Low-density lipoprotein as a carrier of antitumoral drugs: in vivo fate of drug-human low-density lipoprotein complexes in mice

Previous studies have demonstrated that human leukemic cells and certain cancer cells in culture have a higher uptake of plasma low-density lipoprotein (LDL) than the corresponding normal cells. Therefore LDL has been proposed as a drug carrier for anticancer agents. In the present investigation, we have developed a method to incorporate a lipophilic derivative of doxorubicin, N-trifluoroacetyladriamycin-14-valerate, into LDL. The method involves lyophilization of LDL in the presence of sucrose as protective agent and gives an N-trifluoroacetyladriamycin-14-valerate-LDL complex containing about 100 drug molecules per LDL particle. The in vivo fate of the complex in mice as judged from the disappearance from plasma and accumulation in organs was similar to that of native LDL. When cultured human fibroblasts were incubated with N-trifluoroacetyladriamycin-14-valerate-LDL, cellular drug accumulation was dependent on the LDL receptor activity of the cells. The covalent linkage of two anthracycline derivatives to lysine residues of LDL yielded conjugates with drug/LDL molar ratios ranging up to 80. With increasing substitution, there was a progressive decline in the affinity of the conjugate for the LDL receptor in vitro. The in vivo fate of such conjugates was quite similar to that of native LDL. We conclude that it is possible to associate cytotoxic agents with LDL without interfering with its in vivo behavior.     

The Bridge to Health Project: a collaborative model for assessing the health of a community.

The Bridge to Health Project, a collaborative effort of 70 health related organizations, was designed to collect population-based health status data about approximately a half million residents in a primarily rural region in northeast Minnesota and northwest Wisconsin. Funding and staff support were provided by a regional medical center. The importance of sound survey methodology, role clarification, adequate staff support, and a well organized process to foster collaboration have applicability to other regions considering a collaborative process of health status assessment.     

Attitudes of Australian pharmacists towards practice-based research

Background and objective: The aim was to conduct a national cross‐sectional survey of randomly selected Australian pharmacists to determine their attitudes towards and involvement in pharmacy practice research. This included the canvassing of perceived barriers and potential solutions to promote research activity in pharmacy practice. Methods: A questionnaire was developed around those used in UK and Australasian studies of general practitioners’ attitudes towards research. Questions assessed attitudes to research, involvement in research, barriers and facilitators to involvement, self‐assessed understanding of research terminology, and access to and use of electronic bibliographic databases. One thousand pharmacists were randomly and proportionately selected from the State and Territory Pharmacy Board registers to receive the anonymous questionnaire by mail. Non‐respondents were sent a follow‐up reminder and second copy of the questionnaire after 3 weeks. Results: A response rate of 37% was achieved. Approximately, one‐third of responding pharmacists were presently, or had been, involved in research activities, and generally reported positive experiences. Lack of time and never being approached or not being aware of the opportunities were major barriers to pharmacist participation in research. Approximately, one‐third of the pharmacists were not interested in participating in research. There was low usage of publicly available electronic bibliographic databases and of scientific journals. Although there was overwhelming recognition of the value of research to the profession, few pharmacists possessed a good understanding of key terms related to research and evidence‐based practice (e.g. P‐value or number needed to treat). Conclusion: There was overwhelming recognition of the value of research to the pharmacy profession. Important factors encouraging individual pharmacists to participate in research were a desire to improve the profession, the opportunity to learn more about disease management and to provide enhanced services to patients, and personal interest.     

Weight gain as a barrier to smoking cessation among military personnel.

PURPOSE: To assess the relationships between active-duty military status, military weight standards, concern about weight gain, and anticipated relapse after smoking cessation. DESIGN: Cross-sectional study. SETTING: Hospital-based tobacco cessation program. SUBJECTS: Two hundred fifty-two enrollees, of 253 eligible, to a tobacco cessation program in 1999 (135 men, 117 women; 43% on active duty in the military). MEASURES: Independent variables included gender, body mass index (weight/height2), and military status. Dependent variables included about weight gain with smoking cessation and anticipated relapse. RESULTS: In multivariate regression analyses that controlled for gender and body mass index, active-duty military status was associated with an elevated level of concern about weight gain (1.9-point increase on a 10-point scale; 95% confidence interval [CI], 1.0- to 2.8-point increase), as well as higher anticipated relapse (odds ratio [OR] = 3.6; 95% CI, 1.3 to 9.8). Among subjects who were close to or over the U.S. Air Force maximum allowable weight for height, the analogous OR for active-duty military status was 6.9 (p = .02). CONCLUSIONS: Occupational weight standards or expectations may pose additional barriers for individuals contemplating or attempting smoking cessation, as they do among active-duty military personnel. These barriers are likely to hinder efforts to decrease smoking prevalence in certain groups.     

Clinical trials of solcoseryl in the treatment of parodontium diseases

The effect of Solcoseryl on the clinical state of the parodontium was assessed in 26 patients aged from 18 to 57 years with the diagnosis of deep parodontopathies. Each patient received 30 ampoules of 2 ml of Solcoseryl for one course of the treatment. Submucous injections of the drug near the teeth 13, 23, 33 and 43 were done as follows: during the first 10 days one ampoule daily, then 10 injections every other day, and 10 injections at three-day intervals. The condition of the parodontium was assessed before and after the treatment by means of the PI, GI, GBI and teeth mobility indices, and measurements of the depth of gingival pouches--K, and volume of fluid in pouches SFFR according to Brill. The therapeutic method applied in these cases had a good effect on reduction of gingivitis, bleeding and volume of secreted pouch fluid but had only a small effect on teeth mobility and depth of gingival pouches.     

Bleeding peptic ulcer. Epidemiology and nonsurgical management

Bleeding peptic ulcer remains an important problem, particularly for the elderly. Recognition of the rule of nonsteroidal anti-inflammatories in bleeding ulcer and employment of endoscopic therapeutic modalities offer promise that morbidity and mortality from bleeding ulcer may be reduced.