Time-dependent effects of starvation on serum, pituitary and hypothalamic leptin levels in rats.

Leptin is produced by white adipose tissue and other cell types and is involved in both short- and long-term appetite control. Here we studied effects of starvation on serum, pituitary and hypothalamic levels of leptin during 72 h period. Each of the starved groups was sacrificed simultaneously with the group of ad libitum fed animals. The progression of the discrete starvation response phases was monitored by testing the blood glucose, free fatty acid, urea and corticosterone levels. Starvation caused biphasic increase in corticosterone and free fatty acid levels, and significant but transient decrease in urea and glucose levels. Starvation also abolished diurnal rhythm of changes in leptin concentrations in serum and hypothalamic and pituitary tissues. Only 6 h starving period was sufficient to lock serum leptin at low levels, whereas 12 h were needed to silence leptin production/secretion in hypothalamus for the whole examined period. In contrast, leptin production by pituitary tissues of starved animals required 24 h to reach minimum, followed by full recovery by the end of starvation period. These results indicate the tissue specific pattern of leptin release and suggest that the locally produced leptin could activate its receptor in pituitary cells independently of serum levels of this hormone.

Cancer-induced cachexia: a guide for the oncologist.

Cancer-induced cachexia (CIC) is a paraneoplastic syndrome that may account for up to 20% of deaths in cancer patients. Cachexia includes distinct metabolic changes that are the result of an acute-phase response (APR) mounted by the host as a reaction to tumor cells. These changes include increased muscle proteolysis, increased fat lipolysis, and increased hepatic production of acute-phase proteins such as C-reactive protein and fibrinogen. This APR pathogenesis is an important consideration in trying to treat cachectic patients as most therapies do not target the APR and its subsequent metabolic effects. Although there is currently no cure for CIC, the oncologist frequently encounters cachectic patients in practice, and evidence-based management is needed. We review the current data for assessment of starvation and cachexia, providing guidelines for management that include serum markers and functional assessment. In addition, a review of current therapies is provided, including hypercaloric feeding and nutritional intervention to address starvation, as well as data on appetite stimulants such as corticosteroids and megestrol acetate. Experimental therapies are also discussed, including nonsteroidal antiinflammatory drugs, tumor necrosis factor alpha antagonists, tetrahydrocannabinol, growth hormone, ghrelin, oxandrolone, and omega-3 fatty acids.

Hunger and malnutrition: the determinant of development: the case for Africa and its food and nutrition workers.

Hunger and malnutrition in Africa have been on the increase since 1960's reaching a climax in the 1980's when over 150 million people were affected by one form or another. Methods so far used to solve the problem do not seem to succeed, but the scientists and leaders in Africa could now take the opportunity to consider and act on the problem in their own way. The formation of an African food and nutrition group to work with others on the problems, could give an impetus to this kind of initiative. A call is made to all African food and nutrition workers to combine efforts to harness Africa resources, which have not been fully utilized in solving the problem.

PIP: Hunger and malnutrition in Africa have been on the increase since the 1960s. During the 1970s, it is estimated that 30 million people were directly affected by famine and malnutrition. About 5 million children died in 1984 alone. In Mozambique during the 1983-84 famine, about 100,000 people perished. In Ethiopia, Sudan, Somalia, Liberia, and Angola armed conflicts compound the problem. Ethiopia alone had 9 million famine victims in 1983. The most common form of malnutrition in Africa is protein energy deficiency affecting over 100 million people, especially 30-50 million children under 5 years of age. Almost another 200 million are at risk. Iron deficiency, commonly called anemia, also affects 150 million people, mostly women and children. Iodine deficiency leads to disorders like mental retardation, cretinism, deafness, abortion, low resistance to disease, and goiter and this affects 60 million with about 150 million more at risk. Vitamin A deficiency causes blindness and low resistance to disease and affects about 10 million. Protein energy deficiency is treated by using donated foods in hospitals, rehabilitation centers, day care centers, and feeding centers. There are no community programs for anemia, or vitamin A or iodine deficiencies. Vaccines for preventing and drugs for treating diseases that cause malnutrition are imported. Therefore, African food and nutrition professionals met in 1988 and created the Africa Council for Food and Nutrition Sciences (AFRONUS) to eliminate famine and malnutrition in Africa. Activities have started in: 1) developing contacts between the workers in food and nutrition; 2) assessing the situation of food and nutrition in Africa; 3) developing an action plan; 4) implementing the plan; and 5) monitoring progress. Food and Nutrition Policy Guidelines have also been prepared by AFRONUS for food and nutrition workers. Africa has enough natural resources to solve the problem of hunger and malnutrition, but these resources have to be harnessed.

Nutrition and cancer: physiological interrelationships.

There are many tumors that have paraneoplastic syndromes. Furthermore, location of certain tumors can result in very specific effects on the host, especially tumors in the hypothalamus, the intestinal tract, or the liver. Finally, tumors of the immune system can have significant distant consequences. However, from direct experimental evidence, from model systems, and from the utilization of nutritional manipulation in the treatment of cancer, the data suggest very strongly that there is no unique cancer malnutrition. Early diagnosed cancer does not show malnutrition as a presenting symptom. Furthermore, all metabolic disturbances can be explained on the basis of the metabolic differences of tumor cells and normal cells and are very frequently proportional to the bulk of the tumor. The cachexia that is associated with malignancies is more likely cachexia in cancer patients than it is a specific cancer cachexia, unless the tumor burden is very large. This point was clearly made in a short review of the causes of cachexia in nearly 1500 cancer patients in Russia (145). Brennan also feels that most cases of malnutrition are uncomplicated starvation, and cancer cachexia has many features seen in major injury or sepsis (16). This distinction has great implications in the management of cancer patients.

The impact of antitumor therapy on nutrition.

The treatment of the cancer patient by surgery, chemotherapy or radiation therapy can impose significant nutritional disabilities on the host. The nutritional disabilities seen in the tumor-bearing host from antitumor therapy are produced by factors which either limit oral intake or cause malabsorption of nutrients. The host malnutrition caused as a consequence of surgery, chemotherapy or radiation therapy assumes even more importance when one realizes that many cancer patients are already debilitated from their disease.

Liver vitamin A slow release syndrome in cattle with a multiple nutrient imbalance.

Data on liver vitamin A concentrations in malnourished, debilitated, down cattle in tropical, northern Australia support the hypothesis that 12% annual cattle mortality was due, in part, to a slow release of liver vitamin A. High Ca and low Zn levels in the legume forage apparently contributed to the slow release. The cattle showed marked sensitivity to sunlight and exhibited problems of sight. The malnourished yearling steers averaged 183.3 micrograms vitamin A/g wet liver vs 152.3 micrograms for steers slaughtered off good green wet season forage. Indications of a slow release of liver vitamin A were that: (1) only 4 to 7 micrograms vitamin A/g liver were in the alcohol fraction or release form; (2) after adjustments for decreases in liver and blood volume in starving animals, blood vitamin A was lowered to 18 micrograms/100 ml, which was low in relation to the adjusted liver vitamin A level of 91.7 micrograms/g, and (3) after adjustments, the liver had released only 1,667 units of vitamin A/day in the dry season, or about 1/4 of maintenance needs. The cattle were grazing a legume forage pasture containing 7.1% protein and no measurable carotene. The forage was deficient in Zn (25 ppm), which would slow the release of liver vitamin A. High Ca levels in the legume forage (.4 to .54%) in combination with low P levels (.11 to .18%) would further aggravate the low Zn level.