Biomedical subjects

S Mohammad

Publications and source records attributed to S Mohammad.

8 recordsLinked to original sources

PubMed1998

Osmosensitive C1- currents and their relevance to regulatory volume decrease in human intestinal T84 cells: outwardly vs. inwardly rectifying currents.

1. The swelling-activated outwardly rectifying Cl- current (ICl(swell)) recorded in T84 human intestinal cells was completely blocked by 10 microM tamoxifen, while 300 microM Cd2+ had no effect. 2. A ClC-2-like, inwardly rectifying Cl- current was activated after strong hyperpolarization in T84 cells. This current was completely inhibited by 300 microM Cd2+, unaffected by 10 microM tamoxifen, and its magnitude increased slightly in response to cell swelling under hyposmotic conditions. However, the swelling-dependent modulation occurred only after prior activation by hyperpolarizing voltages. 3. T84 cells behaved initially close to perfect osmometers in response to changes in external osmolalities between +20 and -30 %. The cells underwent full regulatory volume decrease (RVD) within 16 min when exposed to 30 or 10 % hyposmotic shocks. 4. Pharmacological tools were used to determine the anionic pathway(s) involved in RVD in T84 cells. Tamoxifen (10 microM), 1,9-dideoxyforskolin (DDFSK; 100 microM) and 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS; 100 microM) blocked RVD while 300 microM Cd2+ had no effect upon RVD following a 30 % hyposmotic shock. The RVD response was similarly unaffected by Cd2+ when cells were exposed to a smaller (10 %) hyposmotic shock. 5. In conclusion, these data show that the anionic pathway primarily activated by cell swelling and relevant to RVD in T84 cells is the tamoxifen-, DDFSK- and DIDS-sensitive ICl(swell) and not the hyperpolarization-activated, Cd2+-sensitive Cl- current associated with the ClC-2 Cl- channel.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1998

Evaluation of the anticonvulsant profile of progesterone in male amygdala-kindled rats.

While there is clinical evidence that progesterone has anticonvulsant activity in women with complex partial seizures, previous studies on the anticonvulsant effect of progesterone in experimental animal models are inconclusive. Moreover, the effect of progesterone on seizure parameters in fully amygdala-kindled rats which best resemble complex partial seizures has not been evaluated. Therefore, in the present work the anticonvulsant effect of progesterone at doses of 10, 30, 60 and 75 mg/kg in fully amygdala-kindled male rats was studied. Only at the high and sedative dose of 75 mg/kg, progesterone suppressed behavioral seizures and afterdischarges elicited 10 min after intraperitoneal (i.p.) administration. Pretreatment with the progesterone antagonist, 17beta-hydroxy-11beta-(4-dimethylaminophenyl)-17alpha-(prop- 1-ynyl)-estra-4,9-dien-3-one (RU 38486) at the dose of 3 mg/kg did not inhibit the anticonvulsant activity of progesterone, while pretreatment with the GABA(A) receptor antagonist, bicuculline (2 mg/kg) blocked the anticonvulsant effect of progesterone. Neither RU 38486 nor bicuculline had any effect on the seizure parameters. These findings suggest that only at large and sedative doses, progesterone has some anticonvulsant activity in male amygdala-kindled rats which may be partly mediated via the GABA(A) receptor complex interaction.

Amygdala↗

PubMed1997

Blockage of the HERG human cardiac K+ channel by the gastrointestinal prokinetic agent cisapride.

Cisapride, a gastrointestinal prokinetic agent, is known to cause long Q-T syndrome and ventricular arrhythmias. The cellular mechanism is not known. The human ether-á-go-go-related gene (HERG), which encodes the rapidly activating delayed rectifier K+ current and is important in cardiac repolarization, may serve as a target for the action of cisapride. We tested the hypothesis that cisapride blocks HERG. The whole cell patch-clamp recording technique was used to study HERG channels stably expressed heterologously in HEK293 cells. Under voltage-clamp conditions, cisapride block of HERG is dose dependent with a half-maximal inhibitory concentration of 6.5 nM at 22 degrees C (n = 25 cells). Currents rapidly recovered with drug washout. The onset of block by cisapride required channel activation indicative of open or inactivated state blockage. Block of HERG with cisapride after channel activation was voltage dependent. At -20 mV, 10 nM cisapride reduced HERG tail-current amplitude by 5%, whereas, at + 20 mV, the tail-current amplitude was reduced by 45% (n = 4 cells). At -20 and + 20 mV, 100 nM cisapride reduced tail-current amplitude by 66 and 90%, respectively. We conclude that cisapride is a potent blocker of HERG channels expressed in HEK293 cells. This effect may account for the clinical occurrence of Q-T prolongation and ventricular arrhythmias observed with cisapride.

Cation Transport Proteins↗

PubMed1996

Torsade de pointes with an antihistamine metabolite: potassium channel blockade with desmethylastemizole.

OBJECTIVES: Proarrhythmic effects have been observed with the selective histamine1 (H1) receptor antagonist drug astemizole, a widely prescribed antihistamine. The metabolites of astemizole and those of other antihistamine compounds have not been implicated as causative agents of cardiac arrhythmias. The purpose of this study was to examine whether desmethylastemizole, the principal metabolite of astemizole, blocks delayed rectifier potassium (K+) channels. BACKGROUND: QT interval prolongation and torsade de pointes are associated with astemizole intake and have been ascribed to block the repolarizing K+ currents, specifically the rapidly activating component of the delayed rectifier iKr. Astemizole undergoes extensive first-pass metabolism, and its dominant metabolite, desmethylastemizole, has a markedly prolonged elimination time. We report the clinical observation of QT prolongation and torsade de pointes in a patient with undetectable serum concentrations of astemizole (< 0.5 ng/ml) and "therapeutic" concentrations of desmethylastemizole (up to 7.7 ng/ml or 17.3 nmol/liter). METHODS: The perforated patch clamp recording technique was used to study the effects of desmethylastemizole (20 nmol/liter) on action potentials and iKr in isolated rabbit ventricular myocytes. RESULTS: Desmethylastemizole produced action potential prolongation and the induction of plateau early afterdepolarizations. Under voltage clamp conditions, desmethylastemizole suppressed iKr amplitude by approximately 65%. The drug E-4031 (100 nmol/liter), which selectively blocks iKr, had a similar effect on current amplitude. CONCLUSIONS: Desmethylastemizole, the major astemizole metabolite, blocks the repolarizing K+ current iKr with high affinity. The clinical observation of QT prolongation and torsade de pointes found with astemizole intake may principally be caused by the proarrhythmic effects of its metabolite desmethylastemizole.

Aged↗

PubMed1996

Hemopericardium with cardiac tamponade after intravenous thrombolysis for acute myocardial infarction.

This report presents 2 patients with hemopericardium and tamponade encountered among a group of 26 patients who had received intravenous thrombolytic therapy for acute myocardial infarction during an 8-month time span. Both responded promptly to pericardiocentesis and pericardial catheter drainage. It is suggested that this rarely reported complication has the potential of occurring more frequently with increasing use of thrombolytics followed by aggressive anticoagulant regimens.

Aged↗

PubMed1995

Autosomal dominant thrombocytopenia with microthrombocytes: a family study.

A family demonstrating autosomal dominant thrombocytopenia is described. A 28-year-old Malay housewife was found to have a platelet count of 40 x 10(9)/l with a low mean platelet volume (6.8 fl) while being investigated prior to ovarian cystectomy. The bone marrow was consistent with immune thrombocytopenia but she failed to respond to appropriate therapy. Five siblings, one parent and one nephew have easy bruising and platelet counts of 39-82 x 10(9)/l. Platelet aggregation studies excluded a major functional defect. Survival of homologous platelets in the circulation was normal. Familial thrombocytopenias are rare but important to differentiate from the common acquired thrombocytopenias in order to spare the patient unnecessary treatments.

Adult↗

PubMed1994

Aortic valve replacement with pulmonary homografts. Early experience.

The increasing use of the aortic homograft as aortic valve substitute and the limited availability of donor valves prompted us to consider the pulmonary homograft as an alternative substitute for aortic valve replacement. The aim of our study is to compare the ultrastructural and biomechanical properties of pulmonary homograft leaflets with those of their aortic counterpart and to present the early results of using the pulmonary homograft for aortic valve replacement. Light and transmission electron microscopy have shown that pulmonary homograft leaflets are thinner than the aortic with a lesser content of elastic tissue in the ventricularis layer. However there were no substantial differences in the ultrastructure. Uniaxial tensile tests were done on 69 cusps from human pulmonary and aortic valves using an Instron testing machine. The strain at 200 KPa was found to be similar for both pulmonary and aortic leaflets (8.20% +/- 2.87% versus 8.98% +/- 1.90%) cut circumferentially. Radial strips appear to be more extensible in pulmonary leaflets than in aortic (32.6% +/- 7.5% and 28.6% +/- 11.1%, respectively). The ultimate tensile strength for circumferential strips was found to be similar for both aortic and pulmonary valves (1460 +/- 857 kPa versus 1450 +/- 689 kPa), but there was relatively little difference between the radial strips (295 +/- 95 kPa versus 252 +/- 104 kPa). A total of 123 patients whose ages ranged between 13 and 78 years received either fresh antibiotic sterilized or cryopreserved pulmonary homografts for aortic valve replacement. The pulmonary homograft was inserted in place of the patient's diseased aortic valve by using one of two different techniques: freehand in the subcoronary position or as a "short cylinder" inside the aortic root. There was three hospital deaths (2.43%; 70% confidence limits = 1.08% to 4.83%). Cumulative follow-up was 184 patient-years (range 1 to 39 months). All surviving patients have been followed up with serial color flow Doppler echocardiography. There were no late deaths. Actuarial late survival was 97.5% (70% confidence limits = 95.7% to 98.6%) at 3 years. Four patients (2.2%/pt-yr) underwent reoperation because of severe aortic regurgitation (1, 4, 12, and 15 months after the operation) because of technical problems (mismatch in size between the pulmonary homograft and aortic anulus) in three patients and probably because of graft rejection in one patient. At 3 years the actuarial rate of freedom from reoperation was 95.5% (70% confidence limits = 92.7% to 97.3%). Mild aortic regurgitation has been detected in three patients (2.6%). No patients incurred thromboembolic episodes or infective endocarditis.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗

PubMedDate not supplied

The Baumann angle in supracondylar fractures of the distal humerus in children.

Radiologic assessment of fracture reduction in displaced supracondylar fractures of the elbow in children is notoriously difficult. The Baumann angle is often used as a guide to the adequacy of reduction. This is based on the assumption that the Baumann angle has a constant relationship to the carrying angle in a displaced fracture. The effect of rotation on the relationship between these angles has not been studied in detail. Computed tomography (CT) studies have shown that < or = 40 degrees of rotation may still be present after closed manipulation of a supracondylar fracture. A computer programme analysing vectors was designed to study the relationship between the Baumann angle and the carrying angle with predetermined displacements of the distal fragment. The relationship between the Baumann angle and the carrying angle was thus defined and, in contrast to the literature, found to be more complex than previously appreciated. The Baumann angle was found to be an inaccurate indicator of the carrying angle when treating displaced supracondylar fractures.

Child↗