Quantitation of the enantiomers of furprofen in biological fluids by high-performance liquid chromatography.
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Biomedical subjects
Publications and source records attributed to G Palumbo.
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The presence of specific LHRH-binding sites within the rat thymus gland and the ability of LHRH and its agonistic and antagonistic analogs to directly modulate thymus function prompted us to study the possible changes in the number of thymic LHRH-binding sites during aging-induced physiological immunosenescence. Moreover, the effects of chronic treatment of aging rats with a potent LHRH agonist (LHRH-A) on thymic LHRH receptors, thymus weight and histology, as well as thymocyte proliferative capacity were assessed. For comparison, the effects of castration on the same parameters was also investigated. The process of aging is accompanied by a sharp reduction in LHRH-A-binding sites within the thymus gland of both female and male rats. Starting at 7 months of age, a 50% decrease in thymic LHRH-A binding was followed, at 11-13 months of age, by a nearly 65% inhibition of receptor numbers. In 16- to 19-month-old rats, LHRH-A binding was almost completely lost. Thymus weight was 30% reduced in 7-month-old animals, while a 50% reduction in thymic size was reached at 11 months of age in males and 13 months in female rats. A further decrease in thymic mass was observed at 16 and 19 months. Chronic (45-day) treatment of aging (15-16 months old) female and male rates with the potent LHRH-A, [D-Trp6,Des-Gly10]LHRH-N-ethylamide, reversed the age-related decreases in both thymus weight and thymic LHRH-binding sites. Similarly, surgical removal of testicular hormones by castration restored thymus weight and increased LHRH-A binding in the thymus of aged rats. While thymus histology in 3-month-old rats was characterized by a clear demarcation of cortical and medullary regions, only thymic remnants were present in 16- to 17-month-old animals. Castration of old rats resulted in a partial restoration of thymic structure, while chronic treatment of aging rats with the LHRH-A produced a homogeneous organization of both cortical and medullary compartments accompanied by a marked increase in the width of the cortical layer, densely packed with lymphocytes. While the process of aging was accompanied by an almost complete loss of the proliferative response of thymocytes to optimal concentrations of the mitogen Concanavalin-A, thymocyte cultures from old rats treated with LHRH-A or from castrated animals, displayed significantly greater proliferative responses. Furthermore, the combination of both manipulations resulted in a further significant increase in thymocyte proliferative capacity.(ABSTRACT TRUNCATED AT 400 WORDS)
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The synthesis of pyrrole analogues of the analgesic drug lefetamine is reported. These derivatives bear the 1-phenyl-2-(1H-pyrrol-1-yl)ethylamino moiety. Compounds were evaluated for analgesic activities in mice by the hot plate and Randall-Selitto tests. Antiinflammatory activity was tested by the carrageenan-induced rat paw edema method. General neuropsychopharmacological effects were also screened. The most interesting compound, N,N-dimethyl-1-phenyl-2-(1H-pyrrol-1-yl)ethylamine, showed an analgesic effect comparable to that of lefetamine, but devoid of the neurotoxicity of this drug.
Reaction between 1-(2-aminomethylphenyl)-1H-pyrrole hydrochloride and methyl 2-methoxyglicolate in methanol afforded methyl 5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepin-4-carboxylate. Aroylation at the 5-position and subsequent hydrolysis of the ester function led to 5-aroyl-5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepin-4-ca rboxylic acids. The pharmacological profile of these acids has been studied with regard to analgesic, antiinflammatory and neuropsychobehavioural effects.
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Chronic atrophic gastritis is considered a precancerous condition for carcinoma of the stomach. To evaluate the correlation between progressive alterations in the mucosa and gastric juice microenvironmental factors, retained involved on N-nitroso compounds carcinogenesis, detailed analyses of biochemical and microbiological parameters such as pH, total viable counts (TVC), nitrate reductase positive bacterial counts (NRPBC), nitrite (NO2-) and thiocyanate (SNC-) levels, were carried out on 56 fasting gastric juices samples obtained at endoscopy from 28 patients with chronic atrophic gastritis (CAG), 14 with gastric cancers (GC), and 14 normal controls (NC). The mean values of pH, nitrite, TVC, and NRPBC were significantly lower in the juices of NC than in those of CAG and GC patients. Furthermore, the mean levels of the same parameters were higher in GC than in CAG juices. No significant difference was found in the three groups for SCN- level which principally resulted influenced by smoke habit. The 28 patients with CAG were subdivided into two groups (Group A = Diffuse chronic atrophic gastritis--DCAG; Group B = Multifocal chronic atrophic gastritis--MCAG) according to the involvement of gastric corpus and fundus besides antrum by a process of mucosal atrophy. The mean levels of pH, nitrite, TVC, and NRPBC were significantly higher in MCAG than in normal controls but statistically lower in reference to DCAG and cancers. In these two groups no difference was found for the same variables. The percentage of contaminated juices was higher for DCAG and cancers in respect to MCAG but no difference was found between DCAG and neoplastic stomachs. The results of this study suggest that the DCAG could be considered as the chronic atrophic gastritis type more exposed to the risk of N-nitroso compounds carcinogenesis.
The effect of Fenclor 42 (PCB) exposure of female rats (Fischer 344 strain) was studied through assessment of the behavioral development of their F1 progeny. Female rats were exposed to PCB according to the following treatment schedule: (A) (5 days) 2 weeks prior to mating, (B) during gestation (Days 6-15 of pregnancy), (C) during lactation (Days 1-21 after delivery). Behavioral endpoints of motor reflexes, motor coordination, activity (preweaning behaviors), and learning (postweaning behavior) were evaluated for PCB ip dosages of 5-10 mg/kg/day for 5 days (preconception exposure), and PCB oral dosages of 2-4 mg/kg/day for 10 days (in utero exposure) and of 1-2 mg/kg/day for 20 days (during lactation exposure). Dosage-dependent differences in the evaluated behaviors were found in the offspring of the PCB-exposed females when compared to the offspring of corn-oil (vehicle)-exposed females. Significant differences in the development of cliff avoidance reflexive behavior, swimming ability, and open field activity were particularly evident. Furthermore the PCB exposure of female rats during gestation and lactation resulted in impaired acquisition of the active avoidance behavior while preconceptional PCB exposure significantly affected active avoidance performance as reflected in increased number of avoidance responses to reach criterion for extinction. These results show that Fenclor 42 does possess a significant risk to the offspring of exposed females, and further illustrate the sensitivity of progeny behavioral assessment in detecting suspected functional teratogenesis.
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The synthesis of 1-aryl-5-(1-pyrryl)pyrazoles bearing at position 4 an acetic or alpha-propionic chain is described. The new compounds can be structurally related to lonazolac and its analogues with analgesic-antiinflammatory activities. When tested pharmacologically in comparison with tolmetin and indomethacin none of the above derivatives showed any appreciable activity.
The formation of dehydroalanine in thyroglobulin is the result of the side chain elimination of an iodophenyl group during the thyroid hormone formation from two iodotyrosyl residues. This amino acid is easily converted to labeled alanine (upon reduction with [3H] borohydride) or changed to labeled aspartic acid (upon addition of Na14CN and subsequent acid hydrolysis). The cleavage of the protein by CNBr produced many stainable electrophoretic bands, but the autoradiography indicated the presence of a much smaller number of radioactive species. Although three major species raised attention, because they could be all jointly labeled and were present in all preparations, only a species of 15,900 Da was fully studied. It was isolated and its sequence partially determined by Edman degradation. It was established that this species corresponded to the thyroglobulin fragment between methionines 2,432 and 2,578. This peptide contains two hormonogenic sites (positions 2,555 and 2,569) which are either tyrosyl residues or hormone residues arising from them, and five additional tyrosines all potentially involved as donor sites in the hormonogenesis. Upon treatment with N-chlorosuccinimide, the fragment was split into three smaller peptides of about 2,900, 8,500, and 4,600 Da containing 1, 2, and 2 tyrosyl residues, respectively. Only the 8,500-Da subfragment contained [3H]Ala. This finding strongly suggests that at least some of the tyrosines involved as donor sites in thyroid hormonogenesis are within this peptide and possibly map at positions 2,469 and/or 2,522. Moreover, at minimum levels of iodination, when thyroglobulin contains the lowest number of hormone molecules, dehydroalanine is mostly found in the 15,900-Da peptide.
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The method described for quantitative estimation of lipids separated on thin layer chromatography plates exploits the observation that most lipids can be stained by iodine vapor and that, in "controlled" conditions, the intensity of this staining is proportional to the actual amount of lipid in the spot. The method consists of exposing the developed plate to iodine vapor; spraying it with a suitable solvent to prevent halogen evaporation; collecting the stained lipids by scraping the spots off the plate; and determining by a rate-sensing method the absorbed iodine. The final determination is performed by measuring spectrophotometrically (at 410 nm) the rate of decolorization of a solution of Ce(IV) by As(III) in strong acidic conditions. The reaction rate, which is positively related to the concentration of iodine, is derived from the slope of the absorbance change plotted vs time. Providing that standards and samples are stained simultaneously, a quantitative estimation of lipid components of a mixture is possible in a reasonable time with excellent accuracy and reproducibility. In our hands, the method has been successfully applied to several common phospholipids, long chain fatty acids, cholesterol and deoxycholate, and triacylglycerols, in the range of 5-60 micrograms.
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The development of the human endocrine pancreas is described. The hormone content and islet responsiveness of foetal and neonatal pancreases of diabetic and non-diabetic pregnant women are reported.
Parieto-occipital EEG alpha was recorded bilaterally, while 20 high- and 20 low-hypnotizable women performed one left-hemisphere and one right-hemisphere task of low difficulty and two other comparable tasks of high difficulty. Every task was performed twice, once with eyes open and once with eyes closed. All subjects were right-handed. The tasks were originally selected to be of high and low difficulty. The subjective rating of task-difficulty was also evaluated. The integrated amplitude alpha and the alpha ratio (R-L/R + L) were the dependent variables. The highly hypnotizable women showed significantly higher alpha amplitude in eyes-closed condition than the low scorers; this difference disappeared during task performance and in the eyes-open condition. The left-tasks showed lower alpha amplitude in both hemispheres than right-tasks and baseline. The right-hemisphere alpha amplitude was lower than left in all experimental conditions. On tasks of high and low difficulty there was different hemispheric behavior on right and left tasks. Performance reflecting the right and left hemispheres in the low-difficulty condition showed no changes between baseline, right- and left-tasks, while under high difficulty there was a decrease in alpha amplitude in the right and even more marked decrease in the left hemisphere during left-tasks. The pattern of task effects for ratio scores was the same as for alpha amplitude, however, despite the analysis of alpha scores, an interaction of hypnotizability X task-difficulty was detected. The highly hypnotizable women showed less negative alpha ratio during a task of low difficulty than during tasks of high difficulty; the reverse was true for the low-hypnotizable women. Finally, the highly hypnotizable subjects showed less subjective difficulty during performance than the low scorers.