Identification of the glutathione conjugate of 4-nitroquinoline 1-oxide formed in the reaction catalyzed by murine glutathione transferases

The product of the enzyme-catalyzed conjugation of glutathioneand 4-nitroquinoline 1-oxide was isolated and its structuredetermined by MS and NMR. The results indicate that the cysteinesulfur of glutathione replaces the nitro group of 4-nitroquinoline1-oxide in the reaction with the formation of 4-(glutathion-S-yI)-quinoline1-oxide. No evidence was found for the binding of glutathioneto any other position of 4-nitroquinoline 1-oxide or throughany group other than the cysteine sulfur.     

New Techniques in Magnetic Resonance and Epilepsy

Summary: Developments in magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and single photon emission tomography (SPECT) have opened new opportunities for noninvasive brain investigation. Functional imaging methods involving noninvasive MRI and minimally invasive PET and SPECT are available that allow investigation of brain abnormality in intractable epilepsy patients. Noninvasive techniques enable the investigation of many aspects of the underlying neuropathologic basis of intractable seizures and of the relationship of functional abnormalities both to structural abnormalities and to the seizure focus. New MRI techniques demonstrate the structure of the brain in fine detail (especially the hippocampus), provide information about the underlying metabolism of brain regions, and demonstrate functional activity of the brain with high spatial and temporal resolution. The clinical impact of this noninvasive information cannot be overstated and these techniques provide indispensable information to neurologists specializing in epi-leptology. The proper use and interpretation of the findings provided by these new technologies will be a major challenge to epilepsy programs in the next few years.     

Resolution of ACE inhibitor cough: changes in subjective cough and responses to inhaled capsaicin, intradermal bradykinin and substance-P.

1. In eight hypertensive patients with ACE inhibitor-induced cough the resolution of the cough was examined in a prospective observational study over 4 weeks duration. Resolution of cough was measured by visual analogue scales and questionnaire at baseline and days 3, 7, 14 and 28. In addition changes in cough sensitivity to inhaled capsaicin, and skin responses to bradykinin and substance-P were measured at the same time points. 2. All patients recorded significant subjective improvement in cough questionnaire scores for severity and night time waking, and by visual analogue scales for severity and frequency of cough (all P < 0.0005 for trend from day 0-28). Significant changes in subjective measures were recorded by 3 to 7 days for most measures, but further reductions were observed up to day 28 (all P < 0.01 day 28 vs day 0). 3. The sensitivity to inhaled capsaicin fell over the 28 days of study after stopping enalapril. The potency of capsaicin relative to day 0 was reduced to 0.25 (95% CI 0.07-0.87) by day 14, and to 0.20 (95% CI 0.06-0.67) by 28 days. 4. After stopping enalapril there was a highly significant reduction in wheal area produced by intradermal bradykinin, with the majority of the effect seen by day 3 (P < 0.0005). The wheal area to intradermal substance-P also declined with time after stopping enalapril, but significant changes were not observed until 14 days (P < 0.01). 5. Multiple regression analysis of the rates of decline for the subjective and objective measures of cough showed significant associations between the response to inhaled capsaicin and the VAS scores for severity of cough (P = 0.005) and frequency of cough (P = 0.011). Capsaicin response was not related significantly to the severity of cough measured by self-administered questionnaire. 6. There was a significant association between bradykinin response and VAS scores for frequency of cough (P < 0.04) and severity of cough (P < 0.05), but not with cough by questionnaire or the capsaicin response. The response to substance-P did not relate significantly to any of the measures of cough. 7. Cough caused by enalapril improved markedly by 14 days but took up to 28 days to resolve. It was associated with increased sensitivity to inhaled capsaicin which decreased over 28 days, and which paralleled changes in subjective cough scores.     

ACUTE LITHIUM ADMINISTRATION IMPAIRS THE ACTION OF PARATHYROID HORMONE ON RAT RENAL CALCIUM,MAGNESIUM AND PHOSPHATE TRANSPORT*

1. Chronic lithium (Li⁺) treatment commonly produces a state of hyperparathyroidism in humans and rat although the mechanism is unknown. 2. The present study evaluated the acute effect of Li⁺ on renal electrolyte transport, particularly Ca²⁺ and Mg²⁺ in thyroparathyroidectomized (TPTX) and intact rats. 3. The acute administration of Li⁺ significantly increased water, sodium, potassium and phosphate excretion in both TPTX and intact animals; however, Ca²⁺ and Mg²⁺ excretion was only increased in the intact group. Fractional excretion (FE) of Ca²⁺ and Mg²⁺ increased from 2.2±0.2 to 3.5±0.3% and 12±2 to 18±2%, respectively (P<0.01). 4. In further experiments in TPTX rats, Li⁺ administration inhibited the usual reduction in urine Ca²⁺ and Mg²⁺ excretion following parathyroid hormone (PTH) administration and inhibited the phosphaturia. However, supramaximal concentrations of PTH overcame this inhibitory effect. For example, an FE_Ca of 3.8±0.2% was reduced to 1.4±0.2% and 1.7±0.2% with maximal and supramaximal PTH concentrations, respectively, while in the presence of Li⁺ an FE_ca of 4.0±0.2 was decreased to 2.8±0.2 and then 1.9±0.3% with the same PTH concentrations. 5. The inhibitory effect of Li⁺ was reduced with a lower plasma Li⁺ concentration (0.7±0.2 vs 1.6–1.8 mmol/L). The FE_Mg results were comparable. 6. These results demonstrate that Li⁺ directly inhibits PTH-mediated renal reabsorption of Ca²⁺ and Mg²⁺ and also blunts PTH-mediated phosphaturia. Therefore, the hyperparathyroidism in humans following Li⁺ treatment may be a consequence of reduced renal Ca²⁺ reabsorption.     

Eradication of schistosomiasis in Guangxi, China. Part 1: Setting, strategies, operations, and outcomes, 1953-92.

Reported are the results of an analysis of a 40-year programme leading to eradication of schistosomiasis in Guangxi, China, a large, poor autonomous region of the country that had the heaviest global burden of the disease. We used historical county data and maps showing the initial distribution and density of Oncomelania snails and the initial prevalence of schistosomiasis to assess the correlation between snail occurrence and human infection. All annual county schistosomiasis reports were collected and analysed, including information on snail abundance and infection, human and animal infection control, stool examinations and patient treatments, clinical and serology examinations, skin test surveillance, patient follow-up, patient treatments, animal examinations, water supply and sanitation, and environmental modification. The findings bear witness to the laborious, systematic and scientific basis of the control programme and how it changed over the 40 years. Of note is the continual search for and treatment of cases, the killing of snails, and the permanent alteration of their habitats using mass community participation and methods adapted to local conditions. The programme has freed more than 10 million people from the risk of schistosomiasis and boosted rural economic development and health. The persistence, good record keeping, evolving and locally flexible strategies, and the clear focus of the control programme were crucial to its eventual success.     

Effects of short-term exposure to high-dose inhaled corticosteroids on novel markers of bone metabolism

Objectives: Novel assays have been developed for markers of type 1 collagen turnover. The aim of this study was to evaluate the effect of short-term exposure to inhaled corticosteroids on both the novel and conventional markers of bone metabolism. Methods: Nine healthy subjects received 2 weeks treatment with inhaled budesonide 800 μg per day in week 1, and 1600 μg per day in week 2, or fluticasone 750 μg per day in week 1 and 1500 μg per day in week 2, with a 1-week washout in between. Measurement of carboxy-terminal propeptide of type 1 collagen (PICP), carboxy-terminal telopeptide of type 1 collagen (ICTP), plasma alkaline phosphatase bone isoenzyme, and 24-h urinary calcium excretion were made at baseline and at the end of each 2-week treatment period. Results: ICTP was significantly reduced following treatment with budesonide but not fluticasone compared with baseline: baseline 4.2 μg⋅1⁻¹ budesonide 3.0 μg⋅1⁻¹, fluticasone 3.6 μg⋅1⁻¹. There were no significant changes in PICP compared with baseline after treatment with budesonide or fluticasone. The ratio of PICP:ICTP increased significantly after treatment with both budesonide and fluticasone compared with baseline: baseline 27.4, budesonide 43.7, t 42.6. There were no significant differences between the two treatments for any of the measured parameters. Conclusions: Thus, when using sensitive markers of collagen turnover, short-term inhaled corticosteroid therapy was found paradoxically to reduced bone resorption. Received: 26 June 1995/Accepted in revised form: 14 November 1995     

Successful use of a transjugular intrahepatic portosystemic stent shunt to control severe refractory oesophageal variceal haemorrhage in a poor risk patient.

This report describes a 44 year old man with a severe gastrointestinal haemorrhage from oesophageal varices. Bleeding could not be controlled with conservative therapy and sclerotherapy. He was successfully treated with a radiologically guided transjugular intrahepatic stent shunt at a time when his condition was too poor to attempt an open surgical procedure.     

Through the looking glass: reflections on the authorship and content of current Australian nursing journals

Over the past three years, Australian nurses have witnessed a proliferation of locally published refereed nursing journals. This paper considers the refereed content published in four selected Australian nursing journals over a recent twelve month period. Material appearing in the Australian Journal of Advanced Nursing (AJAN), Contemporary Nurse, Nursing Inquiry and Collegian was categorized according to subject matter and authorship by gender and discipline. Findings indicate that articles pertaining to clinical practice, the practice of research, and professional nursing issues are well represented in the literature. These findings mark a change from earlier analyses of Australian nursing journals, which suggested that the epistemologies of other disciplines were over-represented in Australian nursing journals, and thus exerted a powerful influence over the development of nursing theory and scholarship. The increase in the number of refereed Australian nursing journals is indicative of the dynamic state of Australian nursing, in terms of confidence, scholarship and clinical practice development.