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Biomedical subjects

G Minisola

Publications and source records attributed to G Minisola.

At least 19 recordsLinked to original sources
PubMed2005

Two single-nucleotide polymorphisms in the 5' and 3' ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus.

OBJECTIVE: To test the association of osteopontin (OPN) polymorphisms with systemic lupus erythematosus (SLE). METHODS: The coding 5' and 3' flanking regions of the OPN gene were scanned for polymorphisms by denaturing high-performance liquid chromatography. A case-control association study was performed in 394 Italian SLE patients and 479 matched controls. OPN serum levels were determined by enzyme-linked immunosorbent assay in 40 patients and 124 controls, and the mean levels were compared between the different OPN genotypes. RESULTS: Among the 13 detected single-nucleotide polymorphisms (SNPs), alleles -156G (frequency 0.714 versus 0.651; P = 0.006, corrected P [P(corr)] = 0.036) and +1239C (0.377 versus 0.297; P = 0.00094, P(corr) = 0.0056) were significantly increased in the SLE patients compared with the controls. The presence of the associated allele in single or double dose conferred an odds ratio (OR) of 2.35 (95% confidence interval [95% CI] 1.38-4.02) for SNP -156 and an OR of 1.57 (95% CI 1.16-2.13) for SNP +1239. These effects were independent of each other, i.e., not a consequence of linkage disequilibrium between the 2 alleles. The risk associated with a double dose of susceptibility alleles at both SNPs was 3.8-fold higher (95% CI 2.0-7.4) relative to the complete absence of susceptibility alleles. With regard to individual clinical and immunologic features, a significant association was seen between lymphadenopathy and -156 genotypes (overall P = 0.0011, P(corr) = 0.046). A significantly increased OPN serum level was detected in healthy individuals carrying +1239C (P = 0.002), which is indicative of an association between the SLE susceptibility allele and OPN levels. CONCLUSION: These data suggest the independent effect of a promoter (-156) and a 3'-untranslated region (+1239) SNP in SLE susceptibility. We can speculate that these sequence variants (or others in perfect linkage disequilibrium) create a predisposition to high production of OPN, and that this in turn may confer susceptibility to SLE.

Disease Susceptibility↗
PubMed1998

Can non-steroidal anti-inflammatory drugs act as metalloproteinase modulators? An in-vitro study of inhibition of collagenase activity.

The in-vitro effects of some non-steroidal anti-inflammatory drugs and some analgesic drugs on collagenase activity were studied by use of a self-quenched fluorogenic esapeptide as substrate. The increased fluorescence signal arising as a result of peptide cleavage by collagenase was recorded and related to the inhibitory potency of the drugs. The effective concentrations in collagenase modulation were also correlated with the levels of the drugs in the plasma and synovial fluids of patients receiving therapeutic doses. Six of the tested drugs, nimesulide, piroxicam, tolmetin, meloxicam, sulindac and sodium meclofenamate, inhibited enzyme activity with IC50 values (concentrations resulting in 50% inhibition) ranging from 1.9 to 28.2 microM and Ki (apparent inhibition constant) ranging from 0.83 to 21.8 microM. Much of the activity was restored after dialysis of the enzyme-drug complex, demonstrating the reversibility of the effect. Although these results indicate that some anti-inflammatory drugs could modulate enzymatic activity involved in the degradation of the extracellular matrix, their possible pharmacological involvement as collagenase inhibitors in collagen degradative diseases remains to be assessed by clinical studies.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Assessment of serum total and bone alkaline phosphatase measurement in clinical practice.

The aim of the study was to measure serum levels of the bone-specific isoenzyme of alkaline phosphatase in normal subjects and patients with metabolic bone disease by using an immunoadsorption assay. We studied 140 healthy adults, 122 patients affected by metabolic bone disease and 15 patients with cholestatic liver disease. Mean values of the bone-specific isoenzyme of alkaline phosphatase in healthy men were significantly higher than those found in premenopausal women (17.8 +/- 4.2 U/l vs 15.6 +/- 4.6 U/l, p < 0.02); postmenopausal women had significantly higher levels of bone-specific isoenzyme of alkaline phosphatase (22.6 +/- 6.4 U/l) than premenopausal women (p < 0.0001). After the menopause total alkaline phosphatase increased by 46%, while the increase in bone-specific isoenzyme of alkaline phosphatase was 39%. No significant correlations were found between bone-specific isoenzyme of alkaline phosphatase and either age or years since menopause, in postmenopausal subjects. In patients with bone-specific isoenzyme of alkaline phosphatase above the upper limit of normal, the assay had a sensitivity of 100% only in patients with Paget's disease of bone. In patients with cholestatic liver disease we found no correlation between bone-specific isoenzyme of alkaline phosphatase and either total alkaline phosphatase and gamma-glutamyl transpeptidase, while a positive correlation was found between total alkaline phosphatase and gamma-glutamyl transpeptidase. Our results confirm the role of bone-specific isoenzyme of alkaline phosphatase assay in clinical research; however, its usefulness in clinical practice is unclear once liver involvement has been excluded.

Adult↗
PubMed1993

Serum osteocalcin in metabolic bone diseases: what is its real significance?

This study has been carried out in order to elucidate the clinical significance of serum osteocalcin measurement. The changes of this marker paralleled those of serum total alkaline phosphatase activity (a marker of bone formation) following parathyroidectomy in hyperparathyroid patients with skeletal involvement. Furthermore, the percentage decrease of serum osteocalcin levels in respect to basal values (85 +/- 12), and the percentage decrease of serum alkaline phosphatase activity levels (82 +/- 7) were significantly lower (p < 0.001) in respect to that of the 24-h hydroxyproline/creatinine ratio (42 +/- 14) one week after parathyroid surgery. Instead, changes of serum osteocalcin levels were similar to those of serum free hydroxyproline (considered to be a marker of bone resorption) following acute calcitonin infusion in normal subjects. These results imply that the antibody used in our assay might recognize not only the entire osteocalcin molecule, but also small epitopes released during the process of bone matrix resorption. Alternatively, if we consider serum osteocalcin only as a marker related to some processes of bone formation, the experiment carried out on normal subjects strongly supports the evidence of calcitonin receptors in osteoblastic surfaces.

Adult↗
PubMed1993

[Clinical experience with the use of piroxicam in fast-dissolving sublingual capsules in acute recurrent osteoarthritis].

Open, non comparative study to evaluate the efficacy and safety of piroxicam Fast Dissolving Dosage Form (FDDF) for sublingual administration in treatment of reacutized osteoarthritis. Fifty-four patients with flare-ups of osteoarthritis involving various joints were enrolled in the study. They were treated with 20 mg/die piroxicam sublingual tablets for a total of 4 weeks. Drug efficacy was evaluated on the basis of the variation of spontaneous pain, pain on passive motion, functional limitation and capacity of performing a specific activity. Intensity of spontaneous pain on the first day showed a statistically significant improvement (p < 0.0001) only 15 minutes after the drug administration. This improvement in pain intensity increased until day 3. All other efficacy parameters showed a statistically significant improvement (p < 0.0001) 7 days after the beginning of treatment. Local and systemic tolerability was good. No patient showed local side effects; only 6 patients experienced systemic side effects. In conclusion, piroxicam sublingual tablets for treatment of osteoarthritis flare-ups showed analgesic efficacy already 15 minutes after drug administration, and good anti-inflammatory efficacy with good local and systemic tolerability.

Acute Disease↗
PubMed1989

[Evaluation of the antalgic activity and tolerability of piroxicam in chronic pain in cervicoarthrosis and lumboarthrosis].

A study was carried out to assess the analgesic efficacy and the safety of piroxicam and to compare them with those of a piroxicam derivative, piroxicam beta-cyclodextrin, in chronic pain caused by arthritis of the neck and lower back. The drugs in question were administered for two weeks at the dose of 20 mg/die per os to 63 patients, 32 of whom were treated with the original molecule and the remaining subjects with its derivative. The study protocol scheduled assessments of pain and its reduction at baseline and after three, seven, and fourteen days of treatment. At the end of the two weeks of treatment, the drugs' efficacy and safety were evaluated. The results confirmed piroxicam's efficacy and safety in pain of the neck and lower back caused by osteoarthritis and did not show any differences, for the parameters examined, between the original molecule and its derivative.

Adult↗
PubMedDate not supplied

Parathyroid storm: immediate recognition and pathophysiological considerations.

A 56-year-old white man was referred for evaluation of severe hypercalcemia following a three-week history of progressive weakness, nausea, and depression. Initial laboratory results showed serum total and ionized calcium (Ca++) values of 5.3 and 2.6 mmol/l, respectively. A short intact PTH assay was immediately performed and an extremely high value was obtained in just 30 min (1315 ng/l, normal values 6.4-70.4). The patient was therefore treated with saline solution and with salmon calcitonin (1200 IU/day, half by continuous i.v. infusion and half by i.m. route) for 10 days. There was a sudden decrease of both Ca++ and intact PTH during the first six days; then there was a trend to reach a steady-state until parathyroidectomy was performed. After withdrawal of calcitonin therapy it was possible to observe a positive uncoupling between bone formation (serum alkaline phosphatase and osteocalcin) and resorption (serum tartrate-resistant acid phosphatase) markers. On day 35 the patient underwent neck exploration, and an enlarged lower left parathyroid gland was removed that on macroscopic examination revealed the presence of a haemorrhagic cyst; microscopic appearance was suggestive of a previous glandular infarction. This is the first time the daily clinical course of a parathyroid crisis has been documented. Furthermore, changes of biomarkers of bone turnover following calcitonin therapy show that high doses of the hormone may cause a prolonged positive uncoupling of the two processes of bone remodeling.

Acid Phosphatase↗
PubMedDate not supplied

Synovial fluid OX40T lymphocytes of patients with rheumatoid arthritis display a Th2/Th0 polarization.

Rheumatoid arthritis (RA) is an autoimmune disease in which T-cell activation plays a pivotal role in the induction of articular damage. CD4+/OX40+ T cells accumulate in the synovial fluid (SF) of RA patients, which suggests that they are involved in the pathogenesis of the disease. In this study, we assessed the intracellular cytokine production of peripheral blood and SF CD4+ and CD4+/OX40+ T cells from RA patients in order to evaluate their role in this disorder. Our results show that SF CD4+ cells are predominantly interferon gamma (IFN-gamma)-positive and express a Th1-like cytokine pattern. In SF, significantly more CD4+/OX40+ T cells expressed interleukin-4 (IL-4) and IL4/IFN-gamma than IFN-gamma alone. Our data demonstrate that SF CD4+/OX40+ T cells express a Th2/Th0 cytokine profile, which suggests that they are involved in inflammatory responses in RA joints.

Adolescent↗
PubMedDate not supplied

[Study of vitamin D status of rheumatoid arthritis patients. Rationale and design of a cross-sectional study by the osteoporosis and metabolic bone diseases study group of the Italian Society of Rheumatology (SIR)].

The fundamental role of Vitamin D has been long known in regulating calcium homeostasis and bone metabolism. An increased contribution of Vitamin D was recently described in association with a lower incidence of Rheumatoid Arthritis (RA). This must not be surprising, as the immunomodulating effects of Vitamin D are clear, which have been attributed protective effects in autoimmune disorders such as some chronic inflammatory bowel diseases, multiple sclerosis and type I diabetes. An interaction was suggested between Vitamin D metabolism and inflammation indexes through mediation of TNF-alpha which is also especially involved in osteoclastic resorption and therefore in bone loss processes. Some preliminary data would indicate an association between seasonal changes of Vitamin D serum levels, latitude and disease activity (DAS28) in RA patients. Consequently, the Osteoporosis and Metabolic Bone Diseases Study Group of SIR believes that there are grounded reasons for assessing the Vitamin D status of RA patients in order to investigate whether this is to be related to physiopathological and clinical aspects of disease other than those of bone involvement. Primary end point of the study will be to assess the levels of 25 OH Vitamin D in RA patients. Secondary endpoints will include correlation with dis-ease activity, densitometry values and bone turnover. The cross-sectional study will enroll patients of both sex genders, age ranging between 30 and 75 years according to the 1988 ACR criteria, onset of symptoms at least 2 years prior to study enrollment. Patients will be excluded suffering from osteo-metabolic diseases, liver and kidney insufficiency and those administered Vitamin D boli in the previous 12 months. Disease activity will be evaluated with the HAQ. Hemato-chemical tests and femoral and lumbar bone densitometry will be performed, unless recently undergone by patients. Blood levels of 25 OH C Vitamin D and PHT and of the two bone remodelling markers (bone alkaline phosphatase and serum CTX) will be measured, as well. Patient enrollment will start on February 2007 and will last 4 months. By the end of 2007 the study will be concluded and results will be published.

Absorptiometry, Photon↗
PubMedDate not supplied

[A case of atrial myxoma with connectivitis-like onset].

A case of cardiac myxoma is reported. This tumor, although histologically benign, may be potentially lethal if an early diagnosis and an adequate surgical treatment is not performed. In an early stage, the disease may be asymptomatic or a large array of aspecific symptoms may be present. In this case, an initial diagnosis of polymyositis was made. This paraneoplastic syndrome is frequently associated with tumors, and should trigger a full evaluation for cancer.

Diagnosis, Differential↗
PubMedDate not supplied

[Metalloproteinase inhibition: therapeutic application in rheumatic diseases].

PURPOSE: Matrix metalloproteinases (MMPs) play an important role in the degradation of articular cartilage in several diseases, including osteorthritis and rheumatoid arthritis. Aiming at developing new drugs with selective inhibiting action against enzyme damaging the extracellular matrix, research is mainly directed towards the: 1) development of new drugs with specific inhibitory effect on MMPs; 2) better understanding of the pharmacologic profile of drugs already used in the treatment of rheumatic diseases, in order to identify those having an inhibiting action on degradative enzymes. MATERIALS AND METHODS: The interaction between rifamycins and collagenase type XI were studied using a fluorogenic substrate MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2. RESULTS: In our experimental conditions rifamycins showed a marked inhibition capacity with a IC50 ranging from 13 to 20.7 microM. This inhibition was reversible after extensive dialysis. CONCLUSIONS: Our results indicate that the effects of rifamycins in rheumatoid arthritis may correlate to the inhibitory activity of these molecules on collagenase activity.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Exogenous glucocorticoids affect in different way the various phases of bone formation in postmenopausal patients.

BACKGROUND: To determine the effect of glucocorticoid excess on the most important circulating markers of bone formation in postmenopausal treated patients. METHODS: The study included 15 postmenopausal women taking glucocorticoids for various medical conditions and two groups of 30 healthy premenopausal and 28 age-matched postmenopausal women as controls. Osteoblastic activity was assessed by measuring both serum levels of osteocalcin (BGP) (N-tact Osteo SP, Incstar Co.) and the bone-specific isoenzyme of alkaline phosphatase (BAP) (Alkphase-B, Metra Biosystems). RESULTS: The mean values of serum BGP found in patients taking steroids were significantly reduced as compared to those found in both fertile and postmenopausal women (p < 0.0001). The mean serum levels of BAP were significantly increased in treated patients as compared to premenopausal women (p < 0.0001), while no significant difference was found between patients and age-matched postmenopausal women. Similar results were also obtained when individual values of both serum BAP and BGP were expressed as standard units in comparison to values obtained in fertile subjects (T-score) or postmenopausal subjects (Z-score). CONCLUSIONS: Steroid therapy in postmenopausal patients differentially affects the various phases of bone formation. Measurement of serum BGP may represent a reliable parameter for monitoring bone formation in postmenopausal treated patients.

Aged↗