Short communication: Associations between blood fatty acids, ß-hydroxybutyrate, and α-tocopherol in the periparturient period in dairy cows: An observational study.

The objective of the present study was to examine the relationships between blood concentrations of fatty acids, ß-hydroxybutyrate (BHB), and α-tocopherol during the periparturient period in dairy cows. Blood samples were collected from 131 cows belonging to 4 different commercial dairy farms in southeastern Europe (Greece and Italy). We determined blood concentrations of fatty acids, BHB, and α-tocopherol at dry-off, at calving, and 30d postpartum. Results indicated that fatty acid concentrations were low at dry-off, reached maximum value at calving, and then declined at 30d postpartum. In fact, fatty acid concentrations at 30d postpartum were 50% lower than at calving. In contrast, BHB concentrations were low at dry-off, increased by 27% at calving, and continued to increase by another 20% at 30d postpartum. Overall, we found a weak correlation between fatty acids and BHB throughout the periparturient period. Concentrations of α-tocopherol were lowest at calving, and we detected no differences in α-tocopherol concentrations at dry-off or 30d postpartum. Negative correlations between fatty acids and α-tocopherol were highly significant at 30d postpartum and approached the level of significance at dry-off. However, both correlations became nonsignificant following the adjustment of α-tocopherol with cholesterol, indicating that the correlations were a reflection of changes in lipid transport. We found significant negative correlations (strong at dry-off and weak at 30d postpartum) between BHB and α-tocopherol after adjustment with cholesterol. The physiological basis for the negative correlations between BHB and α-tocopherol, especially that at dry-off, is not known and should not be taken to imply a cause-effect relationship. However, it opens the door to investigating the effects of vitamin E on liver function in dairy cows.

Short communication: Endoplasmic reticulum stress gene network expression in bovine mammary tissue during the lactation cycle.

The endoplasmic reticulum (ER) has a crucial role in cellular metabolism. Recent studies in nonruminants discovered that components of the ER stress pathway, induced during the unfolded protein response, play critical roles in regulating lipogenesis. The bovine mammary gland faces extreme metabolic stress at the onset of lactation due primarily to the increase in flux through pathways associated with milk fat and protein synthesis. Our objective was to study, via quantitative real-time PCR, the expression of the ER stress pathway components P58IPK, PERK, XBP1, ATF4, ATF3, ATF6, CHOP, MBTPS1, GRP94, and BiP in mammary tissue (n=7 cows × 5 time points) collected at -15, 1, 15, 60, and 240 d relative to parturition. Expression of P58IPK and ATF4 increased to a peak at d 60, followed by a decrease by d 240 postpartum. Despite the decrease in expression by 240 d, P58IPK remained higher than prepartal levels (d -15). Expression patterns of ATF3 and CHOP were similar and peaked at d 15, followed by a decrease through d 240, at which point CHOP expression was still greater than prepartal levels. The sharp increase in milk production postpartum (d 15) as well as apoptosis during late lactation (240 d) may have induced a pseudo unfolded protein response state. This is supported by the similar expression patterns of P58IPK and PERK. In the context of lactation, however, transcriptional changes in the ER stress pathway at different stages of the lactation cycle are a normal aspect of the tissue's adaptation to the changing physiological state.

Taking care of smoker cancer patients: a review and some recommendations.

A cancer patient who smokes is a very fragile person and we identify in scientific literature three main areas of clinical practice and research to develop the care of smokers with cancer. (i) Telling facts: smoking impacts on the survival and on the outcomes of surgery, chemo-, radio- and biological therapies. The aim of our intervention was to enable patients to make informed choices about smoking. (ii) Offering sensitive and effective smoking cessation like an instrument of patient empowerment to motivate change in smoker patient lifestyle. (iii) Assisting smoker patients if they develop acute nicotine withdrawal symptoms. Smoking care and nicotine replacement therapy can support temporary abstinence during the inpatient stay and providing patients with an opportunity for smoking cessation can prompt a future permanent quit attempt. Comprehensive cancer centers must act like a promoter of a better smokers' care, applying guidelines to their reality and try to do more research on smokers' needs and on the resources to assist them. Only the alliance between victims of smoking addiction and health personnel can give a chance against the tobacco epidemic.

Second-hand smoke exposure in a sample of European hospitals.

Smoking in hospitals is banned in many European countries; nevertheless, the level of compliance is diverse, and, in some cases, smoking areas remain. The present study describes the levels of second-hand smoke, as derived from respirable suspended particle measurements, in a sample of European hospitals during the year 2007. The present study was a multicentric descriptive cross-sectional study carried out in 30 hospitals in seven European countries (Austria, Belgium, France, Germany, Greece, Romania and Spain). Particulate matter with a 50% cut-off aerodynamic diameter of 2.5 microm (PM(2.5)) concentration was measured by means of a hand-held laser-operated monitor of particle size and mass concentration in six selected indoor locations. Medians and interquartile ranges of PM(2.5) concentration were computed in order to describe the data by country and location of measurement. The median PM(2.5) concentration in all countries and locations was 3.0 microg x m(-3), with half of the measurements ranging 2.0-7.0 microg. x m(-3). PM(2.5) levels were similar across countries. Eleven (5.5%) measurements were >25.0 microg x m(-3), which is the 24-h mean limit recommended by the World Health Organization outdoor air quality guideline. The present results show that exposure to second-hand smoke in this sample of European hospitals is very low, and can be easily monitored in order to ensure smoke-free legislation compliance.

The effects of superoxide dismutase-rich melon pulp concentrate on inflammation, antioxidant status and growth performance of challenged post-weaning piglets.

Piglets can often suffer impaired antioxidant status and poor immune response during post-weaning, especially when chronic inflammation takes place, leading to lower growth rates than expected. Oral administration of dietary antioxidant compounds during this period could be a feasible way to balance oxidation processes and increase health and growth performance. The aim of the trial was to study the effects of an antioxidant feed supplement (melon pulp concentrate) that contains high concentration of the antioxidant superoxide dismutase (SOD) on inflammation, antioxidant status and growth performance of lipopolysaccharide (LPS) challenged weaned piglets. In total, 48 weaned piglets were individually allocated to four experimental groups in a 2×2 factorial design for 29 days. Two different dietary treatments were adopted: (a) control (CTR), fed a basal diet, (b) treatment (MPC), fed the basal diet plus 30 g/ton of melon pulp concentrate. On days 19, 21, 23 and 25 half of the animals within CTR and MPC groups were subjected to a challenge with intramuscular injections of an increasing dosage of LPS from Escherichia coli (serotype 0.55:B5) (+) or were injected with an equal amount of PBS solution (-). Blood samples were collected at the beginning of the trial and under the challenge period for interleukin 1ß, interleukin 6, tumour necrosis factor α, haptoglobin, plasma SOD activity, total antioxidant capacity, reactive oxygen species, red blood cells and plasma resistance to haemolysis, and 8-oxo-7, 8-dihydro-2'-deoxyguanosine. Growth performance was evaluated weekly. A positive effect of melon pulp concentrate was evidenced on total antioxidant capacity, half-haemolysis time of red blood cells, average daily gain (ADG) and feed intake, while LPS challenge increased pro-inflammatory cytokines and haptoglobin serum concentrations, with a reduced feed intake and gain : feed (G : F). The obtained results show that oral SOD supplementation with melon pulp concentrate ameliorates the total antioxidant capacity and the half-haemolysis time in red blood cell of post-weaning piglets, with positive results on growing performance.

Protein-protein and protein-ligand interactions studied by electrospray-ionization mass spectrometry.

Preservation of non-covalent interactions in biopolymer mass spectrometry offers new approaches to binding analysis. Recent work from our laboratory is reviewed here and discussed with reference to recent literature in the field. Three issues are considered in particular: hydrophobically stabilized complexes, pH-dependent transitions, and linked protein-ligand and protein-protein binding equilibria.

Degree of control of physician-diagnosed asthma and COPD in Italy.

BACKGROUND: It is important for the Italian National Health Service to obtain data on the degree of control of asthma and chronic obstructive pulmonary disease (COPD) in the general population in Italy in order for balanced planning of future investments in these diseases to be made. Currently, precise estimates of these parameters are not available in literature. OBJECTIVES: In collaboration with the Italian Academy of General Practitioners (SIMG; www.simg.it) we have investigated the degree of control of physician-diagnosed asthma and COPD in Italy. METHODS: A standardised questionnaire on asthma and COPD has been self-administered to a sample of 1937 Italian family physicians (representing around 5% of all the Italian doctors involved in general practice) chosen to cover all the Italian counties. RESULTS: We have collected questionnaire data from 19,917 patients with asthma and COPD followed in their practice and 12,438 (62.4%) were correctly filled in enabling evaluation. We selected the number of emergency room visits, hospitalisations and intensive care unit admissions for asthma and COPD in the last 12 months as objective measures of the degree of asthma and COPD morbidity in these patients. The figures were respectively 12.4% (emergency room visits), 17.3% (hospitalisations) and 1.2% (intensive care unit admissions) of all patients with physician-diagnosed asthma and COPD. CONCLUSIONS: This data suggests that in Italy the morbidity of asthma and COPD remains high; representing a significant burden for the Italian National Health Service. There is a clear necessity for further studies to investigate the causes of this incomplete control.

Underuse of spirometry by general practitioners for the diagnosis of COPD in Italy.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) underlines that spirometry is the gold standard as the most reproducible, standardised, and objective way of measuring airflow limitation in the diagnosis and assessment of Chronic Obstructive Pulmonary Disease (COPD). However, studies undertaken in different countries have suggested a widespread underuse of spirometry by general practitioners to establish the diagnosis of COPD. Precise estimates of the prevalence of physician-diagnosed COPD in Italy are not currently available. In collaboration with the Italian Academy of General practitioners (SIMG) we have investigated the degree of use of spirometry to establish the diagnosis of COPD in Italy. METHODS: A standardised questionnaire has been self-administered to a sample of 2425 Italian general practitioners (representing 5% of all the Italian doctors involved in general practice). They have been chosen to cover each of the Italian counties. RESULTS: The prevalence of physician-diagnosed COPD was found to be approximately 4%. However, 30% of general practitioners do not use spirometry to establish the diagnosis of COPD. The main reasons given for the failure to use spirometry are (i) that spirometry is not necessary for the diagnosis of COPD or (ii) there are logistical limitations to the access of the patients to lung function laboratories. CONCLUSIONS: This data suggests that contrary to GOLD Guidelines, in Italy, as with other countries, spirometry is not always used in the diagnosis of COPD. There is a clear necessity for further education initiatives targeted to this group of physicians.

UCP1 and UCP2 expression in different subcutaneous and visceral adipose tissue deposits in 30 days old goat kids and effect of fatty acid enriched diets.

Beside its importance in the first hours of life, brown adipose tissue has also significant roles in the following stages of growth and in adults by regulating energy metabolism, but its identification in adult ruminants is still controversial. Quantitative PCR, followed by histological confirmation, was used to investigate UCP expression and brown and white adipocytes' distribution in 30-day-old goat kids. The influence of maternal diet enriched with either fish oil or stearic acid was investigated as well. Results showed the differential expression of both UCP1 and UCP2 genes between subcutaneous and visceral adipose tissues, suggesting a different thermogenic activity between the two macro areas. The maternal diet influenced neither UCP1 nor UCP2 gene expression. The presence of multilocular adipocytes in 1-month goat kids is remarkable, as suggests thermogenic activity in non-newborn animals. Further insights into characteristics and functions of adipose tissue in young and adult goats are worth exploring.

High-resolution SPECT study of regional cerebral blood flow in drug-free and drug-naive schizophrenic patients.

OBJECTIVE: The purpose of the study was to compare regional cerebral blood flow (CBF) in schizophrenic patients never treated with psychotropic drugs (drug-naive) and in schizophrenic patients free from drugs for various amounts of time. METHOD: Seventeen schizophrenic patients (nine who were drug naive and eight who had been drug free for at least 3 weeks) and 12 healthy volunteers were included in the study. Regional cerebral perfusion was studied with the use of a head-dedicated, high-resolution single photon emission computed tomography (SPECT) system. Cerebral SPECT scans were performed with technetium-99m-hexamethyl-propyleneamine oxime as a tracer. Regional CBF was measured as a ratio of regional tracer uptake to either cerebellar or whole brain tracer uptake. RESULTS: When the cerebellum was taken as the reference region, the drug-naive patients showed a significant bilateral reduction of perfusion in the mesial, dorsolateral, and basal prefrontal cortex, in the temporal cortex, and in the subcortical gray structures: thalamus, caudate nucleus, and putamen/pallidum complex. No significant differences emerged in the comparison between the drug-free patients and the healthy subjects. With correction for whole brain activity, some of the differences that had been found disappeared, but a significant hypoperfusion persisted in the basal ganglia and thalamus of the drug-naive, but not the drug-free, patients. Few correlations between symptom presentation and regional CBF perfusion were observed in the schizophrenic patients. CONCLUSIONS: These results suggest a pattern of cerebral hypoperfusion in schizophrenic patients never treated with neuroleptics that was not detectable in patients who had undergone various periods of pharmacological washout.

Somatostatin receptor imaging of small cell lung cancer (SCLC) by means of 111In-DTPA octreotide scintigraphy.

Somatostatin receptors have been described on the membrane of neoplastic cells derived from the APUD system and their expression has also been demonstrated on small cell lung cancer (SCLC) in vitro and in vivo. 21 patients with SCLC were studied using 111In-octreotide (111In-OCT) scintigraphy. Scintigraphic examinations were performed following intravenous (i.v.) injection of 111 MBq 111In-OCT with whole-body scintigraphy and planar scintigraphy of the thorax as well as the SPET technique. No short-term side effects were described following 111In-OCT administration. We studied the 111In-OCT biodistribution in 3 patients with serial scintigraphies at 1, 5 and 24 h. We used the 5 h as standard scanning time for the following 18 patients. The scintigraphic results were compared with those of other conventional diagnostic procedures. 111In-OCT detected 86% (48/56) of the lesions already known at the time of scintigraphy. It was positive in all 20 SCLC patients and negative in one lung adenocarcinoma. 111In-OCT showed high sensitivity for mediastinal metastases (94%) and good sensitivity for bone metastases (75%) and abdominal lymph node metastases (71%). 111In-OCT did not detect two liver metastases. 111In-OCT detected five unknown lesions which were confirmed by other diagnostic examinations. 111In-OCT was also effective in cancer patients with low levels of NSE. Our study shows that 111In-OCT scintigraphy is a reliable, non-invasive technique to detect primary SLCL and its locoregional or distant metastases. The clinical utility of receptor status characterisation obtained with 111In-OCT scintigraphy should be evaluated by means of an appropriate prospective study.

Depression of cellular immune response during syngeneic pregnancy as measured by the graft-versus-host reaction.

The cellular immune response during the course of intrastrain pregnancies was evaluated in primiparous and multiparous BALB/c females by the graft-versus-host (GVH) activity of the splenic and lymph nodal lymphocytes. Splenic lymphocytes of both primiparous and multiparous pregnant mice had a GVH activity lower than that of the virgin mice. This immune deficit was more evident in multiparous than in primiparous females and occurred at the 6th day and during the last week of pregnancy. A similar although less pronounced phenomenon was found when lymph nodes instead of spleen of multiparous females were used at the source of cells in GVH reaction. The immune deficit was less marked when spleen and lymph node cells of pregnant mice were compared with similar cells of pseudopregnant females. Incubation of virgin BALB/c spleen lymphocytes in the serum of multiparous pregnant mice as compared to normal virgin serum caused a reduction of the GVH activity; incubation of the cells in pseudopregnant serum also inhibited the immune response, but to a lesser extent than the incubation in multiparous sera.

Cross-sectional echocardiographic study of criss-cross hearts and superoinferior ventricles.

From August 1982 to October 1985, 8 consecutive patients, aged 4 months to 8 years (mean 2.6), with criss-cross or superoinferior ventricles, or both, were studied. Seven patients had usual atrial arrangement and 1 had mirror-image arrangement. In 5 patients there was atrioventricular (AV) concordance with crossed AV streams, the ventricular septum was horizontal in 4 and sagittal in 1, and the ventriculoarterial connections were discordant in all. The 3 patients with AV discordance had superoinferior ventricles, but a criss-cross AV relation was not present; the ventriculoarterial connections were concordant in 2 and double-outlet right ventricle in 1. The sequential connections and spatial relations of the cardiac chambers, as well as the associated anomalies, were accurately assessed by echocardiography. The diagnosis was confirmed by angiography in all patients, by surgery in 3 and by autopsy in 2.

The Senning operation for transposition of the great arteries.

The original Senning technique of interatrial transposition of venous return was selectively employed for physiological correction in 24 patients with transposition of the great arteries (TGA) ranging in age from 74 days to 26 months (median 7 months). Twenty-three had intact ventricular septum and one had a large ventricular septal defect and diaphragmatic subpulmonary stenosis. There were no hospital or late deaths, and at follow-up examination 1.5 to 12 months postoperatively, each patient was asymptomatic, in normal sinus rhythm, and had no clinical evidence of caval or pulmonary venous obstruction. Nine patients underwent cardiac catheterization and angiocardiographic studies between 1.3 and 9 months postoperatively which demonstrated widely patent venous pathways and effective "left" and "right" atrial contraction. This experience lends support to the continued use of the Senning technique for interatrial transposition of venous return.

Exhaled carbon monoxide levels elevated in diabetes and correlated with glucose concentration in blood: a new test for monitoring the disease?

PURPOSE: In diabetes, the interaction of glycated proteins with their cell-surface binding sites leads to oxidative stress and induction of the stress protein heme oxygenase (HO)-1. Considering that carbon monoxide (CO) is a product of HO activity, we studied the level of exhaled CO as a marker of oxidative stress in diabetes. METHODS: Eight patients with insulin-dependent diabetes mellitus (type 1) (4 men, 4 women; [mean +/- SEM] age, 50 +/- 8 years) were studied, of whom 2 had peripheral neuropathy and 1 had renal failure. Sixteen patients with non-insulin-dependent diabetes mellitus (type 2) (5 men, 11 women; age 63 +/- 8 years) were studied, of whom 2 had peripheral neuropathy. Glycosylated hemoglobin (HbA(1)c) levels were higher (7.4 +/- 0.3%) in patients with type 1 (mean duration of the disease, 20 +/- 5 years) than in type 2 (4.9 +/- 0.4%; p < 0.05; mean duration of the disease, 11 +/- 2 years). All of the patients were lifelong nonsmokers. RESULTS: Levels of exhaled CO were higher in patients with diabetes (type 1, 4.0 +/- 0.7 ppm; type 2, 5.0 +/- 0.4 ppm) when compared to 37 nonsmoking healthy subjects (20 men, 17 women; age, 33 +/- 3 years) (2.9 +/- 0.2 ppm; p < 0.05). There was a positive correlation between exhaled CO levels and the incidence of glycemia in all subjects (r = 0.52, p < 0.05) and the duration of diabetes (r = 0.48, p < 0.05), but there was not a strong correlation with concentrations of HbA(1)c (r = 0.06, p = 0.8). In addition, an oral glucose tolerance test was performed in five healthy nonsmoking volunteers (three men; age, 33 +/- 4 years). The maximal glucose increase (from 3.9 +/- 0.2 to 5.5 +/- 0.1 mmol/L at 15 min; p < 0.05) was associated with a significant increase in exhaled CO concentration (from 3.0 +/- 0.5 to 6.3 +/- 1.0 ppm; p < 0. 05). Both parameters returned to the baseline at 40 min after glucose administration. CONCLUSIONS: Elevated levels of exhaled CO in diabetes may reflect HO-1 induction and oxidative stress. The measurement of CO may be a new tool for disease monitoring.

Intensification of 111In-DTPA-octreotide scintigraphy by means of pretreatment with cold octreotide in small cell lung cancer.

Small cell lung cancer (SCLC) expresses somatostatin receptors that can be traced with 111In-DTPA-octreotide scintigraphy. Although this technique is currently employed for staging and follow-up of neuroendocrine tumors of the gastrointestinal tract, its role in the clinical work-up of SCLC is at present under discussion. A better imaging contrast is desirable and recent reports suggest that this aim could be achieved by pretreatment with cold octreotide. Here we report on the results of 111In-DTPA-octreotide scintigraphy in 12 SCLC patients carried out before and after octreotide treatment. The patients were treated for 7 days with octreotide 200 micrograms three times a day s.c. Uptake was studied at 5 h with whole body planar and SPET imagings. In all cases studied, pretreatment with octreotide was followed by enhancement of tumor imaging. In one patient a better contrast of the lesions was found at the parenchymal and mediastinal levels as well as at brain level, allowing a clear definition of otherwise questionable metastases. After octreotide treatment, a decrease in background uptake in the subdiaphragmatic area was observed in most cases, allowing a better imaging of liver metastases. The enhancement effect was confirmed by semiquantitative analysis of scintigraphic uptake. Taken together, our results seem to indicate that cold octreotide enhancement can improve 111In-DTPA-octreotide imaging and optimize its clinical role in SCLC.

Age-related differences in kinetics and side-effects of viloxazine in man and their clinical implications.

Dose kinetics and side effects of viloxazine (VLX) in 16 healthy volunteers (range age 25-90 years) were studied after single oral administration of 200 mg of VLX. Significant differences in peak plasma values (P less than 0.01), t1/2 (P less than 0.01) and Cl/F (P less than 0.05) were found between subjects under 50 and over 60 years. Positive correlations were found between age and peak plasma values (P less than 0.05), age and AUC (P less than 0.01). No correlations were found between age, t1/2 and Cl/F, due to the high interindividual variability in pharmacokinetic profiles. Total reported and observed side effects scores were higher overall in subjects under 50 years than over 60 years and were inversely correlated to AUC (P less than 0.05). Drowsiness was inversely related to the age of subjects (P less than 0.05). Our data support the importance of single dose kinetic studies, particularly for new antidepressants, in relation to age, both to emphasize differences in pharmacokinetic profiles and to predict side effects during chronic treatment.

Influence of age on mianserin pharmacokinetics.

The pharmacokinetics of Mianserin (MIA) after acute administration have been studied in nine volunteers, divided into two groups according to age. The subjects were given a single oral dose of 30 mg MIA. The plasma peak time was shorter in the younger subjects than in the older. In general, the concentrations of MIA in the plasma were higher in the older subjects than in the younger, and in the former group there was no relationship between administered dose (mg/kg) and plasma levels. The area under curve, volume of distribution and clearance were significantly different in the two groups. The side effects (both incidence and type) differed in the two groups. There were no significant changes in blood pressure, either supine or standing. The sedative effect was more marked in the young than in the elderly subjects. A relationship between drowsiness and MIA plasma levels was observed only in the younger subjects.

Clozapine metabolism rate as a possible index of drug-induced granulocytopenia.

A possible relationship between haematological adverse reactions and clozapine (CLZ) metabolism rate was studied. Sixteen chronic schizophrenic outpatients (mean age 34.62 years +/- 7.56 SD) were treated with CLZ, 75-600 mg/daily for 9 weeks. CLZ and norclozapine (NCLZ) plasma levels were determined weekly, contemporarily with blood cell counts. CLZ plasma levels ranged from 25 to 1270 ng/ml (mean 266.27 ng/ml +/- 197.44 SD), while NCLZ plasma levels ranged from 25 to 1280 ng/ml (mean 169.0 ng/ml +/- 127.94 SD). NCLZ/CLZ ratio ranged from 0.13 to 1.72 (mean 0.72 +/- 0.28 SD). Leukocyte count ranged from 5.2 to 18.8 10(9)/l (mean 9.37 10(9)/l +/- 2.94 SD) and neutrophil count ranged from 1.8 to 13.4 10(9)/l (mean 5.73 +/- 2.57 SD). No correlation was found between CLZ dosage and NCLZ plasma levels. Both CLZ and NCLZ plasma levels correlated positively with neutrophil count (CLZ: P = 0.001, r = 0.26; NCLZ: P = 0.01, r = 0.20). The correlation between NCLZ/CLZ plasma level ratio and neutrophil count was significantly negative (P = 0.002, r = 0.25). These preliminary data suggest that the NCLZ/CLZ ratio, as an index of CLZ metabolism, might be a possible risk factor associated with CLZ treatment.

Time course of cerebral ventricular enlargement in schizophrenia supports the hypothesis of its neurodevelopmental nature.

In the absence of direct and conclusive data demonstrating the 'neurodevelopmental hypothesis' of schizophrenia, several neuromorphological findings provide relevant clues in support of it. In this paper, we review a number of results obtained by our group in this area of research. In particular, the demonstration of stability of cerebral ventricular dimensions both in chronic schizophrenia and around the onset of the disease, and that of an identical effect of ageing on this morphological feature in large samples of patients and controls, strongly support the neurodevelopmental nature of brain pathomorphology in schizophrenia.