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G Ciabattoni

Publications and source records attributed to G Ciabattoni.

At least 73 records · Page 4Linked to original sources
PubMed1992

Intra-articular osteoid osteoma.

The joint is a relatively rare localization for osteoid osteoma. The location of the tumor and the concomitant synovitis-explain the peculiarity of the clinical features, which makes differential diagnosis with inflammatory diseases of the joint difficult. The authors report the results of three cases of intra-articular osteoid osteoma in which it was possible to determine the levels of prostaglandin (PGE2) and prostacyclin (PGI2), which are synthesized by the tumoral tissue. The increased production of these substances, which can reach up to 70 times their production in normal tissue, explain both the character of the pain and the origin of the synovitis which is so commonly found in this kind of tumor. The results of this study confirm the ability of the neoplastic tissue to produce high quantities of mediators of inflammation and enable the authors to formulate a theory as to the pathogenesis of the concomitant reactive synovitis observed in cases of intra-articular osteoid osteoma.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Human eicosanoid biosynthesis and metabolism.

The development of RIA techniques for the measurement of urinary eicosanoid metabolites has allowed characterization of their biosynthesis and metabolism in health and disease. PGI2, TXA2, and LTC4 share a very low rate of secretion into the human circulation and rapidly disappear from circulation because of extensive enzymatic degradation. Long-term changes as well as episodic increases in their biosynthesis can be detected in association with various disease states, as reflected by increased excretion of major enzymatic metabolites such as 2,3-dinor-6-keto-PGF1 alpha, 11-dehydro-TXB2, and LTE4. Application of the same investigative approach to other recently identified products of arachidonate metabolism (2) may provide further insight into the pathophysiologic significance of this complex mediator system.

Eicosanoids↗
PubMed1991

Prostaglandins in osteoid osteoma.

Osteoid osteoma is a tumour of bone characterised by pain which is relieved by aspirin and nonsteroidal anti-inflammatory drugs. Very high levels of prostaglandins have been found in the lesion. In five patients with osteoid osteoma, prostaglandin E2 (PGE2) and prostacyclin (PGI2) synthesis in the nidus yielded 1155.6 +/- 496.5 (mean +/- SD) and 245.2 +/- 89.8 pg/mg respectively, values which are 33 and 26 times higher than in fragments of normal bone. The sclerotic bone around the nidus produced both prostaglandins at the same rate as normal bone. In three patients the excretion rate of the major urinary metabolite of systemic PGI1 was reduced to 50% one month after removal of the tumour. The urinary excretion rate of 6-keto-PGF1 alpha, reflecting intrarenal PGI2 synthesis, was not changed after operation. These results offer new insight into the pain mechanism in osteoid osteoma.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Tetrodotoxin does not block the epithelium-dependent release of prostaglandin E2 induced by electrical field stimulation in isolated ferret trachea.

Electrical field stimulation (EFS) has previously been shown to induce the release of prostaglandin (PG) E2 from ferret tracheal epithelium. We have now conducted a study to see whether this effect of EFS is due to the activation of nerves or whether it is a non-neural effect. The release of PGE2 and 6-keto-PGF1 alpha into the bath fluid was assayed in isolated ferret tracheas with (E+) or without (E-) epithelium, stimulated by either EFS or direct vagal nerve stimulation (DNS) repeatedly for 120 min. EFS-stimulated E+ preparations showed a gradual decline in the contractile responses (30 +/- 1% of baseline) and an increase in PGE2 to 296 +/- 38 pg/ml. In EFS-stimulated, epithelium-denuded (E-) preparations, the decline was significantly lower (11 +/- 5%), as well as the final concentration of PGE2 (107 +/- 21 pg/ml). In DNS-stimulated E+ preparations, the contraction decline was 8 +/- 1% and the final concentration of PGE2 was less than 6 pg/ml. Although tetrodotoxin (TTX) abolished the contractile response in EFS-stimulated E+ preparations, it did not significantly reduce the release of PGE2 (260 +/- 6 pg/ml), whereas atropine partly counteracted the release. The bath concentration of 6-keto-PGF1 alpha increased, independently of the electrical stimulation, contractile response, or presence of the epithelium. We conclude that EFS activates the epithelium-dependent release of PGE2 by a TTX-resistant mechanism. This may be due to an activation of TTX-resistant nerves, or possibly to a non-neural effect, such as a direct effect on the epithelial cells. The results indicate that the airway epithelium has the ability to respond to certain stimuli with a pronounced release of PGE2, thereby counteracting bronchoconstriction.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Increased prostacyclin biosynthesis in patients with osteoid osteoma.

Osteoid osteoma is a benign osteoid-forming tumor of the bone characterized by pain which is relieved by nonsteroidal anti-inflammatory drugs. Very high levels of prostaglandins have been found in the lesion. In nine patients with osteoid osteoma, prostaglandin E2 (PGE2) and prostacyclin (PGI2) synthesis in explants from the nidus incubated in vitro yielded 947.3 +/- 482.6 (mean +/- SD) and 340.2 +/- 178.1 pg/mg of wet tissue respectively, values 32 and 49 times higher than in fragments of normal bone. In eight patients the excretion rate of the major urinary metabolite of PGI2, i.e. 2,3-dinor-6-keto-PGF1 alpha, was nearly double the control value (499 +/- 93 vs 257 +/- 117 pg/mg of creatinine; mean +/- SD). In six of them, from whom urine was collected 1 month after surgery, urinary 2,3-dinor-6-keto-PGF1 alpha decreased significantly (P less than 0.01) from 487 +/- 100 to 229 +/- 52 pg/mg creatinine. Urinary 6-keto-PGF1 alpha, largely a reflection of intrarenal PGI2 synthesis, was comparable to the control group (4.6 +/- 0.9 vs 4.5 +/- 1.0 ng/h, respectively) and remained unchanged after operation. These results suggest an enhanced PGI2 biosynthesis in vivo in patients with osteoid osteoma. This abnormality of arachidonate metabolism is consistent with enhanced biosynthetic capacity of the tumor in vitro, and is reversible upon its removal.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Thromboxane biosynthesis and platelet function in type II diabetes mellitus.

It has been suggested that platelet hyperreactivity in patients with diabetes mellitus is associated with increased platelet production of thromboxane. We therefore compared the excretion of a thromboxane metabolite and platelet function in 50 patients with Type II diabetes mellitus who had normal renal function and clinical evidence of macrovascular disease and in 32 healthy controls. The mean (+/- SD) excretion rate of urinary 11-dehydro-thromboxane B2 was significantly higher in the patients than in the controls (5.94 +/- 3.68 vs. 1.50 +/- 0.79 nmol per day; P less than 0.001), irrespective of the type of macrovascular complication. Tight metabolic control achieved with insulin therapy reduced the levels of 11-dehydro-thromboxane B2 by approximately 50 percent. The fractional conversion of exogenous thromboxane B2 (infused at a rate of 4.5, 45.3, or 226.4 fmol per kilogram of body weight per second) to urinary 11-dehydro-thromboxane B2 was assessed in four patients, in whom it averaged 5.4 +/- 0.1 percent; this value did not differ from that measured in healthy subjects. Aspirin in low doses (50 mg per day for seven days) reduced urinary excretion of the metabolite by approximately 80 percent in four patients. The fact that thromboxane biosynthesis recovered over the following 10 days was consistent with a platelet origin of the urinary metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Dissociation of platelet activation and spontaneous myocardial ischemia in unstable angina.

A dynamic thrombotic process, coronary spasm or both can be responsible for recurrent episodes of transient reduction of coronary blood flow in unstable angina. We have investigated the temporal relationship between episodic platelet activation, as detected by increased urinary excretion of 11-dehydro-TXB2, and spontaneous myocardial ischemia, assessed by continuous electrocardiographic monitoring and recording in 21 patients with unstable angina pectoris. In order to validate measurements of metabolite excretion as a reflection of intracoronary platelet activation, we have also performed repeated urine sampling from 8 patients undergoing PTCA and from 6 patients with peripheral vascular disease. The latter showed a 16% coefficient of variation in 3 consecutive 8-h urine samples. 11-dehydro-TXB2 increased significantly, by up to 15-fold, in the 2.5- to 5.0-h urine collection encompassing PTCA and decreased by greater than 50% during the following 2-h period. Patients with unstable angina were characterized by episodic increases (greater than 2 SD of controls) in metabolite excretion, in successive 6-8 h specimens. Paired measurements of 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 15 urine samples did not reveal evidence of altered metabolic disposition of endogenously released TXB2. A total of 125 ECG ischemic episodes were recorded, of which 64% asymptomatic. We have compared these biochemical and ECG changes in patients randomized to i.v. low-dose aspirin or i.v. isosorbide dinitrate and oral diltiazem. Twenty-five of 56 (i.e. 45%) urine samples obtained in aspirin-free periods showed increased metabolite excretion as compared to 15 of 88 (i.e. 17%) samples collected during aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Effect of histamine on gastric acid secretion "in vitro": interference with endogenous prostaglandins.

The interference between histamine and endogenous prostaglandins (PGs) was investigated in the isolated gastric fundus from immature rats by evaluating the effect of nonsteroidal antiinflammatory agents (NSAIDs) on the acid response to histamine and the effect of histamine on PGs production by the gastric mucosa. Indomethacin (10(-5) M) and diclofenac (10(-5) M) caused a dose-dependent enhancement of the response to histamine, dimaprit and DBcAMP, but did not affect bethanechol-, isoprenaline- and forskolin-induced acid production. The enhancing effect of indomethacin was abolished in low Ca2+ medium. PGE2 and 6-keto PGF1 alpha levels in the mucosal solution were not modified by histamine, while being reduced by indomethacin. From these data it is concluded that endogenous PGs may negatively modulate the secretory response to histamine. However, a direct effect of the amine on cyclooxygenase to increase PGs synthesis seems to be excluded since histamine did not modify PGs levels in the mucosal solution.

Animals↗
PubMed1990

Paired analysis of thromboxane and prostacyclin metabolites in urine from healthy mothers and their children.

Eicosanoids have been implicated in the adaptation of the fetal to the neonatal circulation, but biochemical support for an activation of their synthesis in relation to birth has not been presented. We addressed this by assessing in pairs the excretion of two metabolites of thromboxane A2, 11-dehydro-TxB2 (dTx) and 2,3-dinor-TxB2 (Tx-M), and one metabolite of prostacyclin, 2,3-dinor-6-keto-PGF1 a (PGI-M), in the first voided urine from 13 healthy term neonates and in the immediate pre-delivery urine from their respective mothers. The excretion of dTx was higher (p less than 0.01) in the neonates than in their mothers (7430 and 1330 pg/mg creatinine, respectively), and so was the excretion of Tx-M (3730 and 900 pg/mg creatinine, respectively, p less than 0.001). Also the excretion of PGI-M was higher (p less than 0.05) in the neonates than in their mothers (2550 vs. 1510 pg/mg creatinine). Amniotic fluid contained detectable levels of both Tx-M and PGI-M. These data indicate that activation of platelets takes place in the neonate after separation of the fetal and maternal vascular circuits. The possible physiological implication of such activation requires further studies.

Epoprostenol↗
PubMed1990

Epithelium-derived PGE2 inhibits the contractile response to cholinergic stimulation in isolated ferret trachea.

We have previously reported that epithelium-dependent inhibitory factors, both prostanoids and non-prostanoids, can be activated by electrical field stimulation (EFS) and direct nerve stimulation (DNS) in an in vitro nerve-muscle preparation of ferret trachea. In this study we set out to compare the release of the inhibitory prostanoids, PGE2 and PGI2, in preparations with intact and with removed epithelium. Ferret tracheae were mounted in organ baths and phasic contractions were induced by EFS and DNS. The bath concentrations of PGE2 and the PGI2-metabolite 6-keto-PGF1 alpha were measured using radioimmuno assays. The gradual decrease in contractile response to DNS, 2 Hz for 120 min, was 95 +/- 2% of baseline (mean +/- SEM) in preparations with intact epithelium compared with 29 +/- 8% in epithelium-denuded preparations (p less than 0.001). The bath-levels of PGE2 showed a slight but significant (p less than 0.01) increase in denuded preparations with a final bath-concentration at 120 min of 13 +/- 3 pg/ml. The release of PGE2 was more pronounced in preparations with intact epithelium which resulted in a final bath-concentrations of PGE2 of 84 +/- 38 pg/ml which was significantly higher compared with epithelium-denuded preparations and also compared with time-matched controls with the same pattern of contraction induced by DNS alone. The concentrations of 6-keto-PGF1 alpha showed a slight increase which was of comparable magnitude (ns) in intact and denuded preparations. In conclusion this study demonstrates that the cyclooxygenase-dependent component of the epithelium-dependent inhibition of the contractile response to cholinergic nerve stimulation in ferret trachea is mediated by PGE2 but not by PGI2.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Hydroxyurea: relationship between toxicity and centrally-induced adrenal activation.

The anticancer drug hydroxyurea (HU) at doses of 300-800 mg/kg/day causes a dramatic lethality (up to 100% after a 5-day treatment) in hypophysectomized as well as in adrenalectomized rats drinking physiological saline + 5% glucose. Mortality in controls was less than 10% over a 5-day period. Adrenal stimulatory or replacement therapies protect pituitary- or adrenal-ablated rats against HU toxicity. They also counteract white blood cell changes induced by the drug. HU (30-800 mg/kg) induces a dose-dependent increase of plasma corticosterone in normal rats after single or repeated treatments that is not observed in hypophysectomized animals. HU also increases plasma levels of epinephrine, although this finding cannot account for the rise in plasma corticosterone; indeed, it is secondary to a strong rise in plasma corticosterone. The stimulation of the hypothalamic-hypophyseal-adrenal axis induced by HU is responsible for the drug-induced adrenocortical activation. This activation appears to be a valuable defence mechanism protecting intact rats against HU lethality, and its failure causes the dramatic HU lethality in pituitary- or adrenal-ablated animals.

Adrenal Glands↗