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Biomedical subjects

I Villa

Publications and source records attributed to I Villa.

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

Responsiveness of urinary markers of bone resorption to orchiectomy and clodronate treatment in mature rats: a comparative study.

OBJECTIVE: The aim of this study was to assess the responsiveness of two classes of bone resorption markers to the enhancement of osteoclastic activity induced by orchiectomy and to its inhibition by clodronate treatment in mature rats. DESIGN: Bone mineral density (BMD) at femural metaphysis, femural diaphysis, lumbar vertebrae, and the urinary excretion of pyridinoline (Pyr), deoxypyridinoline (D-Pyr), galactosylhydroxylysine (GHyl) and glucosylgalactosylhydroxylysine (GGHyl) were monitored at regular intervals for 30 days prior to and for 60 days following orchiectomy in eleven rats, divided into two groups: five rats untreated and the other six treated with clodronate. RESULTS: Prior to orchiectomy, a significant (P < 0.01) decrease in BMD was observed only at the distal femural metaphysis. This decrease appeared to be associated with a time-dependent increase in the urinary excretion of all markers. Following orchiectomy, the BMD of the untreated group decreased significantly (P < 0.01) at all bone sites. The bone loss was accompanied by a significant (P < 0.01) increase in Pyr and D-Pyr concentrations in urine, whereas urinary GHyl and GGHyl did not change significantly. In the clodronate-treated group, the BMD of the three skeletal sites did not change significantly, while the urinary excretion of all urinary biochemical markers decreased significantly (P < 0.001). CONCLUSION: This study showed that pyridinolines are able to monitor the bone response to orchiectomy and to clodronate treatment response in androgen-deficient mature male rat. whereas glycosides appear prone to confounding factors.

Aging↗
PubMed1998

Methotrexate therapy in refractory pediatric onset systemic lupus erythematosus.

OBJECTIVE: To evaluate the efficacy, safety, and corticosteroid sparing potential of methotrexate (MTX) in patients with pediatric onset systemic lupus erythematosus (SLE). METHODS: The medical records of 11 patients with SLE with onset before age 16 years were reviewed. Details of clinical features, previous therapy, indications for MTX, efficacy, toxicity, and corticosteroid reduction during MTX therapy were recorded. RESULTS: At the start of MTX treatment, 7 patients had nephritis, 3 malar rash, 3 arthritis, 2 skin vasculitis, and 2 thrombocytopenia. All patients were given MTX (12.5-17.0 mg/m2/week) as the sole drug therapy along with prednisone. Although many patients showed initial improvement and/or were able to reduce the prednisone dose, after 7 to 23 months 8 patients had a flare of SLE requiring increased doses of prednisone, one patient had unchanged SLE activity, and 2 patients were permanently discontinued from MTX because of toxicity. Side effects were observed in 8 (73%) patients, but only 2 (18%) discontinued MTX due to toxicity. CONCLUSION: MTX given as the sole drug therapy along with prednisone did not show a major corticosteroid sparing potential in our patients with pediatric onset SLE.

Adolescent↗
PubMed1997

Effects of amylin on human osteoblast-like cells.

Amylin has been reported to have bone-conserving effects. In the present study we evaluated the possible activity of the peptide on human osteoblast-like (hOB) cells in primary culture. Amylin between 10(-9) and 10(-6) M, dose-dependently stimulated cell proliferation with a maximal effect (200%) at 10(-6) M. In addition, amylin increased osteocalcin production when hOB cells were exposed to 1,25(OH)2D3 (10(-8)M) but there was a nonsignificant upward trend on alkaline phosphatase activity. The present results suggest that amylin could be included among the group of peptides endowed with osteogenic activity.

Amyloid↗
PubMed1996

Pulmonary function in children with systemic lupus erythematosus.

BACKGROUND: Abnormalities of pulmonary function have been found in children with systemic lupus erythematosus (SLE) even in the absence of clinical or radiographic evidence of pulmonary involvement. It is unknown whether these abnormalities represent an early sign of progressive lung disease or whether they are associated with disease activity. METHODS: After a mean of 4.5 years, respiratory function (forced vital capacity (FVC) and single breath gas transfer factor (TLCO)) and disease activity were reexamined in 13 of 15 previously studied children with SLE. Disease activity was assessed by a validated index of SLE activity (SLE activity measure (SLAM)). RESULTS: In spite of the high prevalence of abnormalities of respiratory function at the baseline investigation, no chest radiographic abnormalities or overt clinical signs of lung disease were found at baseline, in the interval between the two investigations, or at the re-evaluation in any patient. From baseline to the second investigation the mean value of SLAM decreased and there was a trend toward an improvement in FVC and TLCO. TLCO was more severely impaired than FVC, being found as an isolated abnormality in a high percentage of patients (45% at baseline and 35% at follow up). There was a relationship between baseline TLCO and disease activity, expressed as a SLAM score. Moreover, there was a correlation between the changes in the SLAM score from baseline to the second investigation and the corresponding changes in the TLCO value, but not with the corresponding changes in the FVC value. CONCLUSIONS: In this series of patients the decrease in SLE activity from the first to the second investigation was associated with an improvement in pulmonary function. The presence of early isolated functional abnormalities was not associated with subsequent development of lung disease.

Adolescent↗
PubMed1996

Comparison between urinary pyridinium cross-links and hydroxylysine glycosides in monitoring the effects of ovariectomy and 17 beta-estradiol replacement in aged rats.

This study was undertaken to assess the sensitivity of hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), galactosylhydroxylysine (GHyl) and glucosylgalactosylhydroxylysine (GGHyl) to monitor bone response to estrogen deficiency and replacement by comparing their excretory patterns in ovariectomized aged (11-14 months old) rats. The ovariectomized (OVX) rats were randomized into two groups: (1) OVX plus vehicle; (2) OVX plus 17 beta-estradiol (17-beta E, 10 micrograms/kg, s.c., 4 days/week). Treatment with 17-beta E started immediately after OVX and continued for 60 days. The collagen catabolites were measured in urine for 1 month before OVX and thereafter for 60 days. In temporal coincidence with urine collection, bone area and bone mineral density (BMD) of lumbar vertebrae, femoral diaphysis and distal metaphysis were measured by dual-energy X-ray absorptiometry. In the untreated rats, BMD of the femoral metaphysis and lumbar vertebrae decreased significantly and the urinary excretion of LP, HP, GHyl and GGHyl increased with different patterns. In the treated rats, 17-beta E replacement prevented the increment in LP excretion, partially prevented the increase in HP excretion, but had no effect on the excretion of GHyl and GGHyl. In conclusion pyridinolines and glycosides have different sensitivities to the bone response to OVX. Glycoside excretion after OVX also reflects metabolic processes not strictly related to bone loss and, in contrast with LP, is not sensitive to estrogen replacement.

Absorptiometry, Photon↗
PubMed1996

Osteocalcin production in vivo and in vitro after 1,25-dihydroxycholecalciferol stimulation comparison of different assays.

The study was designed to assess the sensitivity of three commercial assays (which differ in methodology, standard and antibodies) for osteocalcin, used for detecting changes in osteocalcin secretion induced by calcitriol (1,25-dihydroxycholecalciferol) in vivo and in vitro. Osteocalcin levels were determined in serum samples of 10 osteoporotic women after short term calcitriol treatment, and in the culture medium of human osteoblast-like cells (n = 22) after 48 h calcitriol exposure. All assays displayed similar sensitivity in detecting osteocalcin production in vivo after a 1 microgram daily dose of calcitriol. A novel IRMA (CIS), claimed to detect intact osteocalcin, showed higher osteocalcin values than the other assays, and in vitro showed the best sensitivity; it provides an appropriate index of the osteocalcin synthetic activity of cultured human osteoblasts.

Aged↗
PubMed1994

Differential effects of CGRP on adenylyl cyclase in adult and embryonic rat brain.

The presence of functional receptors for calcitonin gene-related peptide (CGRP) in the brain of adult rats and on nerve cell cultures was investigated. Neuronal and glial cultures were obtained from mesencephalons of embryos at gestational day 16. The response to CGRP was tested by measuring the adenylyl cyclase (AC) activity on isolated membranes. CGRP binding in adult rat brains was ineffective in activating AC, whereas a dose-dependent stimulation of AC activity was induced by the peptide both in neuronal and glial cultures. This effect was more pronounced in the glial cells where high affinity binding sites for CGRP were detected. The presence of functional CGRP receptors in embryonic mesencephalic cells, suggests a role for CGRP in the development of rat mesencephalon.

Adenylyl Cyclases↗
PubMed1992

[Role of conservative surgery in the multidisciplinary treatment of Ewing's sarcoma in childhood].

BACKGROUND: In order to cure Ewing's sarcoma it is necessary to have an approach which considers the radical local control on the sites of macroscopic disease, along with the systemic control of micrometastases. On the present study the experience of the authors in analyzed, remarking the role of cytoreduction surgery on curability. METHODS: From January 1982 to August 1991, 24 patients with the mean age 13 years, 14 boys and 10 girls, previously untreated and with a pathology proven diagnosis have been treated by the authors. The treatment protocol included: alternating chemotherapy with cyclophosphamide, adriamycin, methotrexate, bleomycin, actinomycin D and vincristine; administered simultaneously with preoperative external radiation with a volume that completely included the affected bone and surrounding soft tissues for a total dose of 45 Gy/4.5 weeks. After a resting period of 4 weeks, resection of the involved bone and adjacent healthy bone was performed, followed by a single dose of 10-15 Gy of intraoperative radiotherapy to the tumor bed. Subsequently a custom prostheses or allograft was implanted. RESULTS: Twenty patients had localized disease and 4 had metastatic disease at diagnosis. In 16 cases the tumor was in extremities, 5 axial, and 3 extraskeletical. In 15 patients surgery with limb sparing techniques was performed, 8 had en block resection and one amputation (calcaneous location). At the time of this report 21 patient are alive (87%). Four had disease progression, of this 3 had died (12%). The actuarial disease free survival rate is 80% +/- 9% with a follow-up of 104 months, being the mean survival time of 85.5 months. CONCLUSIONS: The cytoreduction surgery included into a multidisciplinary approach permits to achieve a high rate of cure in Ewing's sarcoma. The toxicity of the program can be considered acceptable.

Actuarial Analysis↗
PubMed1992

Decrease in rat brain calcitonin binding sites and adenylyl-cyclase activity during ageing.

In order to investigate the effects of ageing on the cerebral receptors for calcitonin (CT), we used an in vitro autoradiographic method to study the distribution of the binding sites for eel CT (eCT) in young and old rat brain. The inhibitory action of eCT on adenylyl-cyclase (AC) activity upon isolated brain cell membranes was also evaluated. The results show area-specific reduction of binding particularly in the hypothalamus and pons medulla of the old rat. The inhibitory action of eCT on AC activity was significantly reduced in the same areas, whereas in the striatum and mesencephalon no changes were observed. The parallel decrease of binding of eCT and of the inhibitory action of eCT on AC in ageing may represent a functional decline of neuronal activities during ageing.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Effects of selective histamine H3-receptor ligands on prolactin and growth hormone secretion in the rat.

The effects of intracarotid (i.a.) administration of the histamine (HA) H3-receptor agonist (R)-alpha-methyl-histamine (alpha MeHA) and of the H3-antagonist thioperamide, (THIO) on basal or morphine (M)-induced prolactin (PRL) and growth hormone (GH) secretion were studied in male rats. M was administered 3 h after the H3-drugs. Neither THIO (2.5 mg/kg) nor alpha MeHA (10 mg/kg) changed basal PRL levels and only THIO enhanced the PRL-releasing effect of M (6 mg/kg). Basal GH secretion was not modified by THIO. alpha MeHA slightly increased GH secretion. THIO significantly decreased M-stimulated GH secretion (1 mg/kg, i.a.) and alpha MeHA slightly increased it. These results, in agreement with previous evidence obtained after central HA administration, indicated that endogenous brain HA facilitates PRL and inhibits GH secretion.

Animals↗
PubMed1990

A selective role for brain histamine in prolactin release induced by opiates.

We studied the effects of histamine (HA) antagonists on the facilitatory action of morphine (M) and beta-endorphin (beta E) on prolactin (PRL) release and the effect of alpha-fluoromethylhistidine (alpha-FMH, inhibitor of HA synthesis) on beta E-induced PRL secretion. Male rats were injected intracerebroventricularly (i.c.v.) with mepyramine (MEP, H1-antagonist, 0.8 mumol/rat) or ranitidine (RAN, H2-antagonist, 0.4 mumol/rat) 10 min before M (6 mg/kg, intracarotid, i.a.) or beta E (0.25 micrograms/rat, i.c.v.). alpha-FMH (200 micrograms/rat, i.c.v.) was administered 3 h before beta E. Plasma PRL levels were measured at various times before and after drug treatment. RAN but not MEP significantly reduced PRL release induced by M whereas neither HA-antagonists nor alpha-FMH modified beta E-induced PRL release. The results obtained show that brain HA contributes through activation of H2-receptors to the PRL facilitatory action of M but not of beta E.

Animals↗
PubMed1990

Inhibitory effects of centrally administered /ASU1-7/eel calcitonin on basal and stimulated prolactin release in rats.

We investigated the effects of /ASU1-7/eel calcitonin (ASU1-7eelCT) on basal and stimulated prolactin (PRL) release in male rats. /ASU1-7/eelCT was administered intracerebroventricularly (icv) into freely moving rats with indwelling catheters. The administration of /ASU1-7/eelCT (2.5 micrograms/rat, icv) significantly inhibited basal PRL secretion. When PRL secretion was stimulated by exposing rats to restraint stress, /ASU1-7/eelCT (250 ng; 800 ng; 2.5 micrograms/rat, icv) dose-relatedly inhibited the PRL surges at 10 min after stress. The same doses of icv /ASU1-7/eelCT were effective in inhibiting morphine (6 mg/kg, intracarotid, ia-induced PRL release. No effect on stress-induced PRL secretion was observed when the peptide was administered intracarotid at the dose of 10 micrograms/rat. These results demonstrate that /ASU1-7/eelCT, as we previously observed with salmon calcitonin (sCT), has central inhibitory activity on PRL secretion, probably through enhancement of hypothalamic inhibitory pathways involved in the control of PRL.

Analysis of Variance↗
PubMed1989

Effects of brain histamine depletion on stimulated prolactin release in rats.

We examined the effects of an irreversible inhibitor of brain histamine (HA) synthesis, alpha-fluoromethyl-histidine (alpha-FMH), on prolactin (PRL) release induced by an opiate agonist (morphine, M) or by a serotonergic agonist (MK212). alpha-FMH was administered intracerebroventricularly (i.c.v., 200 micrograms/rat) into freely moving rats with indwelling catheters in the carotid. M (6 mg/kg, intracarotid, i.a.) was administered simultaneously with or 3 h after alpha-FMH. MK212 (2.5 mg/kg, i.a.) was administered 3 h after alpha-FMH. Blood samples for assay for PRL were drawn at 0, 10, 20, 40 min after M or MK212 administration. alpha-FMH (3 h before) significantly reduced the PRL-releasing effect of M and MK212 but did not modify PRL release by M when administered simultaneously. The present results showing that the facilitatory actions of the opiate and serotonergic systems on PRL are impaired when brain HA synthesis is reduced, suggest that there is an HA-dependent step in opiate and serotonergic control of PRL.

Animals↗
PubMed1988

Immunocytochemical detection of neuroblastoma cells infiltrating clinical bone marrow samples.

To evaluate the feasibility and clinical usefulness of immunocytochemical detection of bone marrow metastases in neuroblastoma, we studied bone marrow samples from patients undergoing intensive therapy, followed in the majority of cases by autologous bone marrow rescue. Two monoclonal antibodies were used in an indirect immunoenzymatic assay to test 384 samples collected from multiple bone marrow sites during 79 staging procedures in 48 patients. Of 578 immunocytochemical tests, 59 (10%) yielded non-evaluable results. Analysis by individual bone marrow sites showed an agreement between cytological and immunocytochemical examinations in 276 of 309 (89%) evaluable tests with 5 A7 and in 179 of 210 (85%) with UJ 13 A. Infiltration by neuroblastoma cells was reported in 9% of samples by cytology, in 6% by immunochemistry with 5 A7 and in 16% with 13 A. Analysis of results by staging demonstrated agreement between cytological examination and immunocytochemical detection with both monoclonal antibodies in 60 of 75 (80%) evaluable stagings. Bone marrow metastasis was detected by cytology in 22% of stagings, by immunochemistry with 5 A7 in 23%, with UJ 13 A in 25%. Detailed analysis of discordant results revealed that they were related partly to bone marrow sampling variability associated with focal and minimal metastasis of neuroblastoma cells. These data suggest the clinical usefulness of immunocytochemical detection as a complementary test to cytological examination for accurate evaluation of bone marrow infiltration in patients with disseminated neuroblastoma.

Antibodies, Monoclonal↗
PubMed1988

Central effects of histamine H2-receptor agonists and antagonists on nociception in the rat.

The effects of intracerebroventricular injection of histamine H2-receptor agonists (4-methylhistamine, 4-MeH; dimaprit, DIM), H2-antagonists (cimetidine, CIM; ranitidine, RAN; famotidine, FAM) and of the DIM chemical analogue SK&F 91487 on hot-plate latency in rats were examined. Both DIM (0.4-0.8 mumol/rat) and 4-MeH (0.4-0.8 mumol/rat) significantly enhanced the pain threshold, whereas SF&F 91487 (0.8 mumol/rat) had no effect, indicating that DIM antinociception is specifically due to its activity on histamine (HA) receptors. The H2-antagonists CIM (0.8 mumol/rat) and RAN (0.6 mumol/rat) also enhanced the pain threshold, while FAM (0.03 mumol/rat) did not modify pain latency. When injected before 4-MeH, FAM reduced the antinociceptive effect of 4-MeH. These findings suggest that the antinociceptive activity of CIM and RAN is not related to specific blockade of H2-receptors and that the activation of HA-H2-receptors is inhibitory to nociception.

Animals↗
PubMed1988

Further evidence that brain histamine H2 receptors are stimulatory in the control of prolactin in the rat.

The effects of administration into the brain ventricle of H2 receptor agonists (4-methylhistamine, 0.8 mumol/rat; dimaprit, 0.4-0.8 mumol/rat), H2 antagonists (cimetidine, 0.8 mumol/rat; ranitidine, 0.4-0.8 mumol/rat; famotidine, 0.03 mumol/rat) and of the dimaprit chemical analogue SK&F 91487 (0.4 mumol/rat) on unstimulated and histamine-stimulated prolactin secretion in normal male rats were studied. The H2 agonist 4-methylhistamine caused a significant increase in unstimulated blood PRL, whereas dimaprit, SK&F 91487, and the H2 antagonists tested did not change PRL levels. 4-Methylhistamine significantly enhanced the stimulatory effects of histamine on prolactin, whereas all the H2 antagonists inhibited histamine-induced prolactin release. The inhibition of histamine-induced prolactin secretion by the H2 agonist dimaprit is nonspecific, since its chemical analogue SK&F 91487, which has no H2 agonist activity, also inhibits it. These results indicate that stimulation of the H2 receptors in the central nervous system is facilitatory for PRL secretion, suggesting that the activation of H2 receptors may contribute to the PRL-releasing effects of histamine.

Animals↗