A new potential cyclooxygenase-2 inhibitor, pyridinic analogue of nimesulide

In this paper, the binding mode of original pyridinic compounds structurally related to nimesulide, a preferential cyclooxygenase (COX)-2 inhibitor, is analyzed by docking simulations in order to understand structure-activity relationships of this family. Structural modifications are proposed to reverse the selectivity of the more active inhibitor of the series characterized by a preferential activity on COX-1. On the basis of these modifications, a new compound with a bromo substituent was designed and showed a COX-2 selective inhibition.     

Apoptosis and proliferation kinetics of T cells in patients having experienced antiretroviral treatment interruptions

Multiple failures of antiretroviral treatments, as a result of multidrug-resistant virus, have led to a proposal for structured therapeutic interruptions (STI). However, a significant decrease in CD4+ T cells may occur. The aim of our study was to determine the kinetics of T cell subpopulation changes, T cell apoptosis and peripheral blood mononuclear cell proliferation after STI. The impact of resistance mutation disappearance on T cell apoptosis was also studied. Ten patients were enrolled prospectively, and blood sampling was performed at weeks 0, 2, 4, 6, 8 and 12. The mean increase in viral load was 1.3 log(10) copies/ml, ranging from 0.1 to 3.2. CD4+ T cell count decreased to a mean of 80 cells/mm(3) from baseline to week 12. In the same period, CD8+ T cells decreased to a mean of 139 cells/mm(3). A significant increase in both T cell apoptosis and proliferation of mononuclear cells was observed. However, proliferation was an early and brief event. The increase in CD4+ T cell apoptosis was obvious in patients exhibiting complete reversion of resistance mutations to antiviral drugs. Our results suggest that during STI, apoptosis is an overwhelming phenomenon compared with proliferation, and may explain the limited immunological impact of this therapeutic option.     

Detection of carbamyl phosphate synthetase 1 deficiency using duodenal biopsy samples

The activity of urea cycle enzymes was assayed in duodenal biopsy specimens obtained from a female infant who presented with neonatal hyperammonaemia. All enzyme levels were normal except N-acetyl glutamate-dependent carbamyl phosphate synthetase 1 (CPS1) which was half the mean activity in normal control specimens. A similar deficiency of CPS1 was also shown in duodenal specimens from the patient's mother who became slightly symptomatic after relatively high protein meals and during pregnancy, and had spontaneously modified her diet to one with protein restriction. The patient is growing normally on a dietary regimen similar to that spontaneously adopted by her mother. Urea cycle enzyme activity in the duodenal biopsy material from the controls was similar to that found in the normal human liver and appears to have distinct advantages as a means of assaying for urea cycle defects in patients with hyperammonaemia and their relatives.     

Antibodies to diphtheria, tetanus and pertussis in infants before and after immunization with DTP (Triple Antigen) vaccine

Objective : To determine antibody levels to the Australian manufactured combined diphtheria, tetanus and pertussis (DTP) vaccine (Triple Antigen, CSL Ltd) in infante before and after their primary immunization course.
Methodology : Serosurvey (antibody prevalence study) in two groups: infants aged 5-9 weeks who had not received any immunizations ( n = 25), and infants aged 7-10 months who had received two ( n = 25) or three immunizations ( n = 57) with DTP, sampled from infants attending the Royal Children's Hospital, Melbourne, either as inpatients or outpatients between February and April 1993. The immunization history for each infant was determined from hospital records, the parent-held child health record, or the local council or family doctor who immunized the infant.
Results : Enzyme immunoassay (EIA) of antibodies to diphtheria and tetanus showed all infants to have adequate protective levels after two or three vaccinations (£0.01 IU/mL). All subjects who had received all three DTP vaccinations had detectable antibody to at least one pertussis antigen. Antibodies to the pertussis antigens filamentous haemagglutinin and pertussigen (pertussis toxin) were comparable to levels determined for whole cell pertussis vaccines used elsewhere in the world. EIA-determined antibodies to pertussis agglutinogen type 2 and agglutinogen type 3 showed substantially higher geometric mean titres when results for pre-immunization and post-immunization subjects were compared.
Conclusions : These data show that the Australian manufactured DTP vaccine has immunogenic properties similar to those of vaccines used elsewhere, and that antibody concentrations following immunization are at levels consistent with efficacy.     

A Third world international health elective for U.S. medical students. The 16-year experience of the State University of New York,Health Science Center at Brooklyn

The Department of Preventive Medicine and Community Health at the State University of New York, Health Science Center at Brooklyn (SUNY, HSCB) instituted an eight-week third world international health elective for fourth year medical students in 1980. Since that time, ninety students have participated. The purposes of this elective are to provide fourth year medical students with an opportunity to observe and study the structure and functions of a health care delivery system in a third world country, to provide medical service, and to have a crosscultural experience. The emphasis in this elective is on public health, preventive medicine, and primary care. There is a high level of student competition for this elective, with 46.9% of applicants having been accepted over a fifteen-year period. Although women comprise 40% of the average medical school class, they represent 50% of participants in this elective program. The percentage of African-American and Hispanic students has been 20%. These two minority groups represented from 8% to 10% of the student body during the period under study. Careful screening, including an examination of academic records and personal interviews, has resulted in the selection of highly motivated, adaptable, and dedicated students who have performed well at overseas sites. Student satisfaction levels with this elective are extremely high, with most rating it the best experience of their medical school years. Students undergo extensive preparation prior to going overseas. This covers issues related to individual health and safety, travel and lodging, and the nature of the host country culture, health care system, and assignment site. Our students are especially experienced at cross-cultural understanding because of the unusual diversity of the patients they treat in Brooklyn, and the ethnic diversity of local hospital staffs and the medical school class. This Brooklyn experience in cross-cultural understanding has been cited by many participants as having been the best preparation for functioning in a foreign culture. The Alumni Fund of the College of Medicine has strongly and consistently supported this elective both with philosophical commitment and financial grants to help defray travel costs. This type of support is unusual among medical schools in New York City. Overseas preceptors have willingly given of their time and institutional resources to make these experiences available and meaningful for students.