Comparison of pH-stat and alpha-stat cardiopulmonary bypass on cerebral oxygenation and blood flow in relation to hypothermic circulatory arrest in piglets

Melagatran, a new, competitive and rapid inhibitor of thrombin with a molecular mass of 429 Da is described. Melagatran is well tolerated when administered in very high doses, and the oral bioavailability in the dog is relatively high. The aim of the study was to determine, in the preclinical setting, the degree of selectivity against the fibrinolytic system required for entering the clinical development phase. Melagatran was compared with two structurally similar thrombin inhibitors, inogatran and H 317/86. The potent inhibition of thrombin by melagatran was demonstrated by a low inhibition constant (Ki) for thrombin (0.002 micromol/l) and prolongation of clotting time to twice the control value in coagulation assays at low concentrations (0.010, 0.59 and 2.2 micromol/l for thrombin time, activated partial thromboplastin time and prothrombin time, respectively). Furthermore, thrombin-induced platelet aggregation was inhibited at the same concentration (IC50-value 0.002 micromol/l) as the Ki-value for thrombin. In two assays of global fibrinolysis, inhibition was observed at a concentration of 1.1 micromol/l in a euglobulin plasma fraction model, while no inhibition was observed at a concentration of < or = 10 micromol/l in a plasma model. In an in vivo model of endogenous fibrinolysis in the rat, inhibition of fibrinolysis was observed at > or = 1.0 micromol/l. In all assays, except the Ki-ratio determinations, the compounds could be graded with regard to selectivity against the fibrinolytic system: inogatran > melagatran > H 317/86. For melagatran, inhibition of fibrinolysis was not observed at concentrations below the upper limit of the proposed therapeutic plasma concentration interval (< 0.5 micromol/l). Thus, melagatran seems to have a sufficient selectivity against the fibrinolytic system, while H 317/86 was considered to be insufficient for clinical development.     

Specificity of the T-cell responses in covalently linked peptides each comprising of a T helper epitope

The selection of T-cell specificities in chimeric peptides comprising of two T helper epitopes (288-302 and 240-252) from the fusion protein of measles virus was investigated. The resulting chimeric peptides (288-P-240 and 240-P-288) were shown to be immunogenic by inducing proliferative responses in both B10.s and C57BL/6 strains of mice. In B10.s mice immunization with the chimeric peptides resulted in proliferative T-cell responses only to the constituent 288-302 peptide, whereas in C57BL/6 mice no proliferative responses to the constituent 288-302 or 240-252 peptides were detected. In vivo competition studies between the 288-302 and 240-252 peptides for binding to the I-As molecule have shown that the peptide 288-302 was dominant in B10.s mice and competed with the non-dominant 240-252 peptide for the induction of an in vivo response. The absence of any proliferative T-cell response to the constituent 288-302 and 240-252 peptides after immunization of C57BL/6 mice with the 288-P-240 or 240-P-288 chimeric peptides, suggests that the dominant T-cell responses might have shifted to newly formed T cell epitope(s) as a result of the covalent linkage of the two peptides. In conclusion, these results indicate that the selection of Th epitopes within chimeric peptides is dependent not only on the amino acid composition of the epitope but also on the context of the epitope within the chimera and the haplotype of the mouse strain used.     

Right and left ventricular dysfunction in patients with severe pulmonary disease

AIM OF STUDY: To measure the effect of specific preoperative information on postoperative anxiety, satisfaction with information, and demand for analgesia, of Chinese males having transurethral resection of the prostate (TURP). DESIGN: A controlled experimental design. The researchers allocated all patients (n = 30) undergoing TURP in a general hospital in Hong Kong, during a 3-month period, to one of two groups. The experimental group (n = 15) received a specific information pamphlet and a general preoperative counselling video. The control group (n = 15) received a video alone. PROCEDURE AND MEASURES: Following ethical approval, a researcher took baseline measures of state and trait anxiety using the Chinese State-Trait Anxiety Inventory (C -STAI). Five days after surgery the researcher administered the C-STAI (A-State), a patients' satisfaction questionnaire, and, recorded requests for analgesia during the first 5 postoperative days. RESULTS: Experimental subjects reported significantly lower anxiety levels post-operatively and a significantly higher level of satisfaction with the preoperative information, than controls. Postoperative demand for analgesia did not significantly differ between groups. CONCLUSIONS: The findings support the importance of providing patients with specific, written preoperative information about their surgery and its effects to minimize their postoperative anxiety levels, and improve their satisfaction with the care provided.     

Antibody responses measured by various serologic tests in pigs orally inoculated with low numbers of Toxoplasma gondii oocysts

OBJECTIVE: To follow antibody responses measured by various serologic tests in pigs orally inoculated with low (< or = 10 oocysts) numbers of Toxoplasma gondii oocysts. ANIMALS: 24, 2- to 3-month-old pigs. PROCEDURE: Pigs (n = 42) were inoculated orally with 10 (14 pigs) or 1 (28 pigs) infective oocysts, and 6 pigs served as uninoculated controls. Blood (serum) samples were obtained at 1- to 3-week intervals until euthanasia. At necropsy, the brain, heart, and tongue of pigs were bioassayed in mice and cats for isolation of T gondii. Modified agglutination test (MAT), using whole, fixed tachyzoites and mercaptoethanol; latex agglutination test (LAT); indirect hemagglutination test (IHAT); Sabin-Feldman dye test (DT); and ELISA were used to evaluate serologic responses to T gondii. RESULTS: T gondii was isolated from tissues of 13 of 14 pigs each fed 10 oocysts, 17 of 28 pigs each fed 1 oocyst, and 0 of 6 control pigs. 29 of 30 T gondii-infected pigs developed antibodies when measured by MAT, DT, and ELISA; the 1 seronegative-infected pig had been fed 10 oocysts and was euthanatized 69 days after inoculation. LAT detected antibodies in 26 of 30 T gondii-infected pigs. IHAT detected antibodies in 11 T gondii-infected pigs. CONCLUSION: MAT, DT, and ELISA were more sensitive serologic assays than LAT and IHAT for detecting antibodies induced by low numbers of T gondii in pigs.     

Tolyporphins J and K, two further porphinoid metabolites from the cyanobacterium Tolypothrix nodosa

Two new porphinoids, tolyporphins J (1) and K (2), have been isolated from the terrestrial cyanobacterium, Tolypothrix nodosa (HT-58-2) and identified by NMR and mass spectral analysis. The activities of tolyporphins J and K in cell sensitization and drug accumulation assays for multidrug resistance (MDR) reversal were compared with those of tolyporphin A. Unusual NMR spectroscopic shifts were observed for tolyporphin J (1) in CDCl3.     

Effects of cytoskeletal inhibitors on the accumulation of vincristine in a resistant human lung cancer cell line with high level of polymerized tubulin

We have previously established a vincristine resistant human lung cancer cell line (PC-9/VCR) by a stepwise exposure of parental line PC-9 to vincristine. In this study the resistant cells showed enhanced vincristine cytotoxicity in the presence of cytochalasin B and D. The increase in cytotoxicity was associated with an enhanced accumulation and a reduced efflux of vincristine. Colchicine and taxol had no effects on vincristine accumulation. Several cytoplasmic proteins were overexpressed in the resistant cells. The two major ones, with molecular weights of 58.8 kDa and 83.2 kDa, were shown by western blotting to be beta-tubulin and actin, respectively. The polymerized tubulin level in the resistant cells was significantly (p < 0.05) higher than that in the parental cells. These results suggest that the cellular cytoskeletons might play an important role in VCR resistance in the PC-9/VCR human lung cancer cell line.     

Coronary artery perforation and delayed cardiac tamponade following balloon coronary angioplasty

A 62-year-old woman who had coronary artery disease and hypertrophic cardiomyopathy received percutaneous transluminal coronary angioplasty and endomyocardial biopsy. She withstood the procedure well. However, delayed pericardial tamponade occurred 2 hours after discharge from the cardiac catheterization laboratory. Despite pericardial drainage with a pigtail catheter and blood transfusion, the patient required emergency surgery. An oozing diagonal branch of the left anterior descending coronary artery was found. Ligation of this small branch stabilized the hemodynamics. Avoidance of improper positioning of the guide wire in the small coronary artery branch is important in preventing arterial wall trauma and subsequent perforation.