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Biomedical subjects

A Conti

Publications and source records attributed to A Conti.

At least 91 records · Page 5Linked to original sources
PubMed1996

Serum bone Gla protein and carboxyterminal cross-linked telopeptide of type I collagen in patients with Cushing's syndrome.

Serum bone Gla protein, a marker of bone formation, and carboxyterminal cross-linked telopeptide of type I collagen levels, an index of bone resorption, were evaluated in eight patients with active Cushing's syndrome and in four with 'preclinical' Cushing's syndrome, before and after surgery. In basal conditions, serum bone Gla protein levels were significantly lower (p < 0.0001) in patients with active Cushing's syndrome (1.0 +/- 0.35 ng/ml) than in controls (5.4 +/- 0.15 ng/ml); two out of four patients with the 'preclinical' form had reduced bone Gla protein levels, while in the other two cases levels were in the normal range. Serum levels of carboxyterminal cross-linked telopeptide of type I collagen (3.0 +/- 0.4 ng/ml), although slightly reduced, were similar to those recorded in controls (4.1 +/- 0.3 ng ml), both in patients with active and with preclinical Cushing's syndrome. After surgery serum levels of both marker proteins significantly increased in seven out of eight patients with active Cushing's syndrome; in one patient, who was not cured after surgery, bone Gla proteins levels remained lower than in normals, while levels of carboxyterminal cross-linked telopeptide of type I collagen had a transient increase after six months. In the two patients with a 'preclinical' Cushing's syndrome who underwent surgery, a significant rise of the levels of both marker proteins was observed, similar to that observed in patients with active Cushing's syndrome. It was concluded that serial determinations of these new markers of bone formation and resorption may be usefully employed to follow-up the clinical course of Cushing's syndrome and provide information on the rate of bone turnover in response to medical and/or surgical therapies. Moreover, the evaluation of these markers in preclinical states of Cushing's syndrome might suggest the need for surgery.

Adult↗
PubMed1996

Growth, growth hormone and cognitive functions.

The interactions among short stature, growth hormone (GH) and cognitive functions have been extensively studied so far. However, although it seems well established that short stature is associated with cognitive problems, little effort has been made to point out the presence of specific psychological effects related to the different forms of short stature. In 'short normal' children, the presence of a scholastic underachievement seems to suggest that short stature 'itself' might predispose these patients to some of their psychosocial difficulties. The higher incidence of academic failure, in presence of a normal intellectual functioning, has been attributed to environmental and psychosocial factors, including over-protective parents and low self-esteem resulting from the impact of short stature. These problems appear to be common also to other forms of short stature (such as Turner's syndrome) where, however, they are frequently associated with other specific deficits. The in vivo model which might allow, at least in part, better understanding of GH (per se)-dependent effects is represented by GH deficiency (GHD), in which, however, the specific role of GH on psychological functioning is frequently masked by the presence of associated hormonal deficiencies. Children with isolated GHD are reported to have specific educational deficits, in particular learning disability and attention-deficit disorders, which have been tentatively attributed to a compromised intellectual potential. The psychological effects of long-term GH treatment in children with GHD still remain controversial, with some retrospective studies describing a generally beneficial outcome. Since early experiences in school are closely related to success in adult life, the possible implications that GHD during childhood holds during adulthood have been recently considered. Although regional differences have been observed in subgroups of adults with GHD, it seems that these patients have normal cognitive functions and educational attainment, but are more likely to be unemployed (and unmarried) than members of the general population. In general, patients with GHD, who have been treated at centers where psychological counselling was an integral part of the treatment program, seem to be better adjusted in adult life. For these reasons, a multidisciplinary treatment approach could allow early detection of problems in academic achievement and psychosocial development in patients with short stature, being immediately able to provide the appropriate educational and counselling interventions.

Adult↗
PubMed1996

No alteration of biophysical parameters in the skin of subjects with respiratory atopy.

BACKGROUND: Skin hyperreactivity to environmental factors in patients with atopic dermatitis has been extensively studied. Conversely, little is known on the biophysical parameters of the skin in patients with respiratory allergy. OBJECTIVE AND METHODS: Functional characteristics of the skin in subjects with allergic asthma and/or rhinitis were studied using evaporimetry, capacitance and pHmetry. Data were compared to those of healthy subjects and patients with atopic dermatitis (AD). RESULTS AND CONCLUSIONS: Our results suggest that the skin of patients with atopic respiratory allergy does not show altered biophysical parameters when compared to normal skin, confirming that the functional alterations in AD skin are linked to the expression of the atopic diathesis in the skin.

Adolescent↗
PubMed1996

A quantitative description of echographic images of sclerotic skin in patients with systemic sclerosis, as assessed by computerized image analysis on 20 MHz B-scan recordings.

The aim of our study was to find image descriptors enabling the characterization of sclerotic skin and its differentiation from normal skin, in order to find an objective method for the assessment of skin involvement in systemic sclerosis (SSc). Echographic evaluations were carried out using a 20 MHz B-scanner, on 18 female patients with SSc and on 20 healthy women serving as controls, at 3 different skin sites (forehead, cheek and back of the hand). Images were processed by a program, based on segmentation procedures and object description, employing 5 different amplitude bands and the following parameters: 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. At all 3 skin sites, marked differences in the echostructure of the tissue between patients with SSc and the controls were observable. In SSc patients forehead skin appeared thinner and more echogenic, with smaller hypo-reflecting objects and greater hyper-reflecting areas; cheek skin showed an increase in intermediate-high amplitude components, with greater and more numerous hyper-reflecting objects, and smaller and less numerous hypo-reflecting ones; the skin on the back of the hand was thicker, less echogenic, with large hypo-reflecting areas and small hyper-reflecting objects. By image processing these parameters were numerically described. Values referring to sclerotic skin significantly differed from those of normal skin. This echographic procedure is proposed as a method representing a first step towards the quantification of the spontaneous course of SSc and of response to therapy.

Adult↗
PubMed1996

The non-xanthine heterocyclic compound SCH 58261 is a new potent and selective A2a adenosine receptor antagonist.

We have characterized the in vitro pharmacological profile of the new potent and selective A2a adenosine receptor antagonist SCH 58261 [7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2, 4-triazolo[1,5-c]pyrimidine]. In binding studies on rat and bovine brain tissues, SCH 58261 showed affinity in the low nanomolar range at A2a adenosine striatal receptors and good A2a adenosine vs. A1 adenosine selectivity (about 50- to 100-fold in rat and bovine brain, respectively). SCH 58261 did not show affinity for either the A3 adenosine receptor or other receptors at concentrations up to 1 microM. Saturation experiments on rat A1 and A2a adenosine receptors indicated the competitive nature of the antagonism. SCH 58261 antagonized competitively the effects induced by the A2a adenosine-selective agonist CGS 21680 (2-[4-(2-carboxyethyl)-phenethyl-amino]-5'-N- ethylcarboxamidoadenosine) in two functional assays, such as inhibition of rabbit platelet aggregation and porcine coronary artery relaxation. Specifically, the compound showed pA2 values of 7.9 and 9.5, respectively. SCH 58261 (300 nM) failed to antagonize 5'-N-ethylcarboxamidoadenosine-induced vasorelaxation in the isolated guinea pig aorta, a response mediated by A2b adenosine receptors. Likewise, at the same concentration, the compound weakly inhibited the A1 adenosine-mediated negative chronotropic effect induced by 2-chloro-N6-cyclopentyladenosine in the isolated rat atria. These data show that SCH 58261 is a potent and selective non-xanthine A2a adenosine antagonist which has competitive properties in biological responses mediated by this receptor subtype. The compound is of interest for investigating the biological role of A2a adenosine receptors and deserves further attention to clarify the therapeutic potential of A2a antagonists.

Animals↗
PubMed1996

Hyperparathyroidism: is it really the major factor affecting glucose tolerance in uremia?

The effects of secondary hyperparathyroidism (sHPTH) on immunoreactive insulin (IRI) release and glucose (G) tolerance were studied in two groups of dialysis patients with normal (NPTH, n = 9) or elevated PTH levels (HPTH, n = 8), 27 +/- 24 and 660 +/- 440 pg/ml, respectively. The patients received an intravenous glucose tolerance test (IVGTT) using 0.33 g/kg of glucose solution. G, IRI and C-peptide (C-p) levels were determined calculating the G constant decay (K) and the relative incremental areas for each study. Regardless of PTH levels, all patients showed an impaired glucose tolerance (GT). IRI secretion and K values were not significantly different between the two groups. However, a significantly lower K value with a reduced (although not significant) early and late IRI secretion was found in the subgroup of patients with more severe. sHPTH (PTH: 560-1,500 pg/ml, n = 5) as compared to patients with moderate sHPTH (PTH: 87-341 pg/ml, n = 4) or normal (5-32 pg/ml, n = 8) PTH levels. No relationship was found between PTH and G, IRI or C-p levels. Our results point to a threshold limit for PTH's inhibitory effect on IRI secretion and suggest that other factors, known to affect IRI secretion and GT besides PTH levels, may modulate the role played by excess PTH levels on carbohydrate metabolism of dialysis patients.

Adult↗
PubMed1996

Melatonin in human breast cancer tissue: association with nuclear grade and estrogen receptor status.

The pineal hormone melatonin has been reported to inhibit tumor growth in a variety of experimental and clinical situations and to be an important immunoregulatory agent. Cancer patients with mammary or prostate tumors show reduced levels of circulating melatonin. Melatonin might, thus, be involved in the development of the malignant disease and act directly on tumor cells. Melatonin concentration in human neoplastic and adipose tissue sampled from mastectomy or tumorectomy products (n = 15) was measured by high-performance liquid chromatography. Melatonin seemed to be 3 orders of magnitude more concentrated in the neoplastic and adipose tissues of the breast than in sera from healthy subjects or cancer patients. Few samples (n = 3) of normal breast tissues showed equally elevated concentrations of melatonin. Most interestingly, we found a significant inverse correlation between nuclear grade and melatonin concentration (p < 0.006) and a positive association between melatonin and estrogen receptor status (p < 0.02). No correlation between age of the patients and melatonin concentration was evident. Melatonin might be produced in situ by mammary epithelial cells and represent a good prognostic marker. The possibility that exogenous melatonin might influence nuclear grade and/or estrogen receptor activity in breast cancer patients should be investigated.

Adipose Tissue↗
PubMed1996

[Transanal ultrasonography in the study of fistulas of perianal abscess].

The fistulous tracks and abscesses may be related anatomically to the anal sphincters and levator ani muscles. Defining the anatomical relationship between the fistulous lesion and the anal sphincters and/or adjacent organs is essential for correct management. Clinical examination can suggest possible sepsis or the direction of the fistulous track. We report the results of anal endosonography in the evaluation of 54 patients affected by perianal sepsis and fistula in ano. Anal endosonography has correctly identified 22 of 22 internal openings seen at the surgery, 14 of 16 intersphincteric tracts while only 7 of the 9 trans-sphincteric tracks described by anal endosonography were present at the surgery. All the abscesses were correctly identified. Anal endosonography provides a high-resolution image of the anatomy of anal canal and defines the anatomy of tracks and abscesses in relation to the sphincters, determines if there has been trans-sphincteric extension of the sepsis and assesses the state of the sphincters. We have observed a good correlation between the preoperative AES findings and those at surgery. We conclude that anal endosonography is a useful diagnostic procedure in patients with perianal sepsis.

Abscess↗
PubMed1995

2-[N'-(3-arylallylidene)hydrazino]adenosines showing A2a adenosine agonist properties and vasodilation activity.

A series of 2-[N'-(3-arylallylidene)hydrazino]adenosines were prepared and studied in binding and functional assays to assess their potency for the A2a compared with the A1 adenosine receptor. These analogs possess A2a receptor affinity in the low nanomolar range associated with weak interaction with the A1 receptor. Among the compounds, in rat tissues, 2-[N'-[3-(4-nitrophenyl)allylidene] hydrazinoadenosine (5g) had the most potent affinity for the A2a receptor, the K(i) value being 23 nM. The type and position of substituents on the phenyl ring show a moderate influence on biological activity, allowing the conclusion that the latter is mostly due to the allylidenehydrazino side chain. From functional experiments 2-[N'-(2-furylmethylidene)hydrazino]adenosine (4b), 2-[N'-(3-phenylallylidene)hydrazino]adenosine (5a) and 2-[N'-[3-(2-furyl)allylidene]hydrazino]adenosine (5b) appeared to be potent in inducing vasorelaxation (an A2a-mediated response) without appreciable effects on the heart rate (an A1-mediated action). While the lack of effects on heart rate is clearly explained by the poor affinity for A1 receptors, more difficult appears the interpretation of vasorelaxant properties displayed by some compounds. Affinity for A2a has a major role, but other types of interactions, yet to be identified, may play a part.

Adenosine↗
PubMed1995

2-Aralkynyl and 2-heteroalkynyl derivatives of adenosine-5'-N-ethyluronamide as selective A2a adenosine receptor agonists.

A series of new 2-aralkynyl and 2-heteroaralkynyl derivatives of NECA were synthesized and studied in binding and functional assays to assess their potency for the A2a compared to A1 adenosine receptors. Compounds bearing an aromatic or heteroaromatic ring, conjugated to the triple bond, showed generally weaker activity at the A2a receptor and lower selectivity (A2a vs A1) than the alkylakynyl derivatives previously reported. However, the (4-formylphenyl)-ethynyl derivative 17 showed affinity in the low nanomolar range and high selectivity (about 160-fold) for the A2a receptor. The presence of heteroatoms improved vasorelaxant activity, the 2-thiazolylethynyl derivative 30 being the most potent in the series. Introduction of methylene groups between the triple bond and the phenyl ring favored the A2a binding affinity, and the 5-phenyl-1-pentynyl derivative 24 was found to be highly potent and selective (about 180-fold) at A2a receptors. With regard to antiplatelet activity, the presence of aromatic or heteroaromatic rings decreased potency in comparison with that of NECA and of N-ethyl-1'-deoxy-1'-(6-amino-2-hexynyl-9H-purin-9-yl)-beta-D-ribofura nuronamide (HENECA). Introduction of a methylene group was effective in increasing antiaggregatory potency only when this group is linked to a heteroatom (31-35). From these data and those previously reported, the structure-activity relationships derived for the 2-alkynyl-substituted ribose uronamides would indicate that potentiation of A2a receptor affinity could be obtained by aromatic rings not conjugated with the triple bond or by heteroaromatic groups. As for A2a receptors on platelets, the presence of aromatic rings, either conjugated or unconjugated to the triple bond, is detrimental for the antiaggregatory activity. However, the introduction of polar groups alpha to the triple bond strongly increases the potency when steric hindrance is avoided. Some of the compounds included in this series retain interesting vasodilating properties and merit further investigation for their potential in the treatment of cardiovascular disorders.

Adenosine↗
PubMed1995

Transanal local resection for benign and malignant rectal tumours.

Local therapy has been widely reported and accepted for benign tumours and carefully selected cancers of the rectum. Thirty-three patients with benign or malignant low rectal tumors have undergone a prospective evaluation after local resection with transanal electroresection as described by Faivre. Patients were divided in three groups: 1) local excision of benign tumours (12 patients), 2) curative resection for localised malignant tumours (7 patients) and 3) palliative local resection for malignant tumours (14 patients). The complications included transient incontinence and rectal bleeding. Patients have been followed for a mean period of 18 months (1-54). In group 3 there were four (28%) recurrences. The remainder of the patients with malignant tumours have been free of disease on follow-up. Although it is ideal for benign neoplasms, further follow-up is needed to determine its true indication in malignant lesions.

Adult↗
PubMed1995

Protective effects of melatonin in mice infected with encephalitis viruses.

We examined the effect of the pineal neurohormone melatonin (MLT) on protection from viral encephalitis. The antiviral activity of MLT was evaluated in normal mice inoculated with Semliki Forest virus (SFV) and in stressed mice injected with the attenuated non-invasive West Nile virus (WN-25). Administration of MLT (s.c.) daily from 3 days before through 10 days after virus inoculation reduced viremia and significantly postponed the onset of disease and death by 7 to 10 days. Moreover, MLT injection reduced mortality of SFV (10 PFU) inoculated mice from 100% to 44%. In mice inoculated with high dose of SFV (100 PFU), MLT postponed death and reduced mortality by 20%. In all of the surviving mice anti-SFV antibodies were detected 22 days after virus inoculation. Infection of mice stressed by either isolation or dexamethasone injection with WN-25 induced mortality of 75% and 50% respectively, which was reduced by MLT administration to 31% and 25%, respectively. The efficiency of MLT in protecting from lethal viral infections warrants further investigations on its mechanisms of action.

Alphavirus Infections↗
PubMed1995

Galanin infusion restores the blunted GH responses to GHRH administration during GH treatment in children with constitutional growth delay.

GH responses to GHRH (in basal conditions), GHRH (after six months of recombinant GH therapy) and GHRH plus galanin administration (after GH therapy) were determined in six children with constitutional growth delay (CGD). Before treatment, GHRH administration caused a clear rise of GH levels (mean GH peak: 38.0 +/- 7.2 ng/ml); mean GH net incremental area under the curve/120 min (GH nAUC) was 2631.0 +/- 519.8 ng/ml/120 min. During GH treatment, both height velocity and IGF-I levels significantly increased from 4.3 +/- 0.1 cm/yr to 9.4 +/- 0.9 cm/yr (p < 0.001) and from 218.7 +/- 12.3 ng/ml to 328.0 +/- 28.2 ng/ml (p < 0.001), respectively. After 6 months of GH therapy, mean GH peak (21.7 +/- 2.2 ng/ml) and mean GH nAUC (847.7 +/- 109.8 ng/ml/120 min) after GHRH administration were significantly lower (p < 0.05) than in basal conditions. Galanin infusion (10 micrograms/kg/bw) was able to completely restore the reduced GH responsiveness to GHRH administration. In fact, mean GH peak and mean GH nAUC after GHRH plus galanin were similar to those recorded after basal GHRH administration (GH peak: 37.5 +/- 4.0 ng/ml; GH nAUC: 2279.8 +/- 430.5 ng/ml/120 min). In conclusion, this study shows that the reduction of pituitary responsiveness to GHRH administration during GH treatment is not dependent on the depletion of the promptly GH releasable pool, since somatotroph refractoriness to GHRH can be overriden by the concomitant administration of galanin.

Child↗
PubMed1995

GH responsiveness to repeated GHRH or hexarelin administration in normal adults.

GH responses, calculated as the net incremental area under the curve (GH nAUC/h), to two consecutive 1 microgram/kg/bw iv GHRH boluses (administered at 0 and 120 min, test a), to one 1 microgram/kg/bw iv GHRH bolus followed by a 1 microgram/kg/bw iv hexarelin bolus (administered at 0 and 120 min respectively, test b) and to two consecutive 1 microgram/kg/bw iv hexarelin boluses (administered at 0 and 120 min, test c) were evaluated in 6 normal adults. The first GHRH injection caused a clear rise in serum GH levels in all subjects (mean GH nAUC/h, test a: 832.1 +/- 59.4 ng/ml/h, range: 723.7-1074.0 ng/ml/h; test b: 859.2 +/- 122.9 ng/ml/h, range 618.0-1422.7 ng/ml/h). Hexarelin administration elicited a marked GH release (test c: 1424 +/- 208.2 ng/ml/h, range: 810.0-2154.0 ng/ml/h), which was significantly higher than those observed after GHRH (vs test a: p < 0.02, vs test b: p < 0.05). After the first GHRH bolus, the second GHRH injection (test a) was unable to sustain GH elevated levels (mean GH nAUC: 74.5 +/- 26.5 ng/ml/h, range: 9.7-182.2 ng/ml/h), while hexarelin administration (test b) caused a clear GH rise in all subjects (GH nAUC: 1049.7 +/- 105.2 ng/ml/h, range: 786.0-1356.0 ng/ml/h). Repeated hexarelin administration (test c) was associated with a significant (p < 0.02) reduction of GH responses to the second bolus (286.6 +/- 43.1 ng/ml/h), which were however significantly higher than those observed after the second GHRH bolus (p < 0.05). In conclusion, these results demonstrate that repeated hexarelin administration causes a reduction of GH responsiveness, which is less marked than that induced by repeated GHRH administration, probably due to the more potent GH-releasing effect of hexarelin. Moreover, when administered after GHRH, hexarelin has a sustained GH-releasing effect in contrast to the poor efficacy of GHRH, thus suggesting that the acute effect of hexarelin is probably not mediated through hypothalamic GHRH pathways.

Adult↗
PubMed1995

The ryanodine receptor/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues.

Ryanodine receptors (RyRs) are intracellular calcium release channels that participate in controlling cytosolic calcium levels. At variance with the probably ubiquitous inositol 1,4,5-trisphosphate-operated calcium channels (1,4,5-trisphosphate receptors), RyRs have been mainly regarded as the calcium release channels controlling skeletal and cardiac muscle contraction. Increasing evidence has recently suggested that RyRs may be more widely expressed, but this has never been extensively examined. Therefore, we cloned three cDNAs corresponding to murine RyR homologues to carry a comprehensive analysis of their expression in murine tissues. Here, we report that the three genes are expressed in almost all tissues analyzed, where tissue-specific patterns of expression were observed. In the uterus and vas deferens, expression of RyR3 was localized to the smooth muscle component of these organs. In the testis, expression of RyR1 and RyR3 was detected in germ cells. RyR mRNAs were also detected in in vitro-cultured cell lines. RyR1, RyR2, and RyR3 mRNA were detected in the cerebrum and in the cerebellum. In situ analysis revealed a cell type-specific pattern of expression in the different regions of the central nervous system. The differential expression of the three ryanodine receptor genes in the central nervous system was also confirmed using specific antibodies against the respective proteins. This widespread pattern of expression suggests that RyRs may participate in the regulation of intracellular calcium homeostasis in a range of cells wider than previously recognized.

Animals↗
PubMed1995

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↗