the biological activity of PGs. Calcitriol treatment attenuated PG-mediated functional responses, including the stimulation of prostate cancer cell growth. The combination of calcitriol with nonsteroidal anti-inflammatory drugs (NSAIDs) synergistically acted to achieve significant prostate cancer cell growth inhibition at approximately 2 to 10 times lower concentrations of the drugs than when used alone. In conclusion, the regulation of PG metabolism and biological actions constitutes a novel pathway of calcitriol action that may contribute to its antiproliferative effects in prostate cells. We propose that a combination of calcitriol and nonselective NSAIDs might be a useful chemopreventive and/or therapeutic strategy in men with prostate cancer, as it would allow the use of lower concentrations of both drugs, thereby reducing their toxic side effects.     

Survival pattern of reported HIV infected individuals in the city of Delhi (India)

There is very little data on the survival period of HIV in India. In this paper survival experience of 836 HIV infected patients was studied whose illness was diagnosed upto Dec. 2003. On analysis, it was observed that the mortality was maximum in the age-group of 41-50 years (25%), 24.4% in males and 24.2% in females. For patients with tuberculosis morality was 23% and was higher among those with unsafe sex (24.5%) as a risk factor. Mortality of AIDS patients in Delhi decreased from 63.2% in 1994 to 24.2% in the year 2003. Also tuberculosis was found to be the major opportunistic infection affecting 83.2% of the patients. An increasing trend was observed with tuberculosis from 84.2% in 1994 to 89.1% in 1997 (p<0.05), but overall tendency was around 84% during the period 1994 to 2003. In AIDS related symptoms chronic diarrheoa accounted for only 5.2%. The median length of survival of HIV infected patients with all subjects was 75 months. The hazard rate showed an increasing trend and reached its peak at 102 months. The survival of HIV infected patients in Delhi was found to be shorter than that of patients in developed countries and developing African countries.     

Isotonic versus hypotonic fluid supplementation in term neonates with severe hyperbilirubinemia - a double-blind, randomized, controlled trial

Aim: To compare the incidence of hyponatremia in full‐term neonates with severe hyperbilirubinemia, receiving intravenous fluid supplementation with 0.2% saline in 5% dextrose versus 0.9% saline in 5% dextrose, to prevent blood exchange transfusion (BET). Methods: In this double‐blind, randomized, controlled trial, full ‐ term newborns (≥37 weeks), appropriate for gestational age, with severe non‐haemolytic hyperbilirubinemia (serum bilirubin ≥ 20 mg/dL) were enrolled. Eligible neonates were randomized to receive either 0.2% saline in 5% dextrose (hypotonic fluid group) or 0.9% saline in 5% dextrose (isotonic fluid group) over 8 hrs, in addition to phototherapy. The primary outcome was proportion of neonates developing hyponatremia (serum Na < 135 mmol/L) after 8 h. Results: Forty‐two neonates were analysed in each group. Proportion of neonates developing hyponatremia after 8 h was higher in hypotonic fluid group as compared to isotonic fluid group (48.8% vs. 10.5%, p < 0.001). However, a larger proportion in isotonic fluid group developed hypernatremia (39.5% vs. 12.2%, p < 0.001). The rate of BET was similar in both groups. Conclusion: In full‐term neonates with severe hyperbilirubinemia, administration of hypotonic fluid to prevent BET was associated with a higher incidence of hyponatremia while isotonic fluid was associated with an increased incidence of hypernatremia.     

Nucleotide deletion in RHCE*cE (907delC) is responsible for a D- - haplotype in Hispanics

BACKGROUND: Lack of Cc and Ee expression is associated with either hybrid alleles in which regions of RHCE are replaced by RHD or nucleotide deletion(s) in RHCE. The former have been found as D– – phenotypes, and the latter as Rh_null when accompanied by deletion of RHD. We investigated RH in eight samples, three presenting as D– –, whose c–E– red blood cell (RBC) typing was discordant with the RHCE genotype that predicted c+E+. STUDY DESIGN AND METHODS: Serologic and molecular testing was performed by standard methods. CASES AND RESULTS: RBCs from Patient 1 were D+C?E?c+e+^w but DNA testing predicted E+. RBCs from Patients 2, 3, and 4 typed as D+C?E?c?e? but DNA testing predicted c+E+. All had alloantibodies strongly reactive with all RBCs tested except D– – and Rh_null. Patient 5 had anti‐c and anti‐E but DNA testing predicted she was c+E+. RBCs from three donors typed D+C+E?c?e+ with DNA testing predicting c+E+. All had RHCE*cE with deletion of nucleotide 907C in Exon 6 predicted to cause a premature stop codon at Amino Acid 303 (Leu303Stop). HphI polymerase chain reaction–restriction fragment length polymorphism was used to confirm the deletion and to screen 100 Hispanic, 100 Caucasian, and 100 African American donor samples. One additional example was found. CONCLUSIONS: A novel allele, RHCE*cE 907delC (ISBT provisional designation RHCE*03N.02), silences c and E and in the homozygous state resulted in a D– – phenotype and production of anti‐Rh17. All eight probands were Hispanic. The allele is associated with discrepant molecular typing, with an approximate frequency of 0.005 in Hispanics.     

The influence of practitioner nationality, experience, and sex in shaping patient preferences for dentists

The present study examined patient preference for dentists as a function of the latter's demographics and experience. A sample of 161 British participants completed a questionnaire in which they were asked to rate eight dentists differentiated by nationality (British vs. Eastern European), sex (male vs. female), and experience (great vs. moderate). A mixed-design analysis of variance showed that there were main effects of dentist nationality (British preferred over Eastern European), sex (female over male), and experience (great over moderate). There were also a number of significant two- and three-way interactions, although the effect sizes of these interactions were relatively small. Participant sex generally did not have an impact on preferences. These results are discussed in relation to the extant literature on patient preferences for different types of health care practitioners.     

Use of polymerase chain reaction in the diagnosis of abdominal tuberculosis

BACKGROUND: Early diagnosis and prompt treatment of abdominal tuberculosis is vitally important as it greatly reduces disease and treatment related morbidity and even mortality in extreme cases. A polymerase chain reaction (PCR) test was evaluated for its feasibility as a diagnostic tool in abdominal tuberculosis (TB) in the Indian scenario. METHODS: PCR for the identification of M. tuberculosis amplified a 340 bp nucleotide sequence located within the 38 kDa protein gene of M. tuberculosis. Tissues for processing were obtained from patients suspected to have abdominal TB. These were from various sources such as abdominal lymph nodes, segments of intestine and bowel obtained at various times and in different ways such as laparoscopy, colectomy, bowel and lymph node resection. Fifty such patients had their tissues sent for PCR. RESULTS: PCR results were compared with histopathology (HP). Of the 50 samples, 31 were positive for abdominal TB by HP whereas 30 were positive by PCR. Twenty-four of these were positive for both HP and PCR while of the seven samples positive for HP, five were negative and two gave inhibition by PCR. Six samples negative by HP were positive by PCR. CONCLUSION: This study demonstrates that PCR can be used as an effective tool to diagnose abdominal TB.