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Biomedical subjects

A Conti

Publications and source records attributed to A Conti.

At least 37 records · Page 2Linked to original sources
PubMed1998

Neural and endogenous catecholamines in the bone marrow. Circadian association of norepinephrine with hematopoiesis?

Members of our research team have recently reported that adrenergic agents may affect hematopoiesis via alpha1-adrenoceptors present on bone marrow B cell precursors. In this paper we demonstrate that murine bone marrow contains a substantial amount of catecholamines. Norepinephrine (NE) and dopamine (DA) exhibited a daily rhythmicity, with peak values observed during the night. The rhythm was disrupted by chemical sympathectomy, whereas epinephrine (E) showed no rhythmicity or sensitivity to 6-hydroxydopamine. High and low values of NE and DA were associated with high and low values of their metabolites, which indicated a rhythmic catecholamine release. NE, but not DA or E, was positively associated with the proportion of cells in the G2/M and S phases of the cell cycle. Moreover, NE and DA were found in both short-term and long-term bone marrow cultures as well as in human or murine B lymphoid cell lines. These findings indicate that endogenous catecholamines in the bone marrow have both neural and cellular origins. The neural input shows a daily rhythm and may be implicated in the regulation of hematopoiesis.

Animals↗
PubMed1998

Evidence for a common epitope between bovine alpha-lactalbumin and beta-lactoglobulin.

The aim of this work was to check and quantify any cross-reactivities among the main bovine whey proteins, utilizing purified polyclonal antibodies against bovine beta-lactoglobulin, alpha-lactalbumin and serum albumin, and to identify possible common epitope(s). Purified polyclonal anti-bovine beta-lactoglobulin antibodies show 10% cross-reactivity with bovine alpha-lactalbumin, both in its native and its denatured form. A continuous stretch of four amino acids common to alpha-lactalbumin and beta-lactoglobulin that might be responsible for this cross-reactivity has been identified. Cross-reactivity between this antibody and bovine serum albumin is, on the contrary, negligible. Purified polyclonal anti-bovine alpha-lactalbumin and anti-serum albumin antibodies do not cross-react.

Amino Acid Sequence↗
PubMed1997

The effect of in vitro modeling conditions on the surface reactions of bioactive glass.

Using one parametric variation in solution composition, this paper documents that the surface reactions on bioactive glass (BG) 45S5 are exquisitely dependent upon the modeling conditions. The solutions used were 0.05 M tris hydroxymethyl aminomethane/HCl (tris buffer), tris buffer complemented with plasma electrolyte and/or serum, and serum. The reacted surfaces were analyzed using Fourier transform infrared (FTIR), scanning electron microscopy (SEM) with energy dispersive X-ray analysis (EDXA), and Rutherford backscattering spectroscopy (RBS). Post-immersion solutions were analyzed for changes in Ca and PO4 concentrations. After a short immersion (3 h), a crystalline, carbonated hydroxyapatite (c-HA) layer formed only in tris. Reaction surfaces of different structure, morphology, and composition were observed after various short and longer term immersions in all other solutions. They comprised two layers with the layer in contact with the bulk consisting mainly of Si; the outer layer, composed of Si, Ca, and P, was amorphous, and had a Ca/P ratio of about 1. Serum proteins adsorbed on the BG surfaces at the early stages of the solution-mediated BG reactions. Formation of a crystalline c-HA layer was delayed up to three or more days in solution with plasma ions. In the presence of serum, only amorphous surfaces composed of Si, Ca, and P were observed for any time up to seven days of immersion. The present data suggest that serum proteins adsorb in tandem with the occurrence of solution-mediated reactions leading to formation of a silica-gel. Amorphous Ca-P phases accumulate in the Si-rich matrix. Furthermore, the present data, in conjunction with the data published before, suggest that physicochemical and cell-mediated reactions occur in parallel to form the glass-tissue interfacial layer.

Biocompatible Materials↗
PubMed1997

Requirement for the ryanodine receptor type 3 for efficient contraction in neonatal skeletal muscles.

The skeletal isoform of Ca2+ release channel, RyR1, plays a central role in activation of skeletal muscle contraction. Another isoform, RyR3, has been observed recently in some mammalian skeletal muscles, but whether it participates in regulating skeletal muscle contraction is not known. The expression of RyR3 in skeletal muscles was studied in mice from late fetal stages to adult life. RyR3 was found to be expressed widely in murine skeletal muscles during the post-natal phase of muscle development, but was not detectable in muscles of adult mice, with the exception of the diaphragm and soleus muscles. RyR3 knockout mice were generated, and it was shown that skeletal muscle contraction in these mice was impaired during the first weeks after birth. In skeletal muscles isolated from newborn RyR3(-/- )mice, but not in those from adult mice, the twitch elicited by electrical stimulation and the contracture induced by caffeine were strongly depressed. These results provide the first evidence that RyR3 has a physiological role in excitation-contraction coupling of neonatal skeletal muscles. The disproportion between the low amount of RyR3 and the large impact of the RyR3 knockout suggests that this isoform contributes to the amplification of Ca2+ released by the existing population of ryanodine receptors (RyR1).

Age Factors↗
PubMed1997

Expression of the ryanodine receptor type 3 calcium release channel during development and differentiation of mammalian skeletal muscle cells.

In vertebrate skeletal muscles, the type 1 isoform of ryanodine receptor (RyR1) is essential in triggering contraction by releasing Ca2+ from the sarcoplasmic reticulum in response to plasma membrane depolarisation. Recently, the presence of another RyR isoform, RyR3, has been detected in mammalian skeletal muscle cells, raising the question of the eventual relevance of RyR3 for muscle cell physiology. The expression of RyR3 was investigated during differentiation of skeletal muscle cells. Using antibodies able to distinguish the different RyR isoforms and Western blot analysis, the RyR3 protein was detected in the microsomal fractions of differentiated skeletal muscle cells but not of undifferentiated cells. Accordingly, blocking muscle differentiation by the addition of either transforming growth factor-beta or basic fibroblast growth factor prevented the expression of the RyR3 protein. In differentiated skeletal muscle cells, RyR3 was expressed independent of cell fusion and myotube formation. The expression of RyR3 was also investigated during development of the diaphragm muscle. The RyR3 content in the diaphragm muscle increased between the late stage of fetal development and the first postnatal days. However, at variance with RyR1, which reached maximum levels of expression 2-3 weeks after birth, the expression of RyR3 was found to be higher in the neonatal phase of the diaphragm muscle development (2-15 days after birth) than in the same muscle from adult mice. The differential content of RyR3 in adult skeletal muscles was found not to be mediated by neurotrophic factors or electrical activity. These findings indicate that RyR3 is preferentially expressed in differentiated skeletal muscle cells. In addition, during skeletal muscle development, its expression is regulated differently from that of RyR1.

Aging↗
PubMed1997

Detection of specific IgE to human milk proteins in sera of atopic infants.

Specific IgE (sIgE) for cow's milk proteins (CMP) have been reported to be present in blood sera of exclusively breast-fed infants. The aim of this study was to find whether the presence of sIgE to human milk proteins in the sera of exclusively breast-fed infants could explain the apparent detection of sIgE to CMP in infants that were never previously in contact with cow's milk. sIgE for human milk whey proteins were found in the blood sera of atopic infants, and these sIgE strongly cross-reacted with the corresponding CMP. In none of the sera examined were sIgE to bovine beta-lactoglobulin detected.

Animals↗
PubMed1997

Cardioprotective effects of adenosine A1 and A2A receptor agonists in the isolated rat heart.

It has been postulated that the adenosine A1 receptor subtype, but also A2a receptors, are involved in mediating the beneficial properties of adenosine during ischemia and reperfusion. We investigated the effects of the selective A1 adenosine receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA), the selective A2A adenosine receptor agonists, 2-[p-(2-carboxyethyl)phenetylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680), 2-hexynyl-5'-N-ethylcarboxamidoadenosine (2HE-NECA), and the non selective agonist, 5'-N-ethylcarboxamidoadenosine (NECA), on ischemia-reperfusion injury in Langendorff-perfused rat hearts. Global ischemia was induced for 15 min in paced hearts followed by 60 min reperfusion. Control hearts developed left ventricular dysfunction, as indicated by the increase in end diastolic pressure to 40.8 +/- 5.1 vs 5.9 +/- 1.0 mm Hg baseline, and in coronary perfusion pressure to 57.6 +/- 8.4 vs 28.8 +/- 2.2 mm Hg before ischemia. After 15 min of reperfusion, ventricular function (LVDP) recovered by 83%, but creatine kinase levels were still significantly increased (294 +/- 55 IUl(-1) vs basal), indicating the occurrence of myocardial injury. All adenosine agonists added to the perfusion medium 15 min prior to ischemia exerted protective effects against myocardial dysfunction and reperfusion injury. Thus, 2HE-NECA (100 nM), CGS 21680 (10 nM), CCPA (3 nM) and NECA (100 nM) significantly (P < 0.05) decreased end diastolic pressure by 50-75% as compared with the control group. Similarly, all compounds significantly (P < 0.05) reduced coronary perfusion pressure by 30-45% vs control. For all drugs, recovery of LVDP occurred immediately after restoration of coronary flow. At 15-min reperfusion the adenosine agonists decreased myocardial creatine kinase release by 80-95% (P < 0.05 vs control). These findings indicate that both A1 and A2A adenosine receptors are involved in protecting the myocardium against ischemia and reperfusion in isolated rat heart, even if through different mechanisms.

Adenosine↗
PubMed1997

Prolonged exposure to 5'-N-ethylcarboxamidoadenosine (NECA) does not affect the adenosine A2A-mediated vasodilation in porcine coronary arteries.

At present, four distinct adenosine receptors (A1, A2A, A2B, and A3) have been cloned and characterized in several species. It is known that prolonged exposure of tissues to receptor agonists induces A1 receptor desensitization. However, controversial data are reported on whether or not prolonged stimulation of A2A adenosine receptors induces tolerance. Using the porcine coronary artery, a sensitive vascular model, studies were designed, with the aim to clarify how prolonged exposure to the adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA) affects A2A receptor responsiveness. The arteries were precontracted with PGF2alpha (3 microM) and cumulative dose-response curves to either NECA itself, or the selective A2A agonists, 2-[4-2(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosi ne (CGS 21680) and 2-hexynyl-5'-N-ethylcarboxamidoadenosine (2HE-NECA) were obtained. In separate experiments, coronary rings were incubated with NECA (10 microM) for 30 min or 2 h. After 2 h washout period, functional response was assessed. The arteries showed high sensitivity to adenosine agonist-induced vasorelaxation. EC50 (nM) values were 71.8 (35.5-145), 20.0 (11.2-32.7) and 40.2 (20.4-79.1) for NECA, 2HE-NECA and CGS 21680, respectively. Vasorelaxant response of A2A selective agonists 2HE-NECA and CGS 21680 was not influenced by preincubation with NECA for 30 min or 2 h. Conversely, dose-response curves to NECA were shifted toward the right by preincubation with NECA itself: ED50 (nM) values were 114 (79.2-165), 211 (161-276) and 412 (132-1290) for 30 min, 2 h and 15 h preincubation, respectively. These effects did not occur after 4 h washout. The present results indicate that prolonged stimulation of A2A receptors does not lead to loss of functional response, suggesting that this receptor subtype does not desensitize after prolonged stimulation by agonists.

Adenosine↗
PubMed1997

Treatment of cancer chemotherapy-induced toxicity with the pineal hormone melatonin.

Experimental data have suggested that the pineal hormone melatonin (MLT) may counteract chemotherapy-induced myelosuppression and immunosuppression. In addition, MLT has been shown to inhibit the production of free radicals, which play a part in mediating the toxicity of chemotherapy. A study was therefore performed in an attempt to evaluate the influence of MLT on chemotherapy toxicity. The study involved 80 patients with metastatic solid tumors who were in poor clinical condition (lung cancer: 35; breast cancer: 31; gastrointestinal tract tumors: 14). Lung cancer patients were treated with cisplatin and etoposide, breast cancer patients with mitoxantrone, and gastrointestinal tract tumor patients with 5-fluorouracil plus folates. Patients were randomised to receive chemotherapy alone or chemotherapy plus MLT (20 mg/day p.o. in the evening). Thrombocytopenia was significantly less frequent in patients concomitantly treated with MLT. Malaise and asthenia were also significantly less frequent in patients receiving MLT. Finally, stomatitis and neuropathy were less frequent in the MLT group, albeit without statistically significant differences. Alopecia and vomiting were not influenced by MLT. This pilot study seems to suggest that the concomitant administration of the pineal hormone MLT during chemotherapy may prevent some chemotherapy-induced side-effects, particularly myelosuppression and neuropathy. Evaluation of the impact of MLT on chemotherapy efficacy will be the aim of future clinical investigations.

Adult↗
PubMed1997

The glutamate receptor/NO/cyclic GMP pathway in the hippocampus of freely moving rats: modulation by cyclothiazide, interaction with GABA and the behavioural consequences.

Monitoring of extracellular cGMP during intracerebral microdialysis in freely moving rats permits the study of the functional changes occurring in the glutamate receptor/nitric oxide (NO) synthase/guanylyl cyclase pathway and the relationship of these changes to animal behaviour. When infused into the rat hippocampus in Mg2+-free medium, cyclothiazide, a blocker of desensitization of the AMPA-preferring receptor, increased cGMP levels. The effect of cyclothiazide (300 microM) was abolished by the NO synthase inhibitor L-NARG (100 microM) or the soluble guanylyl cyclase inhibitor ODQ (100 microM). During cyclothiazide infusion the animals displayed a pre-convulsive behaviour characterized by frequent "wet dog shakes" (WDS). Neither L-NARG nor ODQ decreased the WDS episodes. Both cGMP and WDS responses elicited by cyclothiazide were prevented by blocking NMDA receptor function with the glutamate site antagonist CGS 19755 (100 microM), the channel antagonist MK-801 (30 microM) or Mg2+ ions (1 mM). The AMPA/kainate receptor antagonists DNQX (100 microM) and NBQX (100 microM) abolished the WDS episodes but could not inhibit the cyclothiazide-evoked cGMP response. DNQX or NBQX (but not MK-801) elevated, on their own, extracellular cGMP levels. The cGMP response elicited by the antagonists appears to be due to prevention of a glutamate-dependent inhibitory GABAergic tone, since infusion of bicuculline (50 microM) caused a strong cGMP response. The results suggest that (a) AMPA/kainate receptors linked to the NO/cGMP pathway in the hippocampus (but not NMDA receptors) are tonically activated and kept in a desensitized state by endogenous glutamate; (b) blockade of AMPA/kainate receptor desensitization by cyclothiazide leads to endogenous activation of NMDA receptors; (c) the hippocampal NO/cGMP system is under a GABAergic inhibitory tone driven by non-NMDA ionotropic receptors; (d) the pre-convulsive episodes observed depend on hippocampal NMDA receptor activation but not on NO and cGMP production.

Animals↗
PubMed1997

The unusual amino acid triplet Asn-Ile-Cys is a glycosylation consensus site in human alpha-lactalbumin.

Human alpha-lactalbumin has not been described as a glycoprotein, despite the fact that several alpha-lactalbumins of both ruminant and nonruminant species are known to be glycosylated. In all these species the glycosylation site is the 45Asn in the usual triplet 45Asn-Gly/Gln-47Ser. We have found that human alpha-lactalbumin is glycosylated and the glycosylation site has been determined by protein sequencing and mass spectrometry. We report an unusual glycosylation site at 71Asn in the triplet 71Asn-Ile-73Cys, which is conserved in all known alpha-lactalbumins except red-necked wallaby. That a relatively small proportion of the protein is glycosylated (about 1%) may reflect the importance of this region of the protein sequence to the molten globule state of alpha-lactalbumin.

Amino Acid Sequence↗
PubMed1997

Adults with childhood-onset growth hormone deficiency: effects of growth hormone treatment on cardiac structure.

OBJECTIVES: To evaluate the effects of growth hormone deficiency (GHD) and of growth hormone (GH) therapy on cardiac structure in adults with childhood-onset GHD. SETTING: Out-patient clinic in the Italian Institute for Auxology, Milan. SUBJECTS: Eight adults with childhood-onset GHD and eight healthy controls, matched for sex, age, exercise and body mass index. INTERVENTIONS: Recombinant GH (Saizen Serono, Italy), administered in a conventional dose of 0.5 IU kg-1 week-1 for 6 months. MAIN OUTCOME MEASURES: Cardiac structure parameters, evaluated by two-dimensional, M-mode and Doppler echocardiograms, and stress test, by means of a modified Bruce protocol with a bicycle ergometer, were determined before and after 6 months GH therapy. RESULTS: Before treatment, mean (+/- SE) intraventricular septal thickness (IVST: 7.1 +/- 0.2 mm), LV posterior wall thickness (LVPT: 5.2 +/- 0.1 mm), LV mass (LVM: 94.6 +/- 5.0 g), LV mass index (LVM/body surface area, LVMI: 65.1 +/- 3.0 g m-2) and left ventricular end-diastolic diameter (LVED: 41.4 +/- 0.6 mm) of patients were significantly lower (P < 0.01) than in controls, whilst LV end-systolic diameter (LVES) of patients (25.5 +/- 0.7 mm) was similar to controls (27.5 +/- 0.7). GH treatment significantly (P < 0.01) increased LVPT (6.8 +/- 0.2 mm), LVM (111.6 +/- 4.6 g) and LVMI (80.5 +/- 3.5 g m-2); no significant changes were observed in LVED, LVES and IVST values. The stress test showed a significant improvement of cardiac performance, as demonstrated by the reduction of blood pressure x heart rate product at the same workload (basal: 32,722.5 +/- 897.4 vs. after: 25,574.6 +/- 439.7). CONCLUSIONS: GH plays a role in the maintenance of a normal cardiac structure in adulthood. The present study suggests that GH treatment might be able to improve the cardiac structure of patients with childhood-onset GHD.

Adult↗
PubMed1997

A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state.

Recent studies suggest that the pineal hormone melatonin may reduce chemotherapy-induced immune and bone marrow damage. In addition, melatonin may exert potential oncostatic effects either by stimulating host anticancer immune defenses or by inhibiting tumor growth factor production. On this basis, we have performed a randomized study of chemotherapy alone vs. chemotherapy plus melatonin in advanced non-small cell lung cancer patients (NSCLC) with poor clinical status. The study included 70 consecutive advanced NSCLC patients who were randomized to receive chemotherapy alone with cisplatin (20 mg/m2/day i.v. for 3 days) and etoposide (100 mg/m2/day i.v. for 3 days) or chemotherapy plus melatonin (20 mg/day orally in the evening). Cycles were repeated at 21-day intervals. Clinical response and toxicity were evaluated according to World Health Organization criteria. A complete response (CR) was achieved in 1/34 patients concomitantly treated with melatonin and in none of the patients receiving chemotherapy alone. Partial response (PR) occurred in 10/34 and in 6/36 patients treated with or without melatonin, respectively. Thus, the tumor response rate was higher in patients receiving melatonin (11/34 vs. 6/35), without, however, statistically significant differences. The percent of 1-year survival was significantly higher in patients treated with melatonin plus chemotherapy than in those who received chemotherapy alone (15/34 vs. 7/36, P < 0.05). Finally, chemotherapy was well tolerated in patients receiving melatonin, and in particular the frequency of myelosuppression, neuropathy, and cachexia was significantly lower in the melatonin group. This study shows that the concomitant administration of melatonin may improve the efficacy of chemotherapy, mainly in terms of survival time, and reduce chemotherapeutic toxicity in advanced NSCLC, at least in patients in poor clinical condition.

Adult↗
PubMed1997

Reversal of clinical resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin: efficacy of LHRH analogue plus melatonin in patients progressing on LHRH analogue alone.

OBJECTIVE: Experimental and preliminary clinical studies have suggested that the pineal hormone melatonin (MLT) may stimulate hormone receptor expression on both normal and cancer cells. Moreover, MLT has appeared to inhibit the growth of some cancer cell lines, including prostate cancer, either by exerting a direct cytostatic action, or by decreasing the endogenous production of some tumor growth factors, such as prolactin (PRL) and insulin-like growth factor-1 (IGF-1). On this basis, a study was carried out to evaluate the clinical efficacy of a neuroendocrine combination consisting of the LHRH analogue triptorelin plus MLT in metastatic prostate cancer progressing on triptorelin alone. MATERIAL AND METHODS: The study including 14 consecutive metastatic prostate cancer patients with poor clinical conditions (median age: 70.5 years; median PS: 50%), refractory or resistant to a previous therapy with the LHRH analogue triptorelin alone. Triptorelin was injected i.m. at 3.75 mg every 28 days, and MLT was given orally at 20 mg/day in the evening every day until progression, starting 7 days prior to triptorelin. RESULTS AND CONCLUSIONS: A decrease in PSA serum levels greater than 50% was obtained in 8/14 (57%) patients. Moreover, PSA mean concentrations significantly decreased on therapy of triptorelin plus MLT. In addition, a normalization of platelet number was obtained in 3/5 patients with persistent thrombocytopenia prior to study. Mean serum levels of both PRL and IGF-1 significantly decreased on therapy. Finally, a survival longer than 1 year was achieved in 9/14 (64%) patients. This preliminary study would suggest that the concomitant administration of the pineal hormone MLT may overcome the clinical resistance to LHRH analogues and improve the clinical conditions in metastatic prostatic cancer patients.

Administration, Oral↗