Effects of cysteine on the pharmacokinetics of docetaxel in rats with protein-calorie malnutrition.

The objective of this study is to report the effects of cysteine on the pharmacokinetics of intravenous and oral docetaxel in rats with protein-calorie malnutrition (PCM). The in vivo pharmacokinetics and in vitro hepatic/intestinal metabolism of docetaxel were assessed using control, CC (control with cysteine), PCM and PCMC (PCM with cysteine) rats. The effects of cysteine on the intestinal absorption of docetaxel were further investigated through in vitro transport studies using rat intestine and Caco-2 cell monolayers. The AUCs (the areas under the plasma concentration-time curve from time zero to time infinity) of intravenous docetaxel in PCM rats were significantly greater than in the control rats because of the significant decrease in the hepatic CYP3A. In PCMC rats, the elevated AUCs in PCM rats returned to control levels. The AUC(0-6 h)s of oral docetaxel in PCM rats were significantly smaller than that in the control rats, mainly due to the decrease in gastrointestinal absorption. In CC and PCMC rats, oral cysteine supplement enhanced the gastrointestinal absorption of docetaxel probably via intestinal P-gp inhibition. If the present rat data could be expressed to humans, the alterations in docetaxel absorption and metabolism should be considered in designing a dosage regimen for cancer patients with PCM state after cysteine supplement.

Bone turnover in malnourished children.

Pyridinoline (PYD) and deoxypyridinoline (DPD) are cross-linking aminoacids of collagen that are located mainly in bone and cartilage. When bone matrix is resorbed these cross-links are quantitatively excreted in the urine and therefore represent specific markers. We have measured the urinary excretion rate of PYD and DPD in 46 severely malnourished boys to assess their skeletal turnover and to relate this to their subsequent rate of growth. The children were aged 13 months (SD 6), and height-for-age was -3.6 (1.6) Z-score, and weight-for-height was -2.4 (0.8) Z-score. PYD excretion when malnourished and after "recovery" was 11.2 (4.6) nmol h-1m-2 and 32.2 (10.8) nmol h-1m-2 and DPD excretion was 2.6 (1.3) nmol h-1m-2 and 7.5 (3.0) nmol h-1m-2, respectively. The ratio of the two cross-links did not change with recovery. These data show that cartilage and bone turnover is much lower in the malnourished than in the recovered child. There was no difference in the degree of depression of turnover between the children with marasmus, marasmic-kwashiorkor, or kwashiorkor. The rate of height gain during recovery was significantly related to cross-link excretion, age, and weight-for-height on admission. These three factors accounted for 44% of the variance in the height velocity of the children. PYD and DPD excretion rate could be used to assess therapeutic interventions designed to alleviate stunting.

PIP: The Tropical Metabolism Research Unit at the University of the West Indies in Jamaica made anthropometric measurements of 46 13-month-old male infants to assess changes in bone resorption during malnutrition by measuring the urinary excretion rate of pyridinoline (PYD) and deoxypyridinoline (DPD) and to determine whether bone turnover is associated with recovery. Unit staff used standard methods to treat the malnourished boys, including an energy dense diet (cow's milk formulated from Perlargon and corn or coconut oil). Before treatment, their height-for-age stood at -3.6 Z-score and their weight-for-height was -2.4 Z-score. The rate of excretion of PYD and DPD in malnourished children was only about 33% of that after they recovered (11.2 nmol per hour per sq. meter vs. 32.2 nmol per hour per sq. meter and 2.6 nmol vs. 7.5 nmol per hour per sq. meter, respectively; p .001). Therefore, cartilage and bone turnover was considerably lower in the children when they were malnourished than when they recovered. Recovery did not alter the ratio of these 2 cross-link amino acids, however, suggesting that changes in endochondral growth relative to bone remodelling did not occur. The extent of depression in bone turnover was basically the same between children with marasmus, marasmic-kwashiorkor, or kwashiorkor. The rate of height gain of the children during recovery from malnutrition was significantly associated with age (p .001), PYD excretion at admission (p = .003), and weight-for-height at admission (p = .01), all 3 of which explained 44% of the variance in the rate of height gain of the children. Since this study demonstrated that PYD and DPD are associated with longitudinal growth in children recovering from malnutrition, more research on the effect of dietary manipulation on longitudinal growth should be done, which should define requirements for longitudinal growth and identify needed steps to prevent stunting.

Effect of caloreen supplementation on some haematological values and urinary iron excretion during protein-energy malnutrition.

The effect of caloreen (glucose polymer) supplementation on indicators of iron status during protein-energy malnutrition was studied. Sixty-four children with moderate protein energy malnutrition (PEM) were fed diets supplemented with caloreen or starch (control) for 14 days, following which iron status as packed cell volume (PCV), haemoglobin (Hb), serum iron, total iron binding capacity (TIBC), serum ferritin, and urinary iron levels were determined. Caloreen supplementation significantly increased (P less than 0.05). PCV, serum iron and serum ferritin and decreased (P less than 0.05) TIBC. Also, there was a tendency for Hb to increase and urinary iron to decrease in this group, but these changes were not statistically significant. Such changes were not observed in the starch-placebo-supplemented group. It is concluded that caloreen supplementation to PEM children increases body iron status. These increases in the indices of iron status may contribute to an early recovery of anaemia associated with PEM. Prolonged supplementation of a regular diet with glucose early in the development of PEM may retard the development and severity of anaemia in children.

[Calcium-creatinine in basal urine in relation to calcium intake and nutritional status in children under 3]. / Calcio/creatinina en orina basal en relación a la ingesta de calcio y al estado nutricional, en menores de tres años.

The calcium/creatinine ratio (Ca/Creat.) as an indicator of calcium nutritional status was evaluated in "basal urine" from 24 children comprised within the ages of three to 36 months during a 60-day period. The children were divided in normal or undernourished, according to Waterlow's classification. Children under 12 months of age were fed ad libitum with one of two commercial milk formulas, assigned according exclusively to the pediatric criterium. Children older than 12 months received milk besides the habitual hospital diet. In all cases the food intake was controlled and the calcium intake calculated. At the end of the study, basal urine was collected and calcium and creatinine determined. The results revealed that: a) In the normal children the Ca/Creat. ratio gradually decreased with age tending to a low value of 0.2 at the age of 36 months. The relationship between the Ca/Creat. ratio and the calcium intake showed a change in the slope when the requirements were met according to RNC (60 mg/kg/day); b) In undernourished children, the Ca/Creat. ratio was nearly constant whatever their age or calcium intake. The trend to approach the value of 0.2 for calcium intake (about 250 mg/kg/day), however, and the absence of the inflexion point, would suggest that the requirements of these children are far higher than the NRC recommendation, and that the change of the slope would be found for intakes over those obtained in our study. According to these findings, we conclude that the Ca/Creat. ratio in basal urine does not reflect calcium intake, but would depend on the bone calcium turnover. Consequently, it would be a simple and useful indicator of calcium nutritional status.

Hyperalimentation of the cancer patient with protein-calorie undernutrition.

Because protein-calorie undernutrition is common in patients with neoplastic disease, nutritional support is often recommended. It is uncertain, however, that methods of supplemental alimentation successful in noncancerous subjects are suitable in cancer patients. We measured elemental balances, serum proteins, anthropometrics (triceps skinfold and mid-arm muscle area), and creatinine/height ratio in 15 undernourished patients with advanced cancer and in 10 noncancer undernourished controls during central venous or enteral hyperalimentation and found the following. (a) During central venous hyperalimentation, cancer patients showed significantly less improvement than the noncancerous controls in body weight (median increment, 5 kg in cancer patients and 8.5 kg in noncancerous), albumin (0.1 g/dl in cancer patients and 0.5 g/dl in noncancerous patients), creatinine/height ratio (4% of standard in cancer and 10% of standard in noncancer), and mid-arm muscle area (4% of standard in cancer and 11% of standard in noncancer). During enteral hyperalimentation, gains in body weight and albumin by cancer patients were significantly inferior to those in noncancerous subjects. Triceps skinfold increments, in contrast, were similar during both central venous and enteral hyperalimentation for cancer and noncancerous patients. (b) While nitrogen retention was similar in cancer and noncancer patients, the cancer group retained significantly less magnesium and phosphorus (delta Mg in cancer patients, 3.2 mEq/day central, -2.7 mEq/day enteral; delta Mg in noncancer patients, 11.9 mEq/day central, 10.1 mEq/day enteral; delta P in cancer patients, 0.13 g/day central, 0.07 g/day enteral; delta P in noncancer patients, 0.27 g/day central, 0.33 g/day enteral). The poorer balances of cancer patients were caused by increased urinary, not fecal, loss. These findings indicate a partial block in repletion of lean body mass or abnormal composition of newly deposited lean body mass when undernourished patients with advanced cancer receive hyperalimentation.

Therapeutic index of nutritional depletion in hospitalized patients.

A creatinine height index, which compares the creatinine excretion of a patient with that of an idealized normal adult of the same height, was used to assess protein status in 30 young males serving as controls and 11 malnourished male surgical patients, eight on a metabolic ward and three on a general surgical ward. The mean creatinine height index was 1.09 in the normal males and 0.50 in the 11 who were malnourished, a difference which is highly significant, p less than 0.005. The creatinine height index was more sensitive than other measures of nutritional status in this study, which included weight for height, nitrogen balance and serum albumin levels. These results suggest a role for this technique in the nutritional assessment of the surgical patient, which must play an increasing role in the critical care of this patient population.