Serum interleukin-1beta, interleukin-6, nitric oxide and alpha1-antitrypsin in scorpion envenomed children

During the present study, thirty-eight children in Upper Egypt (less than 12years old) were admitted to Pediatric Intensive Care Unit for scorpion envenomation. They were compared with thirteen apparently healthy children of matching age as controls. The victims and controls were subjected to complete clinical examination and full blood count. The evaluations of the serum levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), nitric oxide (NO) and alpha1-antitrypsin (alpha1-AT) were performed once for the controls and twice for the victims, the first sample on admission and the 2nd sample after 24 h. All victims showed significantly higher mean values of IL-1beta IL-6, NO, alpha1-AT and leucocytic count both on admission and on follow up when compared with controls. Manifestations of mild envenomation were detected among 28.9% of the victims, while 71.1% of the victims manifested severe scorpion envenomation. The severely envenomated children showed significantly higher mean values of IL-1beta, IL-6, NO, alpha1-AT and leucocytic count both on admission and on follow up when compared with mild cases. The case fatality rate in the current study was 7.8%. The non-surviving victims showed significantly higher mean values of IL-1beta, IL-6 and leucocytic count both on admission and on follow up in comparison to the survivors. Furthermore, those fatal cases showed a non-significant decline in the studied biochemical indices on follow up after 24 h, while the survivors showed a significant decline in the serum levels of IL-6, IL-1beta, NO and alpha1-AT after 24h of post arrival to the hospital. In conclusion, these data revealed that cytokines are involved in the pathogenesis of scorpion envenomation and correlated with the severity of envenomation. This may provide a rationale for anticytokine treatment.     

African American-white differences in lipids, lipoproteins, and apolipoproteins, by educational attainment, among middle-aged adults: the Atherosclerosis Risk in Communities Study

Measures of socioeconomic status have been shown to be related positively to levels of high density lipoprotein (HDL) cholesterol in white men and women and negatively in African American men. However, there is little information regarding the association between educational attainment and HDL fractions or apolipoproteins. The authors examined these associations in 9,407 white and 2,664 African American men and women aged 45-64 years who participated in the Atherosclerosis Risk in Communities Study baseline survey, and they found racial differences. A positive association for HDL cholesterol, its fractions HDL2 and HDL3 cholesterol, and its associated apolipoprotein A-I was found in white men and white women, but a negative association was found in African American men, and there was no association in African American women. In whites, there was also an inverse association of low density lipoprotein (LDL) cholesterol and apolipoprotein B with educational attainment. With the exception of African American men, advanced education was associated with a more favorable cardiovascular lipid profile, which was strongest in white women. Racial differences in total cholesterol (women only), plasma triglycerides, LDL cholesterol, apolipoprotein B (women only), HDL cholesterol, HDL2 and HDL3 cholesterol, and apolipoprotein A-I were reduced at higher levels of educational attainment. Apart from triglycerides in men and HDL3 cholesterol in women, these African American-white lipid differences associated with educational attainment remained statistically significant after multivariable adjustment for lifestyle factors. Lipoprotein(a) showed no association with educational attainment. These findings confirm African American-white differences in lipids, lipoproteins, and apolipoproteins across levels of educational attainment that were not explained by conventional nondietary lifestyle variables. Understanding these differences associated with educational attainment will assist in identifying measures aimed at prevention of cardiovascular disease.     

Benefit of a favorable cardiovascular risk-factor profile in middle age with respect to Medicare costs

BACKGROUND: People without major risk factors for cardiovascular disease in middle age live longer than those with unfavorable risk-factor profiles. It is not known whether such low-risk status also results in lower expenditures for medical care at older ages. We used data from the Chicago Heart Association Detection Project in Industry to assess the relation of a low risk of cardiovascular disease in middle age to Medicare expenditures later in life. METHODS: We studied 7039 men and 6757 women who were 40 to 64 years of age when surveyed between 1967 and 1973 and who survived to have at least two years of Medicare coverage in 1984 through 1994. Men and women classified as being at low risk for cardiovascular disease were those who had the following characteristics at the time they were initially surveyed: serum cholesterol level, <200 mg per deciliter (5.2 mmol per liter); blood pressure, < or =120/80 mm Hg; no current smoking; an absence of electrocardiographic abnormalities; no history of diabetes; and no history of myocardial infarction. We compared Medicare costs for the 279 men (4.0 percent) and 298 women (4.4 percent) who had this low-risk profile with those for the rest of the study group, who were not at low risk. Health Care Financing Administration charges for services to Medicare beneficiaries were used to estimate average annual health care costs (total costs, those for cardiovascular diseases, and those for cancer). RESULTS: Average annual health care charges were much lower for persons at low risk - the total charges for the men at low risk were less than two thirds of the charges for the men not at low risk ($1,615 less); for the women at low risk, the charges were less than one half of those for the women not at low risk ($1,885 less). Charges related to cardiovascular disease were lower for the low-risk groups of men and women than for those not at low risk (by $979 and $556, respectively), and charges related to cancer were also lower (by $134 and $189). CONCLUSIONS: People with favorable cardiovascular risk profiles in middle age had lower average annual Medicare charges in older age. Having optimal status with respect to major cardiovascular risk factors may result not only in greater longevity but also in lower health care costs.     

Hypertension optimal treatment (HOT) study: home blood pressure in treated hypertensive subjects

The Hypertension Optimal Treatment Study is a prospective trial conducted in 26 countries. The aims are to (1) evaluate the relationship between three levels of target office diastolic blood pressure (BP) (< or = 80, < or = 85, or < or = 90 mm Hg) and cardiovascular morbidity and mortality in hypertensive patients and (2) examine the effects on cardiovascular morbidity and mortality of 75 mg aspirin daily versus placebo. A total of 19,193 patients between 50 and 80 years of age had been randomized by the end of April 1994. Treatment was initiated with felodipine 5 mg daily, and additional therapy was given in accordance with a set protocol. The present substudy of 926 patients performed in nine countries aimed to (1) compare home with office BP in a representative subsample of the HOT population after the titration of treatment was completed and (2) clarify whether the separation into the target groups could be expanded into the out-of-office setting. The differences between office and home measurements in diastolic BP of 0.2 mm Hg (SD, 9; 95% confidence interval, -0.36 to 0.81; P=.40) and systolic BP of 0.5 mm Hg (SD, 15; 95% confidence interval, -0.53 to 1.46; P=.21) were not significant. The group differences in home BP were 1.9 mm Hg (< or = 80 versus < or = 85) and 1.2 mm Hg (< or = 85 versus < or = 90) for diastolic BP (F=11.69; ANOVA, P<.0001) and 2.6 and 2.1 mm Hg for systolic BP (F=8.44, P=.0002). Thus, office and home BPs measured with the same semiautomatic device are comparable in treated hypertensive subjects in the HOT Study, and the separation into the target groups based on office readings prevails at home.     

Monoamine responses to acute and chronic aerobic exercise in normotensive and hypertensive subjects

OBJECTIVES: The purpose of the present study was to compare the plasma and serum monoamine levels in sedentary, untrained normotensive and hypertensive men at rest with levels measured after an acute bout of exercise and to compare similar measurements following a 12-week aerobic training program. PLACE OF STUDY: The data obtained for this study was collected from a clinic for the prevention of heart disease and cardiac rehabilitation (FITCOR) and analyzed in the Federal University of S?o Paulo (EPM), Laboratory of Experimental Neurology. SUBJECTS: Two groups of untrained male subjects, i.e., normotensive (N = 16) and hypertensive (N = 19), were submitted to an acute bout of exercise to analyze the acute effect of exercise on the monoamine levels. To study the chronic effect of exercise (physical training program), some individuals of each group were arranged in two other groups; normotensive (N = 11) and hypertensive (N = 8). MEASUREMENT: Plasma catecholamines and serum serotonin levels were determined by high performance liquid chromatography coupled with electrochemical detection. RESULTS: A significant reduction in diastolic blood pressure at rest was observed in the hypertensive group after the physical training program (p < 0.05). Only the mean plasma noradrenaline concentration increased significantly post-exercise in all groups of individuals (acute effect of exercise--p < 0.01 for untrained normotensive and hypertensive; chronic effect of exercise--p < 0.001 for untrained and trained normotensive, p < 0.01 for untrained and trained hypertensive). CONCLUSION: These data show the beneficial effect of physical exercise in reducing the blood pressure in hypertensive patients, which does not seem to be related to changes in circulating monoamines.     

Measurement of intercellular electrical coupling in guinea-pig detrusor smooth muscle

Ropivacaine, a new long-acting local anesthetic, is currently being investigated for the treatment of ulcerative colitis. In view of the increased incidence of dysplasia and neoplasia associated with ulcerative colitis, it is important that the medical treatment of these patients does not stimulate cell proliferation further. This study was performed to evaluate the effect of ropivacaine on the proliferation of human colon adenocarcinoma cells (HT-29 and Caco-2) in vitro. A serum-induced proliferation assay of human colon adenocarcinoma cells was used. Ropivacaine inhibited the growth of HT-29 and Caco-2 cells in a dose-dependent manner. Fifty percent inhibition of growth was found at a ropivacaine concentration of 250 microM when the HT-29 cells were cultured in 1% fetal calf serum and of 550 microM when the HT-29 cells were cultured in 10% serum. The effective concentrations are within the range of the therapeutic concentrations obtained in the colon of patients treated rectally with ropivacaine. Lidocaine, hydrocortisone, and 5-aminosalicylic acid were found to be less potent than ropivacaine in inhibiting proliferation. Ropivacaine caused a dose-dependent membrane depolarization that appeared to correlate with the inhibited cell proliferation, whereas the effect was not related to inhibition of leukotriene B4 or prostaglandin E2. In conclusion, the antiproliferative activity of ropivacaine, combined with previously reported anti-inflammatory activities, makes this drug an interesting new alternative for the local treatment of ulcerative colitis.     

Exploring the folding funnel of a polypeptide chain by biophysical studies on protein fragments

We are examining possible roles of native and non-native interactions in early events in protein folding by a systematic analysis of the structures of fragments of proteins whose folding pathways are well characterised. Seven fragments of the 110-residue protein barnase, corresponding to the progressive elongation from its N terminus, have been characterised by a battery of biophysical and spectroscopic methods. Barnase is a multi-modular protein that folds via an intermediate in which the C-terminal region of its major alpha-helix (alpha-helix1, residues Thr6-His18) is substantially formed as is also its anti-parallel beta-sheet, centred around a beta-hairpin (residues Ser92-Leu95). Fragments up to, and including, residues 1-95 (fragment B95), appeared to be mainly disordered, although a small amount of helical secondary structure in each was inferred from far-UV CD experiments, and fluorescence studies indicated some native-like tertiary interactions in B95. The largest fragment (residues 1-105, B105) is compactly folded. The secondary structure in alpha-helix1 in the seven fragments was found by NMR to increase with increasing chain length faster than the build-up of tertiary interactions, indicating that alpha-helix1 is being stabilised by non-native interactions. This behaviour contrasts with that in fragments of the 64-residue chymotrypsin inhibitor 2 (CI2), in which tertiary and secondary structures build up in parallel with increasing length. CI2 consists of a single module of structure that folds without a detectable intermediate. The largest fragment of barnase, B105, has interactions that resemble its folding intermediate, whereas one of the largest fragments of CI2 (residues 1-60) resembles the folding transition state. The folding pathways of both proteins are consistent with a scheme in which there are low levels of native-like secondary structure in the denatured state that become stabilised by long-range interactions as folding proceeds. Neither protein forms a stable fold when lacking the last ten residues at the C terminus. Since at least 20 amino acid residues are bound to the ribosome during protein biosynthesis, these small proteins do not fold until they have left the ribosome, and so the studies of the folding of such proteins in vitro may be relevant to their folding in vivo, especially as the molecular chaperone GroEL binds only weakly to denatured CI2 and does not discernibly alter the folding mechanism of barnase.     

The professions in the 1990s

As they did when they were formed 150 years ago, the professions must again convince the public and a cost-conscious and competition-orientated Government that they should be entrusted with the provision of services their training has made them fit to offer. This article explains why.     

Neuroendocrine changes in luteal function in patients with premenstrual syndrome

The present study evaluates the luteal progesterone (P) and LH secretions in 14 patients affected by premenstrual syndrome (PMS) and in 14 asymptomatic controls through the evaluation of their episodic release. PMS was prospectively confirmed in two consecutive menstrual cycles using Moos' Menstrual Distress Questionnaire. A pulsatility study was performed during the luteal phase. Blood samples were drawn every 10 min for 12 h, beginning at 0800 h. Statistically significant pulses were detected using the Detect program, and the degree of concordance of LH and P pulses was estimated. Similar mean 12-h P levels were found in controls (mean +/- SD, 13.9 +/- 9.3 nmol/L) and patients (14.2 +/- 10.1). LH levels were also similar in the two groups. Patients showed a higher P pulse frequency (13.4 +/- 1.8 vs. 11.4 +/- 2.3; P < 0.02) and a reduced amplitude of secretory episodes (126.5 +/- 61.6% vs. 187.1 +/- 126.7%; P < 0.03) than controls. Similarly, PMS patients showed pulsatile LH release of increased frequency and reduced amplitude than controls. A significant degree of concordance between LH and P pulses was observed in both groups, with a time lag of 0-10 min; that is, P secretory episodes follow LH with a delay of 0-10 min. These findings demonstrate that despite the fact that integrated P levels in PMS patients are similar to those in control subjects, the episodic secretion of the hormone is characterized by pulses of increased frequency and reduced amplitude. This phenomenon is temporally related to LH secretion, thus reinforcing the concept of PMS as a neuroendocrine disorder.     

On the automatic nature of phobic fear: Conditioned electrodermal responses to masked fear-relevant stimuli.

Normal Ss (n?=?64) were exposed either to pictures of snakes and spiders or to pictures of flowers and mushrooms in a differential conditioning paradigm in which one of the pictures signaled an electric shock. In a subsequent extinction series, these stimuli were presented backwardly masked by another stimulus for half of the Ss, whereas the other half received nonmasked extinction. In support of a hypothesis that suggests that nonconscious information-processing mechanisms are sufficient to activate responses to fear-relevant stimuli, differential skin conductance response to masked conditioning and control stimuli was obvious only for Ss conditioned to fear-relevant stimuli. These results were replicated in a 2nd experiment (n?=?32), which also demonstrated that the effect was unaffected by which visual half-field was used for stimulus presentation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)