Effects of glutathione-modulating agents on the covalent binding and toxicity of dichlobenil in the mouse olfactory mucosa.

Twenty-four hours following injection of a single dose of the herbicide dichlobenil (2,6-dichlorobenzonitrile) in C57Bl/6 mice a steep dose-response curve for the histopathological toxicity in the olfactory mucosa was observed. Four hours following injection of a toxic dose of [ring-14C]dichlobenil (12 mg/kg) the covalent binding in the olfactory mucosa was 26 times higher than that in the liver. A dose-dependent decrease of nonprotein sulfhydryls (mainly glutathione, GSH) in the olfactory mucosa was observed 2.5 hr following injection of dichlobenil (6, 12, 25 mg/kg). The synthetic GSH precursor N-acetyl-L-cysteine decreased both the dichlobenil-induced toxicity and the covalent binding, whereas N-acetyl-D-cysteine had no effect. No protective effects of the cyanide antidotes nitrite, thiosulfate, or superoxide dismutase on the dichlobenil-induced toxicity were observed. In mice given the GSH-depleting agent phorone and a subtoxic dose of dichlobenil (6 mg/kg), an extensive toxicity and an increased covalent binding in the olfactory mucosa were demonstrated. Autoradiography showed no change in the distribution of covalent [14C]dichlobenil binding to nontarget tissues of phorone-treated mice. In conclusion, the results demonstrate a relationship between the degrees of covalent binding, GSH depletion, and toxicity of dichlobenil in the olfactory mucosa. Hence, the level of GSH appears to be of importance for the dichlobenil-induced toxicity in the olfactory mucosa.     

Nursing leaders' and nurses' view of health

This study is part of a scientific project, 'Multidimensional Health', the main goal of which is to introduce a broad view on health into health care and nursing The purpose of this study is to examine the view of health among nursing leaders and members of caring staff and to compare it to that of patients (a previous study in the project) The study is based on K Eriksson's theory of caring and its view of the human being with a body, soul and spirit, and health as a dynamic process concerning all aspects of human life An inquiry form with open questions that brought to the fore various aspects and dimensions of health was filled in by 20 nursing leaders and was used in interviewing 49 nurses According to the results many aspects of life are contained in the concept 'health' Health is above all an experience of well-being Ways of promoting one's health are described in terms of various 'healthy' living habits and preventive measures A supporting and humane attitude is hoped for in others There is unanimity that feelings affect health Belief may have a positive influence on health The meaning of life is connected with health Even suffering is part of health In interpreting the answers we assume three dimensions of health 'Health as behaviour' connects health with living in a healthy way 'Health as being' would mean a state of health and is characterized by a search for some kind of balance in one's inner state 'Health as becoming', growing towards health, means that a person becomes whole on a higher level of integration     

Pharmacokinetics of the enantiomers of felodipine in the dog after oral and intravenous administration of a pseudoracemic mixture

1. A pseudoracemic mixture of deuterated (S)-felodipine and unlabelled (R)-felodipine was administered as single i.v. or oral doses to four dogs. Plasma concentrations of the enantiomers and their corresponding pyridine metabolites were determined by g.l.c.-mass spectrometry. 2. No isotope effects were observed after oral administration of equimolar amounts of deuterated and unlabelled (S)-felodipine. 3. The pharmacokinetic parameters of the enantiomers were similar after i.v. administration, indicating that the disposition of felodipine was not stereoselective. 4. After oral administration the bioavailability of (R)-felodipine was slightly higher than that of (S)-felodipine in two of the dogs, presumably due to a lower first-pass extraction of the (R)-enantiomer, while no difference was observed in the other two dogs. 5. No substantial differences in Cmax or AUC were observed between the deuterated and unlabelled pyridine metabolites, indicating that the oxidative clearances of the felodipine enantiomers were similar.     

The intrinsic activities of the partial dopamine receptor agonists (-)-3-PPP and TDHL on pituitary dopamine receptors are lower in female than in male rats

The abilities of the mixed agonists/antagonists on dopamine (DA) receptors, (-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine [-)-3-PPP) and transdihydrolisuride (TDHL), to suppress serum prolactin levels in acutely hyperprolactinemic male and female rats were investigated. gamma-Butyrolactone was used to deplete endogenous DA and raise serum prolactin concentrations. Both (-)-3-PPP and TDHL were found to cause sexually differentiated responses: (-)-3-PPP reduced serum prolactin levels dose dependently and effectively in males but caused only a modest decrease of prolactin release in females. Moreover, (-)-3-PPP antagonized the prolactin-suppressing effects induced by the DA receptor agonist (+)-3-PPP in females. Likewise TDHL decreased prolactin secretion markedly in males while it had only slight effects in females. It can be concluded from these results that the intrinsic activities of the partial DA agonists (-)-3-PPP and TDHL are lower in female than in male rats, suggesting a reduced responsiveness of hypophyseal DA receptors in females. Since DA levels in the pituitary portal circulation are higher in female than in male rats, this study gives further support to the hypothesis claiming an inverse relationship between the intrinsic activity of a mixed agonist/antagonist and the degree of previous stimulation of its receptor.     

Tracers for aerosol ventilation scintigraphy: Tc-99m versus In-113m

113mIn has been proposed as a suitable tracer for aerosol ventilation scintigraphy in combination with 99mTc pulmonary perfusion scintigraphy. The high energy (393 keV) of 113mIn allows it to be detected in the presence of 99mTc, but degrades the spatial resolution which can be achieved. We have compared the resolution obtained with 99mTc and 113mIn in phantom experiments and in aerosol ventilation scans in 14 patients with airways disease. The resolution at the distances from the collimator encountered in lung scintigraphy was 10-20 mm for 99mTc and 15-40 mm for 113mIn. Aerosol ventilation images were abnormal in all patients. The 99mTc images showed peripheral defects and frequently central hot spots reflecting increased local aerosol deposition. In the 113mIn images, the lower resolution had a smoothing effect, the central hot spots were less striking, and the distribution of activity appeared more uniform, some detail was lost in the periphery. It is suggested that 113mIn is useful for ventilation scintigraphy in the diagnosis of pulmonary embolism, but that 99mTc is the tracer of choice if aerosol ventilation scintigraphy is used to study airways disease.     

Comparison of ionic and non-ionic nitroxide spin labels for urographic enhancement in magnetic resonance imaging

Two nitroxide spin labels (NSL) were compared for in vitro relaxivity and in normal rats for efficiency of urographic enhancement. One of the NSL, PCA, a pyrrolidinyl agent, was ionic and one, NAT, was a non-ionic pyrrolidinyl NSL with multiple hydroxyl substituents for water solubility. Using both NSLs the renal medulla and papilla were noted to show greater contrast enhancement than the cortex, with a maximum enhancing effect between 5 and 15 minutes. Using doses of 1.0 and 2.5 mmol/kg, more than 100 per cent increases in spin echo intensities above the baseline were observed. The lowest tested dose of 0.1 mmol/kg showed an easily detectable enhancing effect for NAT. The good contrast enhancing properties of NAT, considered together with its better acute tolerance, justifies further investigation of this non-ionic compound.     

Closing patellar tendon defects after anterior cruciate ligament reconstruction: absence of any benefit

The most common graft in anterior cruciate ligament (ACL) surgery involves using the central one-third of the patellar tendon. Knowledge concerning the postoperative disability after harvesting the patellar tendon is, however, limited. The aim of this study was to evaluate the impact patellar tendon suture and bone grafting of the patellar bone defect might have in terms of functional outcome and patellofemoral pain after harvesting the bone-tendon-bone graft, compared with leaving the harvested site non-sutured and non-grafted. Sixty patients, scheduled for arthroscopically assisted ACL reconstruction, were randomly allocated to two groups. In group I, suture of the patellar tendon and bone grafting of the patellar defect were performed. In group II, the tendon gap and the patellar defect were left open. Preoperatively, there was no significant difference between the groups when comparing objective knee stability, as measured with a KT-1000 laxity meter, Lysholm score, Tegner activity level, IKDC score, or patellofemoral pain score. Both groups had a significantly improved Lysholm score at the 2-year follow-up, without any difference between them. Tegner's activity level was significantly lower at follow-up, compared with the pre-injury level in both groups. The patellofemoral pain score improved significantly after the reconstruction, without any difference between the groups. Ultrasonography did not reveal any difference between the groups in terms of healing of the tendon gap. This study revealed no differences in donor site morbidity, functional outcome, patellofemoral pain score or knee joint stability between the two treatment groups. The conclusion is that suture of the patellar tendon and bone grafting of the patellar defect do not improve the functional results or reduce donor site morbidity after arthroscopically assisted ACL. Received: 17 December 1996 Accepted: 30 July 1997     

Mothers' Anticipation and Prevention of Unintentional Injury to Young Children in the Home

Investigated anticipation and prevention of children's unintentionalinjuries in the home. 150 mothers of 1-, 2-, and 3-year-oldchildren kept weekly diaries of anticipated injuries and unanticipatedinjuries/near injuries to their child. Mothers anticipated between57 and 67% of all injury events, a majority when the child wasin the same room as the injury-causing agent prior to interactingwith it. Few anticipated injuries led to injury. In these casesno significant differences were found depending on child's ageand sex. In contrast, mothers of younger children most frequentlyreported preventing injury by physically restricting or movingthe child away and by changing the environment, whereas mothersof older children more frequently engaged in teaching.     

Isokinetic quadriceps training in patients with patellofemoral pain syndrome

The aims of the present investigation were (a) to evaluate the effect of eccentric quadriceps training in patients with unilateral patellofemoral pain and (b) to compare the effect of eccentric and concentric quadriceps training in patients with bilateral patellofemoral pain. Fifteen patients (9 male and 6 female, aged 17–36 years with a mean of 27.5 years) participated in this study. Nine patients had unilateral pain and trained their painful leg eccentrically, while six had bilateral pain and trained one leg eccentrically and the other concentrically. Quadriceps muscle training was performed on a Kin-Com dynamometer at 90°/s and 120°/s angular velocity twice a week for 8 weeks. Before and after the treatment period the thigh muscle torques were measured on the Kin-Com dynamometer at 60°/s, 90°/s, 120°/s and 180°/s for quadriceps and at 60°/s and 180°/s for hamstrings. Nine controls, matched for gender and age with the group with unilateral pain, were tested in the same way on the Kin-Com dynamometer. For functional evaluation a knee score was calculated before training, after 8 weeks of training and at a mean of 3.4 years after completion of the training. After 8 weeks of training and at follow-up times of 1 and 3.4 years the patients were also questioned regarding whether or not they felt improvement from the training programme. To determine the degree of knee pain during the training Borg's pain scale was used. The results showed that, compared with the controls, the patients had a significantly lower knee extensor torque in their painful leg at all velocities measured. The greatest difference was found during eccentric actions. However, in comparison with the controls there were no significant differences in eccent ic and concentric knee flexor torques. After training there was a significant increase particularly in eccentric but also in concentric torque of the knee extensor in the painful leg of the eccentrically trained group. Of the six patients in the bilateral training group there were five who increased their concentric knee extensor torque and three who increased their eccentric torque. There were no significant differences in concentric and eccentric knee flexor torques before and after training in either of the legs in both training groups. The hamstring/quadriceps ratio was significantly higher in the patients' painful leg before training. However, due to increased quadriceps strength the hamstring/quadriceps ratio dropped after training. Patients in both groups reported no pain or mild pain during the training sessions. The eccentrically trained group was significantly improved both after 8 weeks of treatment and at follow-up 3.4 years later as evaluated using the knee score. The bilaterally trained group was significantly improved 3.4 years after completion of the training programme as evaluated using the knee score.