Use of PC12 Cells as a Neurotoxicological Screen: Characterization of Anticyanide Compounds

A series of six biochemical markers of cyanide toxicity (dopaminerelease, hydroperoxide generation, cytosolic-free calcium levels,catalase activity, cytochrome oxidase activity, and superoxidedismutase activity) in cultured rat pheochromocytoma (PC12)cells were used to establish a screen for evaluation of potentialanticyanide compounds. Thirty-nine substances, including anticonvulsants,adrenergic blockers, antioxidants, and antipsychotics were testedand ranked according to the results. Based on the compositescoring in all six assays, carbamazepine, mannitol, allopurinol,and phenytoin were ranked as the most effective anticyanidecompounds. Additionally, known cyanide antidotes (e.g., pyruvate,mercaptopyruvate, -ketoglutarate, naloxone, and flunarizine)obtained relatively high ranking in the PC12 cell screen. Furthermore,a significant correlation was found between protective effects(based on LD50s) of cyanide antidotes in mice and ranking inthe in vitro screen. This study illustrates that by assayinga series of biochemical markers in a neuronal-type cell line,a rapid, cost-effective in vitro toxicological screen is possible.Several compounds have been identified which inhibit the biochemicaleffects of cyanide and may be used to enhance effectivenessof the standard cyanide antidotes.     

Fibronectin in synovial fluid and tissue in rheumatoid arthritis

Fibronectin is a glycoprotein found in body fluids, loose connective tissue matrix and in basement membranes. Fibronectin in rheumatoid arthritis synovial fluid was immunologically indistinguishable from the plasma form, as shown by double-diffusion analysis. Fibronectin isolated from rheumatoid synovial fluid by affinity chromatography on gelatin--Sepharose had a polypeptide pattern similar to that of plasma fibronectin in SDS--polyacrylamide gel electrophoresis. In fifty-one patients with rheumatoid arthritis and related diseases fibronectin concentrations is synovial fluid were 445 +/- 103 micrograms/ml (mean +/- SD) and within normal range, 335 +/- 52 micrograms/ml, in plasma. Immunofluorescence staining showed a prominent increase of fibronectin in the proliferating synovial connective tissue in rheumatoid arthritis as compared to normal synovial membrane. The results suggest an increased local production of fibronectin in rheumatoid synovial tissue.     

Microvolt T-Wave Alternans During Exercise and Pacing in Patients with Acute Myocardial Infarction

Cardiac Arrhythmias and Risk Stratification after Myocardial infarction (CARISMA) is a prospective multicenter trial designed to document the incidence of cardiac arrhythmias after acute myocardial infarction (AMI), and to assess the predictive accuracy of various arrhythmic risk markers. In this substudy of the CARISMA trial, microvolt T-wave alternans (TWA) was assessed with specific equipment 6 weeks after AMI during bicycle exercise, atrial (A) pacing, and simultaneous ventricular and atrial (V + A) pacing in 80 patients with left ventricular ejection fraction (LVEF) <40%. The agreement between the acute test results was determined by overall proportion of concordance and the kappa statistic. Sustained TWA was observed in 24, 45, and 50% of the patients during the exercise test, A pacing, and V + A pacing, respectively. The number of indeterminate TWA was significantly lower during V + A pacing (n = 7) than exercise test (n = 34). The TWA concordance rate was 71% between exercise and V + A pacing (κ= 0.53, P = 0.001), 79% between exercise and A pacing (κ= 0.54, P < 0.001), and 95% between the two pacing modes (κ= 0.89, P < 0.001). Patients with positive TWA in all tests had lower LVEF (28 ± 7% vs 35 ± 9%, P < 0.01) and wider QT dispersion (99 ± 44 ms vs 67 ± 38 ms, P < 0.01) than those with inconsistent test result. The low number of indeterminate tests and high concordance between the test results indicate that V + A pacing may provide a valuable means to assess TWA in patients who cannot complete the exercise test.     

Twenty year smoking trends in a community-based cardiovascular diseases prevention programme: Results from the North Karelia Project

Objectives: to evaluate long-term changes associated with acommunity-based cardiovascular disease prevention programmeon smoking. Methods: the North Karelia Project was started in1972 to carry out a comprehensive community-based programmeto reduce the exceptionally high rates of cardiovascular diseases(CVD) in North Karelia, an eastern province in Finland. Amongthe main intermediate objectives was the reduction of smokingrates, particularly among the male population. The programmewas evaluated by standardized examinations of large representativecross-sectional population samples in 1972, 1977, 1982, 1987and 1992 in North Karelia and in the Kuopio province, anotherprovince in eastern Finland, which was initially chosen as referencearea for the first project period. Results: in men the percentageof current smokers decreased during the 20 years from 52 to32% in North Karelia and from 50 to 37% in the initial referencearea (p<0.05). Smoking declined faster in the first 10 years(from 1972 to 1982) than in the last 10 years. During the first10 years the decline was more remarkable in North Karelia thanin the reference area. The main reason for the decline in smokingduring the first 10 years was smoking cessation and during thelast 10 years the increase in the number of people who had neversmoked regularly. Among women the proportion of smokers increasedin both areas from approximately 10 to approximately 20%. Thisincrease was greatest in the youngest age group. Conclusions:the community-based cardiovascular disease prevention programmewas an effective way to reduce smoking in the general populationin men and sustained decline could be achieved.     

Trimethoprim Prophylaxis of Acute Exacerbations in Chronic Obstructive Pulmonary Diseases

ABSTRACT. Liippo K, Pelliniemi T-T, Lehto H (Department of Diseases of the Chest and Haematology, University of Turku, and the Research Center of the Farmos Group Ltd., Turku, Finland). Trimethoprim prophylaxis of acute exacerbations in chronic obstructive pulmonary diseases. Acta Med Scand 1987; 221:455–9. A double-blind randomized trial was carried out to study the efficacy and tolerance of trimethoprim with a daily single dose of 300 mg in long-term prophylaxis of acute exacerbations of chronic obstructive pulmonary diseases (COPD). The patients, 13 in the trimethoprim group and 11 in the placebo group, were followed up at fixed intervals and checked for respiratory functions and haematological parameters for six months. The number of exacerbations were significantly lower than during the previous winter in both groups: 0.6 compared to 3.8 in the trimethoprim group, and 0.6 to 3.0 in the placebo group. Tolerance of trimethoprim was good and did not differ from that of placebo. The necessity of double-blind trials in evaluating the prophylactic value of antibiotics in COPD is emphasized, since the exacerbations are also dependent on many unknown factors. There were no statistically significant differences in blood counts of folate levels.     

Autonomic Dysfunction and New‐Onset Atrial Fibrillation in Patients With Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction: A CARISMA Substudy

Predicting New‐Onset AF. Background: Atrial fibrillation (AF) increases morbidity and mortality in patients with previous myocardial infarction and left ventricular systolic dysfunction. The purpose of this study was to identify patients with a high risk for new‐onset AF in this population using invasive and noninvasive electrophysiological tests. Methods: The study included 271 patients from the Cardiac Arrhythmias and RIsk Stratification after Myocardial InfArction (CARISMA) study with an acute myocardial infarction (AMI) and left ventricular ejection fraction ≤40% without previous AF at enrollment. Within 21 days after the AMI, an implantable loop recorder was inserted and used to diagnose AF over the 2‐year study duration. The following tests were performed: heart rate variability (HRV) and turbulence (HRT) analyses from repeated 24‐hour Holter recordings, 2‐dimensional (2D)‐echocardiograms, exercise test, and programmed electrophysiologic stimulation. Results: A total of 101 patients (37%) developed AF during the study. Predictive measures included several indexes of HRV including reduced low‐frequency (LF) power from spectral HRV analysis (adjusted HR = 1.6, P = 0.034), HRT slope ≤2.5 (HR = 1.6, P = 0.032) and Detrended Fluctuation Analysis (DFA1) from HRV analysis (HR = 1.8, P = 0.011); all are measures of cardiac autonomic nervous system dysfunction. Combined with age >60 years, low values for LF, HRT slope, and DFA1 provided a powerful risk score for prediction of new‐onset AF (1–2 points: HR = 4.3, P = 0.001, 3–4 points: HR = 7.0, P < 0.001). Conclusion: Abnormal HRV and HRT parameters, which are associated with disturbances in the cardiac autonomic regulation, are associated with increased risk of new‐onset AF independently of conventional clinical risk variables. (J Cardiovasc Electrophysiol, Vol. 21, pp. 983‐990, September 2010)     

School-based education to improve oral cleanliness and gingival health in adolescents in Tehran, Iran

Background.  Schools can be an important setting for health education programmes, controlling the growing burden of oral diseases and promoting oral health.
Aim.  The aim of this study was to evaluate the short-term effect of school-based educational intervention on oral cleanliness and gingival health of 15-year-olds in Tehran, Iran.
Design.  The present cluster randomized trial was based on exposing students ( n  = 287; control, n  = 130) at public schools to oral health knowledge through a leaflet or a videotape. The outcome was evaluated after 12 weeks. A positive outcome was defined as at minimum a 50% reduction in numbers of teeth with dental plaque or gingival bleeding compared to baseline. Evaluation included percentage changes, number needed to treat (NNT), and students' self-assessment.
Results.  At baseline, all students had dental plaque, and 93% had gingival bleeding on at least one index tooth. Positive outcome for oral cleanliness was 58% ( P  < 0.001) of the students in the leaflet group, 37% ( P  < 0.001) in the videotape group, and 10% of controls. Corresponding figures for gingival health were 72% ( P  < 0.001), 64% ( P  < 0.001), and 30%. For oral cleanliness, NNT was 2 in the leaflet and 3 in the videotape group; for gingival bleeding, NNT in both groups was 3. More than two-thirds of the students assessed their oral health behaviours as having improved moderately.
Conclusion.  An easy-to-organize and inexpensive school-based intervention can in the short term be effective in improving oral cleanliness and gingival health among adolescents; in particular, in countries with a developing oral health system.     

Effects of a chlorhexidine-fluoride-strontium rinsing program on caries, gingivitis and some salivary bacteria among Finnish school children

Abstract – In order to find out if it is possible to prevent caries and gingivitis by periodical use of chlorhexidine-fluoride mouthrinses with or without strontium, and to find out what effects they have on salivary mutans streptococci and lactobacilli counts, a total of 243 schoolchildren aged 11 yr with high DMFS scores were randomly divided into four groups. One group (C) served as a basic control. Subjects in the second group (GXF) rinsed their mouths twice a day every third week with a rinsing solution containing 0.05% chlorhexidine gluconate and 0.04% NaF. In the third group (CXFS) the rinsing solution contained 500 ppm Sr during the first and second year and 15 ppm during the last 6 months, in addition to chlorhexidine and fluoride. In the fourth group (CX) the solution contained only 0.05% chlorhexidine gluconate. All the rinsing solutions had pH 5.8 buffered with succinic acid-NaOH buffer. After 2 yr and 9 months, the mean DMFS (SD) increments in the C, GXF, GXFS, and GX groups were 3.8 (5.7), 2.5 (3.2), 3.5 (4.8), and 3.4 (5.5), respectively. The percentage of subjects with bleeding gingival units had decreased from initial to final values as follows: C, 81–38; GXF, 88–42; GXFS, 89–56; GX, 89–37. The number of lactobacilli and mutans streptococci in saliva remained virtually unchanged throughout the study. For caries increment and gingival bleeding, the differences between groups were not statistically significant. The chlorhexidine-fluoride combination tended to prevent caries, but the effect on gingival bleeding and salivary counts of mutans streptococci and lactobacilli was negligible.     

Thallium Scintigraphy in Prediction of Occlusion of Bypass Grafts in Asymptomatic and Symptomatic Patients

ABSTRACT To evaluate thallium scintigraphy in predicting coronary artery bypass graft patency, exercise thallium scintigraphy and selective graft and native vessel angiograms were performed in 22 asymptomatic and 29 symptomatic consecutive patients three months after coronary artery bypass grafting (CABG). Twelve out of 22 asymptomatic patients (55%) had reversible thallium defects on postoperative images; in 10 patients the postoperative scans were normal. The graft patency was significantly lower in asymptomatic patients with abnormal thallium perfusion compared to those with normal perfusion after CABG (68% vs. 91%. p<0.05). The rate of graft patency in symptomatic patients was 66/87 (76%). Thallium scintigraphy was 77% sensitive and 78% specific in detecting one or more stenosed or occluded bypass grafts in patients without angina (accuracy 77%). When data from exercise electrocardiography were combined with scintigraphy, all but one patient with incomplete revascularization could be detected (positive predictive accuracy 92%). In symptomatic patients, thallium scintigraphy accurately predicted the presence or absence of graft occlusion in 24/29 (83%) cases. Thus, abnormal myocardial perfusion due to stenosis or occlusion of bypass grafts is common in both asymptomatic and symptomatic patients after CABG. Thallium scintigraphy together with exercise electrocardiography appear to be useful non-invasive methods in detecting painless myocardial ischemia and in predicting bypass graft occlusion after CABG.     

Frequency Dependent Effects of d-Sotalol and Amiodarone on the Action Potential Duration of the Human Right Ventricle

Frequency dependent effects of d-Sotalol (2.0 mg/kg IV, n = 6) and amiodarone (400 mg/day for 3 months, n = 9) were studied on the action potential duration (APD) in 14 patients who underwent electrophysiological testing. Monophasic action potentials were recorded from the right ventricle at five different steady-state paced cycle lengths (700 msec, 600 msec, 500 msec, 400 msec, and 350 msec), and during ventricular extra stimuli with coupling intervals between 300 msec and 1000 msec, before and after d-sotalol and amiodarone, respectively. D-sotalol caused a prolongation of the APD at slow steady-state stimulation rates (11 ± 5% at cycle length of 700 msec), which became attenuated at faster cycle lengths (5 ± 3% at cycle length of 350 msec). Prolongation of APD after amiodarone was independent of pacing rate, e.g., 12 ± 9% at cycle length of 700 msec, and 11 ± 6% at cycle length of 350 msec. Similar frequency dependent prolongation of the APD was observed during abrupt changes of cycle lengths after d-sotalol, whereas amiodarone caused uniform prolongation of the APD at different extrasfimulus intervals. Thus, d-sotalol, a nonselective potassium channel blacker, has reverse use-dependent effects on the human ventricular APD, while amiodarone with greater potassium channel selectivity, has equal ability to prolong the ventricular APD at fast and slow heart rates.