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Biomedical subjects

R Marcolongo

Publications and source records attributed to R Marcolongo.

At least 55 records · Page 3Linked to original sources

[Efficacy and safety of amtolmetin guacyl in the treatment of acute osteoarthritis].

BACKGROUND: This open phase IV multicentre trial was carried out to evaluate the efficacy and tolerability of amtolmethin guacyl in patients with acute osteoarthritis in at least one of the following locations: knee, hip, vertebral column. Amtolmethin guacyl is a drug belonging to the NSAID class whose action is comparable to that of other active ingredients belonging to the same class, but it is particularly interesting that a low incidence of collateral effects involving the gastric mucosa, equal to around 5%, has been reported in all clinical trials. It has been demonstrated that amtolmethin guacyl provokes an increased production of nitric oxide (NO), an important mediator of the gastric mucosa defence system through the induction of the nitric oxide synthetase (NOS) enzyme. METHODS: A total of 41 centres took part in the trial and an overall population of 388 patients were recruited. The protocol specified that the drug should be taken for one month at a dose of 1200 mg/die (2 tablets b.i.d.) for 3 days and 600 mg/die (1 tablet) for the remaining 27 days. At screening, after 7 days (T1) and at the end of treatment (T2), the parameters of efficacy were evaluated using a semiquantitative scale for the following symptoms: spontaneous pain and pain on movement, joint function and swelling. All patients were asked to keep a daily diary to evaluate gastric tolerability, whereas overall tolerability was evaluated by recording adverse effects and determining the common laboratory parameters. The statistical analysis was calculated both according to intention to treat (379 patients) and by protocol (372 patients), using Friedman's test to analyse the 4 scales of signs and symptoms (basal visit vs T1 vs T2). RESULTS: A statistically significant difference (p<0.01) was found in both analyses for all 4 parameters examined between the basal evaluation and the two evaluations during and post-treatment. CONCLUSIONS: The analysis of vital parameters, laboratory parameters and adverse effects confirmed the good tolerability of the product.

Acute Disease↗

Clinicopathological features of aggressive large granular lymphocyte leukaemia resemble Fas ligand transgenic mice.

Fas ligand triggers cell death after interaction with its receptor Fas. Altered expression of Fas has been associated with lymphoproliferation and autoimmune disorders in both mice and man. Apoptosis of lung and liver tissue is seen in Fas ligand transgenic mice. It is not known whether constitutive expression of Fas ligand can cause a similar human disease. Four patients with aggressive large granular lymphocyte (LGL) leukaemia involving lung and liver were studied. All four patients were severely ill with pulmonary involvement. Two patients presented with hypoxia and were oxygen dependent; the other two patients had severe pulmonary hypertension. Lung biopsies showed interstitial infiltration by leukaemic LGL. The infiltrating lymphocytes expressed both Fas and Fas ligand, whereas normal pneumocytes expressed only Fas. Similar findings were observed in liver biopsies from these patients. Features mimicking the pathological changes of graft-versus-host disease were observed, including pneumocyte apoptosis. All four patients had high levels of circulating Fas ligand. Successful treatment with oral methotrexate or 2-chlorodeoxyadenosine was associated with disappearance or marked reduction of circulating Fas ligand. These results suggest that dysregulated expression of Fas ligand can lead to human disease with pathological features resembling graft-versus-host disease.

Adult↗

Effects of chondroitin sulfate and interleukin-1beta on human chondrocyte cultures exposed to pressurization: a biochemical and morphological study.

Objective This study investigated the in vitro effects of chondroitin sulfate (CS) on human articular chondrocytes cultivated in the presence or in the absence of interleukin-1beta (IL-1beta) during 10 days of culture with and without pressurization cycles. Design The effects of CS (10 and 100 microg/ml) with and without IL-1beta were assessed in the culture medium of cells exposed to pressurization cycles in the form of synusoidal waves (minimum pressure 1 Mpa, maximum pressure 5 Mpa) and a frequency of 0.25 Hz for 3 h by immunoenzymatic method on microplates for the quantitative measurement of human proteoglycans (PG). On the 4th and 10th day of culture the cells were used for morphological analysis by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Results The presence of IL-1beta determines a significant decrease in PG concentration measured in the culture medium. When the cells are cultured in the presence of IL-1beta and CS, a statistically significant restoration of PG levels is observed. Under pressurization conditions, we observed that PG concentration in the medium of cells presents a significant increase at baseline conditions, in the presence of IL-1beta+CS10 and IL-1beta+CS100, but not with IL-1beta alone. The results concerning metabolic evaluation are confirmed by the morphologic findings obtained by TEM and SEM. Conclusions These in vitro studies confirm the protective role of CS, which counteracts the IL-1beta induced effects and they confirm the importance of pressure on chondrocyte metabolism and morphology.

Aged↗

Density functional geometry optimization and energy calculations of calcium(II)-triphosphate complexes. Polyphosphates as possible dissolving agents for calcium pyrophosphate dihydrate crystals in chondrocalcinosis disease.

Geometry optimizations and energy calculations have been carried out via molecular orbital methods at the density functional B3LYP/LANL2DZ level on the molecules PO3-, OPO3(3-), HOPO3(2-), CH3OPO3(2-), H(CH3OPO3)-, O(PO3)2(4-), HO(PO3)2(3-), CH2(PO3)2(4-), (CH3OPO2)O(PO3)3-, O(PO3)3(5-), HO(PO3)3(4-), (PO3)3(3-), (CH3OPO2)O(PO3)2(4-), [Mg[O(PO3)2)]]2-, [Ca[O(PO3)2]]2-, [Ca[CH2(PO3)2]]2-, [Ca[CH3OPO2)O(PO3)]]-, [Ca(PO3)3]-, [Ca[O(PO3)3]]3-, and [Ca[CH3OPO2)O(PO3)2]]2- with the aim to find reliable and easily accessible computational methods to simulate some phosphate-containing molecules of importance for the living cells and to study the energetics for protonation and metal-complex formation reactions. The analysis is part of a general investigation on phosphate-containing molecules as potential dissolving agents for calcium pyrophosphate dihydrate (CPPD) crystals which deposit in certain articular diseases. The basis set was expanded to 6-31G** for the P atoms for all the molecules investigated and to 6-31G* for the O atoms for OPO3(3-). Calculations at the semiempirical MNDO/d level were also carried out for comparison purposes on the free ligand molecules and on [Mg[O(PO3)2]]2-. The density functional analysis reproduced well the geometry found at the solid state via X-ray diffraction. The analyses of the geometrical parameters and the total electronic energy of the molecules shows that O(PO3)2(4-) and other di- and tri-phosphates are versatile ligands for divalent metal ions like Ca2+. The computed P-O-P bond angle for free O(PO3)2(4-) is 180 degrees and the conformation of the two PO3- groupings is staggered along the P...P vector. The linear arrangement for P-O-P is assisted by P-O pi interactions. The bending of the P-O-P angle when accompanied by a slight P-O(b) elongation requires a very small amount of energy; 4.65 kcal/mol to pass from 180 to 140 degrees , as calculated at the DFT level. The computed Ca-O and Mg-O bond distances for [M[O(PO3)2]]2- are 2.378 and 2.079A, when the metal ions link two oxygen atoms from each PO3 group. The computed Ca-O bond lengths for [Ca[CH3OPO2)O(PO3)]]- are 2.482 (PalphaO2) and 2.358A (PbetaO2), showing a significant lengthening for Ca-OPalpha, when compared to the pyrophosphate derivative. The Ca-O bond lengths for [Ca[O(PO3)3]]3- and [Ca[CH3OPO2)O(PO3)2]]2- are 2.251A and 2.525 (PalphaO2), 2.407 and 2.338 (PbetaO2), and 2.251 and 2.228A (PgammaO2), showing a shortening for the Ca-OPgamma bond upon methylation. The (Pbeta)O-Pgamma bond length increases significantly (0.09 A) upon Ca(II) coordination to (CH3OPO2)O(PO3)2(4-) via all the three PO3 groups. This latter result suggests that metal complexes of linear organic-triphosphates have a larger tendency to release the PgammaO3 group when compared to the free ligand molecules. The electronic contribution to the energy of the complex formation reaction for [Ca[CH2(PO3)2]]2- is only slightly higher (some 1.8 kcal) than that for [Ca[O(PO3)2]]2-; but is much higher (some 63 kcal) than that relevant to the formation of [Ca[CH3OPO2)O(PO3)2]]2-. (ABSTRACT TRUNCATED)

Calcium Phosphates↗

HLA class II alleles associations of anticardiolipin and anti-beta2GPI antibodies in a large series of European patients with systemic lupus erythematosus.

The objective of this study was to determine the HLA class II associations of the anticardiolipin (aCL) and anti-beta2GPI (abeta2GPI) antibodies in a large series of European patients with systemic lupus erythematosus (SLE). A cohort of 577 European SLE patients was enrolled. aCL and abeta2GPI were measured by ELISA methods. Molecular typing of HLA-DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1 loci was performed by the polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method. aCL of IgG, IgM and IgA isotypes were detected in 22.8%, 14% and 13.9% of patients, respectively. IgG and IgM abeta2GPI were detected in 20% of patients. aCL showed positive association with HLA DRB1*04, DRB1*0402, DRB1*0403, DRB1*07, DRB3*0301, DQA1*0201, DQA1*0301, DQB1*0302, and negative association with DQA1*0501, DRB3*0202. abeta2GPI showed positive association with DRB1*0402, DRB1*0403, DQB1*0302. DRB1*0402 carried the highest relative risk for the presence of both aCL (RR=8. 1) and abeta2GPI (RR=4.6). Our results confirm the already described associations of aCL with HLA DR4 and DR7, but also demonstrate that, among the alleles at the DRB1*04 locus, the *0402 was most represented both in aCL and in abeta2GPI positive patients. In addition, HLA class II associations of abeta2GPI are for the first time extensively examined in a large cohort of European SLE patients.

Adolescent↗

Anti-ganglioside antibodies in a large cohort of European patients with systemic lupus erythematosus: clinical, serological, and HLA class II gene associations. European Concerted Action on the Immunogenetics of SLE.

OBJECTIVE: To assay anti-ganglioside antibodies (aGM1) in sera of a large cohort of European patients with systemic lupus erythematosus (SLE) to define the prevalence of these autoantibodies in SLE; to evaluate the association of aGM1 with clinical manifestations and other autoantibodies found in SLE; and to search for aGM1 association with HLA class II alleles. METHODS: Four hundred forty-eight patients with SLE were consecutively enrolled in 8 centers from 6 European countries. All sera were tested for antinuclear antibodies by immunofluorescence on HEp-2 cells as substrate, anti-dsDNA, aGM1, aCL, abeta2-glycoprotein I (abeta2-GPI) antibodies by ELISA, and antineutrophil cytoplasmic antibodies (ANCA) by immunofluorescence and by ELISA. Genomic typing for HLA class II loci was performed by polymerase chain reaction-sequence specific oligonucleotide probe method. Clinical assessment was done at the time of enrolment. RESULTS: We found 41.9% of patients with clinical signs of neuropsychiatric involvement; 15.5% of patients were positive for aGM1, 8% of the IgG isotype and 8.6% of the IgM isotype; aGM1-IgG were associated with neuropsychiatric manifestations (NPM) (RR = 3.7), with migraine (RR = 2.4), with OBS (RR = 7.3), and with peripheral neuropathy (RR = 8.5). aGM1-IgM were associated with NPM (RR = 4) and with depression (RR = 3.4). Furthermore, the genetic study showed that aGM1-IgG were associated with HLA-DQB1*0404 (RR = 7.2) while aGM1-IgM were associated with HLA-DQB1*0605 (RR = 33.3). No associations were found between aGM1 and anti-dsDNA, aCL, abeta2GP1, or ANCA. CONCLUSION: Our results show aGM1 can be found in patients with SLE. aGM1 may play a pathogenetic role for some NPM in this condition.

Adolescent↗

Autonomic nervous system and smooth muscle cell involvement in systemic sclerosis: ultrastructural study of 3 cases.

OBJECTIVE: To investigate morphological abnormalities in nerve and smooth muscle structures of the anorectal wall underlying gastrointestinal dysfunction in patients with systemic sclerosis (SSc). METHODS: We performed deep rectal biopsy in 3 patients with limited scleroderma of relatively recent onset and intestinal symptoms. RESULTS: We found ultrastructural signs of axonal degeneration and cytoskeletal abnormalities in the bundles of unmyelinated fibers. There was also focal degeneration of smooth muscle cells, often in association with the presence of partially degranulated mast cells. Many mast cells were also observed in close relation to nerve fibers and vessels. The enteric vessels often showed basal lamina reduplication and hypertrophied endothelial cells with obliterated lumen. No significant fibrosis was found. CONCLUSION: Our findings indicate early involvement of the autonomic nervous system and to a lesser extent of smooth muscle cells. We confirmed the presence of early vascular lesions and involvement of mast cells in the pathological process.

Adult↗

Image analysis quantification of substance P immunoreactivity in the trapezius muscle of patients with fibromyalgia and myofascial pain syndrome.

OBJECTIVE: Substance P (SP), a neurotransmitter stored within the afferent nociceptive fibers, is likely to be involved in the pathogenesis of musculoskeletal pain. We investigated SP immunoreactive (SP-ir) nerve fibers in the upper trapezius of patients with fibromyalgia (FM) and myofascial pain syndrome (MPS) by immunochemistry. METHODS: Trapezius muscle obtained from tender points of 9 women with primary FM, from trigger points of 9 women with regional myofascial pain, and from 9 control women were immunostained with anti-SP sera. Quantitative evaluation was performed by computerized image analysis. RESULTS: No significant differences in the number of SP-ir areas were detected between groups (one way ANOVA: p = 0.2); in contrast, mean optical density (OD) of SP-ir showed a significant difference comparing the groups (one way ANOVA: p < 0.0001). Mean OD of the immunostaining for SP was statistically greater in trapezius muscle of patients with MPS (0.594 +/- 0.096) compared to specimens from patients with FM (0.436 +/- 0.140) (p < 0.05) and controls (0.314 +/- 0.105) (p < 0.05); mean OD of immunostaining for SP was greater in FM specimens than in controls (p < 0.05). CONCLUSION: Our results point to a peripheral hyperactivity of the peptidergic nervous system in FM as well as in MPS. These findings support the notion of pathogenetic involvement of the afferent nervous system in the development and perception of myofascial pain.

Adult↗

Effective immunosuppressive therapy in a patient with primary pulmonary hypertension.

The case history is described of a young woman who presented with primary pulmonary hypertension and non-specific inflammatory signs. The patient received prolonged immunosuppressive treatment with low dose methotrexate and prednisone without any vasodilator agent. After one year the pulmonary artery pressure fell from a mean value of 47 mm Hg to 30 mm Hg and there was a corresponding clinical response. This case suggests that, in patients with pulmonary hypertension of unknown origin, immunopathogenetic factors should be sought in order to consider the utility of immunosuppressive therapy.

Adult↗

Double-blind controlled clinical study of the efficacy and tolerability of diclofenac-N-(2-hydroxyethyl)-pyrrolidine lecithin gel compared with diclofenac-N-(2-hydroxyethyl)-pyrrolidine gel in patients with peri and extraarticular inflammatory diseases.

To evaluate the efficacy and tolerability of the new diclofenac-N-(2-hydroxyethyl)-pyrrolidine lecithin gel (DHEP lecithin gel, with 1.3% DHEP and 2.4% lecithin) compared with the efficacy and tolerability of diclofenac-N-(2-hydroxyethyl)-pyrrolidine gel (DHEP gel) in peri and extraarticular inflammatory states, a controlled, randomized, double-blind clinical study was conducted. Two groups of 50 patients each were enrolled and were given one of the two different formulations with a slight massage on the painful area three times a day for 10 consecutive days. Patients received a self-evaluation notebook in which to record daily assessment of spontaneous pain (Huskisson's visual analogue scale). On days 0, 3 and 10, the patients were visited by the investigator. All patients completed the study. The assessment of spontaneous pain showed that although pain decreased in both groups, the decrease was more marked in patients taking DEHP lecithin gel and that it reached a statistically significant difference at days 5, 6, 7 and 8. This decrease was also confirmed by assessments on the ordinal scale. Although periarticular swelling disappeared in both groups, swelling severity decreased sooner in patients taking DHEP lecithin gel. The efficacy and safety of both treatments was judged to be good or excellent by 70% of the patients in each group. The efficacy of the active principle, pyrrolidine salt, is confirmed. Moreover, the formulation containing lecithin passes through the skin lipid barrier more easily than the formulation without lecithin and is as valid as the other in the therapy of rheumatic disorders. Finally, DHEP lecithin gel preparation has a quicker therapeutic action on symptoms, such as spontaneous pain and local swelling, than DHEP gel.

Adolescent↗

Anticardiolipin and anti-beta2GPI antibodies in a large series of European patients with systemic lupus erythematosus. Prevalence and clinical associations. European Concerted Action on the Immunogenetics of SLE.

OBJECTIVE: To test the prevalences and the clinical associations of anticardiolipin (aCL) and anti-beta2GPI (abeta2GPI) antibodies in a large series of European patients with systemic lupus erythematosus (SLE). METHODS: 574 SLE patients from 7 European countries were tested for aCL and abeta2GPI by ELISA methods. RESULTS: aCL of IgG, IgM, and IgA isotypes were detected in 22.8%, 14%, and 13.9% of the patients, respectively. IgG and IgM abeta2GPI were detected in 20% of the patients. The presence of aCL was highly associated with the presence of abeta2GPI. Medium-high titer IgG aCL and abeta2GPI were associated with thrombosis, with similar sensitivity, specificity, and positive predictive value. When present at medium-high titer, IgG aCL were associated with thrombocytopenia, IgM aCL with hemolytic anemia, and cerebrovascular accidents. IgA aCL with livedo reticularis and Raynaud's phenomenon. CONCLUSIONS: aCL, when present at medium-high titer, are as important as abeta2GPI, as a risk factor for thrombosis. Medium-high titer aCL, but not abeta2GPI, are associated with other clinical features of the antiphospholipid syndrome.

Adolescent↗