Effect of high and low rates of fluid intake on post-exercise rehydration

The effect of a high (H) and a low (L) rate of post-exercise fluid consumption on plasma volume and fluid balance restoration was investigated. Eight well-trained cyclists were dehydrated at 3% of body weight (BW) by cycling at 28 degrees C. During the recovery period, they ingested a carbohydrate-electrolyte solution in a volume equivalent to 120% of BW loss. Randomly, they ingested 60%, 40%, and 20% in the 1st, 2nd, and 3rd hours of the recovery period, respectively (H), or 24% x h(-1) during 5 hours (L). BW loss was similar for both trials and resulted in a total drink intake of 2.6 +/- 0.1 kg. Urine output in H exceeded significantly that of L in the 2nd and 3rd hours. This was reversed in the 5th and 6th hours. Plasma volume and fluid balance increased more rapidly in H compared to L. After 6 hours this difference disappeared. It is concluded that H results in a faster rate of plasma volume and fluid balance restoration compared to L, despite a temporary large urine output.     

Effects of levobupivacaine,ropivacaine and bupivacaine on HERG channels: stereoselective bupivacaine block

1 Levobupivacaine and ropivacaine are the pure S(-) enantiomers of N-butyl- and N-propyl-2',6'-pipecoloxylidide, developed as less cardiotoxic alternatives to bupivacaine. In the present study, we have analysed the effects of levobupivacaine, ropivacaine and bupivacaine on HERG channels stably expressed in CHO cells. 2 The three drugs blocked HERG channels in a concentration-, time- and state-dependent manner. Block measured at the end of 5 s pulses to -10 mV induced by 20 microM bupivacaine (52.7+/-2.0%, n=15) and ropivacaine (55.5+/-2.7%, n=13) was similar (P>0.05) and both lower than that induced by levobupivacaine (67.5+/-4.2%, n=11) (P<0.05). 3 Dextrobupivacaine (20 microM) was less potent (47.2+/-5.2%, n=10) than levobupivacaine (P<0.05), indicating stereoselective HERG channel block. 4. Block induced by the three local anaesthetics exhibited a steep voltage dependence in the range of channel activation. In all cases, block measured at the maximum peak current at a test potential of 0 mV after promoting recovery from inactivation (I-->O) was lower than that observed at the end of 5-s pulses (I+O). 5. Levobupivacaine, ropivacaine and bupivacaine accelerated HERG inactivation kinetics, slowed the recovery from inactivation and shifted the inactivation curve towards more negative membrane potentials. The three local anaesthetics induced a rapid time-dependent decline after using a protocol that quickly activates HERG channels. 6. All these results suggest that: (1) these drugs bind to the open and the inactivated states of HERG channels, (2) they stabilize HERG channels in the inactivated state, and (3) block induced by bupivacaine enantiomers is stereoselective.     

Health-related quality of life and cost impact of irritable bowel syndrome in a UK primary care setting

OBJECTIVES: To identify the impact of irritable bowel syndrome (IBS) on health-related quality of life (HR-QOL), time off work and the utilisation and cost of health services. DESIGN: A case-control study was undertaken matching patients with IBS and controls. Quality-of-life information was collected using the Medical Outcomes Study 36-item Short Form (SF-36) health survey, EuroQOL instrument (EQ-5D) and IBS Quality-of-Life (IBS-QOL) instruments. Data on time off work was also collected. National Health Service (NHS) resource use in primary and secondary care was estimated by review of general practitioner (GP) and hospital records over a 12-month period. SETTING: Recruitment was from six GPs' surgeries in the Trent Region of the United Kingdom. PARTICIPANTS: 161 patients with IBS, as defined by the Rome Criteria I were recruited. These were compared with 213 controls matched for age, sex and social characteristics. MAIN OUTCOME MEASURES: SF-36 and EQ-5D scores; mean number of days off work; mean NHS costs per person during the 12-month study period. RESULTS: Patients with IBS had considerably lower HR-QOL than controls. They scored worse in all dimensions of the SF-36 and the EQ-5D and they had more time off work. On average patients with IBS cost the NHS 123 UK pounds (95% confidence interval: 35 UK pounds to 221 UK pounds, 1999 values) more per year than individuals in the control group (p = 0.04). CONCLUSIONS: IBS affects patients through reduced quality of life, more time off work and greater healthcare utilisation than a control group of patients without IBS. The difference in quality of life was pronounced and unusual in that it was influential in every dimension of both the SF-36 and the EQ-5D.     

Burden of illness in irritable bowel syndrome comparing Rome I and Rome II criteria

OBJECTIVES: To evaluate the burden of illness in irritable bowel syndrome (IBS), in terms of resource utilisation (direct and indirect) and health-related quality of life (HR-QOL), in individuals with IBS who meet Rome I and Rome II criteria. METHODS: A cross-sectional study, carried out by personal interview, on a representative sample (n = 2000) of the Spanish population. Individuals with suspected IBS were identified via a screening question and subsequently given an epidemiological questionnaire to complete. The questionnaire collected information on IBS symptoms, resource utilisation, and HR-QOL [Medical Outcomes Study 36-item Short Form (SF-36)]. RESULTS: Sixty-five individuals met Rome II criteria for IBS, while 146 individuals met exclusively Rome I criteria. Of Rome II individuals, 67.7% had consulted some type of healthcare professional in the previous 12 months, compared with only 41.8% of those individuals meeting exclusively Rome I criteria (p vs 17.1%); 'drug consumption' (70.8 vs 45.2%); and 'reduced performance in main activity' (60 vs 27.4%). Compared with the general population, the study sample reported significantly worse HR-QOL scores in four dimensions of the SF-36 ('bodily pain', 'vitality', 'social functioning' and 'role-emotional'. Additionally, individuals meeting Rome II criteria reported worse HR-QOL scores than those individuals meeting exclusively Rome I criteria, especially in the 'bodily pain' and 'general health' dimensions. CONCLUSIONS: The burden of illness in IBS is important and correlated to the diagnostic criteria employed. Individuals who met Rome II criteria reported a higher level of resource utilisation and worse HR-QOL than individuals meeting exclusively Rome I criteria.     

N(7)-substituted-5-aryl-pyrrolo[2,3-d]pyrimidines represent a versatile class of potent inhibitors of the tyrosine kinase c-Src

5-Aryl-pyrrolo[2,3-d]pyrimidines incorporating different N(7)-substituents have been prepared and evaluated for their inhibitory potency towards the tyrosine kinase c-Src. Optimization of these compounds resulted in highly potent c-Src inhibitors, some (e.g. 4g, 6g, 7h, 8l) with excellent specificity towards other receptor and nonreceptor tyrosine kinases. In addition compounds 4g, 5b and 5c are characterized by a good pharmacokinetic profile.     

Furosemide and spironolactone reduce transmigration of leukocytes through endothelial cell monolayers

Furosemide and spironolactone reduce transmigration of leukocytes through endothelial cell monolayers. Leukocytes play a tremendous role during inflammation. Leukocytes migrate from intravascular space into the tissue to attack microorganisms. Various agents are able to influence leukocyte recruitment. The influence of diuretics, such as furosemide and spironolactone, on inflammatory processes is not well known. The aim of our study was to examine the influence of furosemide and spironolactone on leukocyte migration through endothelial cell monolayers (ECM). Human umbilical vein endothelial cells were cultured on microporous membranes achieving a monolayer. Polymorphonuclear leukocytes (PMNL) were used in a currently described migration assay. PMNL and/or ECM were pretreated with furosemide and spironolactone using therapeutic, as well as higher and lower, concentrations. Furosemide (76 +/- 7.2%) and spironolactone (70 +/- 7.7%) were able to inhibit PMNL migration through ECM significantly, when both cell types were treated simulating the situation after an iv injection. Furosemide and spironolactone were identified as potent inhibitors of leukocyte migration through ECM.     

Improvement in neuropsychological performance following surgical treatment for obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) is characterized by snoring and apnea during sleep leading to decreased oxygen saturation and disturbed sleep, excessive daytime sleepiness and neuropsychological disturbances. This study investigates cognitive neuropsychological abilities in a group of 53 OSAS patients before and after treatment with uvulopalatopharyngoplasty. General intellectual ability, verbal learning and memory as well as executive functioning were measured at baseline and 6 months postoperatively. After surgery there were significant improvements in verbal learning and memory (mean change -39, SD 57.3, p < 0.001), recall (mean change -24.3, SD 39.3, p < 0.001) and executive functioning (as assessed by percentage of errors on the Wisconsin Card Sorting Test; mean change -9.1, SD 15.7, p < 0.001). These improvements were in accordance with improvements in the degree of sleep apnea, the oxygen desaturation index (mean change -9.7, SD 15.9, p < 0.001) and arterial minimum oxygen saturation (mean change 4.5%, SD 10.2%, p < 0.01). Surgical treatment seems to improve verbal learning, memory and recall and executive functions in parallel with better oxygenation in OSAS.     

Expression of cox-2, tie-2 and glycodelin by megakaryocytes in patients with chronic myeloid leukaemia and polycythaemia vera

When evaluating bone marrow sections for markers of neo-angiogenesis, we found that megakaryocytes stained markedly positive for cyclooxygenase-2 (Cox-2), Tie-2 and glycodelin. This apparently novel finding was further evaluated for disease-specific variations. Bone marrow sections from two patient groups, known to be characterized by clonal megakaryocytopoiesis, viz. chronic myeloid leukaemia and polycythaemia vera, stained, however, similarly to healthy marrows for these markers. The biochemical background and clinical significance of Cox-2, Tie-2 and glycodelin remains to be elucidated.