Dietary iron deficiency in the rat. I. Abnormalities in energy metabolism of the hepatic tissue.

Severe iron deficiency was induced in rats by rearing nursing dams and their offspring on a diet comprising all the requisite nutrients and trace metals except iron. The iron deficient 5-week-old rats exhibited a severe anemia and a drastic decrease in iron content of the hepatic tissue and of the mitochondrial fraction. Cytochromes c + c1 and b were moderately but significantly reduced. A large increase in liver concentration was observed in iron-deficient animals; whereas there was no modification in total lipid, cholesterol, phospholipid and fatty acid composition of the mitochondrial membrane. Mitochondria from iron-deficient rats presented a partial uncoupling of the oxidative phosphorylation process. This functional derangement was completely reversed by the presence of either bovine serum albumin or L-carnitine plus ATP. This behaviour suggested that endogenous long-chain fatty acids could be primarily involved in the onset of mitochondrial dysfunction. The hepatic energy state of the liver appeared dramatically decreased under the pathological condition of severe iron-deficiency anemia. The possibility of a direct link between the partial loss of coupled functions observed in isolated mitochondria and the heavy energy deficit detected in the liver is discussed.

Genetic polymorphisms of Fas (CD95) and FasL (CD178) in human longevity: studies on centenarians.

Apoptosis plays a crucial role in immunosenescence, as also evidenced by the increased expression of Fas in lymphocytes from aged people. However, little is known about the genetic regulation of Fas and its ligand, FasL. We have studied their polymorphisms in 50 centenarians and 86 young donors living in Northern Italy. The first Fas polymorphism, at position -670, has in Caucasian a heterozigosity of 51%; the second, at -1377 position, has the wild type allele (G) with a very high frequency (83%) respect to the mutant allele. Genotype and allele distribution for both polymorphisms were similar in controls and centenarians. Similar results were found as far as two FasL polymorphisms (IVS2nt-124 and IVS3nt169) are concerned. On the whole, our data suggest that Fas and FasL polymorphisms, as well as their haplotypes, are unlikely to be associated with successful human longevity.

Low growth hormone-binding protein in infants with congenital hypothyroidism.

We evaluated the circulating levels of GH, insulin-like growth factor I (IGF-I), GH-binding protein (GHBP), and IGF-binding protein-3 (IGFBP-3) before L-T4 therapy in 19 infants with congenital hypothyroidism (CH), aged 12-29 days, diagnosed by neonatal screening and in a group of age- and sex-matched control infants. The same parameters were reevaluated after several months of treatment. Serum GHBP was measured by the high performance liquid chromatography-gel filtration method; serum GH, IGF-I, and IGFBP-3 levels were determined by commercial kits. The hypothyroid patients, before beginning therapy, presented significantly lower GHBP values than controls (P < 0.0001); during treatment, these values increased significantly; however, after 6 months they were still significantly lower than control values (P < 0.01). The pretreatment levels of GH were not significantly different from control values; after 1 month of treatment, GH did not show the decrease observed in controls and, therefore, was significantly higher (P < 0.01). The pretreatment levels of IGF-I were not significantly different from control values, but were lower in patients with severe than in those with mild hypothyroidism. They decreased at about 4 months of life and became significantly lower than control values at about 7 months of age (P < 0.05). In conclusion, it may be hypothesized that the condition of CH induces a change in GHBP expression, perhaps beginning in fetal life. The intrauterine production of IGF-I seems to be independent of the levels of GHBP and partially affected by fetal thyroid function.

Bile acid binding in plasma: the importance of lipoproteins.

Bile acid (BA) hydrophobicity, evaluated by the octanol-water partition coefficient, decreases along the series deoxycholic acid-chenodeoxy cholic acid-hyodeoxycholic acid-ursodeoxycholic acid-cholic acid (CA)-ursocholic acid (UCA). In vitro experiments carried out using dialysis techniques (to determine the maximum BA binding) and ultrafiltration of plasma pre-incubated with 0.1 mM BA (to assess the distribution of BA between the different lipoprotein fractions) showed that the maximum binding of BA to plasma and lipoproteins follows the same order of hydrophobicity. The fraction not bound to proteins, greater with the hydrophilic BA (UCA and CA), is distributed in the lipoprotein fractions and in particular in high density lipoproteins.

Continuous combined hormone replacement therapy with oral 17beta-estradiol and norethisterone acetate improves homocysteine metabolism in postmenopausal women.

OBJECTIVE: To evaluate the effect of a continuous combined oral hormone replacement therapy (HRT) on basal and post-methionine load homocysteine levels in postmenopausal women. DESIGN: Twenty-two postmenopausal women (PMW) were randomly allocated to receive either continuous combined oral HRT (2 mg of estradiol plus 1 mg of norethisterone acetate; n = 11) or no treatment (controls, n = 11) for 6 months. A methionine oral load (0.1 g/kg body weight) was performed in each subject at time 0 and after 6 months. Serum homocysteine levels were measured by high-performance liquid chromatography in samples collected at time 0 and at 4, 8, and 24 h after the methionine load, while levels of vitamin B6 (by high-performance liquid chromatography) and B12 and folate (both by ELISA) were assayed in samples collected at time 0. RESULTS: Serum levels of glucose and body mass index increased in treated PMW, whereas folate decreased in controls. In treated PMW, basal homocysteine tended to decrease (10.6 +/- 3.3 micromol/L vs. 9.62 +/- 2.8 micromol/L, p = 0.062), whereas in controls it significantly increased (10.7 +/- 2.65 micromol/L vs. 12.17 +/- 3.89 micromol/L, p < 0.05). This increase was not significant after correction for vitamin status (p = 0.072). Homocysteine values 4 h (31.9 +/- 13.53 micromol/L vs. 39.83 +/- 22.53 micromol/L, p < 0.05) and 8 h (35.1 +/- 13.13 vs. 43.34 +/- 22.15 micromol/L) after methionine, and integrated homocysteine response to methionine (392.5 +/- 133.8 micromol/24 h vs. 458.8 +/- 104.8 micromol/24 h; p < 0.05), were significantly reduced in HRT-treated, but not in untreated, PMW. CONCLUSIONS: Continuous combined oral HRT with17beta-estradiol plus norethisterone acetate reduces homocysteine levels, mainly after a methionine load. This effect seems to be independent of vitamin status and may have positive implications for the prevention of cardiovascular diseases in PMW.

Relationships between squalene and cholesterol in bile: effect of ursodeoxycholic acid administration in patients with radiolucent gallstones.

Squalene is an obligate intermediate of cholesterol synthesis and plasma squalene to cholesterol ratio correlates significantly with cholesterol synthesis rate in the liver. Sixteen nonobese patients with radiolucent gallstones were randomly allocated into two treatment groups receiving 15 mg/kg/day ursodeoxycholic acid (group A) or 15 mg/kg/day lactose (group B) administered three times daily for 30 days. In group A, biliary squalene to cholesterol ratio was significantly lowered (from 1.19 to 0.86, P less than 0.02), as was cholesterol saturation (from 1.39 to 0.95, P less than 0.001); levels of plasma very-low-density lipoprotein cholesterol (VLDL-C) (from 30 to 26 mg/dL) and plasma VLDL-triglyceride (VLDL-TG) (from 81 to 68 mg/dL) decreased significantly only in the group taking ursodeoxycholic acid. No variations of squalene concentrations and squalene to cholesterol ratio were observed in the plasma of both groups. Biliary cholesterol saturation during ursodeoxycholic acid administration correlated directly with squalene to cholesterol ratio in bile; reduction of these two parameters is accompanied by decreased VLDL-C levels.

Hyperhomocysteinemia and related factors in 600 hospitalized elderly subjects.

Hyperhomocysteinemia (HHcy) is a metabolic disorder frequently occurring in the elderly population. Recently several reports have suggested abnormalities in homocysteine (tHcy) metabolism implicating HHcy as a metabolic link in the multifactorial processes characterizing many geriatric illnesses-with special emphasis on atherosclerotic vascular diseases and cognitive impairment. The present study was undertaken in a large sample of elderly hospitalized subjects to determine (1) the prevalence of HHcy, (2) the association of HHcy with vascular and cognitive disorders, and (3) the factors independently predicting Hhcy. Six hundred elderly subjects (264 men and 336 women; mean age, 79 +/- 9 years) were randomly chosen from those admitted as inpatients over a period of 3 years. In all patients, body mass index (BMI), mid-upper arm muscle area (MUAMA), plasma cholesterol, triglycerides, total proteins, albumin, lymphocyte count, creatinine, homocysteine (fasting and 4 hours after methionine oral load), serum vitamin B(6), vitamin B(12), and folate concentrations were measured. The presence of disease or use of medications known to affect homocysteine plasma levels were also recorded. The mean fasting tHcy level was 16.8 +/- 12 micromol/L in the whole sample, 18.18 +/- 13.25 micromol/L in men, and 15.86 +/- 12.14 micromol/L in women (P =.005 men v women). The mean Hcy level 4 hours after methionine load was 37.95 +/- 20.9 in the whole sample. Prevalence of hyperhomocysteinemia (fasting Hcy > or = 15 micromol/L or 4 hours after methionine load > or = 35 micromol/L) was 61% (365/600) (67% in men and 56% in women, P <.05). HHcy was rarely (8%) an isolated disorder; in addition to diabetes (20%), renal failure (48.2%), and malnutrition (20.2%), it was often associated with heart failure (30%), malignancies (20.5%), and the use of diuretics (56%) and anticonvulsant drugs (13%). Plasma homocysteine progressively increases across subjects from those with no diabetes, malnutrition, renal failure, obesity, inflammatory bowel disease, heart failure to those with 1, 2, or more concurrent diseases. Multiple stepwise regression analysis showed that 72% of plasma total fasting tHcy variability was explained by age, serum folate, plasma albumin, use of diuretics, and renal function (measured as plasma creatinine clearance). In conclusion, the present study documents that hyperhomocysteinemia, in elderly hospitalized patients is (1) a common finding, (2) frequently associated with vascular and cognitive disorders, and (3) probably a secondary phenomenon in most cases. The major predictor of high plasma homocysteine levels were age, serum folate, plasma albumin, plasma creatinine clearance, and use of diuretic drugs. These variables explain a large proportion of plasma Hcy variability.

Peroxidation indices and total antioxidant capacity in plasma during hyperhomocysteinemia induced by methionine oral loading.

Hyperhomocysteinemia is a risk factor for vascular disease, although its mechanism of action is not fully clear. Different experimental studies have suggested that homocysteine (Hcy) exerts a pro-oxidant effect in the presence of metal ions (Fe and Cu). To test for a similar effect in vivo, we studied plasma markers of lipid and protein oxidation during hyperhomocysteinemia induced by an oral methionine load. Twenty-nine subjects (aged 61 +/- 25 years; 17 women), 25 of whom underwent oral methionine (100 mg/kg) loading, were studied; in every case, we measured total plasma Hcy, malondialdehyde (MDA), conjugated dienes (DIE), and oxidized protein ([PTOX] carbonylic groups) in basal conditions and 4, 6, 8, and 24 hours after methionine loading. Four participants acted as controls. In every case, we also measured total plasma antioxidant capacity (ANTOX) in basal conditions and 8 hours after methionine loading. Eight hours after methionine loading, plasma Hcy increased from 17.6 +/- 11.4 to 54.3 +/- 31.6 nmol/mL, PTOX from 0.33 +/- 0.18 to 0.71 +/- 0.33 nmol/mg protein, DIE from 493 +/- 163 to 590 +/-202 optical density units, and MDA from 1.66 +/- 0.81 to 2.1 +/- 0.93 nmol/mL. There was a significant correlation (Spearman's r) between Hcy and both PTOX (r = .86, P = .01) and MDA (r = .47, P < .05) 8 hours after methionine loading. No significant modifications of the plasma parameters were found during the observation period in controls. ANTOX at 8 hours was significantly (paired ttest) reduced in probands (from 1.74 +/- 0.59 to 1.14 +/- 0.55 mmol/mL, P = .014); no significant difference was observed for plasma ANTOX in controls. Hyperhomocysteinemia due to oral methionine loading induced an increase in plasma oxidation markers. In the absence of hyperhomocysteinemia, no significant modifications were observed. These findings, together with the decrease in ANTOX and the corresponding increase in total plasma Hcy, are consistent with a pro-oxidant effect of acute hyperhomocysteinemia in vivo.

Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity.

This study was designed to collect data on the prevalence of respiratory syncytial virus (RSV) infection in Italy in infants hospitalized for lower respiratory tract infections, and to evaluate which of the recognized risk factors might be associated with disease severity. Thirty-two centers throughout Italy participated in the study. Over a 6-month period (November 1,1999 to April 30, 2000), we evaluated all children < 2 years of age hospitalized for lower respiratory tract infections. All subjects were tested for RSV within 24 hr of hospitalization by using an immuno-enzymatic diagnostic test (Abbott Testpack, RSV). Logistic regression was used to identify the factors that might be associated with more severe disease or could increase the likelihood of RSV positivity in hospitalized infants. Out of a total of 1,232 children enrolled, 40.6% were found to be RSV-positive (RSV+). The peak of the RSV epidemic occurred in February, while the lowest prevalence of RSV positivity was seen in November (P < 0.05). A high proportion of study subjects had low birth weight and low gestational age. The clinical diagnosis at hospitalization was bronchiolitis in 66.7%, pneumonia in 15.3%, and wheezy bronchitis in 18.1%. In the bronchiolitis group, a higher prevalence of RSV+ was found in patients with gestational age or= 36 weeks (P < 0.04). No differences were found in the proportion of RSV+ patients in the three gestational age subgroups with pneumonia and wheezy bronchitis (P > 0.05, each comparison). Independent of the clinical diagnosis at admission, RSV infection was associated with more severe respiratory impairment. Environmental smoke exposure was higher in subjects with bronchiolitis than in those with wheezy bronchitis (P < 0.04), and RSV+ was positively related with the birth order (P < 0.05). The presence of older siblings and birth order plays an important role in RSV infection. The collected data show that, in Italy, RSV is an important cause of lower respiratory tract infection in infants. Gestational age, birth order, birth weight, and exposure to tobacco smoke affected the prevalence and severity of RSV-related lower respiratory tract disease.

Plasma homocysteine after insulin infusion in type II diabetic patients with and without methionine intolerance.

BACKGROUND: A high prevalence of hyperhomocysteinemia has been reported in type II diabetic patients with documented vascular disease; hence the hypothesis that hyperhomocysteinemia may contribute to overall mortality in diabetic patients. The link between insulin and homocysteine metabolism has not been completely clarified yet; in particular, only few data are available on the effects of insulin in vivo on homocysteine metabolism in the presence of abnormalities of sulphur amino acid metabolism (methionine intolerance). MATERIALS AND METHODS: To establish whether methionine intolerance and which of its determinants could influence total plasma homocysteine in response to insulin infusion in vivo in type II diabetic patients, we submitted 18 patients (Group A) with normal and 18 patients with abnormal (hyperhomocysteinemia) (Group B) response to oral methionine load to a glucose/clamp study. At time 0, and 30, 60 and 120 minutes after hyperinsulinemia, homocysteine and methionine plasma levels were assessed. In order to evaluate the cause of methionine intolerance, all patients were assayed for fasting homocysteine-cysteine ratio (as a marker of suspected heterozygosis for cystathionine-beta-synthase deficit), MTHFR C (677)T status and homocysteine-related vitamin status (serum vitamin B (6) [PLP], vitamin B (12) and folate). RESULTS: After hyperinsulinemia, plasma methionine was reduced (by about - 30 % at 120 minutes vs. basal values) within both groups, whereas tHcy tend to decrease in group A following insulin administration (up to - 6.6 +/- 3.6 % vs. basal values at 120 minutes) with a significantly higher variability, while in patients with "methionine intolerance" (group B) tHcy tended to increase (up to + 29.05 +/- 8.3 % vs. basal values at 120 min from the clamp). Serum folic acid (7.45 +/- 2.8 vs. 4.82 +/- 2.5 nmol/L, p < 0.05), Vit. B (12) (348 +/- 78 vs. 242 +/- 65 pmol/L, p < 0.05) and PLP (84.1 +/- 23.6 vs. 50.6 +/- 32.4 nmol/L; p < 0.01) were significantly higher in group A than in group B; PLP levels significantly correlated with homocysteine after 4 h methionine load (n = 36; r = - 0.327, p < 0.05); group A showed also a significantly lower prevalence of suspected heterozygosis for cystathionine-beta-synthase deficit (1/18 [11.1 %] vs. 5/18 [33.3 %], p < 0.05) and MTHFR T allele presence (4/18 [22.2 %] vs. 11/18 [61.1 %], p < 0.01). A stepwise regression analysis with tHcy plasma level variations (event A = reduction; event B = increase) as the dependent variable showed that low serum folate and PLP levels and presence of MTHFR T allele were the variables associated with insulin-induced tHcy increase. CONCLUSIONS: Methionine intolerance may influence the effect of insulin administration on plasma homocysteine in patients affected by type 2 diabetes. To prevent a possible acute (and repeated) hyperhomocysteinemia due to insulin administration in cases of methionine intolerance, it may be useful to assess the presence of methionine intolerance (tHcy after oral methionine loading) and Hcy-related vitamin status in all patients due to be subjected to insulin therapy.

Importance of serum anticholinergic activity in the assessment of elderly patients with delirium.

To evaluate the importance of serum anticholinergic activity (SAA) in elderly patients who developed delirium following hospital admission, we performed a cross-sectional study with consecutively referred inpatients in a university geriatric medical ward. Sixty-one patients aged 66 to 95 years (mean age: 79.2+/-11.6; 54% females) were recruited. Delirium was assessed by means of the Confusion Assessment Method, SAA determination, questionnaire for current drug treatment, past medical history and clinical examination, and blood chemistries. Patients were divided into two groups according to the absence (N = 49) or the presence (N = 12) of delirium. Delirious patients showed a significantly higher SAA (23.0 vs 3.9 pmol/mL atropine equivalents, P < .004); they were using antibiotics (P < .05), neuroleptics (P < .002), barbiturates (P < .004), and benzodiazepines (P < .005) more frequently. Subjects with delirium were more likely to have infections and a lower Body Mass Index; they had higher plasma glucose and creatinine. The multivariate analysis identified SAA and use of neuroleptics, and benzodiazepines as the most important features independently associated with delirium. SAA may be a suitable marker for identifying people at risk of developing delirium. Moreover, neuroleptics and benzodiazepines must be carefully used in the elderly because of their relationship with the onset of delirium.

Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants.

The influence of dietary long chain polyunsaturated fatty acid (LCP) supply, and especially of docosahexaenoic acid (DHA), on evoked potential maturation, was studied in 58 healthy preterm infants using flash visual evoked potentials (VEPs), flash electroretinography (ERG), and brainstem acoustic evoked potentials (BAEPs) at 52 weeks of postconceptional age. At the same time, the fatty acid composition of red blood cell membranes was examined. The infants were fed on breast milk (n = 12), a preterm formula supplemented with LCP (PF-LCP) (n = 21), or a traditional preterm formula (PF) (n = 25). In the breast milk and PF-LCP groups the morphology and latencies of the waves that reflect the visual projecting system were similar; in the PF group the morphology was quite different and the wave latencies were significantly longer. This could mean that the maturation pattern of VEPs in preterm infants who did not receive LCP was slower. Moreover, a higher level of erythrocyte LCP, especially DHA, was found in breast milk and PF-LCP groups compared with the PF group. ERG and BAEP recordings were the same in all three groups. These results suggest that a well balanced LCP supplement in preterm formulas can positively influence the maturation of visual evoked potentials in preterm infants when breast milk is not available.

Prophylactic nasal continuous positive airways pressure in newborns of 28-31 weeks gestation: multicentre randomised controlled clinical trial.

BACKGROUND: The role of nasal continuous positive airways pressure (nCPAP) in the management of respiratory distress syndrome in preterm infants is not completely defined. OBJECTIVE: To evaluate the benefits and risks of prophylactic nCPAP in infants of 28-31 weeks gestation. DESIGN: Multicentre randomised controlled clinical trial. SETTING: Seventeen Italian neonatal intensive care units. PATIENTS: A total of 230 newborns of 28-31 weeks gestation, not intubated in the delivery room and without major malformations, were randomly assigned to prophylactic or rescue nCPAP. INTERVENTIONS: Prophylactic nCPAP was started within 30 minutes of birth, irrespective of oxygen requirement and clinical status. Rescue nCPAP was started when Fio2 requirement was > 0.4, for more than 30 minutes, to maintain transcutaneous oxygen saturation between 93% and 96%. Exogenous surfactant was given when Fio2 requirement was > 0.4 in nCPAP in the presence of radiological signs of respiratory distress syndrome. MAIN OUTCOME MEASURES: Primary end point: need for exogenous surfactant. Secondary end points: need for mechanical ventilation and incidence of air leaks. RESULTS: Surfactant was needed by 22.6% in the prophylaxis group and 21.7% in the rescue group. Mechanical ventilation was required by 12.2% in both the prophylaxis and rescue group. The incidence of air leaks was 2.6% in both groups. More than 80% of both groups had received prenatal steroids. CONCLUSIONS: In newborns of 28-31 weeks gestation, there is no greater benefit in giving prophylactic nCPAP than in starting nCPAP when the oxygen requirement increases to a Fio2 > 0.4.

Infants of immigrant parents in Italy. A national multicentre case control study.

BACKGROUND: The aim of this study was to evaluate health state of newborns of immigrated parents from developing countries. METHODS: Hospital records of 69,605 infants born during 1996/1997 in Italy were reviewed comparing, in a case-control study, each infant of immigrated parents to two infants born immediately before and after to Italian parents. RESULTS: Of the 69,605 newborns 3906 (5.6%) were born to immigrated parents. This prevalence prolongs the increasing trend observed during the last 10 years of infants born to immigrated parents and reduces the fall of the birth rate linked to the few infants born to Italian parents. It was influenced by geographical factors, being higher in Northern-Central Italy (7%) than in Southern and Insular Italy (2.8%), as consequence of more elevated incomes in these Italian regions. The origin countries of immigrated parents were mainly Northern Africa (31.7%), Eastern Europe (18%) and Sub Saharan Africa (11.6%). Infants of immigrated parents showed higher incidences of prematurity, low birth weight, asphyxia and neonatal mortality rate than newborns with Italian parents. These higher incidences appeared related to some risk factors such as higher parity, short gestational age, some maternal infections, maternal drug dependence, maternal age less than 18 years, low familiar income, inadequate obstetric cares, difficulty to accessing the public health services. CONCLUSIONS: The health problems of infants with immigrated parents are mainly related to social disadvantage and can be overcome improving the social state, the lifestyles and the obstetric cares of the immigrated women, so as monitoring their risk pregnancies.

Different resistance of mammalian red blood cells to hemolysis by bile salts.

To evaluate why hemolysis of red blood cells (RBC) by bile acids varies in different mammalian species, we determined the mean corpuscular volume (MCV), lipid content and the concentrations of the conjugates of deoxycholate and of NaCl inducing 50% hemolysis of RBC from healthy humans, pigs, horses, cows, sheep and jaundiced humans. A volume of 0.05 mL of washed RBC at 1% hematocrit, which has the same lipid content but different phospholipid composition and number of erythrocytes (owing to the variable MCV), was incubated in taurodeoxycholate (TDC) solution (0-5 mM) to determine the TDC concentration inducing 50% hemolysis (TDC50). The TDC50 was highest in RBC of sheep and decreased within the series sheep > pig > cow > horse > healthy human > jaundiced human, which have generally increasing MCV. The osmotic resistance followed an inverse order, with jaundiced human > healthy human > horse > cow > pig > sheep. Although we found no correlation between the TDC50 and phospholipid composition of the erythrocytes tested, the extent of bile salt-induced hemolysis seemed to depend on both the MCV and the number of erythrocytes in the incubation medium.

Ultrasonographic appearance of the mega cisterna magna in the newborn.

The mega cisterna magna is a congenital developmental malformation which in the majority of instances is symptomless and does not require further study or surgical treatment. However, differential diagnosis with other cerebellar diseases is often necessary especially in newborn infants. Ultrasonographic recognition of the mega cisterna magna in a newborn infant is reported. The reported case demonstrates the usefulness of the ultrasonographic technique in the study of the posterior cranial fossa abnormalities of newborn infants.

The influence of 2-hydroxypropyl-beta-cyclodextrin on the haemolysis induced by bile acids.

Cyclodextrins improve the water-solubility of drugs and can mask their haemolytic effect in parenteral use. Because the mechanism by which bile acids induce haemolysis is poorly understood, it has been investigated in the presence of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD). The haemolytic effect of 1.8 mM solutions of cholic acid, chenodeoxycholic acid (CDCA), deoxycholic acid and ursodeoxycholic acid (UDCA) in isotonic buffer at pH 7.4 was investigated at 37 degrees C in the presence of HP-beta-CyD at concentrations from 0.18 to 32 mM. No haemolytic effect was evident for cholic acid and UDCA. The haemolytic effect of the other bile acids was reduced by addition of HP-beta-CyD and was prevented at a molar ratio of 1:1 owing to complex formation. An HP-beta-CyD:bile acid molar ratio greater than 5:1 had a different effect on the erythrocyte membrane, irrespective of the identity of the bile acid; the effect was in accordance with the complexion affinities. In the absence of HP-beta-CyD, the haemolytic effect of CDCA and deoxycholic acid appeared related to their capacity to form a surface monolayer and to solubilize the components of the erythrocyte membrane. The haemolytic effect observed after complexation of the bile acids appeared to be solely the effect of HP-beta-CyD, which was able to form a reversible inclusion complex with lipophilic components of the erythrocyte membranes at concentrations higher than 12 mM.

L-acetylcarnitine treatment of mental decline in the elderly.

A single-blind clinical trial was carried out on 481 subjects enrolled in 44 geriatric and neurologic units following a strict selection criteria: age, Mini Mental State Examination (MMSE) Global Deterioration Scale and Geriatric Depression Scale (GDS). After the initial screening and enrollment, the trial was run for 150 days in four phases: phase T0 (placebo treatment for 30 days), phases T1 and T2 (L-acetylcarnitine (LAC) 1500 mg/day for 90 days), phase T3 (further 30 days of placebo treatment). Drug efficacy was evaluated according to changes occurring from the beginning to the end of the tests which evaluate either whole and specific cognitive performances, or emotional-affective and relational behaviour. The outcome of phase T3 enabled the authors to estimate the possible favourable effects persisting after termination of L-acetylcarnitine therapy. The cognitive sphere evaluated by MMSE showed a significant increase in the total score at the end of LAC treatment (p < 0.0001). The Randt Memory Test also revealed that LAC treatment improved the items tested: the total score and the memory index increased significantly and the favourable effect persisted after LAC was discontinued. The emotional-affective area showed a significant improvement in the total score of the GDS after LAC therapy, and the positive results were confirmed by the Hamilton Rating Scale (p < 0.0001). The behavioural-relational aspects evaluated by the Family Stress Scale showed a significant decrease in the total score after treatment (p < 0.0004); the same trend was observed in the scores for instability and negative feeling. No significant adverse drug reaction occurred during the trial. In conclusion, the statistical analysis of the data from this single-blind, multicentre trial of mild mental impairment in the elderly showed a significant improvement of several performances during and after LAC treatment. Other reports indicate that this drug may be effective in the treatment of dementia.

Treatment of postprandial hypotension in the elderly.

Food intake induces splanchnic vasodilation lasting for at least one hour, which can precipitate in postprandial hypotension, if systolic arterial blood pressure falls by more than 20 mmHg. Postprandial hypotension has a high prevalence in the elderly, above all in subjects receiving hypotensive drugs or in those with disorders of the autonomic nervous system. In our total case series of 567 subjects, the prevalence of postprandial hypotension evaluated by 24-hr blood pressure recording, was 14.5%, increasing to 28% in the oldest group. Since relevant cerebral ischemic symptoms may become manifest, a correct diagnosis of the disorder and both pharmacological and non-pharmacological therapeutical approaches are of great importance for the wellbeing of old patients.

A survey of a centenarian population in Italy, focusing on self-sufficiency and cognition.

Eighty-six persons aged 100 years or older (20 males and 66 females) living in urban areas of different Italian regions were examined between 1985 and 1992, aimed at describing the characteristics of centenarians in an entire population. The female/male ratio was 4 to 1, and 69% of the centenarians lived at home. Body mass index was 21.3 in females and 24.5 in males. The subjects typically reported no major diseases, only a few hospital admittances (1.2/lifetime) and a limited use of regular medication (on average: 1.4 drugs). The mothers and fathers of the centenarians lived 76.2 and 74.2 years, respectively. The Activities of Daily Living scale revealed a decrease in instrumental activities, and an adequate self-maintenance in the majority of centenarians; a full score on the Physical Self Maintenance Scale was reached by 10% of the subjects; these scores were not significantly influenced by the isolated sensory deficits but were lower in patients with multiple impairments. The Mini Mental State Examination score was overall 17.7 +/- 8.3 for the group, reaching 24.1 in male and 20.2 in female literate subjects without major hearing or vision defects; these scores varied significantly in relation to sensory deficits and education. In our centenarian population males reached extreme old age less frequently, but with a better quality of life, than females. The good overall performance of the whole population, and especially of the subpopulation without impairments, suggests a selective survival of centenarians, as also demonstrated by the long lifespan of their immediate relatives.