Comparative Study of Salivary, Duodenal, and Fecal Microbiota Composition Across Adult Celiac Disease.

BACKGROUND: Growing evidence suggests that an altered microbiota composition contributes to the pathogenesis and clinical features in celiac disease (CD). We performed a comparative analysis of the gut microbiota in adulthood CD to evaluate whether: (i) dysbiosis anticipates mucosal lesions, (ii) gluten-free diet restores eubiosis, (iii) refractory CD has a peculiar microbial signature, and (iv) salivary and fecal communities overlap the mucosal one. METHODS: This is a cross-sectional study where a total of 52 CD patients, including 13 active CD, 29 treated CD, 4 refractory CD, and 6 potential CD, were enrolled in a tertiary center together with 31 controls. A 16S rRNA-based amplicon metagenomics approach was applied to determine the microbiota structure and composition of salivary, duodenal mucosa, and stool samples, followed by appropriate bioinformatic analyses. RESULTS: A reduction of both α- and ß-diversity in CD, already evident in the potential form and achieving nadir in refractory CD, was evident. Taxonomically, mucosa displayed a significant abundance of Proteobacteria and an expansion of Neisseria, especially in active patients, while treated celiacs showed an intermediate profile between active disease and controls. The saliva community mirrored the mucosal one better than stool. CONCLUSION: Expansion of pathobiontic species anticipates villous atrophy and achieves the maximal divergence from controls in refractory CD. Gluten-free diet results in incomplete recovery. The overlapping results between mucosal and salivary samples indicate the use of saliva as a diagnostic fluid.

Clinical monitoring of safety and functionality of a non-medicated patch for pain alleviation associated to dysmenorrhea.

FIT® Lady patch is an easy-to-use class I medical device, developed to relieve pain associate to menstrual period, without pharmacological substances. The patch is based on far infrared (FIR) electromagnetic waves reflection properties that normally are emitted from the body, as a consequence of body heat dispersion between the difference of cutaneous body and ambient temperature. Consequently, infrared (IR) waves are reflected and resorbed at cutaneous level and thermal energy again locally introduced leads to a better microcirculation. Although biological IR waves properties and mechanisms of action are extensively studied, there are still few references on patches based on FIR properties. The aim of this study was the evaluation of FIR technology applied to FIT® Lady patch thought to be used to alleviate pain associated to menstrual period (dysmenorrhea). The FIT® Lady patch medical device (active patch) was evaluated in comparison with a placebo patch, in order to assess its action in reducing pain related to menstrual period in 40 women patients enrolled according to specific inclusion/exclusion criteria. This study confirmed a good tolerability of the product, by demonstrating the ability to significantly reduce inconvenience and feeling of pain. The mineral that was responsible of the reflection activity (titanium dioxide), conveniently entrapped in a patch, was able to work without any active substances in contact with and absorbed from the skin.

Validation of cleaning procedures used in an Italian Hospital Pharmacy for antineoplastic drug decontamination: a new tool for industrial hygiene.

BACKGROUND: Current Italian regulations and procedures for surface decontamination of antineoplastic drugs (ADs) are not clear. Therefore, most hospital pharmacies follow internal procedures as an interpretation of the recommended handling guidelines. OBJECTIVES: Our study compared 7 different cleaning procedures after controlled contamination of the work surface of a biological safety cabinet workbench in an Italian hospital oncology pharmacy (HOP) to determine which of them is more efficient and practical. Moreover, in order to approximate operative routine and improve risk awareness, cleaning procedures were carried out by the personnel that usually operate in the HOP. METHODS: Measured quantities, i.e. a drop (100 µL) of 5-FluoroUracil, IPhosfamide, CycloPhosphamide and Gemcitabine, were deposited on the work surface within precisely delimited areas. Following the wipe-test analysis using UPLC-MS/MS, the cleaning efficacy was calculated based on the ratio of the residual concentration of the AD, after the cleaning procedure, to the concentration of each AD before the procedure. RESULTS: Tested cleaning procedures were: 1) Hypo-Chlor®, hot water and Farmecol70®; 2) Hypo-Chlor® and hot water; 3) Farmecol70®; 4) Surfa'Safe SH® and hot water; 5) Amuchina® 10%, hot water and Farmecol70®; 6) Incidin® Oxyfoam and hot water; 7) liquid Marseille soap, hot water and Farmecol70®. Within the studied HOP, the Marseille soap was evaluated to be the optimal choice due to its efficacy, low cost, and the very short contact time needed before rinsing. DISCUSSION: The application of the protocol for procedure validation suggested here could be used in every HOP as a reliable industrial hygiene tool to demonstrate the validity of the chosen cleaning procedure.

Evaluation of safety and skin tolerability of organic cotton pads in case of irritative vulvitis.

BACKGROUND: The woman vaginal environment is a fragile and delicate ecosystem that is often impaired by physical and chemical agents. This condition tends to damage skin barrier causing allergic reactions that lead to chronic irritating conditions. METHODS: Clinical and in-vitro studies were performed on organic cotton pads in order to assess if their use can prevent the onset of irritant conditions. During clinical studies, the panelists' skin and mucosae state were checked through a gynecological clinical examination in order to assess tissue dryness and alterations. Moreover, each panelist answered a sensorial questionnaire at the end of the test. Data were gathered and the product acceptability of use was registered in terms of itching, irritations and burning feelings. The panelist score was calculated based on VNS Scale (0-10, where 0 is the minimum value and 10 is the maximum). RESULTS: From a careful analysis of the first part of the study, it is possible to state that the tested product (organic cotton pads) has proved to reduce the onset of irritative phenomena and slight undesired effects caused by the conventional use of synthetic pads. In-vitro tests were conducted to study possible biological processes involved during allergic and sensitizing events produced by vulvitis. In particular, a pro-sensitizing test, a skin irritation on RHE (adapted from OECD 439) and tests to assess the soothing activity were performed on cell substrates. CONCLUSIONS: Results demonstrated that organic cotton pads, in each part, are safe and do not impair any physiological activities of the tissue substrates.

A new, sensitive and versatile assay for quantitative determination of α-fluoro-ß-alanine (AFBA) in human urine by using the reversed-phase ultrahigh performance-tandem mass spectrometry (rp-UHPLC-MS/MS) system.

A method for the quantitation of α-fluoro-ß-alanine (AFBA), the main metabolite of capecitabine (Cape) and 5-fluoruracil (5-FU), is described. Among antineoplastic drugs (ADs), 5-FU and Cape (the new oral prodrug) are the most commonly applied drugs in cancer therapy. The main objective of this study was to develop a reliable method that would be easy to run on a reversed-phase UHPLC system coupled to tandem mass spectrometry. AFBA was derivatized with Sanger's reagent to ensure complete yield of a stable 2,4 dinitrophenil-α-fluoro-ß-alanine derivative. This method was based on the use of a mixed-mode anion exchange solid phase extraction enabling urinary extracts to be clear of endogenous interferences affecting quantitative results. The assay was validated in human urine according to FDA criteria with the use of a labeled internal standard (ß-alanine-d4) to minimize experimental error. Good accuracy and precision were demonstrated by determining spiked urine QC samples in four consecutive days. The recovery of AFBA was between 70.0 and 82.6%, with a matrix effect that was 12.8%-18.5%. The lower limit of quantitation (LOQ) was 0.5 ng/mL with a coefficient of variation of 5.3%. This assay was successfully applied to determine the levels of this metabolite in a large number of urine samples taken from personnel who were occupationally exposed to ADs.

Myofibrillar protein overdegradation in overweight patients with chronic heart failure: the relationship to serum potassium levels.

OBJECTIVES: Muscle release of the amino acid 3-methyl-histidine (3MH) is a sensitive index of myofibrillar protein overdegradation (MPO). We hypothesized that patients with chronic heart failure (CHF) could have increased muscle release of 3MH, which in turn reflects MPO, and that serum electrolyte sodium (Na(+)) and potassium (K(+)) levels may be associated with this 3MH muscle release. METHODS: Thirty-one overweight outpatients (body mass index, 27 ± 4.4 kg/m(2); 22 men and 9 women; age, 56 ± 8.7 y) with clinically stable CHF were studied. After a 24-hour meat-free diet and overnight fasting, patients underwent blood sampling from a cannulated arm vein (V) and concomitantly from the arterial artery (A) to determine plasma 3MH levels and to calculate the A-V difference. Serum levels of Na(+) and K(+) in the venous blood were determined, and the Na(+)/K(+) ratio was calculated. Ten healthy subjects who were matched for gender, age, and body mass index served as controls and underwent the same protocol as the patients with CHF. RESULTS: The patient group had higher arterial (P = 0.02) and venous (P = 0.005) 3MH levels but a similar A-V 3MH difference (P = 0.28) as compared with the controls. Within the CHF group, 67.7% of patients released 3MH, which resulted in a negative A-V value (P < 0.02 as compared with controls). In patients with CHF, the A-V 3MH difference correlated positively with the serum K(+) level (r = 0.62; P = 0.0002) and negatively with Na(+)/K(+) ratio (r = -0.55; P = 0.002). No association was found between the A-V 3MH difference and the Na(+) level. CONCLUSIONS: The study demonstrated the existence of MPO in resting overweight patients with CHF, thereby suggesting that low serum levels of K(+) may contribute to MPO.

Lung anabolic activity in patients with chronic heart failure: potential implications for clinical practice.

OBJECTIVE: The proteins in the lungs are in constant flux, undergoing degradation and resynthesis. We investigated pulmonary protein and amino acid metabolism, the biochemical basis of the remodeling process, in individuals with chronic heart failure receiving or not receiving ß-blocker therapy with bisoprolol (BIS). METHODS: Clinically stable rehabilitative patients with chronic heart failure, without metabolic diseases or liver/renal failure, and with a stable weight over the preceding 3 mo underwent right heart catheterization, and radial artery cannulation. Mixed central venous and arterial blood samples were drawn simultaneously to calculate the venous-arterial difference of amino acids (pulmonary uptake and release). RESULTS: Twenty-two patients on BIS therapy and eight not receiving BIS were analyzed. The two groups showed a net pulmonary protein synthesis (i.e., a positive value of phenylalanine [venous-arterial difference] × cardiac index product) and amino acid extraction, the rates of which were significantly lower in patients on BIS therapy. The two groups had pulmonary hypertension (mean pulmonary artery pressure >19 mmHg). Pulmonary vascular resistance was 57% higher in patients not receiving BIS than in those on BIS therapy (6.65 ± 2.90 versus 4.23 ± 1.49 mmHg/L · min⁻¹ · m⁻², P < 0.05). Pulmonary vascular resistance correlated positively with the pulmonary extraction of total essential amino acids (r = +0.4576, P = 0.01) and leucine (r = +0.5083, P = 0.004), the most important amino acid for protein synthesis. CONCLUSION: Patients with chronic heart failure have increased rates of amino acid extraction and pulmonary protein synthesis, suggesting, at least in part, an increased rate of lung remodeling. Therapy with BIS attenuates lung metabolic abnormalities.

Preserved muscle protein metabolism in obese patients with chronic heart failure.

BACKGROUND: We hypothesized that obese chronic heart failure (CHF) patients, who are known to have less cardiac dysfunction, could show preserved muscle protein balance. The aim of this study was to relate muscle protein balance and cardiac function to body mass index (BMI) in order to provide further insight to the obesity paradox in CHF patients. METHODS: Thirty stable CHF patients were categorized by BMI (n=6, normal; n=14, overweight; n=10, obese) and underwent post-absorptive: (i) right heart catheterization to determine cardiac hemodynamics and (ii) arterial and venous blood sampling to measure arterial and venous levels of essential amino acids (EAAs) and to calculate arterovenous differences (positive = uptake; negative = release). Muscle protein over-degradation was assessed by muscle release of the EAA phenylalanine. Plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) was also determined. Twenty healthy subjects, matched for age, served as controls and underwent radial artery and vein sampling only. RESULTS: Obese CHF patients had normal muscle protein balance, muscle EAA release, and arterial EAA concentration. Among the non-obese patients, normally weighted ones had more pronounced muscle protein over-degradation and greater reduction of arterial EAAs (p<0.01 for both) and EAA release (p<0.06) than overweight ones. Arterial leucine levels correlated negatively with NT-pro-BNP (r=-0.75; p<0.0001) and positively with LVEF (r=+0.68; p<0.0001). Within EAAs, branched chain amino acids were positively associated with stroke volume index (r=+0.51; p=0.004). CONCLUSIONS: Only obese patients with CHF have balanced muscle protein metabolism. This may contribute to explain the obesity paradox.

Spontaneous neurocognitive retrieval of patients with sub-acute ischemic stroke is associated with dietary protein intake.

OBJECTIVE: To document the relationship between neurocognitive recovery and macronutrient intake of patients suffering from ischemic strokes. DESIGN: Thirty day prospective study of 17 patients suffering from sub-acute stroke (> 14 days from the index event; 10 males, 7 females; mean age 75 +/- 8 years) admitted to our rehabilitation unit. RESULTS: At admission (ADM), mean energy intake was inadequate (< 24 kcal/kg) for bodily needs, whereas protein (> 0.8 g/kg) and lipid (> 0.7 g/kg) intake was appropriate. Patients were moderately deficient for neurological (NIHSS 10.3 +/- 3.5) and cognitive tests (MMSE 22.5 +/- 3.3). NIHSS correlated negatively with proteins (r = -0.47, P = 0.05 at ADM; r = -0.52, P = 0.03 at 30 days) and positively with carbohydrate/protein ratio (CHO/protein; r = +0.45, P = 0.06 at ADM; r = +0.48, P = 0.05 at 30 days). However, MMSE correlated positively with proteins (r = +0.77, P = 0.0003 at ADM; r = +0.55, P = 0.02 at 30 days) and negatively with (CHO/Prot; r = -0.57, P = 0.02 at ADM; not significant at 30 days). The relationship remained significant even when the data at ADM and at 30 days where pooled. CONCLUSIONS: In sub-acute strokes, patient neurological and cognitive retrieval could positively be associated with protein intake.

Normalization of zinc intake enhances neurological retrieval of patients suffering from ischemic strokes.

INTRODUCTION: The objective of this study was to investigate whether zinc (Zn2+) supplementation could contribute to neurological retrieval of patients suffering from strokes and low Zn2+ intake. PATIENTS AND METHODS: Twenty-six patients with subacute stroke, having adequate daily energy (> or = 24 kcal/kg/day) and protein (> or = 0.8 g/kg/day) intake (EPI) and Zn2+ ingestion lower than two-thirds of the recommended allowance of 10 mg/day, were randomly allocated either to a control group (n = 13) or Zn2+ group (n = 13) where Zn2+ supplementation consisted of 10 mg Zn2+/day. Neurological gravity was tested with the NIH stroke scale (NIHSS) at patient admission and after 30 days of protocol commencement. RESULTS: At day 30, the improvement in NIHSS was higher in the zinc group than in the placebo (-4.7 +/- 1.3 points versus -3.3 +/- 1.1 points; P < 0.02). NIHSS and Zn2+ intake were negatively correlated (r = -0.46; P < 0.02). CONCLUSION: The normalization of Zn2+ intake in stroke patients with low mineral intake may enhance neurological recovery.

Adequate energy-protein intake is not enough to improve nutritional and metabolic status in muscle-depleted patients with chronic heart failure.

BACKGROUND: An adequate energy-protein intake (EPI) when combined with amino acid supplementation may have a positive impact on nutritional and metabolic status in patients with chronic heart failure (CHF). METHODS AND RESULTS: Thirty eight stable CHF patients (27 males, 73.5+/-4 years; BMI 22.5+/-1.4 kg/m2), with severe depletion of muscle mass and were randomised to oral supplements of essential amino acids 8 g/day (EAA group; n=21) or no supplements (controls; n=17). All patients had adequate EPI (energy> or =30 kcal/kg; proteins >1.1 g/kg). At baseline and 2-months after randomisation, the patients underwent metabolic (plasma lactate, pyruvate concentration; serum insulin level; estimate of insulin resistance by HOMA index), nutritional (measure of nitrogen balance), and functional (exercise test, walking test) evaluations. Body weight increased by >1 kg in 80% of supplemented patients (mean 2.96 kg) and in 30% of controls (mean 2.3 kg) (interaction <0.05). Changes in arm muscle area, nitrogen balance, and HOMA index were similar between the two treatment groups. Plasma lactate and pyruvate levels increased in controls (p<0.01 for both) but decreased in the supplemented group (p<0.01 and 0.02 respectively). EAA supplemented patients but not controls improved both exercise output and peak oxygen consumption and walking test. CONCLUSIONS: Adequate EPI when combined with essential amino acid supplementation may improve nutritional and metabolic status in most muscle-depleted CHF patients.

Effect of calorie-protein supplementation on the cognitive recovery of patients with subacute stroke.

INTRODUCTION: The objective of this study was to investigate whether protein-calorie supplementation may enhance the cognitive retrieval of patients with stroke. PATIENTS AND METHODS: A randomized, double-blind, controlled pilot clinical trial was performed comparing diet and diet plus protein-calorie supplementation regimens. The subjects were 48 patients with subacute stroke (>or14 days from index event). Anthropometric and nutritional (3-day diary) variables, cognitive function (Mini-Mental State Examination; MMSE) were determined before and 21 days after randomization in control and daily supplemented group (formula providing 250 kcal + 20 g protein). RESULTS: At day 21 after starting the protocol, only the supplemented group significantly improved their performance to MMSE (log(10)MMSE +0.6+/-0.4 score; P=0.01 from baseline). CONCLUSIONS: Protein-calorie supplementation may enhance the recovery of cognitive function in subacute stroke patients.

Branched-chain amino acids may improve recovery from a vegetative or minimally conscious state in patients with traumatic brain injury: a pilot study.

OBJECTIVE: To investigate whether supplementation with branched-chain amino acids (BCAAs) may improve recovery of patients with a posttraumatic vegetative or minimally conscious state. DESIGN: Patients were randomly assigned to 15 days of intravenous BCAA supplementation (n=22; 19.6g/d) or an isonitrogenous placebo (n=19). SETTING: Tertiary care rehabilitation setting. PARTICIPANTS: Patients (N=41; 29 men, 12 women; mean age, 49.5+/-21 y) with a posttraumatic vegetative or minimally conscious state, 47+/-24 days after the index traumatic event. INTERVENTION: Supplementation with BCAAs. MAIN OUTCOME MEASURE: Disability Rating Scale (DRS) as log(10)DRS. RESULTS: Fifteen days after admission to the rehabilitation department, the log(10)DRS score improved significantly only in patients who had received BCAAs (log(10)DRS score, 1.365+/-0.08 to 1.294+/-0.05; P<.001), while the log(10)DRS score in the placebo recipients remained virtually unchanged (log(10)DRS score, 1.373+/-0.03 to 1.37+/-0.03; P not significant). The difference in improvement of log(10)DRS score between the 2 groups was highly significant (P<.000). Moreover, 68.2% (n=15) of treated patients achieved a log(10)DRS point score of .477 or higher (3 as geometric mean) that allowed them to exit the vegetative or minimally conscious state. CONCLUSIONS: Supplemented BCAAs may improve the recovery from a vegetative or minimally conscious state in patients with posttraumatic vegetative or minimally conscious state.

[Metabolic frailty in malnourished heart failure patients]. / Precarietà metabolica nei pazienti con scompenso cardiaco cronico e malnutrizione.

UNLABELLED: Muscular wasting (MW) and cardiac cachexia (CC) are often present in patients with chronic heart failure (HF). AIM: To identify whether MW and CC are due to malnutrition or impairment of protein metabolism in HF patients. MATERIAL AND METHOD: In 78 clinically stable HF patients (NYHA class II-III), aged from 32 to 89 years, we measured anthropometrical parameters and nutritional habits. In the identified 35 malnourished patients, we also measured: insulin resistance, gluconeogenetic amino acids blood concentration and nitrogen balance. RESULTS: Seventy-five patients had eating-related symptoms. However we found significant nutritional impairment in 35 patients only. In addition, these 35 patients had: 1) significant increase of blood Alanine independently from both presence of insulin resistance or food intake reduction and 2) positive nitrogen balance. CONCLUSION: Food intake is not impaired in CHF patients. In spite of normal food intake, 35 of 78 patients had nutritional impairment with reduced anthropometric parameters and increased blood Alanine. These findings show alteration of proteins metabolism with proteolysis. We believe that specific physical training with nutritional supplement can be an additional therapy able to prevent protein disarrangement in CHF patients.

School teachers can effectively manage primary prevention of adult cardiovascular disease. The Stradella Project.

OBJECTIVE: To determine whether school teachers educated about Primary Prevention of Adult Cardiovascular Disease (PPCVD) could help their students improve their blood lipid profile. METHOD: Five teachers voluntarily received training about PP-CVD. Thirteen classes of a single high school in Stradella (north Italy) were randomized to receive a 2-month course on PP-CVD (PP-classes; 150 pupils) by their teachers or to a control group (control classes; 130 pupils) during 2004. In all students body weight and fasting venous blood concentrations of total cholesterol (TC), HDL-CHOL, LDL-CHOL, and triglycerides were determined before and 6 months after the completion of the PP-CVD course. RESULTS: Six months after the PP-CVD course, males had significant improvements of all baseline lipid parameters whereas females had improved HDL-CHOL and TC/HDL ratio. No improvements were observed in the control class students. Body weight was unchanged in both groups of students 6 months after the PP-CVD course or the control course. CONCLUSION: This investigation shows that well-trained school teachers are able to manage PP-CVD education so that students can really improve their lipid profile as a consequence of autonomous changes in dietary habits.

Sera of patients with celiac disease and neurologic disorders evoke a mitochondrial-dependent apoptosis in vitro.

BACKGROUND & AIMS: The mechanisms underlying neurologic impairment in celiac disease remain unknown. We tested whether antineuronal antibody-positive sera of patients with celiac disease evoke neurodegeneration via apoptosis in vitro. METHODS: SH-Sy5Y cells were exposed to crude sera, isolated immunoglobulin (Ig) G and IgG-depleted sera of patients with and without celiac disease with and without neurologic disorders, and antineuronal antibodies. Adsorption studies with gliadin and tissue transglutaminase (tTG) were performed in celiac disease sera. Apoptosis activated caspase-3, apaf-1, Bax, cytochrome c, cleaved caspase-8 and caspase-9 and mitochondrial respiratory chain complexes were evaluated with different methods. RESULTS: SH-Sy5Y cells exposed to antineuronal antibody-positive sera and isolated IgG from the same sera exhibited a greater percentage of TUNEL-positive nuclei than that of antineuronal antibody-negative sera. Neuroblasts exposed to antineuronal antibody-negative celiac disease sera also showed greater TUNEL positivity and apaf-1 immunolabeled cells than controls. Antigliadin- and anti-tTG-depleted celiac disease sera had an apoptotic effect similar to controls. Anti-caspase-3 immunostained cells were greater than controls when exposed to positive sera. The mitochondrial respiratory chain complex was reduced by positive sera. Western blot demonstrated only caspase-9 cleavage in positive sera. Cytochrome c and Bax showed reciprocal translocation (from mitochondria to cytoplasm and vice versa) after treatment with positive sera. CONCLUSIONS: Antineuronal antibodies and, to a lower extent, combined antigliadin and anti-tTG antibodies in celiac disease sera contribute to neurologic impairment via apoptosis. Apaf-1 activation with Bax and cytochrome c translocation suggest a mitochondrial-dependent apoptosis.

Branched-chain amino acids enhance the cognitive recovery of patients with severe traumatic brain injury.

OBJECTIVE: To investigate whether supplementation with branched-chain amino acids (BCAAs) in patients with severe traumatic brain injury (TBI) improves recovery of cognition and influences plasma concentrations of tyrosine and tryptophan, which are precursors of, respectively, catecholamine and serotonin neurotransmitters in the brain. DESIGN: Forty patients with TBI were randomly assigned to 15 days of intravenous BCAA supplementation (19.6g/d) (n=20) or an isonitrogenous placebo (n=20). SETTING: Tertiary care rehabilitation setting in Italy. PARTICIPANTS: Forty men (mean age, 32+/-15 y) with TBI and 20 healthy subjects (controls) matched for age, sex, and sedentary lifestyle. INTERVENTION: Supplementation with BCAAs. MAIN OUTCOME MEASURES: Disability Rating Scale (DRS) and plasma concentrations of BCAAs, tyrosine, and tryptophan. RESULTS: Fifteen days after admission to the rehabilitation department, the DRS score had improved significantly in both the placebo group (P<.05 vs baseline) and in the BCAA-supplemented group (P<.01 vs baseline). The difference between the 2 groups was significant (P<.004). Plasma tyrosine concentration improved in the group given BCAA supplementation, and tryptophan concentration increased in patients receiving placebo. CONCLUSIONS: Supplemental BCAAs enhance the retrieval of DRS without causing negative effects on tyrosine and tryptophan concentration.

Plasma precursors of brain catecholaminergic and serotonergic neurotransmitters in rehabilitation patients with ischemic stroke.

OBJECTIVE: To determine levels of plasma amino acid tyrosine and tryptophan, precursors of brain catecholamine and serotonin neurotransmitters, respectively, in rehabilitative patients with ischemic stroke. DESIGN: Controlled, pre-post analysis, consecutive sample. SETTING: Rehabilitation center. PARTICIPANTS: Twenty men with ischemic stroke (age, 68+/-11.3y) consecutively admitted into rehabilitation 15+/-10 days (range, 7-28d) after an acute cerebrovascular insult; 15 healthy sedentary subjects (controls 1); and 13 healthy hypoactive individuals who had recently had knee arthroplasty (controls 2). Both control groups were matched to stroke subjects for age, gender, and body weight. INTERVENTIONS: At 8:00 am, after overnight fasting, venous blood samples were drawn from patients to determine plasma tyrosine and tryptophan levels. A nutritional evaluation, including nitrogen balance, was made. The same procedures were repeated after 45 days of rehabilitation. Amino acid data were compared with those obtained from the controls. MAIN OUTCOME MEASURE: Plasma concentrations of amino acids. RESULTS: Patients with ischemic stroke, on admission, had lower plasma tyrosine concentration than did both controls 1 (P<.0005) and controls 2 (P<.001), but a similar tryptophan level. The plasma content of tyrosine was similar between the 2 control groups. After 45 days of rehabilitation, the stroke patients' tyrosine and tryptophan levels remained virtually unchanged, as did nutritional parameters. Nutritional intakes were adequate to meet body needs but insufficient to correct plasma tyrosine. CONCLUSIONS: Patients experiencing a recent stroke may have low plasma tyrosine levels and, therefore, reduced brain catecholamine formation. It is possible that an imbalance of brain neurotransmitters may occur.

Clenbuterol antagonizes glucocorticoid-induced atrophy and fibre type transformation in mice.

Beta-agonists and glucocorticoids are frequently coprescribed for chronic asthma treatment. In this study the effects of 4 week treatment with beta-agonist clenbuterol (CL) and glucocorticoid dexamethasone (DEX) on respiratory (diaphragm and parasternal) and limb (soleus and tibialis) muscles of the mouse were studied. Myosin heavy chain (MHC) distribution, fibres cross sectional area (CSA), glycolytic (phosphofructokinase, PFK; lactate dehydrogenase, LDH) and oxidative enzyme (citrate synthase, CS; cytochrome oxidase, COX) activities were determined. Muscle samples were obtained from four groups of adult C57/B16 mice: (1) Control (2) Mice receiving CL (CL, 1.5 mg kg(-1) day(-1) in drinking water) (3) Mice receiving DEX (DEX, 5.7 mg kg(-1) day(-1) s.c.) (4) Mice receiving both treatments (DEX + CL). As a general rule, CL and DEX showed opposite effects on CSA, MHC distribution, glycolytic and mitochondrial enzyme activities: CL alone stimulated a slow-to-fast transition of MHCs, an increase of PFK and LDH and an increase of muscle weight and fibre CSA; DEX produced an opposite (fast-to-slow transition) change of MHC distribution, a decrease of muscle weight and fibre CSA and in some case an increase of CS. The response varied from muscle to muscle with mixed muscles, as soleus and diaphragm, being more responsive than fast muscles, as tibialis and parasternal. In combined treatments (DEX + CL), the changes induced by DEX or CL alone were generally minimized: in soleus, however, the effects of CL predominated over those of DEX, whereas in diaphragm DEX prevailed over CL. Taken together the results suggest that CL might counteract the unwanted effects on skeletal muscles of chronic treatment with glucocorticoids.

Inadequate nutritional intake for daily life activity of clinically stable patients with chronic heart failure.

We investigated the nutritional adequacy and energy availability in 57 normal-weight patients with chronic heart failure (HF) and 49 matched healthy sedentary subjects. We found that the chronic HF patients had a higher total energy expenditure (1,700 +/- 53 vs 1,950 +/- 43 kcal/day; p <0.01), a negative calorie balance (104 +/- 35 vs -186 +/- 40 kcal/day; p <0.01), a negative nitrogen balance (2.2 +/- 0.5 vs -1.7 +/- 0.4 g/day; p <0.01), and a hypercatabolic hormonal status (cortisol/insulin ratio 32 +/- 1.7 vs 65 +/- 5.1; p <0.01). We conclude that patients with chronic HF had an inadequate calorie intake to support energetic needs for daily activities, with consequent important protein breakdown that causes muscular wasting.