Effects of fat content on fat hedonics: cognition or taste?

Understanding and perhaps overriding preferences for fat is important, given the relationship between higher dietary fat consumption and poorer health. We have examined the roles of potential mechanisms for differences in fat preference: actual fat content and expected fat content. The subjects were women (n=192, ages=50-69) recruited to a study of low-fat dietary change. Subjects were randomized to one of the four cells: participants received either a high- or low-fat milkshake at baseline, and half of each group was told that their milkshake was low in fat and the other half high in fat. Women who received a high-fat milkshake consumed more grams than women who received a low-fat milkshake. Women who expected low-fat shakes reported liking them more than those who expected high-fat milkshakes. These data indicate that both physiology and cognition play a role in determining consumption of high- and low-fat foods.     

Effects of incentive items on participation in a randomized chemoprevention trial

Behavioral research has an important role in increasing and maintaining participation in disease prevention trials, both in interventions and in follow-up visits. We conducted a randomized experiment among participants in the lung cancer chemoprevention trial, CARET (Carotene and Retinol Efficacy Trial) to test the effects of providing two incentives on retention. The items used for this study were a Certificate of Appreciation and one of two lapel pins, provided in a 2 2 design. Providing incentives, whether alone or in combination, had no statistically significant effect on retention by the two-year follow-up point. The successful implementation of this randomized incentive study has two implications for future research: (1) study of behavioral interventions and issues is feasible in the context of large controlled trials of disease end-points; and (2) such study is necessary to determine whether selected incentives can increase retention.     

A behavioral approach to increasing calorie consumption in children with cystic fibrosis

To increase calorie consumption of 5 mildly malnourished children with cystic fibrosis (CF), intervention was implemented in multiple baseline fashion across snack and three meals. Intervention involved nutritional education establishing gradually increasing calories goals, teaching parents contingency management strategies, and a reward system for achieving calorie goals. Following 6 treatment sessions, the children's calorie intake increased across meals and total calorie intake was 25 to 43% above baseline. The calorie increase was maintained at 9-month follow-up. Significant changes in weight and height were made during treatment and the year following intervention. The results suggest that the long-term oral intake of children with CF can be modified by a short-term behavioral intervention.     

Inhibition of heparin/protamine complex-induced complement activation by Compstatin in baboons

Complement activation products are major components of the inflammatory response induced by cardiac surgery and cardiopulmonary bypass which contribute to postoperative organ dysfunction, fluid accumulation, and morbidity. Activation of the complement system occurs during extracorporeal circulation, during reperfusion of ischemic tissue, and after the formation of heparin-protamine complexes. In this study we examine the efficacy of Compstatin, a recently discovered peptide inhibitor of complement, in preventing heparin/protamine-induced complement activation in baboons. The study was performed in baboons because Compstatin binds to baboon C3 and is resistant to proteolytic cleavage in baboon blood (similar to humans); Compstatin inhibits only the activation of primates' complement system. After testing various doses and administration regimens, Compstatin produced complete inhibition at a total dose of 21 mg/kg when given as a combination of bolus injection and infusion. Compstatin completely inhibited in vivo heparin/protamine-induced complement activation without adverse effects on heart rate or systemic arterial, central venous, and pulmonary arterial pressures. This study indicates that Compstatin is a safe and effective complement inhibitor that has the potential to prevent complement activation during and after clinical cardiac surgery. Furthermore, Compstatin can serve as the prototype for designing an orally administrated drug.     

Effect of peroral immunization of humans with Streptococcus mutans on induction of salivary and serum antibodies and inhibition of experimental infection

Naturally occurring antibodies reactive with Streptococcus mutans whole cells were assayed in whole saliva, parotid saliva, and blood samples collected from eight human volunteers. The levels and serotypes of indigenous S. mutans in plaque and whole saliva samples were also determined. After baseline sampling the teeth were cleaned and the subjects were inoculated with streptomycin-resistant S. mutans strains Ingbritt (serotype c) and OMZ65 (serotype g). The level of implantation and duration of colonization were determined in plaque and saliva, and antibodies reactive with these strains were monitored in saliva and serum. After the implanted bacteria were shed, the subjects wee immunized by the daily ingestion of an enteric-coated capsule containing 25 mg of Formalin-killed, freeze-dried OMZ65 cells for 3 days and inoculation was repeated. The levels of antibodies and of implantation and the duration of colonization were monitored as before. One month after the bacteria could no longer be detected, the immunization and inoculation cycle was repeated except that the subjects were immunized for 7 days. Five of the eight subjects were successfully colonized by strains Ingbritt and OMZ65. The remaining three did not become colonized with either strain. Strain OMZ65 implanted at a higher level than did strain Ingbritt. Oral immunization did not result in a detectable antibody response in saliva or serum to whole bacterial cells. However, after both the first and second immunizations there were marked reductions in the peak levels of infection and the duration of colonization of both OMZ65 and Ingbritt.     

Health and disease in context: a community-based social medicine curriculum.

Despite the increasing attention paid to the role of social forces in determining health, most physicians finish their training ill-prepared to address these issues. The authors describe their efforts to fill that training gap for internal medicine residents at Oregon Health and Science University through a community-based social medicine curriculum, designed in 2006 in conjunction with community partners at Central City Concern (CCC), an organization addressing homelessness, poverty, and addiction in downtown Portland, Oregon. The challenge was to develop a curriculum that would (1) fit within the scheduling constraints of an established categorical internal medicine residency program, (2) give all internal medicine residents a chance to better understand how social forces affect health, and (3) help show how they, as health professionals, might intervene to improve health and health care. The authors maintain that by developing this curriculum with community partners--who took the lead in deciding what residents should learn about their community and how they should learn it--the residency program is providing a relatively brief but extremely rich opportunity for residents to engage the personal, social, and health-related issues experienced by clients served by CCC.The authors first provide a brief overview of the curriculum and describe how the principles and practices of community-based participatory research were used in its development. They then discuss the challenges involved in teaching medical residents about social determinants of health, how their academic-community partnership approaches those challenges, and the recently established methods of evaluating the curriculum.     

Leptin resistance in mice is determined by gender and duration of exposure to high-fat diet

Mice fed a high-fat diet are reported to be resistant to peripheral injections of leptin. We previously failed to induce leptin resistance in female mice fed a high-fat diet for 15 weeks. Therefore, we measured the responsiveness to peripheral infusions (10 microg/day) of leptin, and the responsiveness to third ventricle injections of leptin (1 microg) in male and female NIH Swiss mice fed low-fat (10% kcal) or high-fat (45% kcal) diets. Male and female 15-week-old mice that had been fed low- or high-fat diet from 10 days of age lost fat during a 13-day intraperitoneal infusion of leptin and lost weight in response to a single central injection of leptin. Fifteen-week-old male mice fed a high-fat diet for 5 weeks did not lose body fat during a peripheral infusion of leptin and did not lose weight in response to a central injection of leptin. Female mice fed high-fat diet for 5 weeks remained leptin-responsive. Weight loss was achieved without a significant voluntary decrease in food intake, suggesting that both peripherally and centrally administered leptin increases energy expenditure. These results demonstrate that the development of leptin resistance in NIH Swiss mice fed a high-fat diet is dependent upon the gender of the mice and either the duration of exposure to high-fat diet or the age at which the mice are first exposed to the diet.     

Relationship between dose of methotrexate, apoptosis, p53/p21 expression and intestinal crypt proliferation in the rat

Abstract Previous studies have shown that apoptosis is induced by cytotoxic chemotherapy and precedes hypoproliferation of intestinal crypt cells. However, the relationship between the degree of intestinal apoptosis and crypt cell hypoproliferation may not be directly related. The purpose of this study was to investigate the relationship between apoptosis and hypoproliferation with increasing doses of chemotherapy. Eleven groups of breast cancer-bearing DA rats were treated with two doses of methotrexate (MTX) i. m. at varying concentrations (0.5, 1.5, 2.5 and 5.0 mg/kg) or saline (control). Animals were killed at 6 or 24 h following treatment. The small and large intestines were examined for apoptosis, villous area (small intestine), crypt length and mitotic count per crypt. Immunohistochemical expression of p53 and p21^waf1/cip1 (p21) were examined quantitatively. Data were analysed using Peritz F-test. Low dose MTX (0.5 mg/kg) did not change p53 expression at 6 h but induced a 15-fold increase in apoptosis in the crypts of the small intestine. This was associated with only a minor reduction in crypt cell proliferation. Higher doses of MTX increased p53 expression and caused a lower (7-fold) but more prolonged peak of apoptosis that was accompanied by reduced villous area, shortened crypts and a more profound reduction in crypt cell proliferation. Unlike the small intestine, apoptosis in the colon was 10-fold lower, proportional to the dose of MTX and did not induce overt damage. Expression of p21 did not change with any dose at either timepoint. We conclude that apoptosis is not always associated with crypt cell hypoproliferation and that the small intestine can recover after low dose MTX despite a heightened peak of apoptosis of crypt cells.