Bipyridylium herbicide toxicity: effects of paraquat and diquat on isolated rat hepatocytes

Paraquat (1,1'-dimethyl-4,4'-bipyridylium) and diquat (1,1'-ethylene-2,2'-bipyridylium) are the two most widely used bipyridylium herbicides today. Both compounds, however, have also been found to cause liver damage in animals and man. In this study, isolated rat hepatocytes were used to assess the cytotoxicity of these two compounds. Five indices of cell damage were used to quantitate cytotoxicity: dye (trypan blue) uptake, loss of cell respiration, the extracellular release of lysosomal enzymes, the formation of thiobarbiturate (TBA)-reacting substances, and the oxidation of cellular NADH and NADPH. Diquat was shown to be more toxic than paraquat toward these cells in the first three assay systems. The acute LC50 for diquat was determined to be 80 mM, whereas the acute LC50 for paraquat was estimated to be greater than 1 M. This difference in cell sensitivity could be explained, at least in part, by the observed differences in herbicide uptake rates for these two compounds. Diquat uptake was calculated to be 9.0 +/- 1.1 nmoles/hour/10(6) cells, whereas paraquat uptake was only 5.5 +/- 0.5 nmoles/hour/10(6) cells. The dose-response curves for enzyme release and loss of cell respiration superimposed the lethality curves for both compounds. An oxidative mechanism of cytotoxicity was suggested for diquat by: the establishment of both a concentration-dependent and a time-dependent increase in lipid peroxidation (formation of TBA-reacting substances); complete oxidation of both NADPH and NADH at herbicide levels less than the LC50; and the finding that diquat stimulated glucose oxidation at subtoxic doses.     

Some characteristics of the psychiatric population attending a primary care centre in Kuwait

This study examined the sociodemographic correlates of psychiatric illness in a primary care centre in Kuwait. A total of 164 psychiatric patients seen over a 3-year period formed the experimental group while 165 nonpsychiatric patients attending the same centre formed the control group. Results showed significant differences in basic demographic variables of the 2 groups. The psychiatric patients were significantly more likely to be single, unskilled, young, less educated and living alone or in an overcrowded household and to report more recent life events than controls. The absence of family and social support, lacking a meaningful job and chronicity of illness were significantly correlated with poor treatment response. Possible interpretations of the results were discussed in the cultural context of our patients. The fact that 57% of the psychiatric patients had been ill for more than 6 months prior to consultation highlights the importance of orientation of primary care practitioners to the psychiatric aetiology of somatic presentation of many of their patients.     

Cardiac calcified amorphous tumor in a patient presenting for ventricular tachycardia ablation: intracardiac echocardiogram diagnosis and management

Calcified amorphous tumors (CAT) of the heart are rare primary cardiac tumors characterized by heavy myocardial and valve apparatus calcification. The relationship of the entity with ventricular arrhythmia, if any, is unknown. We describe a case of cardiac CAT in a 58-year-old woman with prior cardiac arrest and recurrent ventricular tachycardia who presented for radiofrequency ablation. Pre-ablation intracardiac echocardiogram revealed the characteristic endomyocardial calcific pattern associated with this tumor that precluded catheter manipulation in the left ventricle. The imaging characteristics and management are described.     

Glutamate-loading Stimulates Metabolic Flux and Improves Cell Recovery Following Chemical Hypoxia in Isolated Cardiomyocyte

The amino acid glutamate is used in cardioplegic solutions, yet evidence is conflicting as to whether or not exogenous glutamate is indeed cardioprotective. This controversy may be because increasing extracellular glutamate does not necessarily lead to an increase in intracellular glutamate. In this study we aimed to determine whether isolation of myocytes in the presence of glutamate resulted in glutamate-loading of the cells, and, if so, whether such loading protected myocytes from simulated (chemical) hypoxia. Single ventricular myocytes were isolated from rat hearts in the presence and absence of 6.4 m glutamate. Levels of glutamate and ATP were determined using HPLC, and NADH/NAD⁺was determined from cell autofluorescence. Chemical hypoxia was induced by superfusion with a solution containing 2.5 m cyanide and no glucose. Intracellular [Ca²⁺] was measured by loading cells with indo-1, and cell length was measured using an edge-tracking device. Isolation of myocytes in the presence of glutamate resulted in increased intracellular glutamate levels compared with cells isolated in the absence of glutamate, 1324±108 v 948±124 pmol/mg protein, respectively (P<0.05). Cells loaded with glutamate showed increased NADH/NAD⁺, (0.384±0.032v 0.281±0.029, P<0.05) and greater ATP levels (36.031±1.633 nmol/mg protein v 19.279±3.327 nmol/mg protein, P<0.005) compared to control cells. When subjected to chemical hypoxia, cells underwent rigor-contracture at various timepoints, and were then reperfused following 5 min in rigor. Cells loaded with glutamate showed better recovery of diastolic [Ca²⁺], Ca²⁺transient amplitude, and improved contractile function compared with cells isolated in absence of glutamate. This study demonstrates an efficient method for loading myocytes with glutamate during cell isolation, and myocytes loaded with glutamate showed increased metabolic flux, as indexed by a higher NADH/NAD⁺and ATP content. Myocytes also exhibited better recovery from chemical hypoxia in terms of both Ca²⁺handling and cell contraction.     

Radial approach to right heart catheterization: early experience with a promising technique.

Transradial cardiac catheterization has been historically limited to arterial catheterization. Using small-diameter introducers and catheters, a technique of combined right and left heart catheterization is described using both the radial artery and its neighboring vein. Evaluation of 55 sequential right and left heart procedures showed that it could be accomplished in > 50% using venous access in the forearm. This approach has many potential advantages, although the ability to access routinely both venous and arterial vessels at the level of the wrist is unclear.     

Seventeen years' clinical and echocardiographic follow up of mitral balloon valvuloplasty in 520 patients, and predictors of long-term outcome

BACKGROUND AND AIM OF THE STUDy: Long-term echocardiographic follow up studies of mitral balloon valvuloplasty (MBV) are scarce. The study aim was to assess the long-term results (up to 17 years) of MBV and to identify predictors of restenosis and event-free survival. METHODS: The immediate and long-term clinical and echocardiographic results for 520 consecutive patients (mean age 31 +/- 11 years) who underwent successful MBV for severe mitral stenosis (MS) and were followed up for a mean of 7.3 +/- 4.35 years (range: 1 to 17 years) after MBV, were reported. RESULTS: Immediately after MBV, the mitral valve area (MVA) was increased from 0.92 +/- 0.17 to 1.96 +/- 0.29 cm2 (p < 0.0001). Restenosis occurred in 133 patients (25.6%), and was less frequent (16.7%) in patients with a low mitral echo score (MES < or = 8). Actuarial freedom from restenosis at 10, 15, and 17 years was 73 +/- 2%, 43 +/- 4%, and 23 +/- 6%, respectively, and was significantly higher in patients with MES < or = 8 (84 +/- 2%, 52 +/- 6%, and 36 +/- 9%, respectively; p < 0.001). Event-free survival (death, redo MBV, mitral valve replacement, NYHA class III or IV) at 10, 15, and 17 years was 82 +/- 2%, 45 +/- 5%, and 31 +/- 6% respectively, and was significantly higher for patients with MES < or = 8 (90 +/- 2%, 60 +/- 5%, and 51 +/- 8%, respectively; p < 0.001). Cox regression analysis identified MES > 8 (p < 0.0001) and post-procedure MVA (p = 0.044) as predictors of restenosis, and MES < or = 8 (p < 0.0001), age (p < 0.0001), and post-procedure MVA (p = 0.016) as predictors of event-free survival. CONCLUSION: MBV provides excellent long-term results for selected patients with MS. The long-term outcome of this procedure can be predicted from the baseline clinical and echocardiographic characteristics of the mitral valve.     

Evolution of drug-resistance genes in Plasmodium falciparum in an area of seasonal malaria transmission in Eastern Sudan

We investigated the evolution of drug-resistant Plasmodium falciparum in a village in eastern Sudan. The frequencies of alleles of 4 genes thought to be determinants of drug resistance were monitored from 1990 through 2001. Changes in frequencies of drug-resistance genes between wet and dry seasons were monitored from 1998 through 2000. Parasites were also typed for 3 putatively neutral microsatellite loci. No significant variation in frequencies was observed for the microsatellite loci over the whole study period or between seasons. However, genes involved in resistance to chloroquine showed consistent, significant increases in frequencies over time (rate of annual increase, 0.027/year for pfcrt and 0.018/year for pfmdr1). Genes involved in resistance to the second-line drug used in the area (Fansidar) remained at low frequencies between 1990 and 1993 but increased dramatically between 1998 and 2000, which is consistent with the advent of Fansidar usage during this period. For mutant alleles of the primary drug-resistance targets for chloroquine and pyrimethamine, higher frequencies were seen during the dry season than during the wet season. This cyclical fluctuation in drug-resistance genes most likely reflects seasonal variation in drug pressure and differences in the fitness of resistant and sensitive parasites.