Inhibition of platelet aggregation by novel triphenylethylene analogs

The present study has evaluated the effect of some newly synthesized triphenylethylene (TPE) analogs on platelet arachidonic acid metabolism and function. All compounds tested inhibited arachidonic acid induced platelet aggregation and several were superior to aspirin in their relative potency. Introduction of a carboxyl function into the alpha-ring, which should enhance binding according to proposed structural models for cyclooxygenase inhibitors, was not found to be beneficial. Increased structural rigidity, which resulted from covalent linkage of two aromatic rings in this series, did not eliminate anti-aggregatory properties.     

Interaction of calmodulin with iodothyronines: effect of iodothyronines on the calmodulin activation of cyclic AMP phosphodiesterase

The interaction between calmodulin and iodothyronines and the effect of iodothyronines on the calmodulin activation of cyclic AMP phosphodiesterase were investigated. Binding of [L-125I]triiodothyronine to calmodulin from pig brain, studied by equilibrium dialysis, was dependent on Ca2+, was saturable and reversible, with an apparent Kd of 2.79 microM and binding capacity of 0.5 nmol/20 micrograms of calmodulin L- and D-thyroxine, D-triiodothyronine and tetrac displaced [L-125I]triiodothyronine at concentrations of 8-10 microM; triac, 3,3'-diiodothyronine and reverse-triiodothyronine were weak displacers. In the presence of the antipsychotic drug trifluoperazine, binding decreased in a dose-related manner. Ultraviolet irradiation of calmodulin in the presence of trifluoperazine reduced the binding of [L-125I]triiodothyronine to calmodulin irreversibly. Calmodulin activation of cyclic AMP phosphodiesterase decreased when iodothyronines were bound to calmodulin; the calmodulin-L-triiodothyronine complex was the most active among the stereoisomers of thyroxine and triiodothyronine. These results suggest that, when triiodothyronine was bound to Ca2+-calmodulin, the activation of cyclic AMP phosphodiesterase by the latter is suppressed.     

Zero-Order Release Formulation of Oxprenolol Hydrochloride with Swelling and Erosion Control

Zero-order release of oxprenolol hydrochloride was obtained by controlling the swelling and erosion of the matrix. This formulation involves only mixing of drug, hydroxypropylmethylcellulose (HPMC), and sodium carboxymethylcellulose (Na CMC) at the ratio of 1:0.4:1.6, respectively, and compressing the mixture directly into tablets. The in vitro release pattern from this optimized matrix tablet was reproducible. Accelerated stability studies revealed that the optimized formulation remains stable for an approximately 2-year shelf life. This sustained-release (SR) tablet was evaluated in dogs, and for comparison a conventional (CV) formulation was also given at the same dose level. Plasma oxprenolol levels were monitored by a sensitive and specific high-performance liquid chromatographic (HPLC) method. Significant differences in the pharmacokinetic parameters, i.e., lower C _max, higher values of t _max, MRT, AUC, and plasma concentration at 24 hr, and nearly constant plasma levels over 12 hr, indicated that the SR matrix tablet is superior to the CV rapid-releasing formulation. The in vitro release parameters and in vivo pharmacokinetics correlated well.     

Lobster-claw syndrome.

Lobster-Claw syndrome is a rare autosomal dominant, hand-foot malformation with Oro-dental features. This is a rare condition and from the available reports so far, cases being reported are less than 1%. Most reports have focused on the hand-foot deformity of this syndrome. This paper highlights the typical Oro-dental features associated with this syndrome such as retained deciduous teeth, hypodontia and variation in crown size, arch length and arch width.     

Immunohistochemical identification of tissue factor in solid tumors.

Patients with cancer experience a much higher than expected incidence of thromboembolic disorders, commonly referred as Trousseau syndrome. Although this association has been well documented, the etiology of the hypercoagulable state is not known. The expression on tumor cells of tissue factor (TF), a membrane-bound lipoprotein that functions as a cofactor to factor VIIa in the initiation of the extrinsic pathway of blood coagulation, has been postulated as a possible mechanism. Whereas the distribution of TF in normal tissues is known, no large survey of TF expression in malignant tissues has been reported. In this study a polyclonal, monospecific rabbit anti-human TF IgG was used for immunohistochemical localization of TF antigen in 85 different tumor specimens. In general, cell types which normally express TF continued to do so after malignant transformation (41 of 60 epithelial tumor specimens were positive for TF). Tumors of nonepithelial origin frequently lacked TF, with only 3 of 19 specimens containing evidence of TF antigen. In addition five of six benign tumors did not express TF. Many tumor types commonly associated with Trousseau syndrome, for example lung, pancreatic, breast, colon and gastric carcinomas, stained positively for TF. Based on this survey, it appears that TF expression by tumors may be an important factor in the pathogenesis of a hypercoagulable state in some patients with cancer.     

Does multi-vessel off-pump coronary artery bypass grafting reduce post operative morbidity compared to on-pump CABG?

Background Cardiopulmonary bypass (CPB) may contribute to the complications and it is assumed that eliminating cardiopulmonary bypass has the potential of reducing post operative morbidity after coronary artery bypass grafting (CABG). The study was carried out to compare mortality and morbidity in the off-pump and on-pump CABG groups. Methods We prospectively analysed 200 patients undergoing CABG. Group A consists of 100 patients underwent multi-vessel off-pump CABG and group B consists of 100 patients underwent CABG with CPB. The incidence of complications (mortality, re-exploration for bleeding, myocardial infarction, atrial fibrillation, neurological events, new onset renal failure (s. creatinine>1.6 mg/dL) pulmonary complications, length of ICU stay and hospital stay were recorded, analysed and compared. Results OPCAB patients received 2.73±0.61 grafts/patient and on-pump CABG patients received 3.39±0.75 grafts/patient (p value<0.00001). There was no significant statistical difference in mortality, incidence of stroke between OPCAB and CABG with CPB patients. Length of ICU stay was 32.84±4.22 vs 44.85±7.18 hrs (p value<0.00001) and hospital stay was 6.52±0.69 vs 7.94±0.92 days (p value<0.00001) between group A and group B respectively. Incidence of atrial fibrillation was less in OPCAB group 7% vs 12% although it was statistically not significant (p value 0.33). It was observed in our study that there was no significant deference in worsening of existing renal failure between on-pump CABG and OPCAB 6% vs 2% (P value 0.28). Blood utilization was significantly less in OPCAB group (p value<0.001). Conclusion There was no statistically significant difference in terms of mortality, incidence of stroke and new onset renal failure in both groups. But there was lesser incidence of post operative atrial fibrillation, worsening of existing renal failure in off-pump group though statistically not significant. There was significant reduction in blood utilization, length of ICU and hospital stay in OPCAB group.