Effect of cimetidine, bicarbonate and glucose on the bioavailability of different formulations of praziquantel

The effects of cimetidine, bicarbonate and glucose on the bioavailability of the two brands of praziquantel (CAS 55268-74-1) available in Egypt were studied in normal healthy volunteers. Brand 1 when coadministered with cimetidine showed elevated concentration of the drug at all time intervals. The difference was statistically significant at 3, 4, 6 and 8 h following treatment. On the other hand coadministration of cimetidine with brand 2 (Distocide) showed elevated concentration of the drug 1 h post treatment. Analysis of the pharmacokinetic parameters revealed insignificant difference comparing brand 1 versus brand 1 plus cimetidine. Significant differences were observed between the elimination rate constant Ke (h-1) for brand 2 (0.017 +/- 0.004) alone versus brand 2 plus cimetidine (0.006 +/- 0.001). Coadministration of bicarbonate or glucose with either brand 2 or brand 1 tended to depress the serum concentration of praziquantel. Possible explanations of these findings are discussed.     

Pharmacokinetics and disposition of triptonide in rats

Triptonide, isolated from Tripterygium wilfordii Hook., was found to show significant antiinflammatory, immunosuppression and antitumor activities. A RP-HPLC method was applied to determine the plasma concentration of triptonide at different times in rats. Concentration-time curves after i.v., 0.7, 1.4 and 2.8 mg.kg-1 of triptonide were fitted to a two-compartment open model with T1/2 alpha of 0.167-0.195 h and T1/2 beta of 4.95-6.49 h. The area under curves (AUCs) were linearly related to the dosages (gamma = 0.9894). Systematic clearances (CLs) were independent of dosages. Mean residence time (MRT) of the three doses was 3.26-5.14 h by noncompartmental (the statistical moment method) analyses. The tissue distribution of triptonide in rats appeared to be wide throughout the body. The triptonide levels were high in the lung and liver, moderate in the heart, kidney, spleen and muscle and low in the testis, intestine and brain. Data of the urine and bile excretion indicated that only a small percent of unchanged triptonide was excreted. Plasma protein binding of triptonide rate was about 75%.     

Hodgkin''s disease of the esophagus

The effects of tilisolol, a nonselective beta-adrenoceptor blocker, on transmembrane ionic currents were studied in single guinea pig ventricular myocytes by using the whole-cell voltage clamp technique. In the absence of beta-adrenergic stimulation, 10 microM tilisolol, a concentration higher than that used in the clinical therapeutic regimen, did not affect the L-type Ca2+ current (ICa), the inwardly rectifying K+ current (IK1), or the delayed rectifying K+ current (IK). In addition, it did not induce currents through the adenosine triphosphate (ATP)-sensitive K+ channels. However, under the nonselective beta-adrenergic stimulation with 1 microM isoproterenol, 1 microM tilisolol almost completely reversed the agonist-induced increase of IK. The increase of ICa by isoproterenol was blocked only by approximately 30% with tilisolol. We concluded that, at therapeutic concentrations (0.01-0.15 microM), tilisolol is a pure beta-adrenoceptor antagonist that has no direct effects on the transmembrane ionic currents of mammalian ventricular myocytes, such as ICa, IK1, or IK. Comparison of the dose-dependent effects of tilisolol on ICa and IK suggested that tilisolol may selectively inhibit catecholamine-induced increase of IK at the therapeutic concentrations. The virtually selective inhibition of IK, leaving ICa intact, may be favorable to prevent the catecholamine-induced arrhythmia without inhibiting contraction.     

Manifolds in random media: Multifractal behavior

1. Corticotropin-releasing factor (CRF) has been suggested to regulate many responses to stress. The authors investigated the effect of single and repeated stress on brain CRF immunoreactivity (CRF-ir) and plasma corticosterone levels in rats, using radioimmunoassay. 2. Single immobilization stress significantly increased plasma corticosterone levels but did not change CRF-ir in the discrete brain regions at all. Repeated immobilization stress (a 180 min session, once a day for 10 days) did not affect plasma corticosterone levels at 24 hr poststress. However, it increased CRF-ir in the median eminence (ME) though not in the other brain regions. 3. The increased level of CRF in the ME after chronic intermittent stress suggests that repeated stimulation by stress may increase the storage pool of CRF in the ME.     

A hybrid computational model for ultrasound phased-array heating inpresence of strongly scattering obstacles

A computationally efficient hybrid ray-physical optics (HRPO) model is presented for the analysis and synthesis of multiple-focus ultrasound heating patterns through the human rib cage. In particular, a ray method is used to propagate the ultrasound fields from the source to the frontal plane of the rib cage. The physical-optics integration method is then employed to obtain the intensity pattern inside the rib cage. The solution of the matrix system is carried out by using the pseudo inverse technique to synthesize the desired heating pattern. The proposed technique guides the fields through the intercostal spacings between the solid ribs and, thus, minimal intensity levels are observed over the solid ribs. This simulation model allows for the design and optimization of large-aperture phased-array applicator systems for noninvasive ablative thermal surgery in the heart and liver through the rib cage     

Case report: successful obliteration of a bleeding duodenal varix using endoscopic ligation

BACKGROUND: To determine the concentration of cytokines having an immunomodulating effect in the first trimester in women who subsequently developed preeclampsia. METHODS: The serum concentrations of IL-10, TNFalpha, IL-6 and IL-2R were determined in ten women who later developed severe preeclampsia and in ten healthy controls. The groups were compared with the Mann-Whitney U test. RESULTS: The IL-2R concentration was significantly higher in the women who later developed preeclampsia than in normal patients (p = 0.028). No significant differences were detected between the groups with respect to the other evaluated cytokines. CONCLUSION: Elevated IL-2R concentrations in maternal serum as early as in the first trimester may be a sign of immunological maladaptation and might be associated with a disturbance of trophoblastic invasion.