Glycemia influences on glucose metabolism in sepsis during hyperinsulinemic clamp

BACKGROUND: We investigated glucose metabolism in septic patients during hyperglycemic clamps and compared the different levels of insulinemia and glycemia. METHODS: In 10 non-diabetic stable septic patients on mechanical ventilation with baseline glycemia >6 mmol/L and continuous insulin infusion, 3 steps of hyperinsulinemic clamp were performed after 8 hours without caloric intake. In step 1, the targets were insulinemia of 250 mIU/L and glycemia of 5 mmol/L; in step 2, insulinemia of 250 mIU/L and glycemia of 10 mmol/L; in step 3, insulinemia of 1250 mIU/L and glycemia of 5 mmol/L. Glucose uptake was calculated as the amount of glucose per time needed to maintain the target level of glycemia. Glucose oxidation was calculated from indirect calorimetry and urinary nitrogen losses. Values are provided as means +/- SD. A two-way analysis of variance and Scheffe's method were used for statistical analysis and p < .05 was considered significant. RESULTS: At step 1, glucose uptake was lower than at step 2 (3.8 +/- 2.48 mg/kg/min and 7.9 +/- 3.45 mg/kg/min, respectively; p < .001). Glucose oxidation was also lower at step 1 (2.6 +/- 0.98 and 4.2 +/- 1.85 mg/kg/min, respectively; p < .01). Glucose storage was low at step 1 (0.7 +/- 1.39) and increased at step 2 (3.5 +/- 2.18; p < .05). In step 3, glucose uptake was 7.0 +/- 2.1, oxidation was 3.6 +/- 1.37, and storage was 2.9 +/- 2.79. There was no significant difference in all these parameters between steps 2 and 3. Energy expenditure between steps 1, 2 and 3 did not change (2294 + 307.42, 2334 + 341.53, and 2342 + 426.67 kcal/day, respectively). Alanine in plasma dropped significantly (p < .05): 10 mmol/L (311 +/- 55.88 mmol/L) at glycemia compared with 5 mmol/L (390 +/- 76 micromol/L) at insulinemia 250 mIU/L. It did not differ significantly from the values obtained at glycemia 5 mmol/L and insulinemia 1250 mIU/L (348 +/- 70.68 mmol/L). Even if the level of cytokines in sepsis was higher, there was no correlation between the insulin level in plasma (250 and 1250 mIU/L), glycemia (5 and 10 mmol/L) and cytokine level (IL-1beta, IL-2, IL-6, IL-8 and TNFalpha). CONCLUSION: At insulinemia 250 mIU/L, a glucose level of 10 mmol/L seems to increase glucose uptake, oxidation, and storage compared with glycemia 5 mmol/L. This glucose uptake and oxidation at glycemia 10 mmol/L is comparable with the effect of extremely high insulinemia (1250 mIU/L) clamped at glycemia 5 mmol/L. A higher level of blood glucose or a high level of insulinemia significantly increases glucose uptake but not energy expenditure.     

Plasma homocysteine levels in hyperinsulinemic patients

In order to evaluate the clinical characteristics of metabolic syndrome, a screening procedure was performed and in a cohort of middle-aged (40-60 years) hyperinsulinaemic (fasting plasma insulin > 15 microU/ml) and/or postprandial [120 min after 75 g glucose load] insulin > 45 microU/ml) subjects (n = 91; men/women: 38/53; age mean +/- SD 47.6 +/- 4.3 years; body mass index: 34.6 +/- 4.9 kg/m2; waist-hip ratio: 0.92 +/- 0.07; actual blood pressure 146 +/- 16/87 +/- 9 mmHg; fasting insulin: 24.2 +/- 11.3 microU/ml; postprandial insulin 125.5 +/- 103.8 microU/ml; serum LDL-cholesterol: 3.73 +/- 1.09 mmol/l; HDL-cholesterol: 1.12 +/- 0.30 mmol/l; triglycerides: 2.97 +/- 2.38 mmol/l; uric acid 279 +/- 79 mumol/l) plasma fasting homocysteine, vitamin B12 and folic acid levels were simultaneously determined. The values were separately evaluated according to the stages of glucose tolerance (normal glucose tolerance [n = 47]; impaired glucose tolerance [n = 24] and diabetes mellitus [n = 20]). Laboratory normal values were determined in 47 healthy subjects (control group, age: 45.0 +/- 7.8 years, men/women: 19/28). There was no significant difference between hyperinsulinaemic and control subjects regarding plasma homocysteine (9.28 +/- 3.81 mumol/l vs. 9.63 +/- 2.70 mumol/l), folic acid (8.5 +/- 5.9 ng/ml vs. 7.5 +/- 2.1 ng/ml) and vitamin B12 levels (423 +/- 141 pg/ml vs. 356 +/- 121 pg/ml). Plasma homocysteine levels were significantly (p < 0.001) higher in hyperinsulinaemic men than women (11.34 +/- 4.72 mumol/l [n = 38] vs. 7.86 +/- 2.13 mumol/l [n = 53]). There was no significant difference between subgroups classified according to the stages of glucose tolerance in hyperinsulinaemic groups. Plasma homocysteine values exceeding the upper limit of normal range (> 12.45 mumol/l) were detected at a similar prevalence rate in control (4/47 = 8.5%) and in hyperinsulinaemic subjects (10/91 = 10.9%). A weak but statistically significant correlation was found between plasma homocysteine values and age of subjects (r = 0.222; p < 0.05) whereas a stronger correlation was documented between plasma homocysteine and serum creatinine values (r = 0.658; p < 0.001) in hyperinsulinaemic groups (n = 91). Plasma homocysteine values independently from the stages of glucose tolerance are not elevated in hyperinsulinaemic subjects. Hyperhomocysteinaemia is not a characteristic feature of hyperinsulinism suggesting that plasma homocysteine levels are of no considerable importance in the complex pathomechanism of atherosclerosis at early stages of metabolic syndrome.     

Occupational exposure to urban pollutants and urinary 5-hydroxy-3-indoleacetic acid

According to the literature, various occupational and environmental stressors may cause alterations in serotonin (5-HT) turnover and in its principal metabolite, 5-hydroxy-3-indoleacetic acid (5-HIAA). The aim of this study is to evaluate whether traffic police exposed to urban pollutants and possible psycho-social stressors could be at risk of alterations in urinary 5-HIAA in 24 hours (5-HIAA[U]) compared with a control group. After the main non-occupational confounding factors were excluded, 5-HIAA(U) excretion was investigated in 140 employees of a municipal police force: 70 traffic police with outdoor activity that exposed them to urban pollutants and 70 administrative workers with indoor activity. Subjects were matched by sex, age, and length of working life. The mean 5-HIAA(U) levels were significantly lower in traffic police than in administrative workers, both males and females (p = .025, and p = .027, respectively), matching modifications in 5-HIAA(U) levels found by other authors in studies on animals and human subjects.     

Exaggerated feedback control decreases brain serotonin concentration and elicits hyperactivity in a rat model of diet-restriction-induced anorexia nervosa

5-Hydroxytryptamine (5-HT; serotonin) system is the major neurotransmitter system of interest in research on anorexia nervosa (AN). The AN patients show extreme dieting weight loss, hyperactivity and low basal levels of 5-hydroxyindoleacetic acid (5-HIAA), a major metabolite of 5-HT in the cerebrospinal fluid (CSF). Studies on animal models show that diet restriction (DR) decreases 5-HT metabolism in the brain and hypothalamus which is not necessarily associated with a decrease in the availability of essential amino acid tryptophan (TRP) the precursor of serotonin. To further investigate the mechanism involved in DR-induced decreases of 5-HT the present study uses 8-hydroxy-(2-di-n-propylamino) tetralin (8-OH-DPAT), a selective 5-HT-1A agonist, as a probe to monitor the responsiveness of negative feedback control over 5-HT metabolism. Effects of DR and of 8-OHDPAT on TRP, 5-HT and 5-HIAA concentrations are determined in the hypothalamus, a region of the brain known to role in the regulation of appetite. Animals of DR group given access to food 2h daily for 6 days exhibited 21.6% decrease in the body weight compared to freely feeding (FF) controls. The levels of TRP in the plasma and of 5-HT in the hypothalamus decreased. No effect was found on the levels of TRP in the hypothalamus. 8-OH-DPAT-induced decreases of 5-HT and 5-HIAA were greater in DR than FF group. 8-OH-DPAT-induced hyperactivity was also greater in DR than FF group. The results show that DR-induced decreases of 5-HT are due to an increase in the responsiveness of negative feedback control over 5-HT and not due to smaller availability of TRP. DR-induced increase in activity and 8-OH-DPAT-induced greater hyperactivity in DR than FF group may also be due to exaggerated negative feedback control over 5-HT. It is suggested that drugs decreasing the responsiveness of negative feedback control over 5-HT may be of use for the treatment and prevention of AN in under weight patients on restricted diet.     

Malnutrition in tubefed nursing home patients with pressure sores.

This study compares the nutritional status and dietary intake of 14 tubefed nursing home patients with pressure sores (age: 70 +/- 5 years, mean +/- SEM) to 12 tubefed patient-controls without sores (age: 60 +/- 7 years). Patients tended to have higher calorie intake (32 +/- 3 kcal/kg) than patient-controls (26 +/- 2 kcal/kg, p = 0.11). Protein intake was significantly higher in patients (1.4 +/- 0.2 g/kg) than patient-controls (0.9 +/- 0.1 g of protein per kg, p less than 0.05). Despite increased calorie and protein intake, biochemical measures of nutritional status were worse in the patients. Serum albumin was lower in patients (33 +/- 1 g/L) than in patient-controls (37 +/- 1 g/L, p less than 0.05) as was level of hemoglobin (patients: 117 +/- 5; patient-controls: 132 +/- 5 g/L, p less than 0.05). Patients with stage IV (severe) sores had lower serum cholesterol levels (3.46 +/- 0.31 mmol/L, n = 5) than patients with stage II/III (milder) sores (4.58 +/- 0.23 mmol/L, n = 9, p less than 0.05). Plasma zinc was low in both patients (11.2 +/- 0.6 mumol/L) and patient-controls (11.5 +/- 0.7 mumol/L, p = NS). Pressure sore surface area was positively correlated with calorie intake per kilogram of body weight (r = +0.59, p less than 0.04) and negatively correlated with body mass index (r = -0.70, p less than 0.03), hemoglobin (r = -0.55, p less than 0.07) and serum cholesterol (r = -0.57, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Lactase deficiency--a comparative study of diagnostic methods.

The diagnostic value of 1-14C-lactose breath test was compared with the standard lactose tolerance test and lactase assay in jejunal biopsies in 16 control subjects, 14 patients with lactase deficiency (LD) proven by lactase assay and 20 patients with irritable bowel syndrome (IBS). 14CO2 specific activity in the 2-hr breath collection after administration of 1-14C-lactose (5 muCi) provided a satisfactory separation between the control and LD group. Values were 7.0 +/- 2.0% dose administered/mmoles 14CO2 X 10(-3) (mean +/- SD) in the control group versus 2.1 +/- 1.5 in LD (P less than 0.001) versus 4.9 +/- 2.3 in IBS (P less than 0.01). 1-14C-lactose breath test was superior to standard lactose tolerance test in specificity (P less than 0.05) and provided a satisfactory correlation between 14C-lactose absorption and lactase assay (r = 0.77). The prevalence of LD in IBS was 40% by the breath test and 35% by lactase assay, suggesting that lactose malabsorption may play a role in the symptoms in the population of some patients with IBS. It appears that 1-14C-lactose breath test is a sensitive, specific and accurate method for the diagnosis of LD in clinical practice and suitable for large scale epidemiological surveys.     

Biochemical antioxidant levels respond to supplementation with an enriched drink in frail elderly people

OBJECTIVE: To investigate whether a drink enriched with essential vitamins and minerals can improve biochemical status of enzymatic and non-enzymatic antioxidants in frail elderly people. METHODS: A six-month randomized, double blind, placebo controlled intervention study. Frail elderly people 65 years of age or older, with a body mass index (BMI) below 25 kg/m(2) and residing in a home for the elderly or in sheltered housing. Enriched (with essential vitamins and minerals in 30% to 150% of RDA and higher levels of antioxidants) drink (n = 28) or placebo (n = 27) to be taken twice a day in addition to the normal food consumed. Plasma levels of vitamin C, vitamin E, antioxidant capacity (TEAC), cysteine, uric acid and whole blood levels of total thiol and glutathione peroxidase (GSH-Px), dietary intake. RESULTS: Changes in vitamin E (16 +/- 2 vs. 2 +/- 1 mmol/L), vitamin C (37 +/- 5 vs. 1 +/- 5 mmol/L), TEAC (38 +/- 15 vs. -10 +/- 11 mmol/L Trolox eq) and cysteine (17 +/- 10 vs. 0.4 +/- 6 mmol/L) were significantly different between groups (p < 0.05). There was a trend towards significant changes in erythrocyte glutathione peroxidase (-0.2 +/- 3 vs. -10 +/- 7 U/mg Hb, p = 0.097). Baseline dietary intake of antioxidant vitamins was below 2/3 RDA for a substantial proportion (43% to 76%) of subjects. CONCLUSIONS: Supplementation with an enriched drink can raise plasma levels of enzymatic and non-enzymatic antioxidants in frail elderly people.     

Hyperhomocysteinemia in poorly controlled type 2 diabetes patients

Elevated blood level of homocysteine is strongly related to an increased risk for atherosclerosis and cardiovascular disease. The role of homocysteine in Type 2 diabetes vascular complications remains unclear. Our objective was to investigate homocysteine levels in poorly controlled Type 2 diabetic patients, who are at increased risk of vascular complications development. Forty-four Type 2 diabetic patients with no symptoms of any cardiovascular disease were divided into 2 groups: 26 patients with poor metabolic control treated with oral agents (aged 66.8 +/- 5.4 yr, diabetes duration 11.9 +/- 4.1 yr, fasting plasma glucose 13.9 +/- 4.6 mmol/l, HbA1C 9.8 +/- 1.6%), 18 well-matched diabetic patients well-controlled with oral agents (aged 65.8 +/- 4.7 yr, diabetes duration 10.9 +/- 4.2 yr, fasting plasma glucose 7.3 +/- 2.4 mmol/l, HbA1c 6.6 +/- 0.7%). The controls were 12 healthy subjects. Fasting total plasma homocysteine and plasma insulin concentrations were measured. Plasma total homocysteine concentrations were significantly higher in poorly controlled than in well-controlled diabetic patients and controls (17.1 +/- 4.5 vs 8.2 +/- 3.9 and 6.5 +/- 4.9 micromol/l respectively, p < 0.001). Insulinemia showed an inverse correlation with homocysteine levels (8.3 +/- 5.2 vs 14.6 +/- 5.2 and 9.3 +/- 6.1 microlU/ml, p < 0.001; r = -0.32, p < 0.05). HbA1c values correlated positively with homocysteine concentrations in poorly controlled subjects (r = 0.41; p < 0.05). In conclusion, chronic poor metabolic control of Type 2 diabetes is characterized by elevation of plasma homocysteine concentration, which also inversely correlates with endogenous insulin levels. These results may add to the understanding of the increased frequency and mechanisms of vascular damage in diabetes mellitus.     

Urinary ethyl glucuronide and 5-hydroxytryptophol levels during repeated ethanol ingestion in healthy human subjects

AIMS: This study investigated the stability and reproducibility of urinary ethyl glucuronide (EtG) and the 5-hydroxytryptophol (5-HTOL) to 5-hydroxyindole-3-acetic acid (5-HIAA) ratio, both of which are used as biochemical markers of recent alcohol consumption, after single and multiple oral doses of ethanol in healthy human subjects. METHODS: Nine females aged 19-27 years drank ethanol (8%, w/v, in juice) or placebo (juice) in random order. The intervention consisted of 0.4 g/kg (22-28 g) of ethanol or placebo twice daily (in the morning and evening) during 8 consecutive days, starting in the evening on day 1. Spot urine samples of the first morning void were collected during the 8-day drinking period and for another 3 days (days 9-11) with no intake of ethanol or placebo. Ethanol, EtG, 5-HTOL and 5-HIAA were determined in the urine samples by headspace GC, LC-MS, GC-MS and HPLC, respectively. RESULTS: The individual results during the drinking period were highly variable, both within and between subjects, ranging from 0-7.3 mmol/l for ethanol, 1.4-71.0 mg/l for EtG, 0.1-4.5 mg/mmol for the EtG/creatinine ratio, and 2-109 nmol/ micro mol for 5-HTOL/5-HIAA. The placebo group consistently showed negative values for ethanol (< 0.1 mmol/l) and 5-HTOL/5-HIAA (< 15 nmol/ micro mol), but two samples were positive for EtG (> 0.1 mg/l). In the morning of day 9 (i.e. approximately 14-15 h after the last dose), ethanol was no longer measurable in urine and the 5-HTOL/5-HIAA ratio had returned to below the reference value, but detectable levels of EtG (11.3 +/- 6.0 mg/l, mean +/- SD) and the EtG/creatinine ratio (1.0 +/- 0.3 mg/mmol) were found in all samples. CONCLUSIONS: The results confirm the increase in urinary EtG and 5-HTOL levels during acute ethanol intake, although the individual values were highly variable both within and between subjects. No significant accumulation of either compound occurred upon multiple-dose administration of 0.8 g/kg (44-57 g) ethanol per day for approximately 1 week.     

Changes in serum leptin levels in chronic renal failure patients with metabolic acidosis.

OBJECTIVE: To examine the relationship between serum leptin levels (SLL) and metabolic acidosis in patients with chronic renal failure (CRF). DESIGN: SLL in control patients and in predialysis patients with CRF were measured and compared. SLL before and after correction of acidosis in patients with CRF were also compared. Patients and Controls: Twenty-five patients with CRF (10 men and 15 women) aged 51.2 +/- 10.4 years and control patients (healthy subjects, 23 men and 25 women) aged 42.1 +/- 12.6 years were studied. INTERVENTION: Five percent sodium bicarbonate (NaHCO(3), 2 to 3 mL/kg) was intravenously infused on the morning of the first day of treatment. NaHCO(3) was taken orally at a dosage of 50 to 200 mg/kg/d for 3 to 5 days thereafter. Main Outcome Measure: SLL before and after NaHCO(3) treatment was measured by radioimmunoassay, and blood gas was measured before and after correction of metabolic acidosis in patients with CRF. RESULTS: SLL in the normal control group (n = 48) was 10.04 +/- 7.0 ng/mL and was realated to body mass index (BMI) (P =.0331). SLL in men (n = 23) was lower than that in female controls (n = 25, P <.01). SLL in patients with CRF (n = 25) before (plasma HCO(3)(-), 13.03 +/- 3.05 mmol/L) and immediately after improvement of metabolic acidosis (plasma HCO(3)(-), 18.35 +/- 4.21 mmol/L) was 14.52 +/- 9.27 ng/mL and 15.34 +/- 11.89 ng/mL (P >.05), respectively. SLL measured 3 to 5 days after treatment for metabolic acidosis (plasma HCO(3)(-), 20.46 +/- 4.03 mmol/L) was 19.33 +/- 14.58 ng/mL, which was significantly higher than that in the normal control group and that in acidotic patients before NaHCO(3) treatment (P <.01). CONCLUSIONS: SLL in acidotic patients with CRF were comparable to that in control subjects, and SLL was significantly increased after correction of metabolic acidosis in patients with CRF. The preliminary results suggest that hyperleptinemia in patients with CRF may be masked by metabolic acidosis and that metabolic acidosis may inhibit leptin synthesis or secretion. Further studies are needed to clarify the mechanisms.     

Effects of long-term supplementation with whey proteins on plasma glutathione levels of HIV-infected patients

BACKGROUND: HIV infection is characterized by an enhanced oxidant burden and a systemic deficiency of the tripeptide glutathione (GSH), a major antioxidant. The semi-essential amino acid cysteine is the main source of the free sulfhydryl group of GSH and limits its synthesis. Whey proteins are rich in cysteine as well as in GSH precursor peptides. AIM OF THE STUDY: In order to evaluate the effects of whey supplementation on plasma GSH levels, HIV-infected patients were treated with whey proteins for a period of six months. METHODS: In a double blind clinical trial, 30 patients were randomized to a daily dose of 45 g whey proteins of either Protectamin (Fresenius Kabi, Germany) or Immunocal (Immunotec, Europe) for 2 weeks. Eighteen patients (16 male, 42 +/- 9.4 yr, 249 +/- 99 CD4+ lymphocytes/l) continued the trial with a daily dose of 45 g of Protectamin for six months. RESULTS: Pre-therapy, total plasma GSH levels (Protectamin: 1.92 +/- 0.6 microM; Immunocal: 1.99 +/- 0.9 microM) were less than normal (2.64 +/- 0.7 microM, p = 0.03). After two weeks of whey protein supplementation, plasma total GSH levels increased in the Protectamin group by 44 +/- 56% (2.79 +/- 1.1 microM, p = 0.004), while the difference in the Immunocal group did not reach significance (+24.5 +/- 59 %, 2.51 +/- 1.48 microM, p = 0.43). Consequently, all patients continuing the trial were openly switched to Protectamin. After six months, total GSH plasma levels were still significantly elevated compared to baseline (day 1: 1.95 +/- 0.8 microM vs. month 1: 2.18 +/- 0.8 microM, p = 0.19; month 3: 2.39 +/- 0.9 microM, p = 0.056; month 6: 2.47 +/- 0.8 microM, p = 0.033). Body weight, T-cell counts, and other clinical parameters did not change. The most common mild side effect was intestinal disturbance; severe adverse events did not occur. CONCLUSION: Supplementation with whey proteins persistently increased plasma glutathione levels in patients with advanced HIV-infection. The treatment was well tolerated. A larger long-term trial is clearly warranted to evaluate whether this positive influence on the glutathione metabolism translates into a more favorable course of the disease.     

Non-attendance at secondary prevention clinics: the effect on lipid management

BACKGROUND: Secondary prevention of coronary artery disease is effective in reducing morbitiy and mortality. Our aim was to assess lipid management following non-attendance to a hospital based secondary prevention clinic. METHODS: Data were collected over 5 years on statin usage and total cholesterol levels for patients with coronary artery disease following attendance at a cardiac nurse led outpatient clinic. Lipid levels were taken from a central laboratory database, for both patients discharged from clinic and non-attenders. RESULTS: From 935 inpatients discharged from hospital, 248 (29%) defaulted from outpatient follow up. Lipid lowering drug usage was similar (72% vs. 74% for non-attenders, p=NS). Attenders at the nurse led outpatient clinic were more likely to achieve a total cholesterol <5 mmol/L at discharge than non-attenders (70% vs. 43%; p < 0.001), with a lower mean total cholesterol (4.75 +/- 0.06 mmol/L vs. 5.33 +/- 0.08 mmol/L; p < 0.001). Non-attenders subsequently had a greater number of cholesterol measurements than those who were discharged from the hospital based clinic (range 0-12, c2 23.8 on 12 df p < 0.005). Lipid profiles in hospital non-attenders remained inferior with fewer achieving a total cholesterol <5 mmol/L (61% vs. 78%; p < 0.001), and having greater mean total cholesterol levels (4.85 +/- 0.06 mmol/L vs. 4.52 +/- 0.05 mmol/L; p < 0.001). CONCLUSIONS: Patients defaulting from hospital follow up have higher total cholesterols with fewer at target level compared to attenders. Though non-attenders receive subsequent lipid measurement, inferior lipid profiles persist compared to patients who completed hospital follow up to be discharged. Further implementation strategies are needed with regard to lipid management in this patient group.     

Nitrite plasma levels in chronic lung disease patients

BACKGROUND: The authors carried out a study in a group of lung disease patients, about the behaviour of the plasmatic levels of nitrites (stable, specific and irreversible end-products of nitric oxide). METHODS: The series consisted of 13 male patients (mean age 65 +/- 7 years) with chronic obstructive pulmonary disease with type 1 respiratory failure; 33 male subjects (mean age 58 +/- 5 years) without internistic disease were considered as controls. For each subject the determination of nitrite plasma levels by the Gutman and Hollywood method based on the Griess colorimetric reaction was performed. RESULTS: The mean value of the plasmatic nitrites was significantly reduced (p < 0.05) as compared to the controls (11 +/- 0.48 mumol/l vs 21 +/- 0.92 mumol/l). CONCLUSIONS: The authors hypothesized that in chronic lung disease patients there would be a condition of initial pulmonary hypertension; in this condition long-term endothelium-dependent nitric oxide production, aimed at the vasodilating effects with secondary excessive exhaled amount of NO, might cause a reduction in nitrite plasma levels. These levels may represent an early marker of pulmonary hypertension and suggest interesting therapeutic treatments through inhalation of exogenous NO.     

Plasma endothelin-1 levels in patients with peripheral arterial occlusive disease at different Fontaine's stages

Endothelin-1 (ET-1) is a potent vasoconstrictor and mitogenic peptide produced and secreted by endothelial cells, which can play a potential role in the development of atherosclerosis and in the pathophysiology of extreme vasoconstriction of various diseases. METHODS: To assess plasma endothelin-1 (ET-1) concentrations in patients with peripheral arterial occlusive disease (PAOD) at different Fontaine's stages, we measured plasma ET-1 by radioimmunoassay in 14 stage II PAOD patients (12 men, 2 women; mean age 59.5 +/- 3.4 years) and in 10 stage III-IV PAOD patients (8 men, 2 women, mean age 61.2 +/- 3.3 years). Ten normal subjects (8 men, 2 women, mean age 58.1 +/- 7.2 years) were considered as controls. RESULTS: Mean (+/- SD) plasma ET-1 levels, as measured by radioimmunoassay, were significantly greater in stage II and stage III-IV PAOD patients than in control subjects (4 +/- 0.4 and 5 +/- 0.4 pmol/L vs 2.5 +/- 0.6 pmol/L, respectively, p < 0.001). Furthermore, plasma levels of ET-1 in stage III-IV patients were significantly higher than in stage II patients (p < 0.01). A significant correlation was found between plasma ET-1 levels and number of the arterial obstructive lesions in PAOD patients (r = 0.698; p < 0.0001). No significant correlation was found between plasma ET-1 concentrations and pain-free walking distance (r = -0.279, p = 0.333, in stage II patients; r = 0.137, p = 0.705, in stage III-IV patients), and between plasma ET-1 levels and ankle/arm pressor index (r = 0.032, p = 0.913, in stage II patients; r = 0.149, p = 0.681, in stage III-IV patients) in the PAOD patients. CONCLUSIONS: Raised plasma ET-1 could be a sensible marker both of endothelial damage and disease extension. It could also promote the progression of atherosclerotic plaques and enhance the microvascular resistance in these patients.     

Effect of sleep deprivation on insulin sensitivity and cortisol concentration in healthy subjects

The objective of this study was to assess insulin sensitivity and cortisol concentration in healthy subjects with 24-hr sleep deprivation. A randomised, single-blind, controlled clinical trial was performed in 28 healthy subjects. Fourteen individuals were studied before and after 24-hr sleep deprivation and 14 volunteers with normal sleep periods (NSP) as a control group. Serum creatinine, uric acid, total cholesterol, high-density lipoprotein cholesterol, and triglyceride concentrations were measured in both groups. Insulin suppression test modified with octreotide (IST) and cortisol levels were performed before and after 24-hr sleep deprivation or NSP. Clinical and metabolic characteristics of the subjects in both groups are similar. Steady-state glucose (SSG) concentration of the IST was significantly higher after 24-hr sleep deprivation (5.7+/-2.1 vs 6.7+/-2.2 mmol/l; p=0.01). SSG level was similar before and after NSP (5.0+/-2.1 vs 5.0+/-1.8 mmol/l, respectively; p=0.91). There were not significant differences in cortisol levels between initial and final tests in both groups. In conclusion, 24-hr sleep deprivation decreased the insulin sensitivity in healthy subjects without changes in cortisol levels.     

Safety and metabolic tolerance of a concentrated long-chain triglyceride lipid emulsion in critically ill septic and trauma patients

BACKGROUND: A concentrated fat emulsion (Intralipid 30%) with a phospholipid/triglyceride ratio of 0.04 was tested for clinical tolerance and metabolic effects in the short-term parenteral nutrition of septic and trauma critically ill patients and compared with Intralipid 20% (phospholipid/triglyceride ratio of 0.06). METHODS: This was a prospective, randomized, multicenter study in the intensive care units in 10 university hospitals, including 90 adult patients in 2 groups: 55 septic and 35 trauma patients. Patients in each group were randomly divided into 2 subgroups according to the fat emulsions administered (1.4 g/kg per day) as part of the calories for at least 6 days of continuous total parenteral nutrition (TPN). One subgroup was treated with 30% long-chain triglycerides (phospholipid/ triglyceride ratio: 0.04) and the other with 20% long-chain triglycerides (phospholipid/triglyceride ratio: 0.06). The parenteral nutrition formula was isocaloric and isonitrogenous with 0.25 g of nitrogen/kg per day and 40% of the nonprotein calories as fat. Clinical tolerance was assessed during the study. At baseline and after 3 and 6 days of TPN, the following biochemical parameters were measured: prealbumin, retinol-binding protein, serum albumin, hematologic, hepatic and renal function variables, triglycerides, phospholipids, total and free cholesterol, nonesterified cholesterol, nonesterified fatty acids, and lipoproteins. RESULTS: At baseline, no differences in age, gender, severity of the condition [Acute Physiology and Chronic Health Evaluation (APACHE II) score], or clinical chemistry were found between the subgroups. The levels of plasma proteins studied and the renal, hematologic, or hepatic function variables did not vary during the study period. Total cholesterol increased significantly, owing to esterified cholesterol, with 20% long-chain triglyceride in septic patients (baseline: 2.1 +/- 0.8 mmol/L, day 6: 2.8 +/- 0.6 mmol/L, p = .026). In septic patients receiving 20% long-chain triglycerides, plasma triglycerides had a similar behavior (baseline: 1.4 +/- 0.6 mmol/L, day 3: 2.2 +/- 0.8 mmol/L, p < .05). The very-low-density lipoprotein content of cholesterol, triglycerides, and phospholipids showed a tendency to decrease in septic patients treated with 30% long-chain triglycerides (NS). None of the emulsions induced the synthesis of lipoprotein X. CONCLUSIONS: Our results indicate that while both fat emulsions used in the TPN of critically ill patients are clinically safe, the 30% long-chain triglyceride fat emulsion with a phospholipid/triglyceride ratio of 0.04 causes fewer lipid metabolic disturbances.     

Goals in risk factor reduction and therapeutic failures

Risk factors' reduction decreases the number of vascular events. The therapy is successful, when target values of risk factors became realised. AIMS: 3 modifiable risk factors - hyperlipidemia, hyperglycemia, hypertension - were checked in 350 high risk patients, comparing the target and the realised values of risk factors. METHODS: 1. Medical history of risk factors' therapy. 2. serum lipids and fasting blood glucose parameters. 3. Physical and ultrasound examinations for cerebro-, cardio- and peripheral vascular diseases, measurement of abdominal circumference and blood pressure. 4. Risk stratification. 5. Statistical analysis. RESULTS: 1. Mean LDL-cholesterol was 3 +/- 0.94 and 3.3 +/- 0.87 in the group of patients with and without therapy, respectively (p < 0.01). Number of not treated patients is high (47.3%). 2. There were significantly (p = 0.053) more treated patients above blood sugar goals (6,7 mmol/l), than in the group of untreated patients. Mean fasting blood glucose were 8.11 +/- 3,036 and 7.25 +/- 1.925 mmol/l in treated and not treated group of patients, respectively (p = NS). 3. There were significantly (p < 0.00001) more hypertensive patients above therapeutic goal in the treated and less in the untreated group of patients. Mean tension (153,4 +/- 22.42 and 139.7 +/- 20.76) was significantly (p < 0,001) higher in the treated, and lower in the untreated group of patients. 4. Number of risk factors are more in high risk patients. Only 5.2% of patients became free of risk factors by recent clinical practice and in 72.3% remained 2 or 3 factors. CONCLUSIONS: Most part of patients do not reach the therapeutic goals, and there are many persons without any therapy for hyperlipidaemia. To cure and to treat are different.     

Acute L-Arginine supplementation does not increase nitric oxide production in healthy subjects

ABSTRACT: Dietary supplements containing L-arginine have been marketed with the purpose of increasing vasodilatation, and thus, blood and oxygen supply to the exercising muscle. The present study evaluated the acute effect of L-arginine supplementation on indicators of NO production, nitrite (NO2 -) + nitrate (NO3 -) (NOx), in healthy subjects. Plasma concentrations of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) have also been addressed. Seventeen healthy males participated in a randomized, double-blind, placebo-controlled study. Blood samples were drawn from a left antecubital vein at baseline (T0). Afterwards, subjects were randomly submittedto 6 g of oral L-arginine supplementation (as L-arginine hydrochloride) or placebo (as corn starch); afterwards, the subjects remained at rest in supine position and blood samples were drawn again at 30 (T1), 60 (T2), 90 (T3) and 120 minutes (T4) after supplementation. To analyze NO production, NO3 - was converted to NO2 - by nitrate reductase, followed by the derivatization of NO2 - with 2,3- diaminonaphthalene. NOx, ADMA and SDMA were analyzed using a high-performance liquid chromatography system and monitored with a fluorescence detector. Two-way ANOVA with repeated measures showed no significant changes in NOx concentrations on the L-arginine group as compared to placebo group at any of the fivetime points (T0: 17.6 +/- 3.9 vs 14.6 +/- 2.3 mumol/L; T1: 15.8 +/- 2.4 vs 14.3 +/- 1.7 mumol/L; T2: 16.8 +/- 4.9 vs 13.7 +/- 2.7 mumol/L; T3: 16.7 +/- 3.9 vs 14.6 +/- 2.1 mumol/L; T4: 15.1 +/- 2.8 vs 13.5 +/- 3.5 mumol/L). Furthermore, plasma levels of ADMA and SDMA were not statistically significant between the L-arginine and placebo groups at T0 (0.43 +/- 0.19 vs 0.39 +/- 0.15 mumol/L and 1.83 +/- 1.13 vs 1.70 +/- 0.62 mumol/L), respectively. In conclusion, acute L-arginine supplementation does not increase plasma concentration of NOx in healthy individuals with normal plasma concentrations of ADMA.     

Control of diarrhea by fiber-enriched diet in ICU patients on enteral nutrition: a prospective randomized controlled trial

BACKGROUND AND AIMS: Enteral fiber-free diets alter intestinal transit and produce diarrhea or constipation. This prospective double blind, controlled study evaluates the use of guar gum, a soluble fiber and a candidate prebiotic in enteral feeds, to prevent diarrhea and potential health benefits in intensive care unit patients. METHODS: Twenty patients on enteral nutrition with persistent diarrhea were randomized to receive a new enteral feed either enriched with 2% soluble guar gum (study group, n = 10) or fiber-free (control group, n = 10) for 4 successive days. RESULTS: The number of liquid stools in response to a soluble fiber-enriched diet was 2.0+/-0.9 (first day) vs. 1.0+/-0.7 (fourth day) (P < 0.01), and in the control group 1.2+/-0.7 (first day) vs. 2.1+/-0.8 (fourth day) (P < 0.05). In the fiber-enriched feed group, plasma glucose and cholesterol levels at termination of the study, respectively, reached 126+/-81 and 164+/-71 mg dl(-1), as compared to 333+/-108 and 378+/-26 mg dl(-1) on Day first (P < 0.01). In the control group, these values on the fourth day were, respectively, 267+/-94 and 263+/-79 vs. 247+/-115 and 315+/-78 on Day first (P > 0.05). CONCLUSIONS: Guar gum-enriched enteral nutrition was related to a decrease of diarrheal episodes in ICU patients with preexisting diarrhea; and to a trend for lower plasma glucose and cholesterol levels.     

Serotonin metabolism in children with kwashiorkor.

Intestinal fat absorption, serum 5-hydroxytryptamine (5-HT) and 24-hour urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) were studied in 13 children with kwashiorkor and 10 matched healthy controls. Eight out of 13 children with kwashiorkor who had steatorrhea also showed raised plasma serotonin levels in parallel with the high urinary excretion of 5-HIAA. In five children with kwashiorkor who showed normal intestinal fat absorption, the serum 5-HT and urinary 5-HIAA levels were comparable to controls. After therapy, concurrent with clinical and biochemical recovery, the intestinal absorption of fat improved, serum 5-HT concentration and the urinary excretion of 5-HIAA returned to normal range. This suggested that the deranged serotonin metabolism in our cases was secondary to the protein-calorie deficiency. The presence of defective metabolism of serotonin (5-HT) in children with kwashiorkor has been reported and its possible role in the etiopathogenesis of steatorrhea-diarrhea, skin lesions and psychomotor changes has been suggested for further work.