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Biomedical subjects

A Liguori

Publications and source records attributed to A Liguori.

At least 19 recordsLinked to original sources

The relationship of Kraepelian affective temperaments (as measured by TEMPS-I) to the tridimensional personality questionnaire (TPQ).

BACKGROUND: There is considerable uncertainty in the current literature about the relationship between personality dimensions and affective temperaments. METHOD: We compared-in a non-ill 14-26-year-old Italian student population of 1010-the affective temperaments of classic psychiatry conceived as subaffective traits [and measured through the Temperament Assessment of Memphis, Pisa, Paris and San Diego-Interview Version (TEMPS-I) in the Akiskal and Mallya Operationalization] with Cloninger's revised Tridimensional Personality Questionnaire (TPQ) deriving from the experimental psychology tradition. RESULTS: The Depressive Temperament (DT) and Harm Avoidance (HA), loaded positively on the same canonical variate, whereas the hyperthymic (HT) strongly, and Novelty Seeking (NS) moderately, loaded negatively. In contrast, the Cyclothymic Temperament (CT) loaded highly positively on a second variate, on which both Novelty Seeking strongly and Harm Avoidance moderately loaded positively. Reward Dependence (RD), Persistence (P), and Irritable Temperament (IT) did not significantly relate to any temperamental and personality constructs. At a subdimensional level of TPQ 'shyness with strangers', 'stoic rigidity', 'detachment', 'fear of uncertainty', 'reflection', and 'anticipatory worry' correlated best with the DT. 'Gregariousness', 'exploratory excitability', 'uninhibited optimism', 'attachment', 'confidence', 'extravagance', 'independence', 'vigor', and 'impulsiveness' correlated best with HT. Lastly, 'anticipatory worry', 'disorderliness', 'sentimentality', and 'fatigability' correlated best with CT. CONCLUSIONS: The data provide concurrent validity to TEMPS-I and, as earlier suggested by Cloninger, indicate that (as expected) high HA and DT are related. High NS is both related to the HT and CT, and (somewhat unexpectedly), the CT is related to high HA. In a more theoretical vein, hyperthymic-novelty seeker can be predicted to be overrepresented among those with high achievement; on the other hand, a moody, restless disposition (a cyclothymic-harm avoidant type) may engage in outrageous behavior and be liable to negative affective arousal. We submit that these considerations could shed some light on the origin of socially adaptive behavior ('sunny' or sanguine types) on the one hand, and borderline conditions, anxious-hostile bipolarity ('dark' types) on the other.

Adolescent↗

IGF-I and IGFBP-3 assessment in the management of childhood onset growth hormone deficiency.

The diagnosis of growth hormone (GH) deficiency (GHD) in childhood is not straightforward, being still based on a comprehensive clinical, anthropometric, endocrine and neuroradiological assessment. Due to their GH dependency and relative stability in circulation, IGF-I and IGFBP-3 serum concentrations were proposed as reliable indicators of daily GH secretion. However, the sensitivity of assays for both IGF-I and IGFBP-3 is inadequate to exclude the diagnosis of GHD merely on the basis of a normal value of the two parameters, although it seems likely that IGF-I values higher than -1 SD reflect a normal GH secretion. On the other hand, as the specificity of both measurements is over 90%, subnormal concentrations strongly support the diagnosis of GHD. Finally, combining the evaluation of growth velocity with IGF-I measurement, sensitivity and specificity reach a value > or =95%, implying that two subnormal values strongly suggest and two normal values strongly oppose the diagnosis of GHD.

Biomarkers↗

A convenient method for the stereoselective conversion of aryl peptidyl ketones into the corresponding aryl aminomethin derivatives, a novel class of modified peptides.

In this paper we describe a reductive amination procedure that can be employed in the preparation of a novel class of pseudopeptides in which a specific amide bond is replaced by a CH(Ar)NH group. The developed methodology, performed using NaBH(3)CN and TiCl(4), is characterized by the formation of diastereomeric intermediates in a relative 1:1 ratio. It provides aryl aminomethin pseudopeptides in moderate but satisfactory yields and with definite stereochemistry on the asymmetric centres next to the modified peptide bond.

Amination↗

Sulfhydryl angiotensin-converting enzyme inhibition induces sustained reduction of systemic oxidative stress and improves the nitric oxide pathway in patients with essential hypertension.

BACKGROUND: Essential hypertension is associated with enhanced LDL oxidation and impaired endothelium-dependent vasodilation. The antioxidant status is linked to the nitric oxide (NO) pathway. Sulfhydryl angiotensin-converting enzyme (ACE) inhibitors inhibit oxidative stress and atherogenesis in experimental models; therefore we tested whether this beneficial antioxidant activity could be also clinically relevant in patients with essential hypertension. METHODS: Plasma LDL oxidizability was investigated initially in untreated normocholesterolemic patients with moderate essential hypertension without clinically evident target organ damage (n = 96) and in control normotensive subjects (n = 46). Patients were then randomly assigned into two age- and sex-matched groups to receive the new sulfhydryl ACE inhibitor zofenopril (15 to 30 mg/d; n = 48) or enalapril (20 mg/d, n = 48). LDL oxidizability was evaluated (generation of malondialdehyde, MDA) and systemic oxidative stress was evaluated by isoprostanes (8-isoPGF2alpha). Asymmetrical dimethyl-L-arginine (ADMA), a competitive inhibitor of endothelial NO synthase, and plasma nitrite and nitrates (NOx) were also measured. RESULTS: LDL from hypertensive subjects had enhanced susceptibility to oxidation in vitro compared with that in control subjects (P <.05). Similarly, isoprostanes were significantly increased (P <.01) in hypertensive subjects versus control subjects. After 12-week treatment, MDA levels were significantly reduced by zofenopril (P <.05) but not enalapril treatment (P = not significant). Isoprostanes were normalized after zofenopril treatment (P <.03), whereas enalapril was ineffective. After treatment with both ACE inhibitors, plasma NOx concentrations were significantly reduced (P <.05). Similarly, hypertension increased ADMA concentration compared with the normotensive state, whereas ACE inihibition elicited a significant decrease. However, the reduction of ADMA concentration was significantly higher in patients receiving sulfhydryl ACE inhibition (P <.05 vs enalapril). CONCLUSIONS: The sulfhydryl ACE inhibitor zofenopril reduces oxidative stress and improves the NO pathway in patients with essential hypertension. If confirmed in a large multicenter clinical trial, our data suggest a possible vasculoprotective effect of the compound in retarding vascular dysfunction and atherogenesis that often develops rapidly in hypertensive patients.

Angiotensin-Converting Enzyme Inhibitors↗

An efficient and highly selective deprotection of N-Fmoc-alpha-amino acid and lipophilic N-Fmoc-dipeptide methyl esters with aluminium trichloride and N,N-dimethylaniline.

A novel procedure for the deprotection of the carboxyl group of amino acid methyl esters is presented. The process is carried out by the reagent system aluminium trichloride/N,N-dimethylaniline that can successfully be applied to unblock the carboxyl moiety either of N-Fmoc-protected amino acid methyl esters and N-Fmoc-protected short dipeptide methyl esters. The chiralities of the optically pure amino acid or peptide precursors are maintained totally unchanged.

Aluminum Chloride↗

Facile approach to enantiomerically pure alpha-amino ketones by Friedel-Crafts aminoacylation and their conversion into peptidyl ketones.

In this article we describe a versatile and straightforward preparative approach to chiral aryl alpha-amino ketones via a Friedel-Crafts-type reaction of stable and enantiomerically pure N-Fmoc protected L-amino acid chlorides with toluene in the presence of aluminum trichloride. The developed methodology provided aryl alpha-amino-p-methylphenyl ketones, which can be obtained and isolated as free bases or recovered as their N-acetyl derivatives, after treatment with acetic anhydride in chloroform at room temperature, subsequent to the Lewis acid induced removal of the 9-fluorenylmethoxycarbonyl protecting group. The Friedel-Crafts-like process and the cleavage of the amino function masking group can selectively be performed since, as verified in all cases, the alpha-aminoacylation step occurred with kinetics that were faster than those required to remove the N-protection. The presented approach was also explored as a facile and useful synthetic tool for the preparation of optically pure ketone di- and tripeptides. These compounds can be obtained in exceptionally overall yields without need of chromatographic purification. Moreover, either aryl alpha-amino ketones or modified di- and tripeptides, in all cases, can be isolated in very high chemical and optical purity without recourse to resolution of diastereomeric mixtures, since the chiralities of the asymmetric amino acid educts were completely conserved throughout the entire process.

Dipeptides↗

Caffeine antagonism of alcohol-induced driving impairment.

The extent to which caffeine antagonizes alcohol-induced impairment of simulated automobile driving at the current lowest legal American limit (0.08% BrAC) was the focus of this study. Fifteen adults swallowed a capsule (0, 200, or 400 mg caffeine) then drank a beverage (0.0 or 0.6 g/kg ethanol) in a within-subject, double-blind, randomized procedure. Forty-five minutes later, participants completed a test battery of subjective effects scales, dynamic posturography, critical flicker fusion (CFF), choice reaction time (CRT), divided attention (Stroop test), and simulated driving. Alcohol alone increased ratings of 'dizzy', 'drug effect', and 'high', slowed CRT and brake latency, and increased body sway. Caffeine alone increased ratings of 'alert' and 'jittery', but did not significantly affect body sway or psychomotor performance. Both caffeine doses comparably counteracted alcohol impairment of brake latency but not CRT or body sway. Brake latency with either alcohol-caffeine combination remained significantly longer than that with placebo. Stroop and CFF performance were unaffected by any drug condition. The results suggest that caffeine may increase alertness and improve reaction time after alcohol use but will not completely counteract alcohol impairment in a driver.

Adult↗

Site selectivity in the synthesis of O-methylated hydroxamic acids with diazomethane.

In this paper we report the results obtained by treating some selected hydroxamic acids with diazomethane in ethereal media. The multitask reagent diazomethane was used either as a base to induce deprotonation of the chosen hydroxamic acids or as conjugated acid which undergoes one-pot methylation processes of the generated anions. Product distributions clearly showed that a high site selectivity is expressed by the different deprotonated species in the alkylation processes. Under the adopted conditions, the prevalent site of methylation is in all the cases the oxygen of the hydroxamic acid. While in aliphatic hydroxamic acids only O-alkylation is observed, in the aromatic substrates, the NH group competes with the OH function as the nucleophilic site, although the OH reactivity still dominates.

Diazomethane↗

Structural characterization of isoxazolidinyl nucleosides by fast atom bombardment tandem mass spectrometry.

4'-Aza-2',3'-dideoxyerythrofuranosyl derivatives of thymine (AdT, 1) and uracil (AdU, 2) are analogues of 2',3'-dideoxyribofuranosyl thymine (ddT, 3) and uracyl (ddU, 4). Compounds 1 and 2 are representative of a new class of antiviral agents where the sugar moiety is replaced by an isoxazolidine ring. The increasing importance of isoxazolidinyl nucleosides has encouraged the exploitation of simple mass spectrometric rules for unambiguously assigning their structure. The species 1, 2, 5 and 6 were therefore synthesized in order to evaluate the role of the basic centre of the modified sugar moiety in their gas-phase chemistry. The tandem mass spectra of these compounds are similar to those of the wild-type nucleosides and display fragment ions corresponding to [B + 2H](+),[M - BH](+) and [B + 27](+) species, where B is the nucleobase. The last species derives from a retrocycloaddition process which is less evident in 2'-deoxyribosides. This behaviour is consistent with protonation of the analytes at the pyrimidine rings. Model isoxazolidines, in which the nucleobase was replaced by a phenyl or a naphthyl moiety, displayed the expected behaviour of species with a localized charge on the N-O moiety of the isoxazolidine ring.

Antiviral Agents↗

Electron transfer vs. proton transfer within radical-cation clusters of guanosine and deoxyguanosine with substituted naphthalenes and sinapinic acid.

Guanosine (G) and deoxyguanosine (dG) radical cations can be generated in the gas phase by single electron transfer (SET) within nucleoside-dimethoxynaphthalenes (1-2) electron-bound heterodimers produced by fast atom bombardment in a four sector mass spectrometer. The nucleobase guanine is much more easily oxidized when it is linked to a ribose moiety. The radical cation dimers formed by G and dG with sinapinic acid behave as proton-bound heterodimers. The experiments mimic to some extent the migration of radical sites within stacking bases which causes DNA damaging through depurination processes.

Cations↗

Marijuana Craving Questionnaire: development and initial validation of a self-report instrument.

AIMS: To develop and validate a multi-dimensional questionnaire on marijuana craving. DESIGN AND MEASUREMENTS: Current marijuana smokers (n = 217) not seeking treatment completed a 47-item Marijuana Craving Questionnaire (MCQ) and forms assessing demographics, drug use history, marijuana quit attempts and current mood. FINDINGS: Exploratory and confirmatory factor analyses indicated that a four-factor solution best described the item structure. Factor subscales derived from the 17 items with significant loadings had respectable internal consistencies and were stable across settings and subgroups. The subscales exhibited low to moderate, positive intercorrelations and were significantly correlated with marijuana use history and a wide range of single-item measures of craving. CONCLUSIONS: Findings suggested that four specific constructs characterize craving for marijuana: (1) compulsivity, an inability to control marijuana use; (2) emotionality, use of marijuana in anticipation of relief from withdrawal or negative mood; (3) expectancy, anticipation of positive outcomes from smoking marijuana; and (4) purposefulness, intention and planning to use marijuana for positive outcomes. These data indicate that the MCQ is a valid and reliable instrument for assessing marijuana craving in individuals not seeking drug abuse treatment and that marijuana craving can be measured in the absence of withdrawal.

Adult↗

Effect of glycaemic control and age on low-density lipoprotein susceptibility to oxidation in diabetes mellitus type 1.

BACKGROUND: Although individuals with diabetes mellitus frequently have dyslipidaemias and high blood pressure, much of the increased risk for coronary heart disease is not explained by these and other classical risk factors. Thus, other less widely recognized risk factors, including increased susceptibility of low-density lipoprotein (LDL) to oxidation, might enhance vascular dysfunction and atherogenesis in diabetes. AIMS: We compared both the rate and extent of LDL oxidation ex vivo between 78 poorly controlled individuals with type 1 diabetes and 78 age- and sex-matched non-diabetic controls. We then initiated intensive insulin therapy for 3 months to determine the impact of improved glucose control on LDL composition and oxidation. RESULTS: Diabetic and non-diabetic individuals did not have significantly different body weights, dietary intake, blood pressure, renal function or plasma lipid levels. LDL composition was also similar in both groups. In contrast, vitamin E content in LDL was significantly lower in diabetic patients. Measures of LDL lipid oxidation, including conjugated diene, lipid peroxide and thiobarbituric acid reactive substances formation, as well as measures of LDL protein modification, were significantly greater in diabetic patients. Levels of hyperglycaemia correlated strongly with each measure of LDL lipid oxidation (r ranges from 0.60-0.81, P<0.05 for each correlation). After improved glucose control (average reduction in % Hb(Alc)of 5.5 units) all measures of LDL oxidation improved dramatically and approached values for non-diabetics. Absolute values of LDL oxidation increased among all categories of age in both diabetic and control individuals, and this relationship persisted even after adjustment for differences in glucose concentrations. CONCLUSIONS: We demonstrate that hyperglycaemia has a potent but reversible effect on LDL oxidation and that age may independently enhance LDL susceptibility to oxidation. These pathophysiological effects may play an important role in determining vascular complications and atherogenesis in poorly controlled type 1 diabetic patients.

Adult↗

Survey of the proton affinities of adenine, cytosine, thymine and uracil dideoxyribonucleosides, deoxyribonucleosides and ribonucleosides.

The kinetic method was applied to the determination of the proton affinities (PAs) of modified deoxy- and dideoxyribonucleosides. A correlation between the measured PAs and the replacement of one of the three hydroxyl groups of the ribose unit is presented. A PA scale was obtained which shows that the replacement of the primary or of one or both secondary hydroxyl groups of a ribonucleoside with a hydrogen atom induces the lowering or the enhancement of the nucleoside PA, respectively. The scale extends over a very narrow range of approximately 2 kcal mol(-1), thus demonstrating the sensitivity of the kinetic method in the evaluation of small differences in thermodynamic parameters.

Adenine Nucleotides↗

A critical view of past NIH research funding on tobacco and nicotine.

We describe past NIH funding for tobacco/nicotine-related research, using data from the CRISP computerized database of NIH grants awarded in 1975, 1980, 1985, 1990, and 1995 (last year available). Two independent raters identified extramural grants whose investigators listed a nicotine/tobacco-related keyword as a primary descriptor for 1975, 1980, 1985, 1990, and 1995. From 1975 to 1985 extramural funding for nicotine/tobacco research (corrected for inflation) increased almost fourfold. From 1985 to 1995, funding increased minimally (< 20%). In 1995, NIH expended $92.1 million on research whose primary interest was nicotine or tobacco. This represented 1.1% of the overall NIH extramural budget. Over time, when contract funding increased, investigator-initiated R01 funding decreased. Nicotine/tobacco research was spread across 18 institutes. Although tobacco use accounts for 20% of all US mortality, historically only 1% of the NIH's budget has focused on nicotine or tobacco. Among nicotine/tobacco grants funded, investigator-initiated research appears to have been limited due to large contracts for clinical trials. Nicotine/tobacco research has no home institute. Funding for nicotine/tobacco research needs to be increased and better coordinated.

Humans↗

Comparison of pharmacological treatment versus acupuncture treatment for migraine without aura--analysis of socio-medical parameters.

This study was carried out in 120 patients affected by migraine without aura, treated in 4 public health centers and randomly divided into acupuncture group (AG) and conventional drug therapy group (CDTG). The evaluation of clinical results was made 6 and 12 months after the beginning of treatment and was worked out as well according to socio-medical parameters. Acupuncture was applied to the following points: Touwei (ST 8), Xuanlu (GB 5), Fengchi (GB 20), Dazhui (GV 14), Lieque (LU 7), treated with the reducing method. In AG, the figure scoring the entity and frequency of migraine attacks drops from 9,823 before treatment to 1,990 6 months after and 1,590 12 months after; while in CDTG, it drops from 8,405 before treatment to 3,927 6 months after and 3,084 12 months after. In AG, the total absence from work amounted to 1,120 working days/year, with a total cost (private + social costs) of 186,677,000 Italian liras. In CDTG, the absence from work amounted to 1,404 working days/year, with a total cost of 266,614,000 Italian liras. If we consider that in Italy the patients affected by migraine without aura are around 800,000, and that acupuncture therapy is able to save 1,332,000 Italian liras on the total average cost supported for every single patient, the application of acupuncture in the treatment of migraine without aura would allow a saving of the health expenses in Italy of over 1,000 billion liras.

Acupuncture Points↗

Loop diuretics enhance the secretion of prostacyclin in vitro, in healthy persons, and in patients with chronic heart failure.

BACKGROUND: Previous studies suggest that the acute haemodynamic effects of loop diuretics are due to a direct dilation of blood vessels and are not related to diuretic properties, but possibly to prostaglandin secretion. OBJECTIVES: We investigated whether in vitro human endothelial and renal epithelial cells responded to torasemide or furosemide with enhanced secretion of the vasodilator prostaglandin prostacyclin (PGI2). We also investigated the effects of loop diuretics on plasma concentrations of PGI2 and its physiological antagonist thromboxane after 25 min of administration of drugs in 44 patients with congestive heart failure (CHF) and 44 healthy volunteers. METHODS: The PGI2 levels were measured after extraction in ethyl acetate by RIA as levels of 6-KetoPGF1alpha, a stable metabolite from a non-enzymatic degradation. TxB2 concentration, the stable hydrolysis product of TxA2, was also measured by RIA. RESULTS: In human endothelial and renal epithelial cells, both loop diuretics induced an increase of 6-KetoPGF1alpha secretion that reached a peak after about 5 min and remained stable for 30 min of exposure to the drugs. The magnitude of the phenomenon was lesser in epithelial than in endothelial cells. Moreover, in both cell lines, there was a significantly higher secretion of 6-KetoPGF1alpha to torasemide than furosemide (P < 0.05). Concentrations of 6-KetoPGF1alpha at baseline were similar between the groups of CHF patients receiving the two different drugs. After 25 min of both drugs, 6-Keto-PGF1alpha significantly increased (P < 0.01), and this was significantly higher in patients treated with 10 mg of torasemide (P < 0.05 vs furosemide). Levels of PGI2 at baseline were lower in healthy controls than those reached by CHF patients and similar between groups. After 25 min of both drugs, PGI2 plasma levels were significantly increased (P < 0.01). Baseline values of TxB2 were significantly higher in CHF patients compared with controls (P < 0.01 vs respective groups). and, more importantly, furosemide but not torasemide increased TxB2 levels in patients and controls (P < 0.05 vs baseline). CONCLUSIONS: Our study is the first demonstration in human tissue of increased secretion of PGI2 both in vitro and in vivo, after torasemide or furosemide administration. This phenomenon, which may explain in part the vasodilatory effects of these drugs, was more evident with torasemide and was reached at lower concentrations of the drug. Accordingly, we also found that furosemide but not torasemide stimulated the release of the PGI2 physiological antagonist thromboxane in CHF patients and healthy controls.

6-Ketoprostaglandin F1 alpha↗

Subjective effects of caffeine among introverts and extraverts in the morning and evening.

In previous studies of psychomotor performance, the stimulant effects of caffeine differed by personality characteristics. For example, caffeine improved the task performance of extraverts but overaroused introverts and thus impaired their performance. The present study compared the effects of caffeine on subjective arousal among introverts and extraverts. Seventeen introverts and 19 extraverts drank coffee that contained doses of 0, 2, and 4 mg/kg caffeine during morning and evening sessions in a within-subjects, randomized, double-blind, crossover design. At 30-min intervals for 180 min after drinking, participants completed the Profile of Mood States, a battery of self-report visual analog scales, and the Digit Symbol Substitution Test (DSST). Caffeine effects on mood and task performance did not significantly interact with extraversion, except for nonsignificant trends for caffeine to increase happiness and vigor more among extraverts than introverts. No 3-way interactions of group, time, and dose were found on any scales or on the DSST. Results do not support the hypothesis that caffeine differentially affects extraverts and introverts, particularly at different times of the day.

Adolescent↗