Rapid Body Weight Loss Research Articles

A Case of Malignant Peritoneal Mesothelioma in Young Man

We report a rare case of malignant peritoneal mesothelioma associated with intestinal obstruction due to peritoneal disseminated metastasis in young man. The patient in early thirties admitted due to exacerbated abdominal pain and rapid body weight loss in Jan 2003. Elevated levels of WBC, CRP and serum CA125 were observed. Barium enema showed marked compression of the transverse colon and the sigmoid colon. Abdominal Computed Tomography examination revealed diffusely thickened peritoneal tumor adjacent to the liver and the spleen. Laparotomy showed a thickened peritoneal tumor and multiple disseminated tumor in large area of the intraperitoneal organs. Construction of catheter cecostomy for intestinal obstruction was underwent. Histopathologically, the tumor was diagnosed as malignant mesothelioma by immunohistological examinations and electron microscopy. The patient received palliative treatment but died 3 months after diagnosis. Autopsy revealed wide spread metastases occupying large part of peritoneal cavity, which involved liver, spleen and gastrointestinal tracts. The unique progressive feature in this rare neoplasm is evaluated and refered to the literature in this report.

Neural plasticity is impaired in cold-exposed hippocampal slices from senescent but not from age-matched presenescent F344 rats

Near the end of their natural life, many mammals enter a terminal state identifiable by a rapid loss of body weight resulting from hypophagia. This study extends characterization of this senescent state by comparing viability of metabolic mechanisms supporting neural plasticity in hippocampal slices from 24 to 30 month old senescent and age-matched presenescent (body-weight stable) F344 male rats. Half of the slices from each rat were incubated at 22–23 °C, and half were immersed in cool incubation medium (12–15 °C) immediately after slicing and allowed to passively warm to room temperature over ∼50 min to impose a cold stressor on recovery mechanisms. Following incubation, CA1 pyramidal cell population spike (PS) amplitudes were measured before and after tetanus. In slices incubated at 22–23 °C, the 221.0±24.2 % increase in PS amplitude following tetanus in seven slices from five senescent rats was not significantly different from the 202.5±23.8% increase in six slices from five age-matched presenescent rats. In contrast, in cold-exposed slices, the 133.8±13.1% increase in PS amplitude following tetanus in 14 slices from 10 senescent rats was significantly smaller ( p<0.05) than the 184.7±10.2% increase in 13 slices from seven age-matched presenescent rats. This smaller PS enhancement in senescent rats cannot be attributed to weight loss because robust potentiation was induced in cold-exposed slices from five food-restricted presenescent rats having a weight loss comparable to their senescent counterparts. Thus, the blunted enhancement observed in cold-exposed slices appears to be a characteristic of senescence.

Multigenic control of disease severity after virulent Mycobacterium tuberculosis infection in mice.

Following challenge with virulent Mycobacterium tuberculosis, mice of the I/St inbred strain exhibit shorter survival time, more rapid body weight loss, higher mycobacterial loads in organs, and more severe lung histopathology than mice of the A/Sn strain. We previously performed a genome-wide scan for quantitative trait loci (QTLs) that control the severity of M. tuberculosis-triggered disease in [(A/Sn x I/St) F1 x I/St] backcross-1 (BC1) mice and described several QTLs that are significantly or suggestively linked to body weight loss. In the present study we expanded our analysis by including the survival time phenotype and by genotyping 406 (A/Sn x I/St) F2 mice for the previously identified chromosomal regions of interest. The previously identified 12-cM-wide QTL on distal mouse chromosome 3 was designated tbs1 (tuberculosis severity 1); the location of the QTL on proximal chromosome 9 was narrowed to a 9-cM interval, and this QTL was designated tbs2. Allelic variants of the tbs2 locus appeared to be involved in control of both body weight loss and survival time. Also, the data strongly suggested that a QTL located in the vicinity of the H-2 complex on chromosome 17 is involved in control of tuberculosis in mice of both genders, whereas the tbs1 locus seemed to have an effect on postinfection body weight loss in female mice. Interestingly, these loci appeared to interact with each other, which suggests that there might be a basic genetic network for the control of intracellular parasites. Overall, linkage data reported here for F2 mice are in agreement with, and add to, our previous findings concerning the control of M. tuberculosis-triggered disease in the BC1 segregation.

Leptin and Obesity

Leptin burst onto the scene in 1994 and transformed research into obesity and energy balance. Immediately, hopes were raised that this peptide, secreted by adipose tissue, might be causally related to human obesity, and that the regulatory mechanisms underlying its action might be manipulated for therapeutic benefit. In the last 6 years, the concentrated effort of the research community, both academic and commercial, has made enormous strides towards understanding the full range of physiological effects of leptin. In the mouse, leptin deficiency (ob/ob) induces hyperphagia, massive obesity and diabetes. Administration of leptin protein reverses this phenotype and results in rapid bodyweight loss, mainly in the form of fat. Leptin also modestly reduces food intake and bodyweight in normal lean rodents on systemic administration. Leptin is much more potent when administered directly into the cerebroventricular system of the brain. This observation, and the identification of leptin receptor expression in hypothalamic nuclei with an established regulatory function in energy homeostasis, confirms the CNS as a primary site of action of leptin. A number of leptin-sensitive, receptor-expressing hypothalamic neurons of different neurochemical phenotype have been identified, and leptin receptor mRNA and protein are widespread elsewhere in the mammalian brain. Leptin provides two forms of feedback to regulatory systems in the brain, a dynamic reflection of diurnal feeding pattern (where it may interact with satiety signals), and a basal level of secretion encoding body fat storage (a plausible lipostat). The absence of leptin is a potent signal of starvation, and in this state reduced leptin feedback regulates the activity of compensatory neuropeptide systems in the hypothalamus to drive the voluntary hyperphagia displayed by rodents when released back to ad libitum feeding. Despite the initial excitement over the therapeutic potential of leptin, these expectations have now begun to wane. Assessments of the value of leptin, and of potential therapies based on its activities, are now more realistic and may involve targeting of specific subpopulations of individuals, or particular weight loss strategies. This review focuses deliberately upon the possible exploitation strategies that are still patent.

Immunotherapy of a murine T cell lymphoma localized to the brain.

Mouse YC8 T cell lymphoma was used as a model to determine whether an effective immunotherapy procedure could be devised for the treatment of lymphoma localized to the brain. Implantation of 5 x 10(4) YC8 cells into the left cerebral hemisphere induced rapid loss of the animal's body weight. Severe loss of weight and early deaths were observed in the untreated control group. Although resistance can be conferred to the brain by immunization of naive BALB/c mice, adoptive chemoimmunotherapy procedures were surprisingly not effective in inducing remissions in animals with lymphoma confined to the brain. Even passive transfer of effector cells from immunized, tumor resistant donor animals combined with systemic IL-2 treatment did not impart resistance to recipients with brain tumors. However, regression of the intracranial tumor and apparent cures could be accomplished, when ex vivo cultured effector cells were transferred intravenously.

Severity of tuberculosis in mice is linked to distal chromosome 3 and proximal chromosome 9.

Genetic factors play a role in host response to infection with Mycobacterium tuberculosis, the number one infectious killer worldwide. Mice of the inbred strains I/St and A/Sn show significant differences in disease severity after intravenous injection of a lethal dose of the virulent human isolate M. tuberculosis H37Rv. Following challenge with H37Rv, only I/St mice have rapid body weight loss and short survival times. A genome wide analysis for linkage with body weight after M. tuberculosis H37Rv infection was done in (A/SnxI/St)F1xI/St mice. Among females, quantitative trait loci (QTLs) on chromosomes 9 and 3 were significantly linked to postinfection body weight (logarithm of the odds ratio [LOD] scores of 6.68 and 3.92, respectively). Suggestive linkages were found for QTLs on chromosomes 8 and 17 (LOD scores of 3.01 and 2.95, respectively). For males, QTLs on chromosomes 5 and 10 showed suggestive linkages (LOD scores of 3.03 and 2.31, respectively). These linkages can be used to identify candidate regions for tuberculosis susceptibility loci in the human genome.

Alterations of Lipid and Cholesterol Metabolism in Cachectic Tumor-Bearing Rats Are Prevented by Insulin

The ascites hepatoma Yoshida AH130 causes in the host a rapid and progressive body weight loss, associated with reduced food intake, and protein and lipid hypercatabolism. Because insulin regulates glucose as well as lipid and protein metabolism, we suggest that the observed alterations are at least in part secondary to hypoinsulinemia and/or to the increase of counterregulatory hormones in AH130-bearing rats. To verify this hypothesis, controls with free access to food (n = 4), controls with free access to food plus insulin (107 μmol · kg body wt−1 · d−1) (n = 4), controls pair-fed to the tumor-bearing rats (n = 4), pair-fed controls treated with insulin (n= 4), tumor hosts (n = 9), and tumor hosts treated with insulin (n = 6) were used. The Yoshida ascites hepatoma cells (∼108 cells/rat) were inoculated intraperitoneally. Daily food intake and body weight were measured; insulin was injected starting the day of tumor implantation for 6 d. The metabolism of both cholesterol and lipids was investigated in tumor cells, and ascitic fluid and blood serum were investigated at the end of treatment. Insulin prevented the reduction of food intake (19 ± 0.6 vs. 13 ± 0.4 g/d, P < 0.01; AH130 hosts treated and not treated with insulin, respectively), the loss of body weight (202 ± 12 vs. 135 ± 9 g, P < 0.01), lowered the circulating triglycerides (48.3 ± 4.9 vs. 84.5 ± 7.1 mmol/L, P < 0.01), and free fatty acids (561 ± 47 vs. 989 ± 54 mmol/L (P < 0.01), while corrected the decrease of adipose lipoprotein lipase activity (1,240 ± vs. 300 ± pmol FA, P < 0.01) observed in AH130 hosts. Moreover, insulin prevented the decrease in HDL cholesterol (13.2 ± 0.8 vs. 9.3. ± 0.7 mmol/L, P < 0.01) and significantly increased hepatic cholesterol synthesis as evaluated by 14C-acetate incorporation into cholesterol, in both liver (3,337 ± 245 vs. 830 ± 115 Bq/g, P < 0.01) and AH130 cells (11,676 ± 1,693 vs. 4,196 ± 527 Bq/106 cells, P < 0.01). Thus insulin treatment ameliorated many metabolic derangements, with a lengthening of rats survival time (7 ± 1 vs. 11 ± 1 d, P < 0.05) without significantly stimulating tumor growth. These data, together with our previous observations on the effectiveness of insulin on protein turnover perturbations, suggest that many metabolic alterations occurring during cancer cachexia can be avoided by the administration of this hormone.

Alterations in endogenous circadian rhythm of core temperature in senescent Fischer 344 rats.

We assessed whether alterations in endogenous circadian rhythm of core temperature (CRT) in aging rats are associated with chronological time or with a biological marker of senescence, i.e., spontaneous rapid body weight loss. CRT was measured in male Fischer 344 (F344) rats beginning at age 689 days and then continuously until death. Young rats were also monitored. The rats were housed under constant dim red light at 24-26 degrees C, and core temperature was recorded every 10 min via biotelemetry. The CRT amplitude of the body weight-stable (presenescent) old rats was significantly less than that of young rats at all analysis periods. At the onset of spontaneous rapid weight loss (senescence), all measures of endogenous CRT differed significantly from those in the presenescent period. The suprachiasmatic nucleus (a circadian pacemaker) of the senescent rats maintained its light responsiveness as determined by an increase in c-fos expression after a brief light exposure. These data demonstrate that some characteristics of the CRT are altered slowly with chronological aging, whereas others occur rapidly with the onset of senescence.

Brown adipose tissue thermogenesis during aging and senescence.

We have found that cold- and norepinephrine-induced brown adipose tissue (BAT) nonshivering thermogenesis (NST) is significantly lower in old male Fischer 344 rats and is associated with the decreased ability of these animals to maintain homeothermy. This decline in BAT thermogenesis is not as great in females. Although the mechanism(s) underlying this gender difference in the age-related decrease in brown fat NST are not completely elucidated, they do not appear to reflect decreased sympathetic neural activity of BAT in the older males vs. females. Rather, our investigations, strongly suggest that the blunted cold-induced heat production of BAT reflects less functional BAT. The fact that the older animals have less functional BAT than do their younger counterparts may predispose them to the accumulation of excess body fat. Our studies have also found that near the end of the natural life of these rats, they enter a state of senescence that can be identified by spontaneous rapid body weight loss, resulting from decreased food intake. In this state, the rats are considerably more susceptible to cold than are comparably aged presenescent (body weight stable) rats of the same chronological age. The greater hypothermia exhibited by the senescent vs. presenescent rats during cold exposure is associated with a significant reduction in the amount of functional brown fat and in the amount of heat each brown fat cell can generate. It is the intent of this review to discuss the findings of these investigations.

Effects of successful adenomectomy on body composition in acromegaly.

The purpose of the present study was to investigate postsurgical change in body composition in patients who have undergone surgery for acromegaly. Eight patients with acromegaly had determination of serum GH, insulin-like growth factor-I (IGF-I), height, body weight, and bioelectric impedance before surgery and at 2 weeks, 1 month, 3 months, and 6 months after surgery. Body composition was analyzed by bioelectric impedance analysis (BIA). We analyzed body fat (BF), body lean mass (BLM), body cell mass (BCM), total body water (TBW), intracellular water (ICW) and extracellular water (ECW). The serum GH concentration and IGF-I had decreased significantly 2 weeks after surgery. Body weight had decreased significantly 1 month after surgery and recovered 3 months after surgery. BIA showed that TBW and BCM had decreased significantly 2 weeks after surgery. BF gradually increased up to 1 month after surgery and was increased significantly at 3 months after surgery. The percent ratio of TBW/body weight decreased and the percent ratio of BF/body weight increased during the 6 months after surgery. The percent ratio of ECW/TBW did not change during the 6 months following surgery. In conclusion, the rapid body weight loss which occurred within 2 weeks after surgery was caused by decreases in TBW and BCM. The recovery of body weight, which was seen later than 1 month after surgery, was caused by an increase in BF. The postoperative change in body composition in acromegaly ceased 3 months after surgery.

New Xenograft Model of Multiple Myeloma and Efficacy of a Humanized Antibody Against Human Interleukin-6 Receptor

AbstractA new xenograft model of multiple myeloma (MM), where growth is strongly regulated by interleukin-6 (IL-6), was established in severe combined immunodeficiency (SCID) mice. In this model, endogenous IL-6 from SCID mice was ineffective at eliciting growth of the established human MM cell line KPMM2; these cells achieved autonomous growth through their autocrine secretion of IL-6. The etiopathology in this disease model is consistent with that of human MM. When greater than 3 × 106 KPMM2 cells were injected intravenously (IV), tumors developed in all mice and were predominantly localized in their bone marrow. Tumors were also apparent in the lymph nodes, but absent from other organs. Immunostaining of cell surface antigen (CD38) showed that more than 40% of bone marrow cells in femur were of myeloma origin in the advanced stage of tumor progression (day 37). Histologic analysis of these mice show that bone marrow was largely occupied by plasmablastic cells and bones had developed osteolytic lesions at multiple sites. Concurrently, there was a decrease in bone density throughout the body and a significant increase in ionized plasma calcium. M-protein was detected in the serum within 10 days after transplantation, which correlated with the tumor progression. Between 30 and 40 days after the transplantation, mice presented with a rapid and severe loss of body weight, hind leg paralysis, and fatigue. Subsequently, the mice died within a week. A single IV injection of 0.2 mg humanized anti–IL-6 receptor antibody (hPM1) into mice on the day after tumor transplantation substantially suppressed the elevation of serum M-protein and development of the tumor-associated abnormalities and significantly increased in the life span of tumor-bearing mice. Our data show the usefulness of this model to analyze the pathologic role of IL-6 in MM and the efficacy of targeting the IL-6 receptor in IL-6–dependent KPMM2 cells.

New Xenograft Model of Multiple Myeloma and Efficacy of a Humanized Antibody Against Human Interleukin-6 Receptor

A new xenograft model of multiple myeloma (MM), where growth is strongly regulated by interleukin-6 (IL-6), was established in severe combined immunodeficiency (SCID) mice. In this model, endogenous IL-6 from SCID mice was ineffective at eliciting growth of the established human MM cell line KPMM2; these cells achieved autonomous growth through their autocrine secretion of IL-6. The etiopathology in this disease model is consistent with that of human MM. When greater than 3 × 106 KPMM2 cells were injected intravenously (IV), tumors developed in all mice and were predominantly localized in their bone marrow. Tumors were also apparent in the lymph nodes, but absent from other organs. Immunostaining of cell surface antigen (CD38) showed that more than 40% of bone marrow cells in femur were of myeloma origin in the advanced stage of tumor progression (day 37). Histologic analysis of these mice show that bone marrow was largely occupied by plasmablastic cells and bones had developed osteolytic lesions at multiple sites. Concurrently, there was a decrease in bone density throughout the body and a significant increase in ionized plasma calcium. M-protein was detected in the serum within 10 days after transplantation, which correlated with the tumor progression. Between 30 and 40 days after the transplantation, mice presented with a rapid and severe loss of body weight, hind leg paralysis, and fatigue. Subsequently, the mice died within a week. A single IV injection of 0.2 mg humanized anti–IL-6 receptor antibody (hPM1) into mice on the day after tumor transplantation substantially suppressed the elevation of serum M-protein and development of the tumor-associated abnormalities and significantly increased in the life span of tumor-bearing mice. Our data show the usefulness of this model to analyze the pathologic role of IL-6 in MM and the efficacy of targeting the IL-6 receptor in IL-6–dependent KPMM2 cells.

Relationship between cold-induced thermoregulation and spontaneous rapid body weight loss of aging F344 rats.

We previously showed that, although cold-induced thermoregulation is attenuated in 26-mo-old male Fischer 344 (F344) rats, not all rats this age exhibit the same degree of cold-exposed hypothermia or diminished brown adipose tissue nonshivering thermogenic capacity. Examination of this heterogeneity suggested the hypothesis that it was associated with a difference in the physiological state between aged rats that were maintaining stable body weight versus those showing the rapid weight loss often occurring near the end of the rat's natural life span. To test this, we acutely exposed male F344 rats to cold (4 h at 6 degrees C) beginning at 24 mo of age. This exposure was weekly for the first 2 wk and then on alternate weeks as long as the rat's body weight was stable. If body weight progressively declined for 3-5 consecutive days, the rat's response to the acute cold exposure was again measured, as was that of two additional rats not displaying this rapid loss in body weight. If body temperature decreased during the cold exposure to intraperitoneal temperatures < or = 32.5 degrees C, the rat was killed with pentobarbital sodium and interscapular brown adipose tissue was removed. One of the age-matched controls was also killed at this time. The age at which body weight showed a spontaneous rapid decline ranged from 24.5 to 29 mos. All eight rats displaying spontaneous rapid weight loss had significant hypothermia during the acute cold exposure, whereas none of the eight weight-stable rats did. The development of hypothermia in the spontaneous rapid weight loss group was not, in general, observed before their weight loss. The weight loss and hypothermia were associated with lower levels of brown fat uncoupling protein and significant changes in body fat and protein. These data suggest that the development of senescence-related hypothermia occurs rapidly and is not a simple function of chronological age or the median life span of the animals. Furthermore, these data imply that the rate of aging in terms of maintenance of thermoregulatory homeostasis has both a gradual and rapid component, the latter being associated with a different physiological state than the former.

Lack of effect of eicosapentaenoic acid in preventing cancer cachexia and inhibiting tumor growth

It has been recently reported that a diet enriched in n-3 polyunsaturated fatty acids reduces the growth of different kinds of tumors as well as the host tissue hypercatabolic state frequently associated. The rat ascites hepatoma Yoshida AH-130 is a fast growing tumor that causes a rapid and progressive body weight loss in the host and tissue waste associated with a hypercatabolic condition. Plasma levels of classical hormones and humoral mediators (prostaglandin E2 and tumor necrosis factor-α) are early perturbed after tumor transplantation (Tessitore L., Costelli P. and Baccino F.M. (1993) Humoral mediation for cachexia in tumour-bearing rats. Br. J. Cancer, 67, 16–23). Enhanced protein degradation rates and alteration of lipoprotein lipase activity mainly account for the wasting of protein and adipose mass, respectively. However, the daily intragastric administration of eicosapentaenoic acid (1.5 g/kg body wt) to AH-130 bearing rats was completely ineffective either in preventing tissue waste or in reducing tumor growth. The low degree of differentiation and the high growth rate of the AH-130 hepatoma probably account for this lack of effect.

Muscle catabolism in lean and obese zucker rats fed a very low calorie diet

In this study we examined the adaptations of adult lean and obese Zucker rats to a very low calorie diet (VLCD) or simple starvation. Lean rats were fed the VLCD or starved until they lost 31% of their starting weight. Obese rats were subjected to the same two treatments until they had lost about 52% of their initial weight. Weights of five skeletal muscles, three fat pads, and three organs were determined. Compared to the lean rats, obese rats relied to a greater extent on catabolism of fat stores for energy and to a lesser extent on lean body mass during both types of food restriction. Obese rats on the VLCD lost significantly less skeletal muscle, but not cardiac muscle, than the starved rats. Both the VLCD and starved groups experienced a 27–28% loss of cardiac muscle mass. This “protein-sparing” effect of the VLCD was seen in both the tissue weights and protein contents of skeletal muscle. Lean rats were not as capable of minimizing muscle losses during the rapid body weight loss due to the VLCD. In conclusion, obese Zucker rats have an enhanced ability to conserve skeletal muscle when fed a VLCD, but cardiac muscle is not “spared” in the same manner as skeletal muscle.

Weight loss and metabolic changes of morbidly obese patients after gastric partitioning operation

Weight loss, alterations in basal metabolic rate, and utilization of body fat, carbohydrate, and protein substrates were studied in nine patients before operation and 3 and 12 months after gastric partitioning operation for morbid obesity. Respiratory oxygen consumption and carbon dioxide excretion measurements were taken three consecutive mornings by the open circuit-Scholander technique. Measurements of urine urea nitrogen were made from 24-hour urine collections. Basal metabolic rate and utilization of fat, carbohydrate, and protein were calculated in kilocalories per minute by indirect calorimetry. Initial body weight was 124.5 +/- 19.0 kg (mean +/- SD). The weight losses between measurements at months 0 and 3 and at months 3 and 12 were 20.8 +/- 4.6 kg and 2.7 +/- 8.4 kg, respectively. Total weight loss between months 0 and 12 was 23.5 +/- 8.3 kg (19.3% +/- 7.4%). At 3 months the fraction of basal metabolic rate contributed by carbohydrate (p less than 0.05) and protein (p less than 0.01) utilization decreased significantly, while that contributed by fat increased (p less than 0.05). Between months 0 and 12 there was no significant difference in protein or carbohydrate utilization, but fat utilization increased (p less than 0.10).Gastric partitioning operation resulted in an initial rapid body weight loss over 3 months with a sustained reduction over 1 year; there was a metabolic utilization shift to fat with carbohydrate and protein sparing; no metabolic parameter was predictive of weight loss; and temporally, the rapid weight loss was paralleled by a significant metabolic utilization shift, and the sustained loss was paralleled by a stabilization of this shift.

Burn trauma induces anorexia and aberrations in CNS amine neurotransmitters.

A 30% surface area, full-thickness, open-flame burn of guinea pigs induced significant anorexia and rapid loss of body weight. Analysis of regional brain concentrations of amine neurotransmitters suggested burn-specific elevation of serotonergic neurotransmission, reduction of dopamine metabolism, and elevation of norepinephrine concentrations in brain areas thought to control feeding. These data suggest that specific regional aberrations in each of these amine neurotransmitters may contribute to the anorexia associated with major thermal injury.

Arginine: An Essential Amino Acid for the Cat

The essentiality of arginine for the near-adult cat was demonstrated in three preliminary and two main experiments. In the pre liminary experiments, changing cats (body weights all in excess of 1.6 kg) from a purified diet containing a complete amino acid mixture (basal) to a similar isonitrogenous diet without arginine ( —Arg) caused rapid loss of body weight ( mean ±SE93.3 ±6.8 g in the first 24 hours ), emesis, and inappetance. In the main experiments the mean ±SE body weight of the cats was 2.6 ±0.4 kg. When eight of these cats were given the —Argdiet after an overnight fast, they all exhibited emesis, had tetanic spasms, and one died. Other symptoms included hypersalivation, depression which in some cases was followed by hyperesthesia, hyperactivity, ataxia, and dyspnea. The plasma of these cats showed hyperammonemia and hyperglycemia indicating that the clinical condition was caused by acute ammonia intoxi cation. The eight cats given the comparable diet with arginine showed no ill effects. Five cats given the basal diet with ornithine replacing arginine on an equimolar basis showed neither an increase in plasma ammonia nor glucose concentrations. Cats given the —Argdiet had extremely low 120 minute post-prandial levels of plasma free arginine (less than one-quarter of the prefceding level ). It was concluded that the cat lacks the ability to synthesize ornithine. The consequence of this metabolic deficiency in the cat is that arginine is an essential nutrient: it provides a unique example of a nutrient so critical that one meal without dietary arginine may result in death. The —Argdiet supported growth in young rats, albeit at a slower rate than rats fed the basal diet. J. Nutr. 108: 1944-1953, 1978. INDEXING

Albumin Catabolism Measurement by a Double Tracer Technique in Uraemic Patients During a Single Dialytic Treatment*

Abstract. In order to explain the pathogenesis of protein depletion in chronic uraemia, 13 measurements of albumin catabolism were performed in uraemic patients undergoing haemo‐or peritoneal dialysis treatment, during either the early phase or steady uraemic state.Catabolism was determined during a single haemo‐or peritoneal dialysis by a double tracer technique (Human Serum Albumin and sodium iodide labelled with two different isotopes of iodine). The output from both albumin and iodine systems was measured in the dialysis solution flowing out from the peritoneum or artificial kidney. The radioactive iodide arising in dialysate from albumin breakdown was concentrated by the use of an anion exchange resin.Catabolic rate was three times the normal in 3 patients showing clinical features of hypercatabolism (true rapid loss of body weight) in the early phase of uraemia, or during relapse of it; albumin turnover rate returned to normal in 2 of these patients, when measured during clinical steady state conditions. This behaviour suggests highly increased catabolism, not counterbalanced by a correspondingly increased synthesis, as the cause of albumin depletion in chronic uraemia.

Albumin Catabolism Measurement by a Double Tracer Technique in Uraemic Patients During a Single Dialytic Treatment*

Abstract. In order to explain the pathogenesis of protein depletion in chronic uraemia, 13 measurements of albumin catabolism were performed in uraemic patients undergoing haemo‐ or peritoneal dialysis treatment; during either the early phase or steady uraemic state.Catabolism was determined during a single haemo‐ or peritoneal dialysis by a double tracer technique (Human Serum Albumin and sodium iodide labelled with two different isotopes of iodine). The output from both albumin and iodine systems was measured in the dialysis solution flowing out from the peritoneum or artificial kidney. The radioactive iodide arising in dialysate from albumin breakdown was concentrated by the use of an anion exchange resin.Catabolic rate was three times the normal in 3 patients showing clinical features of hypercatabolism (true rapid loss of body weight) in the early phase of uraemia, or during relapse of it; albumin turnover rate returned to normal in 2 of these patients, when measured during clinical steady state conditions. This behaviour suggests highly increased catabolism, not counterbalanced by a correspondingly increased synthesis, as the cause of albumin depletion in chronic uraemia.