Dietary habits affect fatty acid composition of visceral adipose tissue in subjects with colorectal cancer or obesity.

PURPOSE: Aim of this study was to identify a possible relationship among dietary fatty acids (FA) intake, FA adipose tissue (AT) profile and cancer condition in lean vs obese subjects affected or not by colorectal cancer (CRC). Actually, inadequate dietary habits together with physical inactivity are primary determinants of obesity and cancer risk. Changes in lipid metabolism play a crucial role in different types of cancer and key enzymes involved in lipid-metabolic pathways, such as stearoyl-coA-desaturase 1 (SCD-1), are differentially expressed in normal and cancer tissues. METHODS: Food frequency questionnaires (FFQ) were analyzed by Winfood software. FA were assessed by gas-liquid chromatography in visceral AT samples. Estimated desaturase activities were calculated as precursor FA/product FA ratio. Desaturase gene expressions were evaluated by RT-qPCR. RESULTS: Lean and obese CRC subjects showed inadequate dietary habits. In particular, lean CRC subjects showed increase in the intake of saturated FA, specifically palmitic (p = 0.0042) and stearic acid (p = 0.0091), and a corresponding reduction of monounsaturated FA consumption, in particular oleic acid (p = 0.002) with respect to lean without CRC. Estimated SCD-1 activity in AT was increased in all the groups vs lean without CRC (pANOVA = 0.029). CONCLUSIONS: Unhealthy eating habits, characterizing obese and CRC subjects, may influence the visceral AT profile and contribute to the alteration of the metabolic pathways. The quality of the diet, other than the quantity, can have a main role in the establishment of inflammatory microenvironment and in metabolic changes favouring CRC.

IFN-alpha and IL-18 exert opposite regulatory effects on the IL-12 receptor expression and IL-12-induced IFN-gamma production in mouse macrophages: novel pathways in the regulation of the inflammatory response of macrophages.

We characterized the IL-12 response of mouse macrophages in terms of modulation of IFN-gamma production by cytokines (IFN-alpha and IL-18) and regulation of IL-12 receptor expression. Beta1 and beta2 IL-12R chain mRNA expression increased with time in culture in the absence of exogenous stimulation, with concomitant acquisition of responsiveness to IL-12 for IFN-gamma production. Expression of the IL-12R beta1 chain mRNA was increased further following IL-12 treatment as a consequence of IFN-gamma expression. IL-12 response was regulated differentially by IFN-alpha and IL-18. Neutralization of endogenous type I IFN increased IFN-gamma secretion, whereas exogenous IFN-alpha reduced it. In contrast, IL-18 enhanced IFN-gamma mRNA accumulation and IFN-gamma secretion in IL-12-stimulated, but not -untreated, cultures. The opposite effects exerted by IFN-alpha and IL-18 mirror their mutual capacity of regulating-in a negative or positive manner, respectively-the expression of the IL-12R beta1 chain. We suggest that differential regulation of IL-12 response by IFN-alpha and IL-18 can represent previously unrecognized regulatory mechanisms for maintaining suitable levels of differentiation/activation in macrophages.

Regulation of chemokine/cytokine network during in vitro differentiation and HIV-1 infection of human monocytes: possible importance in the pathogenesis of AIDS.

The monocyte/macrophage lineage represents heterogeneous cell populations characterized by major differences in the phenotype and functional activities. These cells are a major source of soluble factors, such as cytokines and chemokines, which can both affect HIV replication and AIDS pathogenesis. Although monocytes/macrophages are unanimously considered important targets of HIV-1 infection, the HIV-induced alterations in their physiological functions at different stages of differentiation are still matter of debate. In this article, we review our data on the regulation of chemokine/cytokine network with regard to macrophage differentiation and HIV-1 infection, in comparison with studies from other groups. The ensemble of the results emphasizes that: 1) macrophages markedly differ with respect to monocytes for a variety of responses potentially important in the pathogenesis of HIV infection; and 2) the experimental conditions can influence the HIVmonocyte/macrophage interactions, reflecting the possible in vivo existence of a spectrum of responses among macrophage populations.

Chronic treatment with pirenzepine decreases growth hormone secretion in insulin-dependent diabetes mellitus.

We and others previously reported that nocturnal GH secretion in patients with insulin-dependent diabetes mellitus is blunted by acute cholinergic muscarinic blockade with pirenzepine. In this study, we investigated whether this inhibitory effect on GH secretion persists during chronic pirenzepine administration, and if pirenzepine administration affects glycemic control. Nocturnal GH secretion was studied from 2300-0800 h before and after one month of pirenzepine administration (100 mg/day, orally, given at 2300 h) in 13 diabetic patients receiving their usual insulin treatment. GH secretion (GH area under curve) was blunted after pirenzepine administration [mean, 877 +/- 215 (+/- SE) vs. 1407 +/- 311 micrograms/L.min; P less than 0.002]. During pirenzepine administration, hemoglobin A1c significantly decreased (P less than 0.02), and 4 of the 13 patients had lower daily insulin requirements (5-23 U/day), but there was no significant change for the group as a whole. These results indicate that the inhibitory effect of pirenzepine on GH secretion persists when pirenzepine is given chronically and that pirenzepine seems to improve the metabolic control of the patients.

DNA superstructural features and nucleosomal organization of the two centromeres of Kluyveromyces lactis chromosome 1 and Saccharomyces cerevisiae chromosome 6.

Superstructural features of the Kluyveromyces lactis chromosome 1 (KlCEN1) and of the Saccharomyces cerevisiae chromosome 6 (SCEN6) centromeric DNAs were evaluated using a theoretical method, developed by our group, and experimentally measured by gel electrophoretic retardation. Both methods show that, in spite of the remarkable AT richness of the two centromeric sequences, their curvature is not very high. However the peculiar sequence features of the two centromeres allow to organize highly stable nucleosomes, with a free energy about that of the nucleosome formed on the 5S RNA gene. The good agreement between experimental and theoretical evaluation of nucleosome free energies as well as of their multiple positioning shows that in centromeres both DNA curvature and flexibility are relevant in determining nucleosomal features.

Auditory and visual verbal short-term memory in aphasia.

Phonological short-term memory was investigated in 24 aphasic left brain-damaged patients and in 12 matched controls. Aphasic patients have a reduced auditory and visual immediate memory span and show the standard detrimental effect of phonological similarity on immediate retention only when the stimuli are auditorily presented, while in the control group the effect is present with both auditory and visual input. Most patients have phonological processing deficits, but two patients have an impaired immediate verbal memory in the absence of analysis disorders. These results, in line with most individual case studies of patients with selective deficits of verbal short-term memory, are interpreted with reference to a model distinguishing a phonological short-term store component of memory, to which auditory input has direct and automatic access, and a rehearsal component, that, after phonological recoding, conveys visually presented stimuli to the phonological store. This latter system, that appears to become fully operational later in development, is less resistive to brain damage.

Stimulating visual exploration of the neglected space in the early stage of stroke by hemifield eye-patching: a randomized controlled trial in patients with right brain damage.

BACKGROUND: It has been well established that the presence of neglect is a predictor of poor functional outcome after stroke. Most rehabilitation studies on neglect have been performed with at least two months post-stroke. However, a recent series of stroke management indications highlight the importance of early rehabilitation treatment and evidence regarding neglect rehabilitation in the early phase after stroke is needed. AIM: To evaluate the effectiveness of right half-field patches in treating neglect in patients during the early phase of stroke. DESIGN: Randomized controlled trial. SETTING: Acute care setting in an urban general hospital. POPULATION: Eighteen patients with left unilateral neglect recruited among 56 patients consecutively admitted with right hemispheric stroke. METHODS: The patients were evaluated at pre-treatment, post-treatment, and at a 7-day follow-up. The experimental group received right half-field patch treatment (n=10) for approximately 8 hours a day for 15 consecutive days. The control group received visual scanning training (n=8) for 40 minutes every weekday in a 15 day period. RESULTS: Both groups significantly improved their performance in all outcome measures. No difference in the amount of improvement between the two groups was found. CONCLUSION: Right half-field eye patching could be a promising technique for treating visual spatial neglect during the early stages of stroke. CLINICAL REHABILITATION IMPACT: The eye-patching technique may represent an easily applicable and inexpensive method for neglect rehabilitation in the early stage after stroke.

Evolution of oral and written confrontation naming errors in aphasia. A retrospective study on vascular patients.

Impaired naming is a common finding in aphasia but while it is known that naming errors diminish over time, longitudinal studies are rare. In this retrospective study, naming errors of 84 vascular aphasic patients are studied. Errors in oral and written confrontation naming tasks in two successive evaluations are tabulated and coded into one of 10 error types. No Response, Word-Finding Difficulty, Semantic Paraphasia, Unrelated Paraphasia, Phonemic/Orthographic Paraphasia, Neologism, Paraphasic Jargon, Phonemic/Neologistic Jargon, Stereotypy, and Other. All analyses were carried out on the difference scores, that is, the score in the second examination minus the score in the first examination. Results indicate that there is a significant decrease of No Responses (in oral and written naming) and Neologisms (in oral naming), and a significant increase of Orthographic Paraphasias in written naming. Moreover, the difference score for Phonemic/Orthographic Paraphasias was higher in written than oral naming. The difference scores for the other types of error were not statistically significant.

Danazol and internal carotid artery thrombosis.

The case of a 47-year-old woman suffering from a CT-assessed ischemic right hemisphere stroke, which occurred after a 2-month treatment with danazol (a synthetic androgen), is reported. The patient's thrombocytosis in association with danazol treatment and its possible correlations with the thrombotic event are discussed.

Antiallergic agents. IV - Substituted 2-benzylidene-3(2H)-benzofuranone-5-carboxylic acids.

A series of substituted 2-benzylidene-3(2H)-benzofuranone-5-carboxylic acids were synthetized and tested for antiallergic activity by the passive cutaneous anaphylactic reaction in the rat. Many compounds display an antiallergic activity comparable to that of disodium chromoglycate when administered parenterally: in addition some derivatives are effective when given by mouth.

[Myocardial response to ischemia produced by repeated coronary occlusions: an experimental study]. / Risposta miocardica all'ischemia prodotta da occlusioni coronariche ripetute: studio sperimentale.

BACKGROUND: The fact that brief repeated episodes of ischemia may induce prolonged functional depression of the left ventricle is still a matter of debate. During an angioplasty several brief (20-90 sec) coronary occlusions are performed, with the potential risk of inducing myocardial jeopardy. METHODS: We performed 4 repeated LAD occlusions in 7 open chest pigs under general anesthesia and controlled ventilation. The following parameters were evaluated: mean systemic arterial pressure (MAP), left ventricular peak systolic pressure (LVPSP), heart rate (HR), and peak negative and positive dP/dt (dP/dt- and +). Each parameter was measured in the basal state and every 4 sec, in the expiratory phase, during the coronary occlusion, the first min and after 10 min of reperfusion. The percent change from control values for each parameter was also calculated and, by means of the ANOVA test, the differences among the 4 consecutive occlusions for each parameter were tested. RESULTS: The results showed that: 1) coronary occlusions significantly depressed dP/dt + and -, MAP and LVPSP, while HR did not change; 2) each variable returned to control values within 1 min of reperfusion; 3) the response to ischemia (percent change) was the same in each of the 4 consecutive occlusions for all parameters at every recording time. CONCLUSIONS: We can conclude that: 1) each experimental coronary occlusion induces a depression of myocardial function that is reversible in 1 min of reperfusion; 2) four repeated 2 minutes coronary occlusions do not induce cumulative effects on myocardial response to ischemia.

HIV-1 gp120 and chemokine activation of Pyk2 and mitogen-activated protein kinases in primary macrophages mediated by calcium-dependent, pertussis toxin-insensitive chemokine receptor signaling.

Human immunodeficiency virus type 1 (HIV-1) uses the chemokine receptors CCR5 and CXCR4 as coreceptors for entry. It was recently demonstrated that HIV-1 glycoprotein 120 (gp120) elevated calcium and activated several ionic signaling responses in primary human macrophages, which are important targets for HIV-1 in vivo. This study shows that chemokine receptor engagement by both CCR5-dependent (R5) and CXCR4-dependent (X4) gp120 led to rapid phosphorylation of the focal adhesion-related tyrosine kinase Pyk2 in macrophages. Pyk2 phosphorylation was also induced by macrophage inflammatory protein-1beta (MIP-1beta) and stromal cell-derived factor-1alpha, chemokine ligands for CCR5 and CXCR4. Activation was blocked by EGTA and by a potent blocker of calcium release-activated Ca++ (CRAC) channels, but was insensitive to pertussis toxin (PTX), implicating CRAC-mediated extracellular Ca++ influx but not Galpha(i) protein-dependent mechanisms. Coreceptor engagement by gp120 and chemokines also activated 2 members of the mitogen-activated protein kinase (MAPK) superfamily, c-Jun amino-terminal kinase/stress-activated protein kinase and p38 MAPK. Furthermore, gp120-stimulated macrophages secreted the chemokines monocyte chemotactic protein-1 and MIP-1beta in a manner that was dependent on MAPK activation. Thus, the gp120 signaling cascade in macrophages includes coreceptor binding, PTX-insensitive signal transduction, ionic signaling including Ca++ influx, and activation of Pyk2 and MAPK pathways, and leads to secretion of inflammatory mediators. HIV-1 Env signaling through these pathways may contribute to dysregulation of uninfected macrophage functions, new target cell recruitment, or modulation of macrophage infection.