Biomedical subjects

M Muscaritoli

Publications and source records attributed to M Muscaritoli.

47 records · Page 3Linked to original sources

PubMedDate not supplied

Exogenous lipid clearance in compensated liver cirrhosis.

The tolerance to exogenous fats has been evaluated in patients with liver cirrhosis. A three-stage lipid clearance test with continuous infusion (3 hr) of a triglyceride emulsion, Intralipid, was performed on 10 patients with well compensated liver cirrhosis and 10 normolipidemic volunteers. During the infusion, blood samples were collected for the measurement of particulate triglycerides (TG) by nephelometry; samples were also collected for total TG, free fatty acids (FFA) and free tryptophan (TRP) determinations. Plasma endogenous triglycerides were calculated as the total minus exogenous, particulate, TG. The fractional removal rate (K2) and the maximal clearing capacity (K1) for exogenous TG were lower in patients than in controls, though a significant difference (p less than 0.05) was found only for K1. Endogenous TG and FFA showed a comparable rise in patients and controls during Intralipid infusion. A significant increase in free TRP was noted in cirrhotics upon maximal infusion rate. It is concluded that: in patients with well compensated liver cirrhosis the maximal clearing capacity (K1) for exogenous TG is impaired. Nonetheless, moderate amounts of fat may be removed at a normal rate from the bloodstream; a normal synthesis rate of exogenous TG may be maintained even in a severely damaged liver; considering the possible role of free TRP in the pathogenesis of hepatic encephalopathy (HE), the use of large amounts of lipids should be discouraged in patients with decompensated liver cirrhosis, or even avoided in those with impending or overt HE.

Adult↗

PubMedDate not supplied

Abnormal substrate metabolism and nutritional strategies in cancer management.

Impairment of the nutritional state plays a major role in the morbidity and mortality of cancer patients. However, the opportunity of providing artificial nutritional support to these patients is still debated, because of the concern that energy substrates administered to replete the host may concomitantly stimulate tumor growth. A correct nutritional approach to cancer patients should thus be based on a thorough knowledge of both host and tumor metabolic needs and host-tumor metabolic interactions. Specific modifications of plasma levels of glucogenic, aromatic, sulfur-containing and branched-chain amino acids have been demonstrated in cancer patients, indicating a specific influence of the tumor on amino acid metabolism. Little is known about protein metabolism in neoplastic tissue. Interference with tumor growth has been attempted by deprivation of single amino acids with controversial results. Increased gluconeogenesis and insulin resistance are responsible for the two main abnormalities in carbohydrate metabolism in cancer patients, namely increased glucose turnover and impaired glucose tissue disposal. Lipid metabolism is also affected by the neoplasm: soluble factors such as "lipid-mobilizing factor" lead to increased fat mobilization from adipose tissue; plasma elimination of exogenous triglycerides has also been found to be reduced probably because of a tumor-related decrease in lipoprotein lipase activity. The differences in glucose and fat utilization between tumor and host should be considered in the nutritional approach to cancer patients. Data in this respect are controversial and have been obtained only in experimental animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbohydrate Metabolism↗

PubMedDate not supplied

The early cancer anorexia paradigm: changes in plasma free tryptophan and feeding indexes.

Tumor growth is accompanied by an anorexia mediated by humoral factors that appear to influence appetitive mechanisms in the brain. Because tumor resection is followed by resumption of normal food intake, the circulating anorexigenic substance(s) are produced either by the neoplastic tissue or by the host in response to the tumor. Increased levels of plasma free tryptophan and plasma ammonia have been proposed to mediate cancer anorexia. With animal models, it is often difficult to ascertain whether changes in food intake depend upon metabolic changes or the progressively increasing tumor mass per se. The feeding patterns and biochemical changes that occur during tumor growth were evaluated in 96 male Fischer rats that were inoculated with 10(6) methylcholanthrene sarcoma cells or saline (controls). Rats were placed into metabolic cages equipped with an Automated Computerized Rat Eater Meter to continuously determine meal size and meal number. Plasma free tryptophan and ammonia were evaluated 6, 10, 16, 18, 22, and 26 days after tumor inoculation. Anorexia developed by day 17-18, when food intake started to decrease via a decrease in meal size but not meal number and reached 60% of control by day 26. However, long before anorexia developed, free tryptophan was significantly higher 6 days after tumor inoculation, and the greatest increase occurred after 18 days. Ammonia did not differ from control at any time. Data confirm tumor-associated increases in plasma free tryptophan that occurred before the manifestation of anorexia and support a possible role of brain serotonin in cancer anorexia.

Ammonia↗

PubMedDate not supplied

[Pathogenetic and therapeutic aspects of secondary anorexia].

Anorexia is an often underrated symptom in the clinical management of patients suffering from chronic diseases. Moreover, the anorexia accompanying chronic diseases (secondary anorexia) is often confused with anorexia nervosa, a typically neuropsychiatric disorder involving completely different pathogenic mechanisms and therapeutic strategies. Secondary anorexia is one of the main factors responsible for the development of malnutrition, which in turn negatively affects patient morbidity and mortality. Different mechanisms have been proposed to explain the pathogenesis of secondary anorexia. However, consistent experimental and clinical evidence seems to point to hypothalamic serotonergic system hyperactivity as a preeminent cause; this hyperactivity appears to be triggered by enhanced brain availability of tryptophan, the aminoacid precursor of serotonin. The hyperactive hypothalamic serotonergic system might also represent the final effector where different regulatory and modulating pathways, including cytokines, converge. The involvement of tryptophan and the hypothalamic serotonergic system is further supported by the effectiveness of a therapeutic strategy, based on the inhibition of tryptophan entry into the brain, in increasing the food intake of anorectic patients. Although these results represent an encouraging approach to the treatment of secondary anorexia, with possible beneficial effects on the nutritional status of patients, they need to be validated in larger trials.

Adolescent↗

PubMedDate not supplied

Increased plasma free tryptophan levels in human cancer: a tumor related effect?

High free tryptophan (F-TRP) plasma levels are found in cancer patients (CP). F-TRP plasma concentrations are affected by the levels of its carrier, albumin (ALB), and free fatty acids (FFA) competing with TRP for ALB binding sites. The lack of correlation between F-TRP, ALB and FFA in CP suggests a tumor-dependent effect on the rise in F-TRP. To verify this hypothesis, F-TRP, ALB and FFA levels were assayed in 12 lung and 16 breast CP susceptible to radical surgery, before and 15 days after surgical removal of the tumor. F-TRP levels significantly decreased after tumor ablation. Since no correlation was found between F-TRP, ALB and FFA variations, it is conceivable that the tumor itself may be responsible for the high F-TRP levels in CP.

Adult↗

PubMedDate not supplied

Plasma clearance of exogenous lipids in patients with malignant disease.

Abnormalities in lipid metabolism have been widely described in cancer-bearing patients and animals. In particular, the presence of the tumor seems to profoundly affect triglyceride (TG) utilization by interfering with lipoprotein lipase (LPL) activity. Exogenous TG plasma clearance was evaluated in 10 nonmalnourished patients with cancers of various origin and 10 normolipidemic volunteers by means of a three-stage intravenous lipid clearance test. This technique allows precise determination of both the fractional removal rate (K2) and the maximal clearing capacity (K1) for exogenous lipids. Mean K2 values (min-1) were found to be significantly reduced in cancer patients compared with control subjects (0.07 +/- 0.006 vs 0.13 +/- 0.013 SEM, p less than 0.005). K1 values (mumol/L/min) were also found to be significantly lower in cancer patients than in the control group (109.43 +/- 6.3 vs 143 +/- 6.3 SEM, p less than 0.01). The data obtained indicate that the capacity to eliminate exogenous lipids from the bloodstream is reduced in cancer-bearing patients. This may be the consequence of a tumor-related impairment of LPL system activity.

Adult↗

PubMedDate not supplied

Plasma amino acid imbalance in patients with lung and breast cancer.

In order to evaluate whether different solid tumors may specifically influence plasma free amino acid (PFAA) profile, PFAA were analysed in seventy-four patients with lung (41 patients) and breast cancer (33 patients) and 28 healthy subjects. In lung cancer patients a significant reduction of gluconeogenic amino acids, threonine, serine, glycine and a significant increase of free tryptophan and glutamic acid was found. In breast cancer patients a significant increase of ornithine, glutamic acid and free tryptophan was found. The comparison of PFAA profiles between lung and breast cancer suggests that different tumors have a different influence on the host's PFAA pattern.

Adult↗

PubMedDate not supplied

Cytokines, tryptophan and anorexia in cancer patients before and after surgical tumor ablation.

Serotoninergic system activity and cytokine production have been both implicated in the pathogenesis of cancer anorexia. To verify the existence of relationships between tryptophan, cytokines and anorexia, twenty cancer and six non-neoplastic patients were studied. Plasma amino acid concentration, including tryptophan, and spontaneous and LPS stimulated tumor necrosis factor and interleukin-1 release from peripheral blood mononuclear cells were determined before and after surgery in both groups of patients. A close relationship between plasma free tryptophan concentration and anorexia was observed, whereas no relationship between cytokine production and either anorexia or plasma tryptophan was found in cancer patients.

Adult↗

PubMedDate not supplied

Densitometry-based equations for estimating body composition in Fischer rats.

Male Fischer rats are widely used to evaluate the effects of nutritional repletion or deprivation on the rat's nutritional status. Practical methods are needed to evaluate changes in body composition. Chemical analysis is expensive, time consuming, and often not available; bioelectrical impedance analysis in laboratory animals lacks standardization. Postulating that the measurement of densitometry would allow reliable estimation of body composition in the male Fischer rat, we studied 27 male Fischer rats. Densitometric measurements of the carcasses and their chemical analysis were performed to obtain reference values. Initial estimation of the fraction of body fat based on densitometry was attempted with the Siri equation intended for use in humans. We found that this equation was not suitable for use in the male Fischer rat because it underestimated fat mass at high carcass weights and overestimated fat mass at low carcass weights. Therefore, the Siri equation was modified to more accurately predict carcass composition in the male Fischer rat. Three different predictive equations based on simple densitometric measurements were developed that allow separate estimation of carcass fat, carcass water, and carcass protein in the male Fischer rat. These equations were found to be accurate to within 2-5-3% of carcass weight.

Adipose Tissue↗

PubMedDate not supplied

Biochemical indices may not accurately reflect changes in nutritional status after allogeneic bone marrow transplantation.

The validity of biochemical indices routinely used for nutritional assessment was evaluated in patients undergoing allogeneic bone marrow transplantation for hematologic malignancies. Sixteen patients received total parenteral nutrition (TPN) for 15 days (35 kcal kg.body wt-1.day-1; 1.4 g amino acid.kg body wt-1.day-1) starting 1 day after transplantation. Nutritional status was evaluated before and after the TPN period by determining anthropometric (body weight, triceps skinfold thickness, and midarm circumference) and biochemical (transferrin, prealbumin, ceruloplasmin, and C3c) indices. Anthropometric indices, which were within the normal range before TPN, were not changed on day 15; transferrin and prealbumin concentrations significantly (p = 0.03) decreased whereas ceruloplasmin and C3c significantly (p = 0.03) increased. The levels of acute-phase proteins (alpha-1-acid glycoprotein, alpha-1-antitrypsin, and C-reactive protein), determined in 8 of the 16 patients at the same time intervals, were increased after 15 days of TPN and were significantly inversely correlated with transferrin and prealbumin. On the basis of these data, it appears that biochemical indices are not sufficiently reliable in the nutritional assessment of bone marrow transplantation patients because the levels of these substances are markedly affected by the acute-phase response secondary to febrile episodes and graft-versus-host disease, which frequently complicate transplantation.

Acute-Phase Proteins↗

PubMedDate not supplied

Tumor-induced changes in host metabolism: a possible marker of neoplastic disease.

A large number of "biologic markers" for cancer have been described, including tumor-associated antigens, ectopic hormones, enzymes, and effects of tumor on the host's metabolism. Although tumors may metabolically differ from each other, they may induce similar derangements in glucose, lipid, and protein metabolism in the host. In particular, changes in carbohydrate metabolism may induce glucose intolerance that may be early and easily detected using an oral glucose tolerance test. Hypertriglyceridemia and reduced exogenous lipid clearance may represent an early marker of deranged lipid metabolism. Changes in protein metabolism, as reflected by plasma amino acid profile, may also represent a new diagnostic tool for cancer. Among other amino acids, free tryptophan seems to be the best candidate as a new useful marker for monitoring neoplastic disease. It is conceivable that, based on the understanding of the differences in plasma amino acid profiles, more specific and rational antineoplastic strategies may arise.

Biomarkers, Tumor↗