Holothurins B(2), B(3), and B(4), new triterpene glycosides from mediterranean sea cucumbers of the genus holothuria

Triterpene glycosides of three species of the Mediterranean sea cucumbers Holothuria polii, Holothuria tubulosa, and Holothuria sp. were studied. Three new monosulfated biosides, holothurins B(2) (1), B(3) (2), and B(4) (3), along with the previously known holothurins A (4) and B (5) were isolated from the sea cucumber H. polii. Triterpene glycosides belonging to holothurin A and B groups were found in H. tubulosa, while only one individual glycoside, holothurin A (4), was isolated from Holothuria sp. Structures of new substances were elucidated on the basis of spectral data (2D NMR and MS). The significance of holothurins as chemotaxonomic markers of the animals belonging to the genus Holothuria and taxonomic status of some representatives of the holothurians studied are discussed.     

Mollisosides A, B1, and B2: minor triterpene glycosides from the New Zealand and South Australian sea cucumber Australostichopus mollis

Three new monosulfated triterpene glycosides, mollisosides A (2), B(1) (3), and B(2) (4), have been isolated from the sea cucumber Australostichopus mollis. Their structures were determined by NMR and mass spectra. The presence of sulfated glycosides in sea cucumbers belonging to the family Stichopodidae is uncommon.     

Phrygiasterol, a cytotoxic cyclopropane-containing polyhydroxysteroid, and related compounds from the pacific starfish Hippasteria phrygiana

The new cyclopropane-containing steroid phrygiasterol (1) and steroid glycoside phrygioside B (2), along with previously known borealoside C (2a) and (20R,24S)-5alpha-cholesta-3beta,6alpha,8,15alpha,24-pentaol (3), have been isolated from the Pacific starfish Hippasteria phrygiana. On the basis of spectroscopic analyses, using 1D and 2D NMR techniques and some chemical transformations, the structures of 1 and 2 have been established as (20R,24R,25R)-24,26-cyclo-5alpha-cholesta-3beta,6alpha,8,15alpha,16beta,27-hexaol (1) and the sodium salt of (20R,24S)-24-O-(3-O-methyl-4-O-sulfate-beta-d-xylopyranosyl)-5alpha-cholesta-3beta,6alpha,8,15alpha,24-pentaol (2), respectively. Compound 1 inhibited the growth of Ehrlich carcinoma cells with an IC(50) of 50 microg/mL, whereas 2 induced apoptosis of the same cells (EC(50)=70 microg/mL) and inhibited Ca(2+) influx into mouse spleenocytes (EC(50)=20microg/mL).     

Monte Carlo study of the potential reduction in out-of-field dose using a patient-specific aperture in pencil beam scanning proton therapy

This study is aimed at identifying the potential benefits of using a patient-specific aperture in proton beam scanning. For this purpose, an accurate Monte Carlo model of the pencil beam scanning (PBS) proton therapy (PT) treatment head at Massachusetts General Hospital (MGH) was developed based on an existing model of the passive double-scattering (DS) system. The Monte Carlo code specifies the treatment head at MGH with sub-millimeter accuracy. The code was configured based on the results of experimental measurements performed at MGH. This model was then used to compare out-of-field doses in simulated DS treatments and PBS treatments. For the conditions explored, the penumbra in PBS is wider than in DS, leading to higher absorbed doses and equivalent doses adjacent to the primary field edge. For lateral distances greater than 10 cm from the field edge, the doses in PBS appear to be lower than those observed for DS. We found that placing a patient-specific aperture at nozzle exit during PBS treatments can potentially reduce doses lateral to the primary radiation field by over an order of magnitude. In conclusion, using a patient-specific aperture has the potential to further improve the normal tissue sparing capabilities of PBS.     

Laser-induced modification of the patellar ligament tissue: comparative study of structural and optical changes

The effects of non-ablative infrared (IR) laser treatment of collagenous tissue have been commonly interpreted in terms of collagen denaturation spread over the laser-heated tissue area. In this work, the existing model is refined to account for the recently reported laser-treated tissue heterogeneity and complex collagen degradation pattern using comprehensive optical imaging and calorimetry toolkits. Patella ligament (PL) provided a simple model of type I collagen tissue containing its full structural content from triple-helix molecules to gross architecture. PL ex vivo was subjected to IR laser treatments (laser spot, 1.6 mm) of equal dose, where the tissue temperature reached the collagen denaturation temperature of 60 ± 2°C at the laser spot epicenterin the first regime, and was limited to 67 ± 2°C in the second regime. The collagen network was analyzed versus distance from the epicenter. Experimental characterization of the collagenous tissue at all structural levels included cross-polarization optical coherence tomography, nonlinear optical microscopy, light microscopy/histology, and differential scanning calorimetry. Regressive rearrangement of the PL collagen network was found to spread well outside the laser spot epicenter (>2 mm) and was accompanied by multilevel hierarchical reorganization of collagen. Four zones of distinct optical and morphological properties were identified, all elliptical in shape, and elongated in the direction perpendicular to the PL long axis. Although the collagen transformation into a random-coil molecular structure was occasionally observed, it was mechanical integrity of the supramolecular structures that was primarily compromised. We found that the structural rearrangement of the collagen network related primarily to the heat-induced thermo-mechanical effects rather than molecular unfolding. The current body of evidence supports the notion that the supramolecular collagen structure suffered degradation of various degrees, which gave rise to the observed zonal character of the laser-treated lesion.     

Transfer for urgent percutaneous coronary intervention early after thrombolysis for ST-elevation myocardial infarction: the TRANSFER-AMI pilot feasibility study

BACKGROUND: Most hospitals in Canada do not have percutaneous coronary intervention (PCI) facilities and use thrombolysis as reperfusion therapy for ST-elevation myocardial infarction (STEMI). Urgent PCI after thrombolysis may optimize reperfusion and prevent reinfarction and recurrent ischemia. OBJECTIVE: To determine the feasibility of transferring high-risk STEMI patients from community hospitals in Ontario to PCI centres for urgent PCI within 6 h of thrombolysis. METHODS: Patients with anterior or high-risk inferior STEMI received tenecteplase and were urgently transferred to PCI centres. PCI was performed if at least 70% stenosis was present in the infarct-related artery, regardless of flow, using coronary stents. Transfer of stable patients back to community hospitals was encouraged 24 h to 48 h after PCI. RESULTS: Eighteen patients were transferred and underwent PCI a median of 3.9 h (range 2.7 h to 6.4 h) after thrombolysis. No complications occurred during transfer. One death occurred that was related to failed reperfusion and cardiogenic shock. Minor access-site bleeding occurred in five patients. Fifteen patients were transferred back to their community hospitals within 24 h of PCI. There were no further deaths or reinfarctions at one-year follow-up. CONCLUSIONS: Transfer of high-risk STEMI patients for urgent PCI within 6 h after thrombolysis appears feasible. The randomized trial phase of the Trial of Routine ANgioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) will compare this strategy with standard treatment after thrombolysis.     

Decrease in the lgl tumor suppressor dose in Drosophila increases survival and longevity in stress conditions

Recent studies suggest that downregulation of tumor suppressor genes might not only favor cancer development but also postpone organisms' aging and increase longevity. However, there is lack of population-based studies directly supporting this idea. We studied the lgl lethal alleles which are widespread in natural Drosophila populations. We demonstrate, for the first time, that animals heterozygous on the loss-of-function lgl tumor suppressor gene display a clear pre-adult viability advantage under stressful conditions (high 29 degrees C and low 16 degrees C temperatures). We found also the survival and longevity advantage effect of the lgl loss-of-function in the temperature stress conditions. The main features of this longevity influence are following. First, the lgl-dependent life span increase is sex-dependent; in all experimental combinations males are more sensitive than females of relevant genotypes. Second, the effect is stronger under the life-shortening temperature stress, 29 degrees C, where the hormesis was demonstrated. Third, the favoring effect of reduced dosage of tumor suppressor displays clearly in old but not young animals, delaying aging. Forth, the maternal or epigenetic inheritance of thermotolerance from mother to offspring appears to strengthen the observed longevity effects. One possible explanation of this stress-adaptive effect of reduced tumor suppressor dose might be a better resistance of Drosophila post-mitotic cells to a stress-associated apoptosis at old ages.     

Contemporary management of dyslipidemia in high-risk patients: targets still not met

Purpose

Our objective was to evaluate treatment patterns and the attainment of current National Cholesterol Education Program (NCEP)-recommended lipid targets in unselected high-risk ambulatory patients.

Methods

Between December 2001 and December 2004, the prospective Vascular Protection and Guidelines Oriented Approach to Lipid Lowering Registries recruited 8056 outpatients with diabetes, established cardiovascular disease (CVD), or both, who had a complete lipid profile measured within 6 months before enrollment. The primary outcome measure was treatment success, defined as the achievement of LDL-cholesterol < 2.6 mmol/L (100 mg/dL) according to NCEP guidelines. We examined patient characteristics and use of lipid-modifying therapy in relation to treatment outcome, which included the recently proposed optional LDL-cholesterol target (<1.8 mmol/L [70mg/dL]) for very high-risk patients.

Results

Overall, 78.2% of patients were treated with a statin and 51.2% had achieved the recommended LDL-cholesterol target. Treatment success rate was highest in diabetic patients with CVD (59.6%), followed by nondiabetic patients with CVD (51.8%), and lowest (44.8%) in diabetic patients without CVD (P < .0001). Compared with untreated patients, those on statins were more likely to achieve target (34.4% vs 55.9%, P < .0001). Of the patients who failed to meet target, only 9.9% were taking high-dose statin, while 29.3% were not prescribed any statin therapy. Among very high-risk patients, 20.8% attained the optional LDL-cholesterol goal. In multivariable analysis, advanced age, male sex, diabetes, coronary artery disease, coronary revascularization, and use of statin were associated with treatment success (all P < .0001).

Conclusion

Despite the well-established benefits of available lipid-modifying drugs, current management of dyslipidemia continues to be suboptimal, with a substantial proportion of patients failing to achieve guideline-recommended lipid targets. There remains an important opportunity to improve the quality of care for these high-risk patients.     

Coping patterns as a valid presentation of the diversity of coping responses in schizophrenia patients

This study aimed to identify coping patterns used by schizophrenia inpatients in comparison with those used by healthy individuals, and to explore their association with selected clinical and psychosocial variables. The Coping Inventory for Stressful Situations (CISS) was used to assess coping strategies among 237 inpatients who met DSM-IV criteria for schizophrenia and 175 healthy individuals. Severity of psychopathology and distress, insight into illness, feelings of self-efficacy and self-esteem (self-construct variables), social support, and quality of life were also examined. Factor analysis, analysis of covariance and correlations were used to examine the relationships between the parameters of interest. Using dimensional measures, we found that emotion-oriented coping style and emotional distress were significantly higher in the schizophrenia group, whereas the task-oriented coping style, self-efficacy, perceived social support and satisfaction with quality of life were lower compared with controls. When eight CISS coping patterns were defined, the results revealed that patients used emotion coping patterns 5.5 times more frequently, and task and task-avoidance coping patterns significantly less often than healthy subjects. Coping patterns have different associations with current levels of dysphoric mood and emotional distress, self-construct variables, and satisfaction with quality of life. Thus, the identified coping patterns may be an additional useful presentation of the diversity of coping strategies used by schizophrenia patients. Coping patterns may be considered an important source of knowledge for patients who struggle with the illness and for mental health professionals who work with schizophrenia patients.