PubMed Health⌕ Search

Biomedical subjects

F Lanza

Publications and source records attributed to F Lanza.

At least 163 records · Page 9Linked to original sources
PubMed1989

An endoscopic comparison of the gastroduodenal injury seen with salsalate and naproxen.

Forty endoscopically normal healthy subjects were randomized to receive either BID salsalate (3500 mg/day) or BID naproxen (750 mg/day) for 14 days followed by repeat endoscopic examination. Gastroduodenal lesions were found in 55% (11/20) of the subjects taking naproxen, and 10% (2/20) of those taking salsalate (p = 0.002). Twenty-five percent (5/20) of the subjects taking naproxen and none of the subjects taking salsalate were noted to have severe gastric injury (p = 0.003). There was no difference between the 2 groups in subjective gastrointestinal system adverse experiences. Overall, 95% (19/20) of subjects taking salsalate reported at least 1 adverse experience compared with 60% (12/20) of those taking naproxen (p = 0.02). This was due primarily to the higher number of subjects taking salsalate reporting reversible tinnitus or hearing loss. There was no significant treatment difference in adverse experiences reported for any other organ system. The results of our study support previous observations in patients with rheumatoid arthritis that salsalate produces less gastroduodenal mucosal toxicity than the widely used antiinflammatory agent, naproxen.

Alanine Transaminase↗
PubMed1988

Epinephrine potentiates human platelet activation but is not an aggregating agent.

Epinephrine can in certain in vitro conditions induce the aggregation of human platelets and could play an important role in vivo in the appearance of thrombotic disorders when catecholamine levels are increased. This study examines some functional and biochemical responses to epinephrine. Epinephrine induces the aggregation and serotonin secretion of human platelets in citrated plasma. This is not due to a direct effect of citrate itself, such as the lowering of plasma free Ca2+ but more likely to the generation of traces of thrombin during blood collection, as suggested by abrogation of these platelet responses when hirudin was added before citrate. When washed human platelets suspended in Tyrode buffer containing 2 mM Ca2+, 0.35% albumin and apyrase, and 0.1-100 microM epinephrine were used, no shape change, aggregation, or secretion of serotonin was observed, nor was the platelet ultrastructure modified. Epinephrine does not modify platelet membrane fluidity, as studied with the lipophilic fluorescent probe trimethylammonium-diphenylhexatriene. It has no direct effect on fibrinogen binding to intact platelets, intracellular Ca2+ levels measured by quin2, or protein phosphorylation. Epinephrine potentiates the action of all types of aggregating agents on aggregation, secretion, intracellular Ca2+ levels, membrane fluidity, fibrinogen binding, or protein phosphorylation. These effects are mediated by alpha 2-adrenergic agonists and inhibited by alpha 2-adrenergic antagonists. This study shows that epinephrine alone does not induce modifications of morphology, metabolism, or function of intact and functional washed human platelets and that it cannot be considered per se as an aggregating agent. However, epinephrine interacts with alpha 2-adrenergic receptors on human platelets and potentiates biochemical and aggregatory responses induced by other platelet agonists.

Adenosine Diphosphate↗
PubMed1988

A blinded endoscopic comparative study of misoprostol versus sucralfate and placebo in the prevention of aspirin-induced gastric and duodenal ulceration.

In a series of previous studies, we showed that misoprostol protects the gastric and duodenal mucosae against ulceration seen with the administration of both aspirin and the nonsteroidal antiinflammatory drug tolmetin. The purpose of this study was to confirm, in addition, that misoprostol protects the mucosae against aspirin-induced damage and, for the first time, to compare its cytoprotective properties with those of sucralfate. Thirty healthy volunteers were randomized into three equal groups receiving either misoprostol 200 micrograms, sucralfate 1 g, or placebo, co-administered with 650 mg of aspirin, four times a day for 7 days. All subjects had endoscopically normal mucosae on entry and were reendoscoped 2 h after a single final dose on day 7. The mucosae were graded on a 0-4 scale as follows: 0 = normal, 1 = single hemorrhage or erosion, 2 = 2-10 hemorrhages or erosions, 3 = 11-25 hemorrhages or erosions, 4 = more than 25 hemorrhages or erosions or an invasive ulcer of any size. Utilizing a previously established criterion of a score of 2 or less as a clinically significant degree of protection to the gastric mucosae, we found that the success rate for misoprostol was 100% (10/10), compared to 20% (2/10) for sucralfate and 0% (0/10) for placebo. Misoprostol was statistically significantly superior to both sucralfate (p = 0.0001) and placebo (p = 0.00001), with 95% confidence intervals on the difference in success rates between misoprostol and sucralfate and between misoprostol and placebo of (44%; 100%) and (61%; 100%), respectively. In the duodenum, nine of 10 subjects taking misoprostol showed no damage (0 grade), whereas this was seen in only five sucralfate and three placebo patients. Misoprostol was significantly superior to placebo (p = 0.020) and marginally superior to sucralfate (p = 0.141) with confidence intervals of (29%; 91%) and (-5%; 67%), respectively. Adverse experiences were minor and did not differ in the three groups.

Alprostadil↗
PubMed1987

Increased aggregation and secretion responses of human platelets when loaded with the calcium fluorescent probes quin2 and fura-2.

Incorporation into human platelets of the calcium fluorescent indicators quin2 or fura-2 at low concentrations used to measure intracellular free calcium leads to the potentiation of the effects of agonists on platelets. This was shown by increased aggregatory and secretory responses of quin2 or fura-2 loaded platelets after stimulation with ADP, PAF and with low concentrations of thrombin, collagen, the endoperoxide analog U-46619 and the calcium ionophore A 23187. Quin2 and fura-2 mediated platelet sensitisation could be due to altered arachidonic acid metabolism since it was inhibited by prior treatment with the cyclooxygenase inhibitor acetylsalicylate. In contrast, platelets loaded with higher concentrations of calcium chelators exhibited diminished aggregation responses to all aggregating agents. This latter effect was accompanied by increased fluidity of the platelet plasma membrane bilayer and by the exposure of a new pool of membranes to the outer surface of platelets, as monitored with trimethyl-ammonium-diphenylhexatriene (TMA-DPH) in platelets loaded with the non-fluorescent calcium probe analog MAPT. In contrast, low concentrations of quin2 did not potentiate shape change of platelets activated with ADP. Thus, shape change and aggregation can be influenced separately by intracellular Ca2+ chelators. We conclude that platelet responses are altered by the incorporation of intracellular calcium chelators at concentrations used to monitor intracellular calcium changes.

Aminoquinolines↗
PubMed1987

Parallel investigation of exocytosis kinetics and membrane fluidity changes in human platelets with the fluorescent probe, trimethylammonio-diphenylhexatriene.

A simple, flexible and sensitive fluorescence method is described, which, from the same experiment, provides coupled quantitative informations on membrane fluidity changes and exocytosis, and reliable kinetic analyses of these effects, in intact cell suspensions. The method is based on the features peculiar to trimethylammonio-diphenylhexatriene (TMA-DPH), a fluorescent hydrophobic probe, which, in intact cells, is incorporated specifically into the plasma membranes, according to an instantaneous partition equilibrium. The method was tested on human platelets upon stimulation with various agents, such as human alpha-thrombin, adenosine diphosphate (ADP), adrenaline and ionomycin, which act through different types of mechanism. The experimental conditions were chosen to allow platelet shape change and exocytosis, but no aggregation. The kinetics and the dose-dependence of the changes in TMA-DPH fluorescence intensity and anisotropy were compared to the simultaneous physiological responses of platelets to the same stimuli, under the same conditions. Quantitative correlations were established between serotonin secretion and the increase in fluorescence intensity, whereas fluorescence anisotropy, which monitors membrane fluidity changes was associated with platelet shape change. The specificity of the effects was confirmed with appropriate antagonistic or modulating agents.

Adenosine Diphosphate↗
PubMed1987

Cyclic nucleotide phosphodiesterase inhibitors prevent aggregation of human platelets by raising cyclic AMP and reducing cytoplasmic free calcium mobilization.

Cyclic nucleotide phosphodiesterase inhibitors (HL-725, RO 15-2041, cilostamide, quercetin and MY-5445) potently inhibit human platelet aggregation induced by ADP. In parallel, PDE inhibitors inhibit the increase in cytoplasmic free Ca2+ evoked by ADP, as measured with the fluorescent probe quin 2. The inhibition of ADP-induced aggregation and rise in [Ca2+]i is potentiated by PGE1 which stimulates adenylate cyclase and is inhibited by adrenaline which inhibits adenylate cyclase. PDE inhibitors increase human platelet cAMP levels in the presence of low concentrations of PGE1. It is suggested that PDE inhibitors prevent platelet aggregation by raising cAMP levels and by subsequent inhibition of cytoplasmic free Ca2+ mobilization.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1987

Platelet functions, alpha 2-adrenergic receptors and cytoplasmic free calcium are normal in the myotonic dystrophy of Steinert.

Platelet function tests were performed on 11 patients with myotonic dystrophy of Steinert (MD) and on 21 healthy control subjects. Using citrated platelet-rich plasma or washed platelets, MD patients had normal aggregation and secretion responses after stimulation with adrenaline, ADP, collagen, PAF, arachidonic acid and thrombin. Using intact and functional washed platelets, MD patients responded normally to adrenaline and had a similar affinity and number of alpha 2-adrenergic receptors as control patients as measured by [3H]dihydroergocryptine and [3H]yohimbine binding. In addition platelets from MD patients had normal basal and stimulated levels of cytoplasmic free Ca2+ as measured with the fluorescent Ca2+ probe quin2. Thus platelet functions, alpha 2-adrenergic receptors and cytoplasmic free Ca2+ are normal in MD.

Adenosine Diphosphate↗
PubMed1987

Monoclonal origin of B cells producing k, lambda and k lambda immunoglobulin light chains in a patient with chronic lymphocytic leukemia.

Immunoglobulin gene rearrangements can be used as genetic markers of clonality in the study of B-cell populations [4]. We have therefore analysed the structure and expression of heavy and light chain immunoglobulin genes in lymphocytes of a patient with chronic lymphocytic leukemia, where we found both k and lambda producing B cells, but in most of the cells both k and lambda chains were co-expressed on the same surface membrane. Single rearrangements were observed in mu, JH, k and lambda DNA sequences, thus providing strong evidence for the monoclonal origin of the cells bearing different light chains. Moreover, the analysis of Ig sequence RNA showed, in addition to normal mu, k and lambda mRNA molecules, high levels of a small lambda related RNA sequence. These findings are discussed in relation to a model of B-lymphocyte differentiation which could be either an additional or an alternative hypothesis to the current one of isotypic exclusion.

Aged↗
PubMed1987

Cytogenetic aspects of B-cell chronic lymphocytic leukemia: their correlation with clinical stage and different polyclonal mitogens.

Blood lymphocytes from 23 patients with B-cell chronic lymphocytic leukemia were stimulated with different mitogens (lipopolysaccharide from E coli, phorbol myristate acetate ester, Staphylococcus aureus, and phytohemagglutinin M form). Functional properties of stimulated cells (blastic transformation, mitotic index, cIg production, Ig secretion, and acid phosphatase positivity) were evaluated and correlated with the stage of disease and chromosomal findings. Early stages of the disease are characterized by a relatively homogeneous response to polyclonal B-cell and activators and by a restricted number of chromosomal aberrations. Advanced stages show a more heterogeneous pattern of response and a higher incidence of abnormal karyotypes suggesting an involvement of various subclonal lines.

Antibody-Producing Cells↗
PubMed1987

[Adrenergic receptors of blood platelets].

Blood platelets possess adrenergic receptors and are stimulated by adrenaline in the circulation. This review summarizes the state of knowledge of the pharmacology of adrenergic receptors and the biochemical mechanisms of platelet activation by adrenaline in various physiological and pathological conditions.

Blood Platelets↗
PubMed1987

An endoscopic comparison of the effects of etodolac, indomethacin, ibuprofen, naproxen, and placebo on the gastrointestinal mucosa.

To assess the effects of various nonsteroidal antiinflammatory drugs on gastroduodenal mucosa, 72 normal men were administered either etodolac, indomethacin, ibuprofen, naproxen, or placebo for 7 days. Gastric and duodenal mucosa were scored before and after treatment by direct endoscopy and evaluation of photographs taken during endoscopy. Subjects treated with indomethacin, ibuprofen, and naproxen had significantly worse direct gastric scores, and those treated with indomethacin and naproxen also had significantly worse direct duodenal scores, when compared with pre-treatment and placebo scores. Subjects given either of 2 doses of etodolac had gastric and duodenal scores comparable to pretreatment and placebo scores. The direct gastric scores of the etodolac groups were significantly better than the scores of subjects receiving indomethacin, ibuprofen and naproxen. Similar results were obtained when endoscopy photographs were scored.

Acetates↗
PubMed1987

Does a relationship exist between neutrophil myeloperoxidase deficiency and the occurrence of neoplasms?

36 unrelated individuals with neutrophil MPO deficiency, (10 totally MPO deficient) were found on screening a population of 148,000 subjects. A further 2 subjects with total and 22 with partial MPO deficiency were identified through family studies. The assessment of neutrophil function, i.e., peroxidase activity, superoxide anion generation, microbicidal activity towards fungi and bacteria, and locomotor behaviour, was carried out in 10 subjects with total and 4 with partial MPO deficiency. We found that the enzyme defect is associated with a marked impairment in the killing of both S. aureus and C. albicans, without affecting microbicidal activity against S. faecalis. There appears to be a high incidence of malignancy in patients with complete MPO deficiency, suggesting a relationship between a defective MPO system and neutrophil-mediated tumor cell cytotoxicity.

Adolescent↗
PubMed1986

Potentiation by adrenaline of human platelet activation and the inhibition by the alpha-adrenergic antagonist nicergoline of platelet adhesion, secretion and aggregation.

Adrenaline (1 to 10 microM) can induce the aggregation of human platelets suspended in citrated plasma but does not induce the aggregation of washed human platelets at doses as high as 1 mM, although these platelets respond normally to ADP, PAF-acether, collagen, arachidonic acid, thrombin, the endoperoxide analog U-46619 and the Ca2+ ionophore A23187. Adrenaline (0.5 microM) potentiates the aggregation and secretion induced by all the previous agonists in citrated platelet-rich plasma (cPRP) or in washed platelets. The activation by adrenaline of human platelets is mediated by alpha 2-adrenergic receptors, as demonstrated by inhibition with a series of adrenergic antagonists. The alpha-adrenergic antagonist nicergoline inhibits the activation of human platelets by adrenaline in the following situations: nicergoline inhibits the aggregation and secretion caused by adrenaline in cPRP (IC50 0.22 microM and 0.28 microM respectively); nicergoline inhibits the aggregation and secretion induced by the combination of adrenaline and each aggregating agent listed above in cPRP (IC50 ranging from 0.1 to 2.5 microM) or in washed platelets (IC50 ranging from 0.1 to 0.8 microM); nicergoline inhibits the binding of 3H-yohimbine to washed human platelets (IC50 0.26 microM); the intravenous administration of nicergoline (0.5 mg/kg per day) to patients inhibits significantly the ex vivo response of their platelets to adrenaline in cPRP. High concentrations of nicergoline also inhibit the aggregation and secretion induced by the aggregating agents listed above in cPRP (IC50 range 108 to 670 microM) and in washed platelets (IC50 range 27 to 140 microM) and the adhesion of platelets to collagen-coated surfaces. This latter effect is not mediated through blockade of alpha-adrenoceptors. A possible role of adrenaline in platelet activation in vivo could justify the use of nicergoline (Sermion), an alpha-adrenergic antagonist in combination therapy to prevent arterial thrombosis.

Blood Platelets↗