Cytotoxic constituents of Achillea clavennae from Montenegro

Examination of the aerial parts of Achillea clavennae afforded eight guaianolides (1-8), three bisabolenes (9-11), four flavonols (12-15), sesamin (lignan) and isofraxidin (coumarin). The structures of the new compounds (2, 4, 5, 7 and 10) were determined by spectroscopic methods. The antiproliferative action of 2, 8, 9 and 12 were tested to HeLa, K562 and Fem-X human cancer cell lines. Guaianolides 2 (9alpha-acetoxyartecanin) and 8 (apressin) showed significant cytotoxic effects to all tested lines and inducumenone (9) exhibited a moderate activity. The most active was flavonol centaureidin (12), already known as cytotoxic compound.     

Application of alkaline elution, Fast Micromethod and flow cytometry in detection of marine contamination.

DNA damage is an inescapable aspect of life in the biosphere. The presented investigations were an attempt to examine the response of a DNA damage as a biomarker of environmental quality in the mussels Mytilus galloprovincialis sampled at differently contaminated areas of Istrian coast, Northern Adriatic. The investigations were performed in order to get information about the genotoxic risk for marine organisms exposed to mixed environmental pollution, as well as the information about the presence of unknown mixture of genotoxic contaminants in the marine environment. Types of DNA damage detected are alkali-labile sites and single-strand breaks measured by Fast Micromethod, interstrand cross-links and DNA protein cross-links by alkaline filter elution and cell cycle disturbation by flow cytometry. The applicability of all three methods for marine quality control is discussed.     

Increased pulmonary vascular resistance and reduced stroke volume in association with CO2 retention and inferior vena cava dilatation.

Changes in cardiovascular parameters elicited during a maximal breath hold are well described. However, the impact of consecutive maximal breath holds on central hemodynamics in the postapneic period is unknown. Eight trained apnea divers and eight control subjects performed five successive maximal apneas, separated by a 2-min resting interval, with face immersion in cold water. Ultrasound examinations of inferior vena cava (IVC) and the heart were carried out at times 0, 10, 20, 40, and 60 min after the last apnea. The arterial oxygen saturation level and blood pressure, heart rate, and transcutaneous partial pressures of CO(2) and O(2) were monitored continuously. At 20 min after breath holds, IVC diameter increased (27.6 and 16.8% for apnea divers and controls, respectively). Subsequently, pulmonary vascular resistance increased and cardiac output decreased both in apnea divers (62.8 and 21.4%, respectively) and the control group (74.6 and 17.8%, respectively). Cardiac output decrements were due to reductions in stroke volumes in the presence of reduced end-diastolic ventricular volumes. Transcutaneous partial pressure of CO(2) increased in all participants during breath holding, returned to baseline between apneas, but remained slightly elevated during the postdive observation period (approximately 4.5%). Thus increased right ventricular afterload and decreased cardiac output were associated with CO(2) retention and signs of peripheralization of blood volume. These results indicate that repeated apneas may cause prolonged hemodynamic changes after resumption of normal breathing, which may suggest what happens in sleep apnea syndrome.     

Metabolic syndrome--community nursing evaluation and intervention: the CroHort study

This prospective study of 1277 participants investigated patient risk self-assessment, motivation for changes in main determinants of the metabolic syndrome and the impact of community nursing intervention on cardiovascular risk reduction. Observed values of metabolic syndrome determinants indicated an elevated cardiovascular risk. Participants showed greatest motivation for positive changes regarding blood pressure, (3.70 +/- 1.26) then hyperglycemia (3.55 +/- 1.28), hyperlipidemia (3.46 +/- 1.30), overweight and obesity (3.43 +/- 1.28), and physical activity habits (3.29 +/- 1.31). Changes in physical activity and nutritional habits were not related to self-reported motivation regardless of the age and sex (p > 0.05). The most pronounced median improvements were observed in cholesterol (men 4.43%, women 4.89%) and triglycerides (men 3.41%, women 1.49%), with only slight changes in BMI (men 1.08%, women 1.18%) and no change in waist-to-hip ratio and glucose. This study revealed that, although aware and motivated, patients often do not succeed in changing habits. Concomitant changes of the environment and multisectoral prevention approach is necessary.     

Mucormycosis of the nasal ala in a leukemic (M7 AML) child. Is surgery of the nasal defect indicated?

Anterior tamponade with Surgicel (oxidized cellulose) was performed on a 5-year-old girl with megakaryoblastic leukemia (M7 AML) and epistaxis. Several days later necrosis of the nasal ala occurred. Debridement was performed and mucormycosis caused by Rhizopus was found in the material. Having cured mucormycosis, a defect of the complete nasal ala remained. The question of a surgical resolution of the disfiguring nasal defect arises.     

The relationship between prolonged cerebral oxygen desaturation and postoperative outcome in patients undergoing coronary artery bypass grafting

58 patients who underwent on-pump coronary artery bypass graft surgery were evaluated for changes in regional cerebral oxygen saturation (rSO2) measured by near infrared spectroscopy (NIRS). If rSO2 during the operation fell to more than 20% under the baseline, standardized interventions were undertaken to maintain rSO2. Despite those interventions, in some cases we observed inability to maintain rSO2 above this threshold. Therefore we divided patients in two subgroups: 1. without prolonged rSO2 desaturation; 2. with prolonged rSO2 desaturation (area under the curve >150 min% for rSO2<20% of baseline and >50 min% for rSO2<50% of absolute value). The data were analyzed to determine whether there were major differences in outcome of these two groups. 18 out of 58 patients (31%) had prolonged rSO2 desaturation during operation. There was significantly higher number of diabetic patients in group with prolonged rSO2 desaturation (p=0.02). Intraoperative data revealed significantly more blood consumption during cardiopulmonary bypass (p=0.007) and the need for inotropes (p=0.04) in desaturation group. Three patients in prolonged desaturation group and no one in another group had stroke, coma or stupor (p=0.03). Logistic regression analysis revealed diabetes mellitus and age as predictors for prolonged rSO2 desaturation. We concluded that prolonged intraoperative rSO2 desaturation is significantly associated with worse neurological outcome in patients - nonresponders to standardized interventions for prevention of rSO2 desaturation.     

Morphology of hypoxia following cryoablation in a prostate cancer murine model: Its relationship to necrosis, apoptosis and, microvessel density

The aim of this study is to investigate the tumor tissue changes in terms of hypoxia and demonstrate its relationship to vascularity and apoptosis following therapeutic cryoablation in a prostate tumor murine model. Total 67 male C57BL/J6 mice were assigned into sham-operation group and cryoablation group. Murine prostate tumors (RM-9) were inoculated subcutaneously in a right hind leg and treated with cryotherapy. Of 30 mice, tumor volumes were measured for 12 days following operation. Of 37 mice, tumor tissues were harvested in 24 h following operation, and histological/molecular changes were analyzed. Hematoxylin and eosin or immunohistochemical staining were utilized to quantify tumor necrosis, hypoxia (pimonidazole), vascularization (CD31), and apoptosis (cleaved caspase-3). The results showed that cryoablated tumors demonstrated significant delayed growth following treatment compared to controls. Pathological analysis revealed that the severity of hypoxia increased in the cryoablation arm compared to controls. Necrotic and apoptotic populations were also found to be increased in the cryoablation arm (P = 0.028 and 0.021). Hypoxia demonstrated a positive correlation with necrosis (r = 0.520, P = 0.001) and apoptosis (r = 0.474, P = 0.003), while showing negative correlation with microvessel density (MVD) (r = −0.361, P = 0.021). We concluded that in the peripheral areas from the cryoneedle impact site, strong hypoxic responses were found, which may play important role in tumor freezing injury. To our knowledge, this is the first report describing cryoablation-mediated changes of hypoxia at a molecular level in the prostate cancer murine model.     

The effect of analgesics and physical therapy on respiratory function after open and laparoscopic cholecystectomy

In this study we present prospective clinical trial included 100 patients. One half of the patients underwent open cholecystectomy, whereas laparoscopic cholecystectomy was performed in the other half Spirometric parameters, arterial blood gases, acid-base balance, were determined preoperatively, and then at 6 h, 24 h, 72 h and 144 h postoperatively. The impact of physical therapy on the respiratory parameter patterns, VAS-pain score and use of tramadol were studied after cholecystectomy. Significantly lower VAS-pain score and less tramadol use, higher values and faster recovery of ventilation parameters and PaO2 were recorded after laparoscopic cholecystectomy than after open cholecystectomy (p = 0.001 for both). Physical therapy resulted in a significant improvement in the values of respiratory parameters in the open cholecystectomy group within a short time (30 min) after therapy was performed. Physical therapy failed to produce any improvement of respiratory parameters in laparoscopic cholecystectomy, whereas in open cholecystectomy group who had a favorable although transient effect, strictly limited to the short time from its application. (p = 0.005). The patients operated on by open cholecystectomy had statistically significantly more pronounced disturbances including hypoxia, hypocapnia and hyperventilation when compared to the group submitted to laparoscopic cholecystectomy. It is recommended that physical therapy be more frequently performed during the postoperative period in patients submitted to open cholecystectomy.     

The role of endothelin-1 and nitric oxide in the pathogenesis of hypertension in diabetic patients

The pathogenesis of renal hypertension has not yet been fully clarified. As the potential role of endothelin-1 (ET-1) and nitric oxide (NO) has been postulated, their concentrations were determined in plasma and urine of diabetic patients. The study included 30 diabetic patients (both IDDM and NIDDM) with initial or advanced diabetic nephropathy (decreased endogenous creatinine clearance, proteinuria) and 20 healthy control subjects. The correlation with blood pressure and other renal function parameters was monitored and compared with the control group. Also, the effect of ACE inhibitors (ACEI) on ET-1 and NO patterns was monitored in correlation with arterial hypertension. In diabetic patients that did not receive ACEI therapy, the increase in plasma ET-1 was associated with both systolic and diastolic blood pressure elevation, whereas in those administered ACEI the increase in plasma ET-1 was associated with a systolic blood pressure decline. In addition, the increase in plasma NO was accompanied by a statistically significant decline of both systolic and diastolic blood pressure in diabetic patients receiving ACEI.