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Biomedical subjects

A Angeli

Publications and source records attributed to A Angeli.

At least 145 records · Page 8Linked to original sources
PubMed1989

Antinociceptive properties of lysozyme fragments.

The in vitro digestion of hen egg white lysozyme with artificial gastric juice gave a complex mixture of peptides, from which a peptide corresponding to the aminoacid sequence 39-53 was isolated. Its further hydrolysis with artificial enteric juice gave two smaller fragments having the aminoacid sequence 39-45 and 46-53 respectively. These products, like lysozyme, showed antinociceptive activity in rats against foot hyperalgesia induced by a subplantar injection of brewer's yeast.

Analgesics↗
PubMed1988

Ketoconazole treatment in Cushing's disease. Effect on the circadian profile of plasma ACTH and cortisol.

Ketoconazole is an inhibitor of adrenal steroidogenesis used in the treatment of Cushing's disease. Previous data obtained with single blood sampling were controversial as to increased ACTH levels compensatory to the cortisol fall. We have evaluated by chronobiological procedures the circadian profiles of plasma ACTH and cortisol in three patients with Cushing's disease before and after a six-month course of therapy with ketoconazole (600 mg daily). None of the patients complained of any adverse subjective reaction; in particular no sign or symptom of hypoadrenalism and/or hepatotoxicity was recorded. Ketoconazole treatment markedly improved the clinical setting and caused a highly significant (p less than 0.0001) reduction of mean 24-h cortisol values (ciradian MESOR). The expected rise of ACTH did not take place; rather, we detected a slight decrease of the mean circadian MESOR (p less than 0.05). Our data, althought obtained in a very small number of patients, suggest that ketoconazole may have an additional action at central level, at least in some cases of Cushing's disease.

Adrenocorticotropic Hormone↗
PubMed1988

Apocrine cells in breast cyst fluid and their relationship to cyst type: a morphometric study.

The morphology of apocrine cells exfoliated in breast cyst fluid (BCF) was studied in 78 BCF samples obtained from 39 premenopausal patients with gross cystic disease who were bearing two simultaneously aspirated cysts. 57/78 samples showed cell clusters suitable for computer-assisted cytometry. This was performed on 5820 cells using a Leitz Texture Analysis System (TAS). We measured the surface areas of cytoplasm, nucleus and nucleolus; we also calculated the nuclear/cytoplasmic (N/C), nuclear/nucleolar (N/n) ratios and the nuclear roundness factor (RF). Cysts were divided according to the cationic pattern of BCF: Type I, K+/Na+ greater than 1.5; Type II, K+/Na+ less than 0.66. The cytometric analysis was made on 47 samples of Type I and 10 samples of Type II. At the light microscope, no difference was apparent between the apocrine cells coming from Type I or Type II cysts. Cytometric measurements showed significant differences for the apocrine cells aspirated from Type I vs. Type II cysts for the mean cytoplasmic area (97.13 +/- 24.28 S.D. mu2 vs. 59.66 +/- 14.90 S.D. mu2, respectively) and the mean nucleolar area (4.35 +/- 0.99 S.D. mu2 vs. 2.75 +/- 0.71 S.D. mu2, respectively). Our data do not allow the inference of apocrine changes in the epithelium lining the cysts simply from the cationic pattern of BCF. The significantly wider cytoplasm and nucleoli of the apocrine cells aspirated from Type I cysts could reflect different functional stages of these particular cells.

Adult↗
PubMed1988

Circadian variations of interferon-induced enhancement of human natural killer (NK) cell activity.

We searched for circadian changes in the enhancement of the NK activity after exposure to IFN-gamma of peripheral blood mononuclear (PBM) cells obtained serially throughout the 24-h cycle. In August-October 1986, blood was drawn from 7 healthy, diurnally active and nocturnally resting male volunteers (22-34 yr) at 4-h intervals for 24 h starting at 08:00. PBM cells were immediately separated and assayed for NK cell activity, using K 562 cultured cells as a target in a 4-h 51Cr release assay after prior incubation for 20 h with buffer or 300 IU rIFN-gamma. Circadian variations of the spontaneous NK cell cytotoxicity were apparent; the activity was at its maximum at the end of the night or in the early morning and then declined in the afternoon. The 24-h rhythmic pattern was validated with statistical significance by the Cosinor method (p less than 0.02; acrophase 04:22). Maximum enhancement by IFN-gamma was attained in the second part of the night or in the early morning, i.e. in phase with the peak of the spontaneous NK cell activity. A significant circadian rhythm of the percent increase above control levels was validated by the Cosinor method (p less than 0.01; acrophase 04:03). Our findings may be of relevance to a better understanding of the mechanisms of control of human NK activity and warrant consideration as an approach to improve the effectiveness of time-qualified immunotherapy.

Adult↗
PubMed1987

Acute administration of melatonin at two opposite circadian stages does not change responses to gonadotropin releasing hormone, thyrotropin releasing hormone and ACTH in healthy adult males.

We evaluated the effect of a single oral administration of 100 mg melatonin (MT) vs placebo (PL) on the pituitary release of LH, FSH, TSH and prolactin (PRL) after GnRH + TRH and on the adrenocortical release of cortisol, aldosterone and progesterone after ACTH in healthy adult males. We carried out a double blind study in 6 volunteers in winter, at two opposite stages of the circadian cycle: 08:00 and 20:00 h. Injection of GnRH (100 micrograms), TRH (200 micrograms) and ACTH (10 micrograms of the synthetic ACTH 1-17 analogue, Alsactide) was performed one h after MT or PL ingestion. Plasma MT levels were 200-4,000-fold higher after MT than PL thus confirming the effective gastrointestinal absorption of the pineal hormone. The hormonal patterns were superimposable after MT and PL. A higher response of PRL, FSH and cortisol was observed in the evening vs morning protocols independently of previous MT or PL. Our data demonstrate that the acute oral administration of a pharmacological dose of MT at two opposite circadian stages is ineffective to change a variety of pituitary and adrenocortical responses in human male subjects. The circadian chronosusceptibility of pituitary and adrenocortical cells to specific stimuli deserves interest to future investigation.

Adrenocorticotropic Hormone↗
PubMed1987

Inhibition by cortisol of human natural killer (NK) cell activity.

The effects of cortisol on the natural killer (NK) activity of human peripheral blood mononuclear (PBM) cells were studied in vitro using a direct 4-h 51Cr-release assay and K 562 cell line as a target. Preincubation for 20 h of PBM cells drawn from healthy donors with 1 X 10(-8) to 1 X 10(-5) M cortisol resulted in a significant decrease of NK cell activity. The magnitude of the suppression was directly related to the steroid concentration and inversely related to the number of effector cells. Cortisol was able to minimize the enhancement of NK cytotoxicity obtainable in the presence of immune interferon (IFN-gamma). A significantly higher suppression was achieved after sequential exposure of PBM cells to cortisol and equimolar levels of prostaglandin E2 (PgE2). The concomitant incubation with theophylline and isobutyl-methylxanthine failed to enhance the cortisol-induced suppression, whereas PgE2-dependent inhibition significantly increased after exposure of PBM cells to methyl-xanthines. The inhibitory effect of cortisol was partially or totally prevented by the concomitant incubation with equimolar amounts of 11-deoxycortisol and RU 486 but not of progesterone. Treatment of NK effectors with a monoclonal anti-human corticosteroid-binding globulin (CBG) antibody produced an enhancement of the spontaneous NK activity and a partial suppression of cortisol-mediated effects. Our results suggest that endogenous glucocorticoids play a role in the regulation of NK cell-mediated cytotoxicity. Since the effect of cortisol was additive to that of PgE2 and was not changed by phosphodiesterase inhibitors, it is conceivable that the hormone acts at a level different from the adenylate cyclase-phosphodiesterase system. Data obtained with the use of antiglucocorticoids and the anti-CBG antibody are compatible with a role both of high-affinity glucocorticoid receptors and of CBG in mediating cortisol action on the human NK cell activity.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Studies on the mechanism of cortisol inhibition of human natural killer cell activity: effects of calcium entry blockers and calmodulin antagonists.

The role of Ca2+ in mediating the inhibition by glucocorticoids of human natural killer (NK) activity was investigated using Ca2+ entry blockers (verapamil and its desmethoxy-derivatives LU46973 and LU47093) and calmodulin antagonists (pimozide and two naphthalenesulfopamide derivatives, W-7 and W-13). Peripheral blood mononuclear (PBM) cell preparations were incubated for 20 h with 1 x 10(-6) M cortisol and these agents in various combinations (concentration range: 1 x 10(-7) - 1 x 10(-5) M) and then assayed in a direct 4-h cytolytic assay using 51Cr-labeled K 562 target cells. Exposure to cortisol led to a significant reduction of NK cell activity (about 50% with respect to the spontaneous activity). Ca2+ entry blockers displayed per se a dose-dependent depressive effect on cytotoxicity and gave significant enhancement of cortisol-dependent inhibition. Calmodulin antagonists were per se minimally effective but clearly amplified the cortisol-mediated inhibition. Raising extracellular Ca2+ by CaCl2 or intracellular Ca2+ by the ionophore A23187 yelded an appreciable reduction of these effects. Our data are compatible with the view that extracellular and intracellular Ca2+ play a role in the control of human NK cell activity. Moreover, it is conceivable that the mechanisms involved in glucocorticoid inhibition of NK cell activity involve Ca2+-dependent pathways.

Adult↗
PubMed1987

Shifted distribution of cation-related cyst types in post-menopausal patients with gross cystic disease of the breast.

Gross cystic disease of the breast (GCD) is rarely seen after the menopause. Recent work has shown that by measuring electrolytes in the breast cyst fluid (BCF) it is possible to identify two principal classes of cyst, designated Type 1 (K+/Na+ greater than 1.5) and Type 2 (K+/Na+ less than 0.66). A smaller, intermediate class (Type 3) also appears to exist. We measured K+, Na+ and dehydroepiandrosterone sulphate (DHA-S) in 38 BCF samples aspirated from 33 women with GCD who had undergone spontaneous menopause at least 1 yr previously. Statistically significant correlations were found between DHA-S and cations (positive in relation to K+, P less than 0.001; negative in relation to Na+, P less than 0.001). The distribution of cyst types was shifted with respect to that characteristic of cases that occur at an earlier age: whereas Type 1 cysts predominate in menstruating women, Type 2 cysts proved more numerous in the post-menopausal subjects. The difference was statistically validated (P less than 0.001). The results seem to indicate a sharp reduction in high K+, high DHA-S cysts after the menopause, which may be paralleled by a decrease in the associated apocrine metaplasia. In view of the major biochemical differences between Type 1 and Type 2 cysts and of the suggested differences as regards cancer risk, classification of post-menopausal patients with GCD by cyst type is critical prior to any clinical trial or follow-up.

Adult↗
PubMed1987

Circadian changes in human natural killer-cell activity.

The circadian changes in natural killer (NK) activity of peripheral blood mononuclear cells (PDM) were studied in five clinically healthy, diurnally active, nocturnally resting women. Data on spontaneous NK-cell activity were complemented by data on the chronosusceptibility to in vitro inhibition by 1 X 10(-6) M cortisol and by the rhythmometric evaluation of rectal temperature and plasma cortisol as potential circadian markers. In April-July, 1985, blood was drawn at 4-hr intervals for 24 hr starting at 0800 hr. Cells were immediately separated and assayed for NK activity using K 562 cultured cells as a target and a 4-hr 51Cr-release assay. Circadian variations of the spontaneous NK activity were apparent; the maximum of the activity occurred in the morning or in the early afternoon. In individual subjects, peak-to-through differences were 50% or more of the 24-hr mean. Chronosusceptibility to cortisol (20 hr incubation prior to the cytotoxic assay) was ecphasic with respect to the spontaneous NK-cell activity, with a maximum in the evening or night. Data obtained by immunofluorescence using specific anti-NK cell monoclonal antibodies confirm the occurrence of a higher number of phenotypically identifiable NK effectors in the morning vs. other circadian stages. Our data confirm previous findings and extend their scope to immunopharmacology emphasizing the need for time-qualified investigations on immune coordination in vivo.

Adult↗
PubMed1987

Circatrigintan rectal temperature and endocrine rhythms of clinically healthy, menstrually cycling women.

Rectal temperatures were measured automatically every 10 min for part or most of two menstrual cycles in ten clinically healthy young women, 20-30 years of age, with a wearable instrument, the Polychronor. Occasional malfunction of the instrumentation resulted in corresponding gaps in the series. Data were examined by chronograms, plexograms, and chronobiologic serial sections computed with the fit of a 24-hr period, population-mean cosinor, and linear-nonlinear least-squares analyses. Single cosinor-derived circadian parameters were next fitted with a cosine curve of a period equal to the number of days of the corresponding intermenstruum. Second-order infradian inferential statistics were calculated next; the first day of menstruation was used as acrophase reference. A population-mean cosinor at the intermenstrual period yields a temperature acrophase of -279 degrees, with the 95% confidence interval extending from -254 degrees to -312 degrees. Since the intermenstruum differs in different subjects and/or in different menstrual cycles of a given woman, this acrophase corresponds to different time intervals from the first day of menstruation in different cases. This acrophase thus indicates the relative timing within the menstrual cycle of overall high rectal temperatures. On four subjects in four stages of their menstrual cycle, plasma was also obtained at 2-hr intervals around the clock. Ten hormones were determined. The sparse endocrine sampling along the menstrual cycle notwithstanding, a circatrigintan rhythm in all hormones investigated was demonstrated for a woman 26 years of age. At the period corresponding to the intermenstrual interval, the acrophases for T3, cortisol, FSH, testosterone, DHEA-S, T4, and LH occurred before the circatrigintan rectal temperature acrophase, whereas the acrophases for prolactin, estradiol, and progesterone occurred near or shortly after the rectal temperature acrophase. Whereas earlier circatrigintan mapping of adult women had been summarized on a group basis, this study allows individualized circatrigintan rhythm assessment. Circatrigintan, like circadian and circannual, acrophase and amplitude relations do not necessarily imply causal relations, yet they are an indispensable quantitative reference standard for the study of basic mechanisms and for diagnosis and intervention, including endeavors in planned parenthood that might take into account the organism's dynamics with multiple frequencies.

Adult↗
PubMed1986

Short term ethanol ingestion can affect the testicular response to single-dose human chorionic gonadotropin in normal subjects.

Ten sober adult male subjects, with normal sexual development and function, were examined under basal conditions and after a short-term period (7 days) of alcohol ingestion (200 g/daily). Plasma concentrations of testosterone (T), 17 beta estradiol (E2), progesterone (P) and 17-hydroxyprogesterone (17-OH P) were measured on blood samples drawn before and then every 24 h until the 96th h following a single dose of human chorionic gonadotropin (hCG, 2,000 IU im). Basal plasma T was significantly decreased after short-term ethanol ingestion (p less than 0.01) whereas E2, P and 17-OH P were comparable in both conditions. The magnitude of the T response to hCG injection was significantly lower after ethanol ingestion but still significantly higher than the corresponding one obtainable in chronic alcoholics. At the 7th day of ethanol ingestion plasma LH levels were higher than controls (p less than 0.05). These results demonstrate that short-term ingestion of 200 g ethanol daily can lead to altered testicular response to hCG in normal adult males and corroborate the view that ethanol is a gonadal toxin.

17-alpha-Hydroxyprogesterone↗
PubMed1986

Cortisol at physiological concentrations and prostaglandin E2 are additive inhibitors of human natural killer cell activity.

The effects of cortisol and prostaglandin E2 on preparations of human peripheral blood mononuclear cells that mediate natural killer cytotoxicity were evaluated. Natural killer cell activity was measured using 51Cr-labelled K562 target cells and effector to target cell (E:T) ratios of 50:1, 25:1, 12.5:1 and 6:1. In vitro preincubation of mononuclear cell preparations for 20 h with 1 X 10(-8) to 1 X 10(-5) M cortisol resulted in a significant decrease of natural killer cell activity. The magnitude of the suppression was directly related to the steroid concentration and inversely related to the E:T ratio. Exposure of cortisol-treated mononuclear cells to 1 X 10(-6) M prostaglandin E2 resulted in a significantly higher level of inhibition than after treatment with the two agents singularly. In contrast, the concomitant incubation with 1 X 10(-5) to 1 X 10(-4) M theophylline, or with 1 X 10(-6) to 1 X 10(-5) M isobutyl-methylxanthine, two widely used phosphodiesterase inhibitors, failed to demonstrate a significant enhancement of cortisol-induced suppression. Prostaglandin E2-dependent inhibition, on the other hand, was more intense after the inhibition of phosphodiesterase activity. Taken together, these results show that cortisol at physiological concentrations has the property of depressing human natural killer cell activity in vitro and suggest that endogenous glucocorticoids play a role in the in vivo regulation of this natural cytotoxicity. Additionally, cortisol and prostaglandin E2 are additive inhibitors of natural killer cell activity. Since the effect of cortisol in our experiments was not changed by theophylline or isobutyl-methylxanthine it is conceivable that the hormone acts at a level different from the adenylate cyclase/phosphodiesterase system.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Cations and dehydroepiandrosterone-sulfate in cyst fluid of pre- and menopausal patients with gross cystic disease of the breast. Evidence for the existence of subpopulations of cysts.

Cations (K+ and Na+) content was evaluated in 444 breast cyst fluid (BCF) specimens, aspirated from 391 patients with gross cystic disease of the breast (GCD), a benign form admittedly at major risk of cancer. In 306/444 BCF, dehydroepiandrosterone-sulfate (DHA-S) content was also evaluated. A positive correlation (P less than 0.001) was observed between log K+ vs. log DHA-S whereas a negative correlation was found between log Na+ and log DHA-S (P less than 0.001). Cysts were subdivided in three types according to their cationic concentration: most were of type I (K+/Na+ greater than 1.5) and type II (K+/Na+ less than 0.66) whereas only 10% was of the type III (intermediate). No statistical difference in subtype distribution was apparent when considering patients aspirated in the follicular vs. luteal phase of the menstrual cycle; on the contrary, a significant difference (P less than 0.001) was found between menstruating vs. menopausal patients (type I = 54.8% vs. 32.2%; type II = 34.5% vs. 58.1%, respectively). Ninety-four BCF samples were aspirated simultaneously in 41 patients bearing multiple cysts: the same cationic subtype was present in 29/41 patients. Our data confirm and extend previous observations, and provide conclusive evidence that breast macrocysts can be divided on the basis of their electrolyte composition into different types. Accordingly, the composition of BCF should always be assessed for prospective studies on GCD and breast cancer risk.

Adult↗