Alpha1-adrenoceptor-mediated formation of glycerophosphoinositol 4-phosphate in rat heart: possible role in the positive inotropic response.

In the present study, we investigated whether phospholipase A2 (PLA2)/lysophospholipase activity producing glycerophosphoinositols from phosphoinositides was operating in rat heart and could be stimulated by alpha1-adrenergic agonists. PLA2/lysophospholipase activity was found in homogenates from rat right ventricles. The stimulation of PLA2/lysophospholipase activity by noradrenaline (NA) was prevented either by the alpha1-adrenergic antagonist prazosin or arachidonyl trifluoromethyl ketone, a selective inhibitor of the 85-110 kDa, sn-2-arachidonyl-specific cytosolic PLA2. The selective alpha1-adrenergic agonist phenylephrine induced a concentration- and time-dependent increase in glycerophosphoinositol (GroPIns) and glycerophosphoinositol 4-phosphate (GroPIns4P) in rat right ventricle slices prelabelled with D-myo-[3H]inositol. In electrically driven strips of rat right ventricles, prelabelled with D-myo-[3H]inositol, the positive inotropic effect induced by 20 microM NA in the presence of propranolol was accompanied by the formation of GroPIns and GroPIns4P. The concentration of the formed GroPIns4P (1.33+/-0.12 microM, N = 6) was similar to that previously reported to inhibit the Na+/Ca2+ exchanger in cardiac sarcolemmal vesicles (Luciani S, Antolini M, Bova S, Cargnelli G, Cusinato F, Debetto P, Trevisi L and Varotto R, Biochem Biophys Res Commun 206: 674-680, 1995). These findings show that the stimulation of alpha1-adrenoceptors in rat heart is followed by an increase in the formation of GroPIns4P, which may contribute to the positive inotropic effect of alpha1-adrenergic agonists by inhibition of the Na+/Ca2+ exchanger.

Recent developments in glycine antagonists.

This paper covers the relevant scientific and patent literature published in the last two years concerning different classes of glycine antagonists and their potential application to therapeutic targets. Many of the molecules described here are approaching the final stages of clinical studies.

Primary osteosarcoma of the uterine corpus. Report of a case and critical review of the literature.

Uterine osteosarcoma represents an extremely rare pure heterologous sarcoma of the uterus. In the present case osteosarcoma occurred primarily in the uterine cavity of a 56-year-old woman. The tumor was anaplastic and the presence of different proliferative patterns caused differential diagnostic problems with various malignant tumor types. The osteoid features of extracellular matrix were demonstrated by electron microscopy. Clinical and pathological features of previously reported cases of uterine osteosarcoma are critically reviewed.

Plateletpheresis during plasma collection.

New systems for collection of platelet concentrate (PC) and platelet poor plasma (PPP) are presently available. The aim of our work was to test the possibility of preparing PC routinely from normal plasma donors in a minimum amount of time and, at the same time, providing a second product that can be used as source-plasma or fresh-frozen plasma. Over a 3 year period (from 1990 to 1992) we performed 3503 procedures using 2 Haemonetics PCS machines (1236 procedures) and 3 Autopheresis-C (2267 procedures). With the PC produced we were able to satisfy all the requests coming from the hospitals of our region. The platelet yield was 1.95 x 10(11) with PCS and 3.2 x 10(11) with Auto-C in a PC volume of 150 and 200 ml respectively; collection times were quite similar (56 and 63 min). The results show that plasma-plateletpheresis is an efficient and competitive system. Regarding platelet yield, the best results were obtained with the Auto-C.

Uptake of chromate by rat thymocytes and role of glutathione in its cytoplasmic reduction.

1. Chromate is taken up by rat thymocytes over a wide range of extracellular chromate concentrations (0.074 +/- 5.0 mM). 2. Chromate uptake followed Michaelis-Menten kinetics and was inhibited by 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulphonic acid, suggesting that the anion carrier was responsible for the uptake by rat thymocytes. 3. The decrease in chromate uptake by the thiol(SH)-blocking agent diethyl maleate, the increased chromate uptake caused by the thiol-protecting agent dithiothreitol, and the reduction of glutathione/glutathione disulphide ratio indicated that the maintenance of the integrity of SH-groups greatly influenced the uptake and reduction of Cr(VI), and that glutathione may be responsible for the intracellular reduction of Cr(VI) to Cr(III).

Diamide: positive inotropic effect in isolated atria and inhibition of Na+/Ca2+ exchange in cardiomyocytes.

The influence of frequency of stimulation and external calcium on the positive inotropic response of guinea-pig left atria to diamide and the inhibitory action on Na+/Ca2+ exchange activity of rat cardiomyocytes by this oxidant of sulphhydryl groups have been investigated. Diamide (50-500 microM) induces a concentration-dependent positive inotropic effect which is more pronounced when atria are driven at 1.0 Hz rather than at 0.5 and 0.1 Hz, and are bathed in 2.72 mM rather than in 1.36 mM external calcium. A decrease in the positive inotropic effect at 35 degrees C with respect to 29 degrees C is also observed. In addition, diamide in positive inotropic concentrations (100-300 microM) significantly reduces Na+/Ca2+ exchange activity and cytoplasmic glutathione levels in adult rat cardiomyocytes. The thiol reducing agent dithiothreitol either reverses or prevents diamide effects both in isolated atria and cardiomyocytes, suggesting that the actions of diamide are correlated to its property to oxidize sulphhydryl groups to disulphides. In view of the functional importance of Na+/Ca2+ exchange in myocardial contractility, it is proposed that diamide may increase the heart force of contraction by an inhibition of the sarcolemmal Na+/Ca2+ exchange activity.

Effect of amiloride on sodium-calcium exchange activity in rat cardiac myocytes.

The effect of amiloride on Na+/Ca2+ exchange activity and adenylate energy charge in isolated rat cardiac myocytes has been studied. Amiloride inhibits Na+/Ca2+ exchange activity in rat cardiac myocytes with an IC50 of 1.76 mM when added to the external side of the cell membrane, whereas it is a weaker inhibitor when present at the cytoplasmic side. The adenylate energy charge in rat cardiac myocytes is unaffected by amiloride.

[Dipyridamole test and myocardial scintigraphy with Tl-201 in the diagnosis of myocardial ischemic pathology]. / Il test al dipiridamolo e la scintigrafia miocardica con 201-Tl nella diagnosi della patologia ischemica miocardica.

We studied 19 consecutive subjects affected by effort angina using following tests: ecg stress test, stress 201-Tl scan, coronary arteriography; 201-Tl scan, coronary arteriography, hemodynamic, echo 2 D, ecgraphic monitoring during Dipyridamole test (D). Basing on coronary arteriography results we divided patients; in the group A (10 patients with significant stenoses greater than or equal to 50%) stress ecg and scintigraphy were positive in 9 patients; Dipyridamole test induced angor and ecgraphic changes in 5 patients and in 4 left ventricle wall motion disorders, 201-Tl scan was positive in all 9 patients tested. In the group B (9 subjects with no significant stenosis) ecgraphic changes were observed in 2 subjects and 201-Tl scan was positive in 6 subjects; D induced in 2 cases angor, in 1 case ecgraphic changes, in 1 case left ventricle wall motion disorders and the same 201-Tl defects in 6 previously individualized patients. In both groups we observed at coronary arteriography during D identical findings in comparison with the immediately before performed. In our experience D infusion is confirmed as provocative test of ischemia. The same ischemic pattern observed at stress and Dipyridamole scintigraphy in patients with no significant coronary stenosis suggests as pathogenetic mechanism the regional lack of dilatory reserve.

[3H]5,7-dichlorokynurenic acid recognizes two binding sites in rat cerebral cortex membranes.

Binding of [3H]5,7-dichlorokynurenic acid ([3H]DCKA), a competitive antagonist of the strychnine-insensitive glycine site of the N-methyl-D-aspartate (NMDA) receptor channel complex, was characterized in synaptic plasma membranes from rat cerebral cortex. Non linear curve fitting of [3H]DCKA saturation and homologous displacement isotherms indicated the existence of two binding sites: a specific, saturable, high affinity site, with a pKD value of 7.24 (KD = 57.5 nmol/l) and a maximum binding value (Bmax) of 6.9 pmol/mg of protein and a second site, with micromolar affinity. The pharmacological profile of both binding components was determined by studying the effect on [3H]DCKA and [3H]glycine binding of a series of compounds known to interact with different excitatory and inhibitory amino acid receptors. These studies confirmed the identity of the high affinity site of [3H]DCKA binding with the strychnine-insensitive glycine site of the NMDA receptor channel complex. 3-[2-(Phenylaminocarbonyl)ethenyl]-4,6-dichloroindole-2-carb oxylic acid sodium salt (GV 150526A), a new, high affinity, selective glycine site antagonist (1), was the most potent inhibitor of this component of binding (pKi = 8.24, Ki = 5.6 nmol/l). The low affinity component of [3H]DCKA binding was insensitive to the agonists glycine and D-serine and the partial agonist (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA 966), though recognised by glycine site antagonists. The precise nature of this second, low affinity [3H]DCKA binding site remains to be elucidated.

Malignant schwannoma of the submandibular gland. A case report.

The first case of malignant schwannoma of the submandibular gland in a 23-year-old man with neurofibromatosis is reported. Light microscopy showed typical features of neurogenic sarcoma and an immunocytochemical study confirmed the schwannian differentiation of the neoplasm. The patient is still well without evidence of metastases or local recurrence of the tumor 80 months after the excision of the neoplasm.

Analogues of 4,5-bis(3,5-dichlorophenyl)-2-trifluoromethyl-1H-imidazole as potential antibacterial agents.

A preliminary exploration of analogues of 4,5-bis(3,5-dichlorophenyl)-2-trifluoromethyl-1H-imidazole, 1, as novel antibacterial agents was carried out to determine the basic features of the structure responsible for the observed biological activity. The presence of two aryl rings, the imidazole NH and either a good electron withdrawing group or an aldehyde or amino group at C-2 were required for good levels of activity against methicillin resistant Staphylococcus aureus (MRSA).

Effects of left bundle branch block on left ventricular function in apparently normal subjects. Study by equilibrium radionuclide angiocardiography at rest.

To determine the independent effects of left bundle branch block (LBBB) on global and regional left ventricular (LV) function we performed equilibrium radionuclide angiocardiography at rest in 3 patients with chronic LBBB (group I, mean age 53.6 years and in 6 patients with intermittent LBBB (group II, mean age 41.5 years). All patients were judged to have an apparently normal heart. In 2 of 3 patients of group I a LV ejection fraction lower than 50% was observed, and in all 3 patients septal motion abnormalities were present. In all patients of group II the global LV ejection fraction was normal during normal conduction and decreased during LBBB; the inferoapical regional ejection fraction decreased in 5 of 6 cases and the posterolateral regional ejection fraction in 3 of 6 cases. Moreover, septal hypokinesis was observed both during normal and abnormal conduction in all group II patients. These findings seem to confirm that LBBB, chronic or intermittent, is able to deteriorate LV performance at rest, even in patients with an otherwise normal heart.

Inhibition of cardiac sarcolemmal sodium-calcium exchanger by glycerophosphoinositol 4-phosphate and glycerophosphoinositol 4-5-bisphosphate.

The enrichment in phosphatidylinositol 4-phosphate and phosphatidylinositol 4-5-bisphosphate of cardiac sarcolemmal vesicles stimulate Na+/Ca2+ exchange activity. On the contrary the deacylation products of polyphosphoinositides are powerful inhibitors of Na+/Ca2+ exchange: half maximal inhibition of 1.6 and 2.1 microM have been observed for glycerophosphoinositol 4-phosphate and glycerophosphoinositol 4-5-bisphosphate, respectively. The data indicate a bidirectional regulation of Na+/Ca2+ exchanger and suggest that phosphorylated glycerophosphoinositols can be regarded as novel signal transducers of intracellular Ca2+ regulation in heart cell.

Effects of uncomplicated coronary artery bypass graft surgery on global and regional left ventricular function at rest. Study by equilibrium radionuclide angiocardiography.

To evaluate the effects of uncomplicated revascularization surgery on resting global and regional left ventricular function we studied 34 patients, enrolled consecutively, by radionuclide angiocardiography. After surgery, we found no significant change in global left ventricular ejection fraction; this was true even in the subgroup of 14 patients who developed paradoxical septal motion. This finding indicates that the development of paradoxical septal motion after uncomplicated cardiac surgery does not compromise global left ventricular function. Both in the subgroup of patients with paradoxical septal motion and in the subgroup without paradoxical septal motion regional ejection fraction calculations showed the same postoperative pattern consisting of increase of the proximal and distal posterolateral regional ejection fraction, increase in the inferoapical regional ejection fraction and unchanged proximal and distal septal regional ejection fraction. In our patients paradoxical septal motion is not due to pericardial effusion, conduction disturbance, septal ischemia or infarction. Our data suggest that the anteromedial translation of the entire heart during systole, due to surgical removal of constraints, may account for both the false improvement of posterolateral and inferoapical regional wall motion and the development of paradoxical septal motion.

The role of indium-111 antimyosin (Fab) imaging as a noninvasive surveillance method of human heart transplant rejection.

The identification of rejection after heart transplantation in patients receiving cyclosporine immunosuppressive therapy requires the endomyocardial biopsy, an invasive method associated with a finite morbidity. To evaluate the role of indium-111 antimyosin (Fab) scintigraphy as a noninvasive surveillance method of heart transplant rejection, the Fab fragment of murine monoclonal antimyosin antibodies labeled with indium-111 was administered intravenously in 30 scintigraphic studies to 10 consecutive heart transplant recipients. Endomyocardial biopsy specimens were obtained 72 hours after each scintigraphic study. Nineteen scintigraphic studies had negative findings; no false negative finding was obtained. Eleven antimyosin scintigraphic studies had positive findings, and in these studies endomyocardial biopsy revealed mild rejection in two cases, moderate acute rejection with myocyte necrosis in two cases, myocyte necrosis as a consequence of ischemic injury in six cases, and possibly cytotoxic damage in one case. Antimyosin scintigraphy may represent a reliable screening method for the surveillance of heart transplant patients. In the presence of a negative finding from antimyosin scintigraphy, it may be possible to avoid endomyocardial biopsy. Conversely, in patients who have a positive finding from antimyosin scintigraphy, the endomyocardial biopsy is mandatory to establish the definitive diagnosis by histologic examination of the myocardium.

Prevalencia al nacimiento de aberraciones cromosómicas en el Hospital Clínico de la Universidad de Chile. Período 1990-2001 / Prevalence of chromosomal aberrations at birth in the Clinical Hospital of Universidad de Chile, 1990-2001

BACKGROUND: A cytogenetical study should be performed to every newborn with malformations. If a chromosomal aberration is found, parents must be studied to give an adequate genetic advise. AIM: To study the frequency of chromosomal aberrations in newborns with malformations. PATIENTS AND METHODS: In the Clinical Hospital of the University of Chile all malformations in newborns are registered, as part of the Collaborative Latin American Study of Congenital Malformations (ECLAMC). The frequency of chromosomal aberrations, determined by cytogenetical studies, was determined in newborns with malformations. RESULTS: In the study period, there were 32,214 births. Of these, 2,268 live newborns and 43 stillbirths had malformations. Ninety nine children with malformations had chromosomal aberrations (4.3 per cent). Trisomy 21 was the most common aberration with a rate of 23/10,000 births, followed by trisomy 18 with a rate of 4/10,000 and trisomy 18 with a rate of 1.2/10,000. Ninety four percent of these children were born alive and 16.1 per cent died before discharge from the hospital. The masculinity indexes for Down syndrome and for trisomy 18 were 0.38 and 0.61 respectively. CONCLUSIONS: A higher frequency of female gender for trisomy 21 and male gender for trisomy 18 has not been reported previously.