PubMed Health⌕ Search

Biomedical subjects

M Muscaritoli

Publications and source records attributed to M Muscaritoli.

At least 37 records · Page 2Linked to original sources
PubMed1996

Mechanism of early tumor anorexia.

Whether in tumor-bearing rats a temporal relationship exists between an increase in plasma free tryptophan (FTRP), an increase in brain serotonin (5-HT), and onset of anorexia was studied. Rats were assigned to three groups: tumor-bearing (TB), pair fed (PF), and controls. Food intake was recorded daily. In TB rats anorexia developed on Day 18 and thereafter food intake decreased progressively until end of study. After tumor inoculation, tumor became palpable on Day 10 and continued to grow exponentially until end of study. Rats were killed on Days 6, 10, 16, 18, 22, and 26 to determine plasma FTRP, FTRP/LNAA, and brain 5HT and compared to PF and controls. On Day 6, before tumors became detectable, FTRP and FTRP/LNAA were increased (P < 0.05) in TB rats vs controls. Both continued to increase so that by Day 18 when food intake had started to decrease (P < 0.05), brain 5-HT increased and correlated with the onset of anorexia (R2 = 0.6, P < 0.05). Increases in plasma FTRP the precursor to brain 5-HT occurred in TB rats before physical appearance of tumor and increased until an increase in brain 5-HT occurred, leading to anorexia.

Amino Acids↗
PubMed1996

Cancer anorexia: new pathogenic and therapeutic insights.

During tumor growth, anorexia and reduced food intake markedly contribute to the development of malnutrition, thus worsening overall patients' survival. A better understanding of the pathophysiology of eating behavior may lead to new and more effective therapies, aiming at counteracting the detrimental effects of anorexia and reduced food intake on nutritional status and survival in cancer patients. Brain tryptophan and serotonin concentrations seem to play a pivotal role in the regulation of eating behavior. Increased brain serotonin activity is indeed associated with a reduction of food intake. It has been recently hypothesized that increased availability of tryptophan to the brain and the consequent increased serotonin activity may represent the pathogenic mechanism for cancer-associated anorexia. According to this hypothesis, the modulation of brain serotonin activity may result in an improvement of anorexia. Reducing brain tryptophan availability represents a possible mechanism to restore brain serotonin activity to normal. There is evidence that the oral administration of neutral amino acids competing with tryptophan for brain entry results in a significant improvement of cancer anorexia. The same treatment may also be effective in improving secondary anorexia, which is associated with other chronic illnesses, including renal and liver failure, sepsis, and so forth, sharing a similar pathogenic mechanism.

Animals↗
PubMed1994

Comparative effects of arginine and other amino acid deprivation on in vitro expression of lymphocyte activation markers.

Enteral or parenteral arginine supplementation enhances lymphocyte activation after mitogenic stimulation, in rats and humans. Arginine deprivation in culture media is associated with a reduction of lymphocyte activation; this effect, however, has not yet been proven to be specific for arginine. This study was designed to evaluate the specificity of arginine deprivation from culture media on the reduction of in vitro lymphocyte activation. Peripheral blood mononuclear cells, obtained from 11 healthy volunteers, were cultured in RPMI 1640, selectively deprived of single amino acids (i.e. arginine, phenylalanine, leucine, methionine, and threonine) and supplemented with phytohemagglutinin (PHA). The expression of interleukin-2 receptor and transferrin receptor was evaluated by cytometric analysis; the levels of soluble IL-2 receptor were determined by immuno-enzymatic assay. Results were compared with those obtained by culturing cells in non-deprived, RPMI 1640 medium. The expression of transferrin and IL-2 receptor, as well as the levels of IL-2 soluble receptor, were significantly reduced in all deprived media irrespective of the lacking amino acid. These results suggest that the reduction of in vitro lymphocyte activation is not an arginine specific effect. Therefore, the known enhancement of immune response, following arginine supplementation in vivo, is likely to involve a more complex series of events.

Journal Article↗
PubMed1993

Current uses of total parenteral nutrition.

Total parenteral nutrition has become a well-established intervention for the following indications: to sustain life in patients with short-bowel syndrome; for perioperative use in nutritionally deprived patients; to improve quality of life for patients with inflammatory bowel diseases; to assist the healing of enterocutaneous and pancreatic fistulas; for supportive care in patients with acute pancreatitis; as an adjunct to therapy in patients with acute renal or hepatic failure; for hypermetabolic states such as sepsis, trauma, burns and acquired immunodeficiency syndrome; in neonatal and pediatric patients; in transplantation recipients, including bone marrow, renal, cardiac and liver transplants; for precoronary artery bypass graft myocardial glycogen loading; in the field of obstetrics; to enhance survival in patients with closed head injuries; to treat life-threatening anorexia nervosa; in patients with cystic fibrosis and for nutritional support in home use.

Critical Care↗
PubMed1993

Dynamics of central venous catheter-related sepsis in rats.

To determine when catheter-related sepsis clears after removal of an infected central venous catheter (CVC) and when a new sterile CVC can be inserted without risk of recolonization, a catheter infected with 10(5) CFU of Staphylococcus epidermidis per ml was inserted into 40 Fischer 344 rats. Five control rats had sterile catheters. Insertion of an infected CVC was followed by a significant rise in leukocytes after 4 days and the presence of S. epidermidis in lungs, livers, spleens, kidneys, and the catheter tip, as examined by bacteriological assay. After the infected catheter was removed, the rat recovered from the induced catheter-related sepsis within 12 h. When a new sterile CVC was inserted into the femoral vein, the leukocyte count remained normal, and all catheter tips and tissue cultures were sterile 4 days later.

Animals↗
PubMed1992

Muscle performance and adenine-nucleotides status in MCA-sarcoma tumor-bearing rats.

The reduction in DNA, RNA, amino acid, and total protein in muscle tissue of tumor-bearing rats may influence muscle function. The effects of MCA-sarcoma tumor burden on muscle performance and adenine nucleotides was evaluated in three fiber types of skeletal muscle. Twenty-one days after MCA-sarcoma tumor inoculation, the gastrocnemius-soleus muscle group of Fischer 344 rats was stimulated using an in situ preparation; tetanic stimulation for 10 min at 7.5, 15, or 30 tetani per min (TPM) or 60 TPM for 5 min (n = 6 control and six tumor-bearing rats/group). ATP, ADP, AMP, IMP, phosphocreatine, and creatine content in white and red gastrocnemius muscle and soleus muscle was measured. There were no differences among controls and tumor-bearing rats in force output; however, ATP content in the soleus muscle of tumor-bearing rats was significantly reduced after 30 TPM for 10 min or 60 TPM for 5 min. The performance of skeletal muscle, over a wide range of stimulation frequency, in tumor-bearing rats does not appear to be influenced by changes in adenine nucleotide content.

Adenine Nucleotides↗
PubMed1992

Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan.

Previous observations have shown that oral administration of 5-hydroxytryptophan (5-HTP) without dietary prescriptions causes anorexia, decreased food intake, and weight loss in obese subjects. To confirm these data over a longer period of observation and to verify whether adherence to dietary restriction could be improved by 5-HTP, 20 obese patients were randomly assigned to receive either 5-HTP (900 mg/d) or a placebo. The study was double-blinded and was for two consecutive 6-wk periods. No diet was prescribed during the first period, a 5040-kJ/d diet was recommended for the second. Significant weight loss was observed in 5-HTP-treated patients during both periods. A reduction in carbohydrate intake and a consistent presence of early satiety were also found. These findings together with the good tolerance observed suggest that 5-HTP may be safely used to treat obesity.

5-Hydroxytryptophan↗
PubMed1991

Effect of energy substrate manipulation on tumour cell proliferation in parenterally fed cancer patients.

The effects of isocaloric carbohydrate-based vs. fat-based total parenteral nutrition (TPN) regimens on cancer cell proliferation and host nutritional status were evaluated in 27 patients with tumours of the gastro intestinal tract consecutively assigned to receive for 14 days: a glucose-based (A) or a lipid-based (B) TPN formula, or an oral diet (C) isocaloric and isonitrogenous to A and B. Cancer cell replication rate was evaluated by thymidine labelling index (LI) on tumour samples before and at the end of each nutritional regimen. The number of replicating cells increased by 32.2% in patients receiving regimen A. LI decreased by 24.3% in patients given regimen B. LI values were slightly increased (+15%) in patients maintained on regimen C. Nutritional status remained within normal limits. None of the LI changes observed between and within the three arms of the trial were found to be statistically significant. Thus we failed to prove that glucose consistently stimulates or lipids inhibit tumour proliferation despite a trend in this sense.

Journal Article↗
PubMed1990

Plasma and CSF tryptophan in cancer anorexia.

Eighteen untreated cancer patients and ten sex- and age-matched healthy volunteers were studied. In all patients eating behavior was investigated by means of a specific questionnaire from which the presence of anorexia and anorexia-related symptoms was assessed. To investigate the role of tryptophan in cancer anorexia, fasting plasma and CSF levels of tryptophan and other neutral amino acids were assayed in patients and controls. Cancer patients showed abnormally high plasma free tryptophan levels. In case of patients with cancer anorexia a significant rise of the ratio in plasma between free and tryptophan/large neutral amino acids, competing with tryptophan for its brain entry, was observed. This increase was correlated to a consistent rise of CSF tryptophan levels suggesting a specific role of the serotoninergic system in the pathogenesis of cancer anorexia.

Aged↗
PubMed1989

The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects.

Nineteen obese female subjects with body mass index ranging between 30 and 40 were included in a double-blind crossover study aimed at evaluating the effects of oral 5-hydroxytryptophan administration on feeding behavior, mood state and weight loss. Either 5-hydroxytryptophan (8 mg/kg/day) or placebo was administered for five weeks during which patients were not prescribed any dietary restrictions. Feeding behavior was investigated by means of a questionnaire designed to establish the onset of anorexia and related symptoms. Food intake was evaluated using a three-day diet diary. BDI, SI, STAI-T, and STAI-S were used to assess mood state. The administration of 5-hydroxytryptophan resulted in no changes in mood state but promoted typical anorexia-related symptoms, decreased food intake and weight loss during the period of observation.

5-Hydroxytryptophan↗
PubMed1989

[Metabolico-nutritional changes in the cancer patient].

The severe impairment of the nutritional state, which usually accompanies malignant diseases, heavily contributes to the high morbidity and mortality rates observed in cancer patients. Nevertheless, the utility of an artificial energy supply to these patients is still controversial because the nutrients given to replete the host may also stimulate tumor growth. Consequently, a correct nutritional approach for cancer patients should be based upon a well-defined understanding of tumor as well as host-metabolic needs. In this regard, the most typical metabolic abnormalities observed in cancer patients and experimental animals are examined. Specific modifications of the plasma levels of different groups of amino acids--including glucogenic, aromatic, sulphur-containing and branched-chain amino acids--have been observed in cancer patients independently of the their degree of malnutrition, glucose tolerance and tumor diffusion. This may reflect a series of specific modifications induced by the neoplastic tissue on host's protein turnover. Little information is available regarding the protein metabolism in the neoplastic tissue. A number of attempts have been made to reduce tumor growth by withholding single amino acids considered essential to the tumor; nevertheless, the results obtained are still controversial. The two major abnormalities of carbohydrate metabolism observed in cancer patients are an increased glucose turnover and an impaired glucose tissue disposal. The former seems to be due to an increased glucogenesis, whereas the latter may be attributed to an insulin resistance in contrast to the high anaerobic glucose utilization observed in the neoplastic tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1988

Uptake of amino acids by brain microvessels isolated from rats with experimental chronic renal failure.

The neurological disorders seen in patients with chronic renal failure and liver cirrhosis are analogous. Previous in vivo studies have shown that the impaired blood-brain amino acid transport seen in rats with chronic renal failure is similar to that of rats with portocaval anastomosis. To elucidate whether a comparable underlying pathogenic mechanism plays a role in both pathological conditions, blood and brain amino acid levels together with amino acid transport by isolated brain microvessels have been studied in rats with chronic renal failure and in sham-operated rats. Brain microvessels isolated from rats with experimental chronic renal failure showed that the uptake of labeled large neutral amino acid, i.e., leucine or phenylalanine, but not of lysine or alpha-methylaminoisobutyric acid, was significantly increased with respect to sham-operated rats; conversely, the uptake of glutamic acid in rats with chronic renal failure was significantly lower compared with values in controls. Kinetic analysis indicated that this was mainly due to increased exchange transport activity (Vmax) of the L-system, rather than to changes in the affinity (Km) of the carrier system for the relative substrate. These data, together with the significant rise of brain glutamine levels and an increased brain-to-plasma ratio of the sum of large neutral amino acids, are analogous to what was previously observed in rats with portocaval anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1987

Amino acids and hepatic encephalopathy.

The consideration of HE and its etiology has undergone a radical turn within the past decade. At present HE is seen in the context of severe metabolic derangements, which failure of the liver, the central biochemical powerhouse of the body, must bring with it. The increased awarenesses on the biochemical mechanisms involved in the pathogenesis of HE have found, step by step, their own place in a complex but consequential mosaic of events, in which amino acid and HE are tightly linked. Clinical and experimental studies are needed to further improve the knowledge in this field, nontheless a certain number of corner-stones can be identified: A profound alteration of the central nervous system neurotransmission is responsible for most, if not all, of the symptoms characterizing HE. The plasma amino acid imbalance observed in cirrhotic patients represents a 'condicio sine qua non' HE may develop. A functional impairment of the amino acid transport systems at the level of the blood-brain barrier seems to play a crucial role in causing deleterious modifications of the synaptic neurotransmission in the central nervous system. The reduction of the brain entry of the "toxic" aromatic amino acids usually obtained by parenteral administration of especially tailored amino acid mixtures is most frequently followed by awakening from HE. In conclusion, most of the results obtained have demonstrated that HE represents a research field in which progresses in the knowledge of some of the pathogenic mechanisms have brought the investigators to new therapeutic approaches which have clearly improved the prognosis of patients suffering from this severe neuropsychiatric syndrome.

Amino Acids↗
PubMed1986

Plasma tryptophan and anorexia in human cancer.

A correlation between anorexia and brain levels of serotonin and tryptophan (TRP) has been reported in tumor-bearing animals. In the present investigation 45 patients with various types of cancer and 13 control subjects were studied. Prior to the study the patients had received no antineoplastic therapy and were unaware of the malignancy of their disease. Feeding behavior was investigated by means of a questionnaire in which the presence of anorexia (A), aversion to meat (MA), taste (TA) or smell (SA) alterations, nausea and/or vomiting (NV) and early satiety (ES) was assessed. Plasma levels of free TRP, the other neutral amino acids (NAA), albumin and non-esterified fatty acids (NEFA) were assayed. Plasma-free TRP was significantly increased in anorectic cancer patients. The free TRP/competing NAA ratio, which might better predict brain TRP levels, was significantly higher in patients with A, MA, TA, SA, NV and ES than in controls or in non-anorectic (NA) cancer patients. These findings seem to confirm that free TRP may play an important role in human cancer anorexia.

Adult↗
PubMed1986

Use of branched chain amino acids for treating hepatic encephalopathy: clinical experiences.

The efficacy of branched chain amino acids in two consecutive clinical studies in patients with severe hepatic encephalopathy was tested. In the preliminary uncontrolled study 19 patients with grade 3-4 hepatic encephalopathy were given an intravenous solution containing leucine 11 g/l, isoleucine 9 g/l, and valine 8.4 g/l in 20% dextrose. A complete recovery of mental state was obtained in all patients in a mean time of 20.5 hours. In a subsequent controlled study 40 patients with grade 3-4 hepatic encephalopathy were randomly assigned to receive intravenous branched chain amino acid in 20% dextrose (group A) or oral lactulose (group B). Twelve patients (70.6%) in group A and eight (47%) in group B regained consciousness in a mean time of 27.6 and 31.5 hours, respectively. The difference in the recovery rate between the two groups, although evident, was not significant. Intravenous branched chain amino acids are thus at least as effective as lactulose in reversing hepatic coma. These data argue strongly in favour of a therapeutic effect of branched chain amino acids in the treatment of hepatic encephalopathy in patients with chronic liver failure.

Amino Acids, Branched-Chain↗