Temporal integration of melatonin infusion duration: signal averaging versus frequency dependence

Day length affects somatic and reproductive physiology of Siberian hamsters via regulation of the duration of nocturnal pineal melatonin secretion. Nightly 'long' (e.g. 12 hr) or 'short' (e.g. 6 hr) melatonin signals inhibit or stimulate gonadal growth, respectively. When long and short signals are presented in combination, however, neuroendocrine mechanisms exhibit a frequency-dependent response, stimulating gonadal growth only if short signals are presented every second night or more frequently. The present experiments further assessed formal models for the temporal integration of melatonin signals changing abruptly in duration from night to night. Photo-inhibited Siberian hamsters were housed in constant light and infused subcutaneously with various combinations of nightly short or long melatonin signals according to one of the several regimes that varied the frequency of short melatonin signal occurrence, average duration of the nightly melatonin signal, or both. Six weeks of nightly alternating short and long signals yielded different gonadal responses depending on the average melatonin signal duration. Moreover, when average melatonin signal duration was held constant between groups, gonadal stimulation was independent of the frequency of the constituent melatonin signals except when the duration of the short signal was reduced to 3 hr. Thus, neuroendocrine mechanisms do not solely categorize melatonin signals as either long or short but attend also to the duration of each component signal. In the majority (six of seven) of infusion regimes, reproductive responses to chimeric patterns of long and short melatonin signals were compatible with a simple signal-averaging mechanism.     

Analysis of serum metabolic profiles in women with endometrial cancer and controls in a population-based case-control study

Context: Endometrial cancer is associated with metabolic disturbances related to its underlying risk factors, including obesity and diabetes. Identifying metabolite biomarkers associated with endometrial cancer may have value for early detection, risk assessment, and understanding etiology. Objective: The objective of the study was to evaluate the reliable measurement of metabolites in epidemiological studies with nonstandardized blood collection; confirm previously reported correlations of metabolites with body size; and assess differences in metabolite levels between cases and controls. Design: This was the Polish Endometrial Cancer Study (2001-2003). Setting: This study was a population-based case-control study. Patients: Patients included 250 cases and 250 controls. Intervention: The intervention included the measurement of serum metabolite levels of 15 amino acids, 45 acylcarnitines, and nine fatty acids. Main Outcome Measure: The main outcome measure was endometrial cancer. Results: Body mass index was correlated with levels of valine (r = 0.26, P = 3.4 × 10(-5)), octenoylcarnitine (r = 0.24, P = 1.5 × 10(-4)), palmitic acid (r = 0.26, P = 4.4 × 10(-5)), oleic acid (r = 0.28, P = 9.9 × 10(-6)), and stearic acid (r = 0.26, P = 2.9 × 10(-5)) among controls. Only stearic acid was inversely associated with endometrial cancer case status (quartile 4 vs. quartile 1: odds ratio 0.37, 95% confidence interval 0.20-0.69, P for trend = 1.2 × 10(-4)). Levels of the C5-acylcarnitines, octenoylcarnitine, decatrienoylcarnitine, and linoleic acid were significantly lower in cases than controls (odds ratios ranged from 0.21 to 0.38). Conclusions: These data demonstrate that previously reported variations in metabolomic profiles with body mass index can be replicated in population-based studies with nonfasting blood collection protocols. We also provide preliminary evidence that large differences in metabolite levels exist between cases and controls, independent of body habitus. Our findings warrant assessment of metabolic profiles, including the candidate markers identified herein, in prospectively collected blood samples to define biomarkers and etiological factors related to endometrial cancer.     

The design,synthesis and catalytic performance of vanadium-incorporated mesoporous silica with 3D mesoporous structure for propene epoxidation

V-containing mesoporous silica with 3D structure was prepared by a hydrothermal procedure using NH₄VO₃ as the vanadium precursor and with varied reaction mixture pH values (pH = 3 and pH = 5). The combined use of DR UV-vis and H₂-TPR techniques confirmed the successful incorporation of vanadium into the structure of the mesoporous silica material. The number of acid sites, evidenced by ammonia TPD, strongly correlates with the vanadium content. Propene oxidation with N₂O revealed the noticeable activity of the synthesised vanadium-containing mesoporous materials in epoxidation reactions. The activity of the synthesized vanadosilicates is compared with the performance of vanadium-supported catalysts (on mesoporous silica of 3D structures) prepared by wet-impregnation method. On the basis of TOF analysis indicating the activity of particular vanadium ions, it was evidenced that although the presence of isolated V species is crucial in propene epoxidation, the availability of the active species is of paramount importance for proper vanadium utilization.

Novel promising vanadium catalysts based on mesoporous silica of 3D structure, namely KIT-6, SBA-12, and MCF, for the direct propene epoxidation with N₂O.     

Exercise training after coronary angioplasty improves cardiorespiratory function

Aim. The aim of this prospective randomized study was to evaluate the impact of long-term aerobic exercise training on respiratory function, left ventricular systolic function and remodeling in patients with coronary heart disease and ischemic heart failure after successful angioplasty. Design. Patients (n=185) have undergone Doppler echocardiography and ergospirometry. Ninety-five patients practiced 6 month-term aerobic exercise training, less by 10% to their anaerobic threshold. Ninety patients were studied as controls. They were given only drug treatment without training. Measurements were repeated after 6 and 12 months. Results. Training group patients after 6 months showed significant (p<0.05) improvement in exercise capacity, oxygen consumption and ventilating equivalents. The Doppler echocardiographic findings revealed significant (p<0.05) improvement in ejection fraction, left ventricular and atria morphometric data. Improved ergospirometric and echocardiographic data were established after 12 months, too. Conclusions. Long-term aerobic exercise training is an effective and workable measure improving respiratory efficiency, left ventricular systolic function, attenuating negative remodeling and stopping further progression in patients with coronary heart disease and chronic heart failure after successful angioplasty.     

Platelet Inhibition by Abciximab Bolus-Only Administration and Oral ADP Receptor Antagonist Loading in Acute Coronary Syndrome Patients: The Blocking and Bridging Strategy

Introduction

Current guidelines still recommend the bolus and infusion administration of glycoprotein IIbIIIa inhibitors in patients with high-risk acute coronary syndrome undergoing percutaneous coronary intervention. We sought to evaluate the extent of platelet inhibition by a blocking and bridging strategy with intracoronary abciximab bolus-only administration and oral loading of adenosine diphosphate receptor antagonists.

Patients and methods

Fifty-six consecutive high-risk acute coronary syndrome patients with bolus-only abciximab administration (0.25 mg/kg i.c.) and loading with 600 mg clopidogrel (55%) or 60 mg prasugrel (45%) were included in this study. Platelet aggregation induced by thrombin receptor-activating peptide and adenosine diphosphate was measured by multiple electrode aggregometry up to 7 days.

Results

Thrombin receptor-activating peptide induced platelet aggregation was significantly suppressed for a minimum of 48 h (45 ± 17 U) and returned to a normal range (> 84 U) after 6 days (90 ± 26 U; p < 0.001). Co-medication with prasugrel significantly reduced adenosine diphosphate-induced (p = 0.002) and thrombin receptor-activating peptide-induced (p = 0.02) platelet aggregation compared with clopidogrel throughout the observation period. No stent thrombosis or repeat myocardial infarction occurred at 30-day follow-up.

Conclusions

Immediate blocking of platelet aggregation in high-risk acute coronary syndrome patients by intracoronary abciximab bolus-only administration and bridging to prolonged inhibition via oral blockade of ADP receptors effectively inhibited overall platelet reactivity for at least 48 h, questioning the value of continuous abciximab infusion. Co-medication with prasugrel vs. clopidogrel synergistically augmented platelet inhibition.     

Pain among the oldest old in community and institutional settings

The relationship between pain and increasing age was investigated using data from two different care settings collected on a province-wide basis in Ontario. Home care clients (HC) and complex continuing care patients (CCC) are assessed using the Resident Assessment Instrument-Home Care and Resident Assessment Instrument 2.0 instruments, respectively, as part of normal clinical practice. For this study, the sample was restricted to those aged 65 years and older and totaled 193,158 individuals. Centenarians (those 100 years of age or older) made up 0.41% (n=788) of the sample. Pain was assessed according to a previously validated pain scale embedded in both assessments that uses items on frequency and intensity. Based on 5-year age groups beginning at 65, the mean reported pain score was lower with each increment in age for men and women. Multiple logistic regression models were constructed and the odds ratios for pain in both HC and CCC groups decreased consistently in higher age groups after adjusting for disease diagnoses, cognition, functional status and health indicators. A model that included categories of analgesic medications coded based on the WHO pain ladder showed the relationship persisted after controlling for analgesia. In clinical settings, the oldest old appear to have lower levels of pain compared with the young old after adjusting for a variety of potential confounding variables.