Sensitization to white petrolatum used as a vehicle for patch testing.
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Adult↗
Biomedical subjects
A Conti
Publications and source records attributed to A Conti.
The clinical neuroimmunotherapeutic role of melatonin in oncology.
In the past several years, interest in the immunophysiological role of the pineal gland and melatonin has grown to the extent that now their immunoregulatory role is widely recognized. Melatonin has immunoenhancing properties and it is able to counteract the immunodepression induced by acute stress, drug treatment (i.e., anticancer drugs), and viral infections. Here we review the therapeutic efficacy of melatonin alone or in combination with interleukin-2 (IL-2) in cancer patients who did not respond to standard anticancer chemotherapies and/or refused any aggressive treatment. In this review, we summarize a series of reports from 1986 through 1994 in which patients affected by metastatic solid tumors, metastatic non-small-cell lung cancer, advanced solid neoplasms, myelodysplastic syndrome, hepatocellular carcinoma, and advanced endocrine tumors were studied. The conclusion drawn from these studies is that melatonin protects against IL-2 and synergizes with the IL-2 anticancer action. This combined strategy represents a well tolerated intervention to control tumor growth. In most cases performance status and quality of life seem improved.
Animals↗
Growth hormone treatment in adults with childhood onset growth hormone deficiency: effects on psychological capabilities.
The psychological aspects (personal traits, way of relating to the surrounding environment, perception of body image, degree of self-esteem) of eight adults with childhood onset growth hormone (GH) deficiency (GHD) were studied before and after 6 months of recombinant GH therapy. Each subject was evaluated using the following tests: the Bem Sex Role test, the non-verbal scales of the WAIS test for adults, the State-Trait Anxiety Inventory, the Experiential-World Inventory, the Image-Marking Method and the Draw-a-Person test; a psychoneurophysiological profile was also evaluated in order to monitor, by means of four neurophysiological variables (muscular tension, galvanic resistance, skin temperature and heart rate), the reactions to specific and aspecific stress. Before treatment, adults with GHD tended to underestimate their body size by an average of 30%, with peaks of 47% for the head area; furthermore, they showed a low level of self-esteem, a closed attitude towards social relationships, a pessimistic attitude with a tendency towards depression and a strong sense of detachment from the outside world. After 6 months of GH treatment, patients presented an overall improvement in relation to intellectual tasks, accompanied by a lower level of stress during their performance. A clear improvement was also observed in terms of emotional control during specific and aspecific stress, which might contribute a positive effect on their interrelationships. As expected, the treatment was not able to reduce the subjects' highly distorted perception of body image, due to the fact that GH treatment, despite a clear amelioration of lean/fat body mass ratio, did not change their body proportions.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
alpha-Interferon treatment of chronic hepatitis C: a controlled, multicentre, prospective study.
This prospective, controlled study was designed in order to evaluate the response rate to alpha-interferon (IFN) versus no treatment in 63 patients affected by chronic hepatitis C. Fifty-two patients were randomly chosen to receive no treatment of IFN alfa-2b (6 MU 3 times weekly for the first month and 3 MU for the next 11 months). Eleven additional patients were crossed to active treatment after a 1-year control period without any change of serum pattern and were therefore enrolled both as controls and cases. Four patients had to be withdrawn from the active treatment for adverse effects. Sixteen out of the remaining 23 had normal alanine aminotransferase (ALT) values at the end of the treatment, and 14 were still normal 12 months later. A liver biopsy, taken 6 months after the end of the treatment, showed improvement in 12 patients and normalization in 1. Only 1 out of the 25 controls had transaminase normalization and 5 a decrease. One of them showed also a histological improvement. Eight of the 11 case/control patients showed ALT normalization after IFN administration, 5 of them histological improvement and 2 liver normalization. Hepatitis C virus (HCV) RNA became negative in 13 of 17 cases in whom the assay was carried out. Therefore this study confirms that the longterm administration of alpha-IFN induced a prolonged remission of disease activity in over 50% of the patients and the clearance of HCV RNA in the majority of the responders.
Adult↗
Quadriceps and hand-grip strength in adults with childhood-onset growth hormone deficiency.
The effects of chronic growth hormone (GH) deficiency on muscle size and strength of postural (quadriceps) and non-postural (hand-grip) muscle groups, as well as on vertical jump capacity, were evaluated in six adults with childhood-onset GH deficiency. Data obtained were compared to those recorded in an age-, sex- and exercise-matched healthy control group. Thigh muscle plus bone cross-sectional area (CSAM+B) of the dominant quadriceps was significantly lower (p < 0.001) than in controls, while the CSAM+B/(Body height)2 ratio was similar to that of controls. The maximum voluntary contraction (MVC) of the quadriceps of patients was significantly lower (p < 0.002) than in controls, while no differences existed in the quadriceps force expressed per unit area (MVC/CSA) between patients and controls. As far as hand-grip was concerned, the CSAM+B of the dominant forearm was significantly lower (p < 0.003) than in controls, while the CSAM+B/(Body height)2 ratio was no different. The hand-grip MVC of patients was significantly lower (p < 0.004) than in controls, while no differences existed in the MVC/CSA ratio. It is noteworthy also that no difference existed in the hand-grip to quadriceps MVC ratio of the two groups. Furthermore, no differences were found in the vertical jump capacity, because both delta Height and delta Height/Body weight of patients were not significantly different from those of controls. In conclusion, our study suggests that GH deficiency seems to reduce the size and strength of postural and non-postural muscle groups to the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Quantitative description of echographic images of morphea plaques as assessed by computerized image analysis on 20 MHz B-scan recordings.
In order to find image descriptors enabling the characterization of sclerotic skin of morphea plaques and their objective differentiation from normal skin, we studied 52 lesions in 35 patients affected by plaque type morphea. Echographic evaluations were carried out using a 20 MHz B-scanner, providing cross-sectional images of the skin. Images were processed by a program providing a numerical representation of the picture data, based on the following parameters, which were considered for 7 different amplitude intervals: 1) the extension of image areas marked by amplitude bands of interest, 2) the percentage of the image surface reflecting within a homogeneous amplitude band, 3) the number of objects composing the image, 4) the average object size, and 5) the "density" of the objects. For all parameters considered, marked differences between sclerotic skin and normal tissue were observable. When assessment is performed with amplitude bands covering the lower part of the scale, the image referring to sclerotic tissue appears relatively homogeneous with few, large objects within a thickened skin block, which occupy a more extended image surface in comparison to images of normal skin, characterized by spots, which are small and closely packed. On the contrary, binary images of morphea plaques transformed by intermediate to high amplitude intervals appear with fewer objects of approximately the same size or smaller, which are less compressed in respect to healthy skin images.
Adult↗
Prevention of interleukin-2-induced thrombocytopenia during the immunotherapy of cancer by a concomitant administration of the pineal hormone melatonin.
Thrombocytopenia is a frequent haematologic complication of IL-2 immunotherapy of cancer. Preliminary results suggest a role of melatonin in the regulation of platelet production, so a study was started to evaluate the influence of the pineal hormone on IL-2-induced thrombocytopenia. Of 25 lung cancer patients, 10 were treated with melatonin alone, 7 received IL-2 alone and 8 patients were concomitantly treated with IL-2 and melatonin. Thrombocytopenia occurred in 3/7 patients treated with IL-2 alone, and in none of those treated with IL-2 plus melatonin; this difference was statistically significant. Platelet number increased during IL-2 plus melatonin, even though not significantly; on the contrary, platelet number decreased during IL-2 alone. Platelet number observed in patients treated with IL-2 plus melatonin was significantly higher than in those who received IL-2 alone. Finally, melatonin alone did not substantially influence platelet number. These results show that melatonin may abolish IL-2-induced thrombocytopenia. This might be due to an inhibitory effect of melatonin on macrophage-mediated platelet destruction, with a following increase in platelet number due to an enhanced IL-3 production in response to IL-2.
Adult↗
[Effect of GH/IGF-I deficiency on bone and collagen turnover in children and adults with GH deficiency].
Serum bone Gla protein (BGP), marker of osteoblastic function, carboxyterminal cross-linked telopeptide of type I collagen (ICTP), index of bone resorption, and aminoterminal propeptide of type III procollagen, marker of collagen synthesis, were evaluated in children with GH deficiency (GHD), in adults with childhood-onset GHD and in adults with acquired GHD in adultlife. In children with GHD, serum BGP (12.7 +/- 0.5 ng/ml), ICTP (8.5 +/- 0.9 ng/ml) and PIIINP (3.4 +/- 0.4 ng/ml) were significantly lower (p < 0.0001, p < 0.0001 and p < 0.001, respectively) than those observed in a sex and age matched control group (BGP:18.9 +/- 0.9 ng/ml, ICTP: 14.4 +/- 0.6 ng/ml, PIIINP: 6.7 +/- 0.7 ng/ml). In adults with childhood onsed GHD, BGP levels (3.7 +/- 0.4 ng/ml) were significantly lower (p < 0.0001) than those recorded in a sex and age matched control group (5.4 +/- 0.1 ng/ml), while ICTP (4.7 +/- 0.7 ng/ml) and PIIINP (3.7 +/- 0.5 ng/ml) levels were similar to those found in controls (ICTP: 4.1 +/- 0.3 ng/ml; PIIINP: 3.3 +/- 0.2 ng/ml). In adults with acquired GHD, serum BGP (5.3 +/- 0.4 ng/ml), ICTP (3.8 +/- 0.4 ng/ml) and PIIINP (3.6 +/- 0.3 ng/ml) levels were not significantly different from those recorded in controls (BGP: 5.4 +/- 0.1 ng/ml, ICTP: 4.1 +/- 0.3 ng/ml, PIIINP: 3.3 +/- 0.2 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Colony-stimulating activity and hematopoietic rescue from cancer chemotherapy compounds are induced by melatonin via endogenous interleukin 4.
We have reported that melatonin may rescue bone marrow cells from apoptosis induced either in vivo or in vitro by cancer chemotherapy compounds via bone marrow T-cells and endogenous release of granulocyte-macrophage colony-stimulating factor. Here we show that the number of granulocyte/macrophage colony-forming units cultured with suboptimal concentrations of colony-stimulating factor was higher in the presence of melatonin both at physiological and pharmacological concentrations. CD4+,Thy-1.2+ cell depletion or addition of anti-mouse interleukin 4 monoclonal antibodies prevented both effects of melatonin. Upon incubation with etoposide, the concentration of myeloid precursors was 43 +/- 8 per 10(5) cells. The melatonin+etoposide value was 68 +/- 7, whereas that of melatonin+etoposide+anti-interleukin 4 was 38 +/- 6. Melatonin was also ineffective when bone marrow cells were separated in adherent and nonadherent populations. Supernatants from nonadherent cells incubated with melatonin proved to contain interleukin 4 activity which, however, showed its influence on unseparated bone marrow and adherent cells but not on nonadherent cells. It is proposed that melatonin represents a neuroendocrine regulator of interleukin 4 production in bone marrow T-helper cells. Interleukin 4 may then stimulate adherent stromal cells to produce granulocyte/macrophage colony-stimulating factor. Such a neuroendocrine-cytokine mechanism may explain the hematopoietic rescue of melatonin as well as its antitumoral and immunoenhancing properties.
Animals↗
2-Alkynyl derivatives of adenosine-5'-N-ethyluronamide: selective A2 adenosine receptor agonists with potent inhibitory activity on platelet aggregation.
A series of new 2-alkynyl and 2-cycloalkynyl derivatives of adenosine-5'-N-ethyluronamide (NECA) and of N-ethyl-1'-deoxy-1'-(6-amino-2-hexynyl-9H-purin-9-yl)-beta-D- ribofuranuronamide (1, HE-NECA), bearing hydroxy, amino, chloro, and cyano groups in the side chain, were synthesized. The compounds were studied in binding and functional assays to assess their potency for the A2 compared to A1 adenosine receptor. The presence of an alpha-hydroxyl group in the alkynyl chain of NECA derivatives accounts for the A2 agonist potency, leading to compounds endowed with sub-nanomolar affinity in binding studies. However, these analogues also possess good A1 receptor affinity resulting in low A2 selectivity. From functional experiments the 4-hydroxy-1-butynyl (6) and the 4-(2-tetrahydro-2H-pyranyloxy)-1-butynyl (16) derivatives appear to be very potent in inducing vasorelaxation without appreciable effect on heart rate. The new compounds were also tested as inhibitors of platelet aggregation induced by ADP. Introduction of an alpha-hydroxyl group in the alkynyl side chain caused a greater increase in antiaggregatory activity than either NECA or HE-NECA, resulting in the most potent inhibitors of platelet aggregation so far known in the nucleoside series. The presence of an alpha-quaternary carbon such as the 3-hydroxy-3,5-dimethyl-1-hexynyl (12) and the 3-hydroxy-3-phenyl-1-butynyl (15) derivatives markedly reduced the antiaggregatory potency without affecting the A2 affinity. The hydrophobicity index (k') of the new nucleosides barely correlated with the binding data, whereas high k' values were associated with increased A2 vs A1 selectivity but with reduced activity in all functional assays. Some of the compounds synthesized possess interesting pharmacological properties. Compounds having an appropriate balance between vasorelaxation and antiplatelet activity, if confirmed in vivo, deserve further development for the treatments of cardiovascular disorders.
Adenosine↗
Hematopoietic rescue via T-cell-dependent, endogenous granulocyte-macrophage colony-stimulating factor induced by the pineal neurohormone melatonin in tumor-bearing mice.
We investigated whether melatonin can affect tumor growth and/or hematopoiesis in mice transplanted with Lewis lung carcinoma and treated with cyclophosphamide or etoposide. These agents were injected i.p. for 5 days at two different cumulative doses (cyclophosphamide, 40 and 160 mg/kg body weight; etoposide, 20 and 40 mg/kg body weight) from day 8 through day 12 after tumor transplantation. Melatonin was injected s.c. at a dose of 1 mg/kg body weight/day, from day 8 throughout the experiments and from days 8 through 12 or from day 13 onwards. Melatonin did not influence tumor growth but selectively counteracted bone marrow toxicity when administered together with the cancer chemotherapy compounds without interfering with their anticancer action. In vitro, melatonin proved to counteract apoptosis in bone marrow cells incubated with etoposide. Such protection was reflected by an increased frequency of granulocyte/macrophage-colony forming units but not of the pluripotent spleen-colony forming units. The effect of melatonin was neutralized by anti-granulocyte/macrophage-colony-stimulating factor monoclonal antibodies. When athymic, T-cell-deficient mice were used as bone marrow donors, melatonin did not exert any protective effect. This suggested that melatonin is able to stimulate the endogenous production of granulocyte/macrophage-colony-stimulating factor via bone marrow T-cells. Due to the well known lack of toxic and undesirable side effects of melatonin, these findings might have a straightforward clinical application.
Animals↗
A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasms.
BACKGROUND: Unresectable brain metastases remain an untreatable disease. Because of its antitumor cytostatic action and its anticonvulsant effect, the pineal hormone melatonin could constitute a new effective agent in the treatment of brain metastases. The current study was performed to evaluate the effect of melatonin on the survival time in patients with brain metastases due to solid neoplasms. METHODS: The study included 50 patients, who were randomized to be treated with supportive care alone (steroids plus anticonvulsant agents) or with supportive care plus melatonin (20 mg/day at 8:00 p.m. orally). RESULTS: The survival at 1 year, free-from-brain-progression period, and mean survival time were significantly higher in patients treated with melatonin than in those who received the supportive care alone. Conversely, steroid-induced metabolic and infective complications were significantly more frequent in patients treated with supportive care alone than in those concomitantly treated with melatonin. CONCLUSIONS: The pineal hormone melatonin may be able to improve the survival time and the quality of life in patients with brain metastases due to solid tumors.
Adult↗
Prevalence of anti-HCV in institutionalised mentally handicapped subjects.
Data on the prevalence of antibody to hepatitis C virus among 278 subjects in an institution for the mentally handicapped were analysed by risk factors. A prevalence of 4% was found, higher than blood donors belonging to the same area (1.4%). No differences in prevalence with regard the length of residence, age, sex, degree of retardation or for presence of HBV markers were observed.
Adolescent↗
Noradrenergic modulation of lymphohematopoiesis.
Adrenergic agents can affect hematopoiesis after syngeneic bone marrow transplantation (BMT) in mice. In particular, chemical sympathectomy by 6-hydroxydopamine and/or administration of various doses of the alpha 1-adrenergic antagonist prazosin were shown to increase the concentration of blood granulocytes, platelets and bone marrow granulocyte--macrophage-colony forming units (GM-CFU), and to induce a granulocytic hyperplasia of the spleen. Here we show that while enhancing myelopoiesis, prazosin decreased the number of spleen B- and T-lymphocytes as well as the number of thymocytes after BMT. The relative proportion of thymocyte subpopulations was not affected, suggesting a non-corticosteroid related mechanism. Furthermore, NK activity and primary cytotoxic T-lymphocyte (CTL) response to Lancy vaxinia virus was impaired in mice treated with prazosin after BMT. When noradrenaline was added in bone marrow cultures, it decreased the number of GM-CFU and such an effect was counteracted by prazosin. These findings suggest that hematopoiesis is under an alpha-adrenergic control.
Animals↗
Low-dose interleukin-2 subcutaneous immunotherapy in association with the pineal hormone melatonin as a first-line therapy in locally advanced or metastatic hepatocellular carcinoma.
Experimental studies have showed that hepatocellular carcinoma (HCC) cells are susceptible to cytolysis of interleukin (IL)-2-activated lymphocytes. Moreover, our previous studies demonstrated that the pineal neurohormone melatonin (MLT) may enhance IL-2 efficacy. On this basis, a study was started with low-dose IL-2 (3 million U/day subcutaneously for 6 days/week for 4 weeks) plus MLT (50 mg/day orally every day given in the evening) as a first-line therapy of unresectable HCC. The study included 14 patients. Objective tumour regressions were obtained in 5/14 (36%) patients (one complete response, four partial responses), with a median duration of 7+ months. 6 patients had stable disease, while the other 3 progressed. Toxicity was low in all cases. This study shows that the neuroimmunotherapy with low-dose IL-2 plus MLT is a new well-tolerated and effective therapy of advanced HCC.
Adult↗
Effects of the new A2 adenosine receptor antagonist 8FB-PTP, an 8 substituted pyrazolo-triazolo-pyrimidine, on in vitro functional models.
1. We have characterized the in vitro pharmacological profile of putative A2 adenosine antagonists, two non-xanthine compounds, 5-amino-8-(4-fluorobenzyl)-2-(2-furyl)-pyrazolo [4,3-e]-1,2,4-triazolo[1,5-c] pyrimidine (8FB-PTP) and 5-amino-9-chloro-2-(2-furyl 1,2,4-triazolo [1,5-c] quinazoline (CGS 15943), and the xanthine derivative (E)7-methyl-8-(3,4-dimethoxystyryl)-1,3-dipropyl- xanthine (KF 17837). 2. In binding studies on bovine brain, 8FB-PTP was the most potent (Ki = 0.074 nM) and selective (28 fold) drug on A2 receptors, whereas CGS 15943 and KF 17837 exhibited affinity in the low and high nanomolar range, respectively, and showed little selectivity. 3. In functional studies, 8FB-PTP antagonized 5'-N-ethyl-carboxamidoadenosine (NECA)-induced vasorelaxation of bovine coronary artery (pA2 = 7.98) and NECA-induced inhibition of rabbit platelet aggregation (pA2 = 8.20). CGS 15943 showed weak activity in the platelet aggregation model (pA2 = 7.43) and failed to antagonize NECA-induced vasodilatation. KF 17837 was ineffective in both models up to micromolar concentrations. 4. Antagonism of A1-mediated responses was tested versus 2-chloro-N6-cyclopentyladenosine (CCPA) in rat atria. 8FB-PTP and CGS 15943 also antagonized competitively the negative chronotropic response induced by CCPA. Conversely, KF 17837 was unable to reverse A1-mediated responses. 5. 8FB-PTP is a potent and competitive antagonist of responses mediated by A2 adenosine receptors. The data provided a basis to reduce, by further chemical modifications, the affinity at A1 receptor and therefore enhance A2 receptor selectivity.
Adenosine↗
Adrenal medulla secretion in Cushing's syndrome.
To investigate whether chronic endogenous hypercortisolism might alter adrenomedullary phenylethanolamine N-methyltransferase activity, we measured epinephrine/norepinephrine (E/NE) ratios in the adrenal venous blood of 8 patients undergoing surgery for Cushing's syndrome and in 12 control subjects undergoing surgery for left kidney diseases. To investigate the adrenomedullary secretory activity in Cushing's syndrome, we measured basal E plasma levels in 24 patients and 32 age- and sex-matched normal control subjects, and we evaluated the adrenomedullary response to glucagon in 9 patients and in 22 age- and sex-matched normal subjects. Last, to clarify whether chronic endogenous hypercortisolism might modify E plasma levels through a modification of E metabolism, we measured the E MCR in four patients and four age-matched controls. Mean (+/- SEM) E/NE ratio in adrenal venous blood was similar in patients with Cushing's syndrome (4.61 +/- 0.78) and in the control group (4.71 +/- 0.74). Mean (+/- SEM) basal plasma E was significantly lower in patients with Cushing's syndrome (98.2 +/- 10.9 vs. 184 +/- 25.1 pmol/L, P < 0.01) than in the control group. Similarly, plasma NE also was reduced (0.75 +/- 0.09 vs. 1.10 +/- 0.07 nmol/L, P < 0.01). In patients with Cushing's syndrome the E response to glucagon was significantly reduced (P < 0.01). E MCR was almost identical in patients with Cushing's syndrome (1.48 +/- 0.10 L/min.m2) and in control subjects (1.51 +/- 0.10 L/min.m2). Our data demonstrate that: 1) chronic endogenous hypercortisolism is not able to change adrenomedullary phenylethanolamine N-methyltransferase activity and therefore the quality of adrenomedullary secretion; and 2) chronic endogenous hypercortisolism causes a decrease in basal and stimulated adrenomedullary activity without altering E MCR significantly. Therefore the adrenal medulla does not seem to play a pathogenetic role in the hypertension of Cushing's syndrome.
Adrenal Medulla↗
Human alpha S1-casein like protein: purification and N-terminal sequence determination.
Casein components of human milk are generally reported to belong to the beta- and kappa-groups. In this research human casein fraction was obtained from pooled mature milk, either by ultracentrifugation or by acid precipitation. In both cases a minor component with a slightly higher mobility in SDS-PAGE than beta-casein was identified. The protein was purified to homogeneity, the N-terminal sequence of the first 14 amino acid residues of this new human casein subunit shows a high degree of homology with the alpha s1-casein sequences from other species.
Amino Acid Sequence↗