Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum testosterone concentrations are frequently in the low-normal range (lowest quartile, <500 ng/dl) in men with AIDS-wasting syndrome (AWS) and in other chronic wasting disorders. The response of patients in this group to androgen treatment has not been determined, however. Eighteen men with AWS (mean +/- standard error [SE]: 87% +/- 1% usual body weight; CD4 count 90 +/- 24) and borderline low serum testosterone concentrations (382 +/- 33 ng/dl) completed a 21-day placebo-controlled inpatient metabolic ward study comparing intramuscular (i.m.) placebo (n = 7) with low-dose (65 mg/week; n = 4) and high-dose (200 mg/week; n = 7) nandrolone decanoate, a testosterone analogue. Nitrogen balance, stable isotope-mass spectrometric measurement of de novo lipogenesis (DNL), resting energy expenditure, and gonadal hormone levels were measured. Both low-dose and high-dose nandrolone resulted in significant nitrogen retention (33-52 g nitrogen/14 days, representing gains of 0.5 to 0.9 kg lean tissue/week) compared with placebo (loss of 11 g nitrogen/week). This was reflected biochemically in a borderline significant reduction of high DNL (p < .06). Serum testosterone and gonadotropins were suppressed whereas resting energy expenditure was unchanged by nandrolone treatment. In 10 study subjects completing a 12-week open-label follow-up phase, body weight increased by 4.9 +/- 1.2 kg, including 3.1 +/- 0.5 kg lean body mass, and treadmill exercise performance also improved. In summary, nandrolone decanoate therapy in the absence of an exercise program in borderline hypogonadal men with AWS caused substantial nitrogen retention compared with placebo, similar in extent to the nitrogen retention previously achieved with recombinant growth hormone. It is reasonable to expand the criteria for androgen treatment in AWS to include at least patients in the lowest quartile of serum testosterone.
 ...
PMID:Effects of nandrolone decanoate therapy in borderline hypogonadal men with HIV-associated weight loss. 1004

The case mortality for severe malnutrition in childhood remains high, but established best approaches to treatment are not used in practice. The energy and protein content of the diet at different stages of treatment appears important, but remains controversial. The effect on growth, urea kinetics and the urinary excretion of 5-L-oxoproline was compared between a standard infant formula (HP group) provided in different quantities at each stage of treatment and a recommended dietary regimen, which differentiates the requirements of protein and energy during the acute phase of resuscitation (maintenance intake of energy and protein, relatively low protein to energy ratio, LP group) from those during the restoration of a weight deficit (energy and nutrient dense). The energy required to maintain weight was less in the HP than the LP group, but the HP group was not able to achieve as high an energy intake during repletion of wasting because of the high volume which would have had to be consumed. Compared to the LP group, in the HP group during catch-up growth there was significantly greater deposition of lean tissue and higher rates of urea production, hydrolysis and salvage of urea-nitrogen. These, together with higher rates of 5-L-oxoprolinuria, suggest a greater constraint of the formation of adequate amounts of nonessential amino acids, especially glycine, in the face of enhanced demands. Although more effective rehabilitation might be achieved using a standard formula, there is the need to determine the extent to which it might impose metabolic stress compared with the modified formulation.
 ...
PMID:Dietary protein, growth and urea kinetics in severely malnourished children and during recovery. 1022 88

The immunosuppressive drug cyclosporine A (CsA) exhibits significant nephrotoxicity. Disturbance of magnesium (Mg) homeostasis may be an important component of this nephrotoxicity. It has been suggested that transmigration of Mg from plasma to tissues may be an important component of CsA-induced alterations in Mg homeostasis. In this study, CsA nephrotoxicity in male Wistar rats was investigated and alterations in Mg homeostasis along with other indices of toxicity were assessed. Animals were dosed daily for 14 days i.p. with CsA (20 mg/kg body weight). Control animals received vehicle alone. CsA toxicity was evidenced by i) lower gain in body weight, ii) reduced thymus/body weight ratio, iii) increased blood urea nitrogen and creatinine, iv) a tendency for reduced plasma magnesium and v) increased urinary Mg excretion and greatly increased fractional excretion of Mg. Tissue Mg analysis did not reveal any changes in thymus or skeletal muscle Mg while Mg in kidney tissue tended to be reduced. Electron microscopy revealed some damage in renal tubules of rats treated with cyclosporine including translucent cytoplasm, vacuolization, rounded and swollen mitochondria, damage to brush border and disruption of basal infoldings. These results indicate that direct renal tubular damage may result from CsA exposure. No evidence was found for CsA-induced movement of Mg from plasma to tissues. CsA-induced altered renal handling of Mg and this renal Mg wasting may be an important consequence of the nephrotoxicity.
 ...
PMID:Cyclosporine A-induced alterations in magnesium homeostasis in the rat. 1022 85

The objective of this investigation was to determine the influence of distinct forms of acute weight loss on the expression of the quiescence marker, CD45RA, by T cells in several lymphoid compartments including the blood. Male and female weanling mice, CBA/J and C57BL/6J strains, were allocated to the following groups: ad libitum intake of a complete purified diet; restricted intake of the complete diet; and ad libitum intake of an isocaloric low-protein diet. The restricted intake protocol produced weight loss through energy deficiency (marasmic-type malnutrition), whereas the low-protein diet caused wasting through inadequate protein nitrogen and induced a condition mimicking incipient kwashiorkor. In one experiment, weanling mice of both strains were maintained for 14 days according to each of these dietary protocols and, in a supplementary study, C57BL/6J weanlings consumed either the complete diet or the low-protein diet ad libitum for 21 days. Zero-time control groups (19-days old and 23-days old in C57BL/6J and CBA/J strains, respectively) were included in the first experiment to control for ontogeny-related change. Expression of CD45RA was assessed by two-colour flow cytometry in CD4+ and CD8+ T cells from the spleen, mesenteric lymph nodes and blood. Within 14 days, energy-restricted mice exhibited a high percentage of CD4+ T cells expressing CD45RA in all three lymphoid compartments in both mouse strains (an average of 50% CD45RA+ versus 9% in well-nourished controls), and a similar outcome was apparent in the CD8+ subset (93% CD45RA+ versus 63%). Mice fed the low-protein diet required up to 21 days to exhibit the same imbalance within the CD4+ T-cell subset (33% CD45RA+ versus 4% in well-nourished controls). A shift toward a quiescent phenotype occurs throughout the peripheral T-cell system in acute wasting disease. Consequently, the quiescence-activation phenotype of blood T cells reflects the same index in secondary lymphoid organs in such pathologies. Naive-type quiescence among T cells is implicated as a component of depressed adaptive immunocompetence in the advanced stages of diverse forms of acute weight loss.
 ...
PMID:T cells with a quiescent phenotype (CD45RA+) are overabundant in the blood and involuted lymphoid tissues in wasting protein and energy deficiencies. 1023 2

Testosterone-induced nitrogen retention in castrated male animals, eunuchoidal men, pre-pubertal boys and women, and the sex-related differences in the size of the muscles between male and female animals, have been cited as evidence that testosterone has anabolic effects. Recent studies have reported that replacement doses of testosterone in hypogonadal men and supraphysiological doses in eugonadal men increase fat-free mass, muscle size and strength. These effects have provided the rationale for exploring these anabolic applications in sarcopenic states. Although emerging data demonstrate modest gains in fat-free mass in HIV-infected men given replacement doses of testosterone, we do not know whether testosterone supplementation can produce clinically meaningful changes in muscle function and disease outcome in patients with wasting disorders.
 ...
PMID:Androgen effects on body composition and muscle function: implications for the use of androgens as anabolic agents in sarcopenic states. 1033 59

We have shown previously that chronic hyperchloremic metabolic acidosis (CMA) induces severe negative nitrogen balance and renal phosphate depletion and decreases serum insulin-like growth factor-1 (IGF-1) in association with growth hormone (GH) insensitivity in humans. The present study investigated whether acidosis-induced renal nitrogen wasting and renal phosphate depletion are mediated by GH insensitivity/low IGF-1 and thereby responsive to GH treatment. The effects of GH on acidosis-induced changes in divalent cation metabolism and acidosis-induced hypothyroidism were also investigated. CMA (delta[HCO3], -10.5 mmol/L) was induced in six healthy male subjects ingesting 4.2 mmol NH4Cl/kg body weight [BW]/d for 7 days. Recombinant human GH (0.1 U/kg BW/12 h subcutaneously) was administered for 7 days while acid feeding was continued. GH increased serum IGF-1 from 22.1 +/- 1.4 to 87 +/- 8.4 nmol/L (control level, 36.4 +/- 2.2). GH decreased urinary nitrogen excretion, resulting in a cumulative nitrogen retention of 2,404 mmol, thereby correcting the acidosis-induced cumulative increase in nitrogen excretion (2,506 mmol) despite continued acid feeding. GH attenuated the acidosis-induced hyperphosphaturia (cumulative phosphate retention, 91 mmol) and corrected the hypophosphatemia. GH did not affect acidosis-induced ionized hypercalcemia, but further exacerbated acidosis-induced hypercalciuria (cumulative loss, 27.3 mmol). GH significantly further increased serum 1,25-dihydroxyvitamin D (1,25(OH)2D) and further decreased intact PTH (from 10 +/- 1 to 6 +/- 1 pg/mL). Acidosis also induced hypomagnesemia and hypermagnesuria (cumulative loss, 9.4 mmol, ie, renal magnesium wasting), a novel finding, which was significantly attenuated by GH (cumulative retention, 5.0 mmol). In conclusion, GH corrected acidosis-induced renal nitrogen wasting, which may be caused, at least in part, by decreased IGF-1 levels. GH further increased serum 1,25(OH)2D and the systemic calcium load, which account for the suppression of parathyroid hormone (PTH) despite renal PO4 retention and correction of hypophosphatemia. GH attenuated acidosis-induced renal magnesium wasting.
 ...
PMID:Growth hormone corrects acidosis-induced renal nitrogen wasting and renal phosphate depletion and attenuates renal magnesium wasting in humans. 1038 Nov 52

Substantial losses of total body protein (TBP) can occur in chronic diseases and in aging. Such losses impact negatively on immunity and quality of life, and on growth rates in children. Direct measurements of total body nitrogen (TBN) monitor the integrated changes in TBP over time and allow comparison with normal subjects. TBN assessment via neutron capture analysis is therefore the gold-standard method of TBP estimation, so that risk factors for protein deficit can be identified and patient management optimized. The nitrogen index (NI) can be used to predict prognostic outcome: an NI < 0.9 is associated with substantial wasting in HIV disease, an NI < 0.8 predicts significant pathophysiology in chronic renal failure, and a low NI is predictive of neutropenia in breast-cancer patients. These findings emphasize the central importance of adequate protein stores in recovery from disease or in maintaining quality of life. Aging appears to involve a gradual loss of TBP throughout adulthood. Cross-sectional data suggest that TBP declines curvilinearly with age, such that there is an accelerated decline after 65 years of age. However, longitudinal data are scarce, and little is known about the relative loss of visceral protein, as opposed to skeletal muscle protein. More clearly-defined data are essential if the effects of aging per se are to be separated from the effects of chronic disease. A further complication is the knowledge that physical activity also declines with age. Thus sarcopenia, the loss of skeletal muscle mass, could primarily result from disuse rather than aging. The economic impact of unsuccessful aging places a pressing need for multicompartment data in longitudinal study designs.
 ...
PMID:Total body protein in chronic diseases and in aging. 1086 69

Cachexia is frequently associated with advanced or terminal cancer states, but it can also develop early during the course of neoplastic disease. This syndrome, which is characterized by body weight loss and negative nitrogen balance, significantly affects patient survival and quality of life. Studies on experimental models have shown that a complex interplay of different factors, such as anorexia, classical hormones, cytokines and other less well defined factors, concur in causing tissue wasting. On the basis of these results, it has been possible to prevent the onset of experimental cachexia by targeting therapeutic interventions at the underlying metabolic perturbations. Anticytokine treatments, either acting centrally or peripherally, have received particular attention, and are currently reaching the stage of clinical trials.
 ...
PMID:Cancer cachexia: from experimental models to patient management. 1087 Dec 30

Data show that starved head-injured patients lose sufficient nitrogen to reduce weight by 15% per week. Class II data show that 100-140% replacement of resting metabolism expenditure with 15-20% nitrogen calories reduces nitrogen loss. Data in non-head injured patients show that a 30% weight loss increased mortality rate. Class I data suggests that nonfeeding of head-injured patients by the first week increases mortality rate. The data strongly support feeding at least by the end of the first week. It has not been established that any method of feeding is better than another or that early feeding prior to 7 days improves outcome. Based on the level of nitrogen wasting documented in head-injured patients and the nitrogen sparing effect of feeding, it is a guideline that full nutritional replacement be instituted by day 7.
 ...
PMID:The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Nutrition. 1093 99

This is a brief review of human immunodeficiency virus (HIV)-associated wasting with expanded discussion of one treatment agent, oxandrolone. HIV-associated wasting is the involuntary loss of more than 10% of baseline body weight in the presence of chronic diarrhea, weakness, or fever lasting longer than 30 days. For patients, this clinical syndrome has special importance because it affects not only their survival but also their physical appearance and social interactions. Pharmacologic treatment is only one of the many approaches that need to be explored in every patient who presents with this condition. In 1964, oxandrolone became the first drug approved for the treatment of wasting. Since then its role has expanded to HIV-associated wasting. As an anabolic agent oxandrolone reverses many of the metabolic abnormalities characteristic of HIV-associated wasting leading to dose dependent increase in nitrogen retention. Similar to many other HIV treatments, gaps exist in our knowledge of the role of oxandrolone in HIV-associated wasting. These gaps will be filled only by years of field exposure and further clinical research.
 ...
PMID:HIV-associated wasting: brief review and discussion of the impact of oxandrolone. 1097 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>