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Biomedical subjects

M Francesconi

Publications and source records attributed to M Francesconi.

At least 37 records · Page 2Linked to original sources
PubMed1995

Type IIB von Willebrand factor induces phospholipase A2 activation and cytosolic Ca2+ increase in platelets.

Von Willebrand factor (vWF) is a large glycoprotein which plays a central role in thrombus formation and blood clotting. The type IIB variant of vWF is characterized by an abnormally high affinity for the platelet receptor GPIb. Type IIB vWF purified from plasma and added to a platelet suspension induced a rapid, dose-dependent (1.2-9 micrograms/ml) increase in the cytosolic Ca2+ concentration. ATP secretion and platelet aggregation also occurred with type IIB vWF concentrations higher than about 5 micrograms/ml, which corresponds to the original plasmatic level. The IIB vWF-evoked (3 micrograms/ml) cytosolic Ca2+ increase was negligibly affected by ADP scavengers or protein kinase C inhibitors; it was drastically reduced by EGTA, La3+, Ni2+ or acetylsalicylate and abolished by the phospholipase A2 inhibitors ONO-RS-082 or oleolyloxyethyl-phosphocholine. Platelet exposure to IIB vWF caused arachidonic acid release, thromboxane B2 and inositoltrisphosphate formation. LJIB1, a monoclonal antibody against GPIb, completely suppressed all platelet responses, whereas LJCP8, an antibody against the receptor GPIIb-IIIa (alpha IIb beta 3 integrin), or the tetrapeptide RGDS, caused a complete inhibition of the aggregation but a partial inhibition of the activation-linked parameters. It is concluded that type IIB vWF-binding to GPIb induces phospholipase A2 activation, arachidonic acid release and GPIIb-IIIa dependent cellular Ca2+ influx. These events may lead to platelet secretion and aggregation.

Arachidonic Acid↗
PubMed1995

[Effect of dexfenfluramine on eating behavior and body weight of obese patients: results of a field study of Isomeride in Austrian general practice].

In a multicenter study by 243 practicing physicians in Austria 819 severely obese subjects of both sexes without overt disease were encouraged to keep a calorie-restricted diet to reduce weight. After a run-in period of more than two weeks of dieting patients started taking 15 mg dexfenfluramine (Isomeride) twice daily for three month. While their weight was fairly stable during the run-in period progressive weight loss occurred during taking dexfenfluramine due to obvious changes in eating habits and appetite allowing to keep the reducing diet more strictly. Females lost 7.7 +/- 3.9 kg while obese men lost 9.32 +/- 4.6 kg. Laboratory tests obtained before starting dexfenfluramine and after 3 months at termination of medication showed blood glucose, cholesterol, LDL and triglycerides to decrease while HDL-cholesterol increased moderately. Dexfenfluramine was well tolerated by the majority of patients. Side effects such as fatigue, sedation, flatulence or diarrhea occurred in only 7.9% of the probands initially and dropped to 2.1% during the third month of the medication. It is concluded that Dexfenfluramine modifies eating habits and appetite thus making weight reducing diets easier acceptable and resulting in weight loss. It is suggested that Dexfenfluramine has a role in treatment regimes for morbid and refractory obesity.

Adult↗
PubMed1993

[Intraoperative awareness: a true or false problem?].

The authors base their remark on a few cases of awareness which have been reported in their hospital and on the history a patient who experienced intraoperative awareness during cesarean section. Attention is focused on the ethical, social and medico-legal aspects of this phenomenon. Awareness may severely affect the patient's psychic equilibrium with the consequent onset of severe neuroses leading to the possibility of legal action and claims for compensation. Clinical experience has shown that the use of halogenate anesthetics, even in low concentrations, may help to avoid this phenomenon. Correct relations between the anesthetist and patient before and after surgery may also, even in the event of awareness, reduce the incidence and severity of consequent psychological sequelae.

Adjustment Disorders↗
PubMed1992

The antioxidant butylated hydroxytoluene (BHT) inhibits the dioctanoylglycerol-evoked platelet response but potentiates that elicited by ionomycin.

Preincubation of aspirin-treated human platelets with butylated hydroxytoluene (BHT) inhibits secretion, aggregation, and protein phosphorylation induced by dioctanoylglycerol or phorbol 12-myristate 13-acetate (PMA). BHT alone elicits a rapid and transient phosphorylation of a 47-kDa protein, which is indistinguishable from the well-recognized major substrate of protein kinase C (PKC). Inhibition of diacylglycerol- or PMA-induced platelet activation is also observed after decay to the basal level of the BHT-evoked phosphorylation of the 47-kDa protein. By contrast BHT potentiates platelet responses elicited by the calcium ionophore ionomycin. In the presence of the PKC inhibitor staurosporine BHT fails to increase the ionomycin-promoted platelet aggregation, indicating that its effect occurs through a PKC activation, even if no correlation with the 47-kDa protein phosphorylation is observed. BHT does not significantly modify the affinity of protein kinase C purified from calf brain for Ca2+ or dioctanoylglycerol. It is concluded that: (a) a short exposure of platelets to BHT induces an activation, whereas a long exposure an inhibition of PKC, (b) at variance with diacylglycerols BHT decreases the platelet responses promoted by subsequent challenge with PKC activators themselves, and (c) similarly to other PKC activators BHT potentiates the cellular response elicited by calcium ionophores most likely by activating the phospholipase A2.

Adenosine Triphosphate↗
PubMed1992

Inhibition of thrombin-induced platelet activation by dioctanoylglycerol pretreatment is not correlated with the 47 kDa protein phosphorylation.

The effect of platelet pretreatment with moderate amounts of 1,2-dioctanoylglycerol on subsequent thrombin-induced activation and its correlation with the degree of protein phosphorylation is studied. Protein kinase C preactivation (treatment with 1 microM dioctanoylglycerol for 20 min) significantly reduces thrombin-promoted platelet aggregation, cytosolic calcium-rise, ATP-secretion and, albeit to a lesser extent, protein phosphorylation. Exposure of platelets to dioctanoylglycerol brings about a transient phosphorylation of a 47 kDa protein and a slight but more persistent phosphorylation of proteins of approximate molecular mass 26 and 68 kDa. It is hypothesized that the latter phosphoproteins are responsible for the inhibition of the thrombin-promoted platelet activation. Agonist-evoked aggregation is more affected by a long (20 min) rather than a short (1 min) pretreatment with dioctanoylglycerol, showing no correlation with the phosphorylation of the major substrates of protein kinase C.

Adenosine Triphosphate↗
PubMed1991

[Quantitative flow measurement of the art. dorsalis pedis in normal probands and patients with arterial occlusive disease of a low Fontaine stage].

Quantitative blood flow measurements of the dorsal foot artery were performed with a multichannel digital pulsed Doppler device in normal volunteers and in patients with Fontaine IIa stage peripheral arterial occlusive disease. The measured parameters were: 1. vessel diameter, 2. maximum systolic flow volume, 3. minimum diastolic flow volume, 4. maximum systolic velocity, 5. minimum diastolic velocity. The calculated parameters were: pulsatility index, mean velocity and mean flow volume. Pulsatility index, maximum systolic flow volume and velocity were found to be reduced--although not statistically significant--in patients compared to volunteers.

Adult↗
PubMed1991

[Moenckeberg media sclerosis: clinical aspects in diabetic patients].

We assessed in 1662 consecutive diabetic patients systolic arm-ankle indexes by a Doppler ultrasonic method. In those patients with indexes greater than or equal to 1.3 directional Doppler sonometry and mercury strain gauge plethysmography were performed. In some instancies electronic oscillography, duplex sonography and vital microscopy were additionally done. In 4.45% of the patients functional findings of a mediasclerosis could be encountered. Location of arterial mediacalcinosis was documented by x-ray examinations. Sensitivity of none invasive methods was merely 100%, specificity ranged from 96% (Dopplersonometry) to 80% (Duplexsonometry). In 18.9% an occlusive arterial disease could additionally be found. Mediasclerosis preferentially was encountered in Type II diabetics of older age. In this group painful distal neuropathy in many instances existed mimicking claudication, retinopathy and nephropathy was as frequent as in other diabetics. Normal or elevated Doppler indexes did not exclude occlusive arterial disease whereas diabetics with mediasclerosis and ulcero-gangreneous lesions or amputations in most of the cases did not have occlusive arterial disease.

Adult↗
PubMed1989

Effect of L-carnitine and L-aminocarnitine on calcium transport, motility, and enzyme release from ejaculated bovine spermatozoa.

Experiments were performed to further elucidate the role of gamma-amino-beta-hydroxybutyric acid trimethylbetaine (carnitine) on the metabolism and functions of spermatozoa. Addition of 20 mM L-carnitine to suspensions of ejaculated bovine spermatozoa resulted in an increase of cellular calcium transport, whereas 20 mM L-aminocarnitine (an inhibitor of carnitine palmitoyltransferase) caused an inhibition of this process. Both L-carnitine and L-aminocarnitine inhibited the progressive motility of spermatozoa, and the oxygen consumption as well as the release of the enzymes hyaluronidase and glutamate-oxaloacetate transaminase from spermatozoa. Labeled carnitine was rapidly taken up by spermatozoa by a process strongly dependent on temperature and extracellular concentration of carnitine. It is concluded that the effects produced by high concentrations of carnitine or aminocarnitine are mainly due to interactions of these compounds with the cellular membranes of spermatozoa.

Acyltransferases↗
PubMed1988

Effects of calcium chelators, divalent cations and sulfhydryl reagents on calcium uptake and motility of bovine spermatozoa.

Addition of 1 mM Ca/EGTA complex (1:1 ratio) to an incubation medium containing 1.5 mM Ca2+ produced a notable increase in the Ca2+ cycling in ejaculated bovine spermatozoa. Similar results were also obtained with the Ca/EDTA and Ca/EDTA complexes or with the heavy metal chelator DTPA (50 microM). Ba2+, Ni2+ or Co2+ added at 0.1 mM concentration abolished the stimulatory effect of the Ca/EGTA complex on Ca2+ cycling, whereas it did not affect the calcium movement in the absence of the calcium chelator complex. It is concluded that small amounts of these cations should be bound to the plasma membrane of bovine spermatozoa and inhibit the cellular calcium influx. 0.1 mM Cd2+ and NEM or 1 mM diamide produced a calcium efflux from the spermatozoa together with an inhibition of cellular motility and an increase in glutamate-oxaloacetate transaminase release. Conversely the impermeant sulfhydryl reagent mersalyl caused a net calcium efflux but did not alter the cellular motility nor the transaminase release. It is suggested that the permeant thiol reagents could decrease the spermatozoal mobility by impairing the mitochondrial ATP-synthesis.

Animals↗
PubMed1987

Effect of 3-hydroxy-3-methylglutarate treatment on plasma ketone bodies, triglycerides, and HDL-cholesterol in streptozotocin-diabetic rats.

3-Hydroxy-3-methylglutaric acid administration to streptozotocin-diabetic rats produced a net decrease of plasma ketone bodies and triglycerides together with a slight decrease of total cholesterol. A nonsignificant enhancement of HDL-cholesterol and a negligible change in HDL-phospholipid was also observed. The effect of 3-hydroxy-3-methylglutarate was dose dependent and was more evident with the compound intraperitoneally injected than orally administered with drinking water. [14C]-3-hydroxy-3-methylglutarate was administered either orally or intraperitoneally both to diabetic and control groups of animals, and a higher radioactivity accumulated in liver and kidneys of diabetic rats compared to the controls. The possible mechanism of action of 3-hydroxy-3-methylglutarate is briefly discussed.

Animals↗
PubMed1987

Danazol therapy in refractory chronic immune thrombocytopenic purpura.

We report our experience with danazol in the treatment of patients with refractory immune thrombocytopenic purpura (ITP). The effects of this drug were investigated in 10 patients, 6 males and 4 females, aged from 40 to 85 years, (median 58 years), with a platelet count below 50 X 10(9)/l. The patients had previously been treated with steroids; one of them had also been unsuccessfully splenectomized. Danazol was administered at a dosage of 600 mg/day for 3 months. Before and after treatment, detection of antiplatelet antibodies was performed. Seven patients were treated for 3 months. One of them showed a transient increase of platelet count, in the others, no significant rise was noted. Six patients experienced side effects during treatment. We think that danazol does not appear to be an alternative therapeutical approach in refractory ITP.

Adult↗
PubMed1987

Estimation of poly (C) avid serum ribonuclease in hepatoma patients.

Human poly (C) avid serum ribonuclease (RNase) differs in physico-chemical, electrophoretic, and catalytic properties from ribonuclease activity encountered in liver preparations. The first is reported as "secretory type", the latter, because it is undetectable in body fluids, as "nonsecretory type". We determined RNase activity in 11 hepatoma patients. A statistical difference from a normal control of corresponding age was encountered in both age groups investigated (51-60 years, P less than 0.05; 61-70 years, P less than 0.01). The circumstances mentioned above make the tumor itself unlikely to be the source of RNase elevation. Besides a diminished synthesis of RNase inhibitor by hepatoma cells, tumor-derived polyamines could contribute to enhanced RNase activity. The influence of polyamines on RNase activity has already been demonstrated by in vitro experiments. Simultaneous estimation of polyamines and RNase is required to elucidate in vivo circumstances.

Aged↗
PubMed1986

Pipobroman therapy of essential thrombocythemia.

We report our results with pipobroman (PB) therapy in patients with essential thrombocythemia (ET). 21 consecutive untreated patients were treated with PB from 1975 to 1984. PB was given at a dose of 1 mg/kg/d until platelet count dropped below 600 X 10(9)/l. In 18 patients (86%) a hematological remission was obtained. Median duration of induction phase was 49 d. In all cases a maintenance regimen was required at a dose ranging from 0.2 mg/kg/d to 0.5 mg/kg/d, according to platelet number. Follow-up of responder patients ranged from 6 to 108 months (median 17 months). Treatment was well tolerated and we observed only a very moderate and transient hematological toxicity. No patient had relapsed or developed secondary neoplasms at the time of writing. Median survival time of all patients was 24 months (range 10-115).

Adult↗
PubMed1986

Serum thyroid autoantibodies as a risk factor for development of hypothyroidism after radioactive iodine therapy for single thyroid 'hot' nodule.

Hypothyroidism is often observed after radioiodine treatment in Graves' disease, but it is considered a rare complication in single hyperfunctioning thyroid nodule ('hot' nodule). This concept has been recently challenged, but the available data are conflicting. In the present study we therefore assessed the development of permanent hypothyroidism in 126 patients with thyroid hot nodule treated with 131I (180 muCi/g of estimated nodule weight, total dose 5.5-28.9 mCi). Follow-up ranged between 1 to 11 years. Hypothyroidism was observed in 5 (4%) patients, corresponding to a cumulative incidence by life-table analysis of 4.8% ten years after treatment. No relationship was found between the development of hypothyroidism and the size of the nodule or the total amount of administered dose. Fifty-six patients with euthyroid hot nodule at the time of treatment had higher cumulative incidence of hypothyroidism after 10 years (9.7%) than those with toxic adenoma (1.5%) (0.1 greater than P greater than 0.05 by logrank test). When the patients were analyzed according to the presence or absence of serum antithyroglobulin and/or antithyroid microsomal autoantibodies, the prevalence of hypothyroidism after 131I treatment was higher (4/25 = 16%) in patients with significant serum antibody titres (greater than or equal to 1/400 by passive haemagglutination), when compared to that observed in subjects with negative antibody tests (1/101 = 1.0%). Life-table analysis showed in antibody positive patients a cumulative incidence of hypothyroidism after 10 years of 18.0% vs 1.4% in antibody negative patients (P less than 0.001 by logrank test).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗