Effect of the peroxisome proliferator perfluorodecanoic acid on growth and lipid metabolism in Sprague Dawley rats fed three dietary levels of selenium

The possible interrelationships between the effects of dietary selenium and perfluorodecanoic acid (PFDA) on growth and lipid metabolism were studied in the male Sprague Dawley rat. Rats were divided into groups and placed on diets containing three levels of selenium (0.04, 0.2, and 1.0 ppm as sodium selenite). Two weeks later, half the rats in each group received a single 35 mg/kg IP injection of PFDA in corn oil, while their pair-fed companion received only vehicle. Rats injected with PFDA stopped gaining weight, and weighed less than pair-fed controls, despite equal food intakes. Two weeks following PFDA administration the rats were killed and plasma cholesterol and triglycerides, and liver peroxisomal enzyme activities were quantified. In contrast to other peroxisome proliferators, PFDA increased plasma triglycerides while decreasing plasma cholesterol. The rate of peroxisomal fatty acid -oxidation was decreased, even though the activity of fatty acyl-CoA oxidase, the first enzyme in the peroxisomal fatty acid -oxidation pathway, was increased. Dietary selenium, other than increasing the liver to body weight ratio, did not alter growth or lipid metabolism. This study demonstrates, for the first time, the existence of a non-hypotriglyceridemic peroxisome proliferator-PFDA.     

Differences in Caffeine 3-Demethylation Activity among Inbred Mouse Strains: A Comparison of Hepatic Cyp 1a2 Gene Expression between Two Inbred Strains

The 3-demethylation of caffeine can be used as an index of cytochromeP450 CYP1A2 activity in vivo. We compared the plasma levelsof caffeine and the 3-demethylated metabolite, 1,7-dimethylxanthine,in six common inbred strains (A/J, P/J, BALB/cJ, C3H/HeJ, AKR/J,and SWR/J) and one inbred strain (APN) derived in our laboratoryfrom outbred Swiss-Webster mice on the basis of its relativesusceptibility to acetaminophen-induced hepatotoxicity. We foundsignificant variations between a number of the common strains,all of which produced significantly higher caffeine 3-demethylationindices than our APN strain. In three of the six common strains,there was a significant difference between males and females,with the females having consistently lower 1,7-xanthine/caffeineratios. Hepatic Cyp1a2 expression was compared between APN andC3H/HeJ males. Microsomal methoxyresorufin O-demethylation,acetanilide 4-hydroxylation, and CYP1A2 immunoreactive proteinlevels were significantly higher in C3H/HeJ relative to APNmice, as were hepatic CYP1A2 mRNA levels. These results indicatethe importance of strain and gender to the outcome of pharmacologicalor toxicological studies involving CYP1A2-mediated metabolism,as well as the suitability of the plasma 1,7-dimethylxanthine/caffeineratio as a marker of CYP1A2 activity in the mouse. The strikingdifferences observed between the APN and C3H/HeJ mice suggestthat these strains may be suitable for a genetic analysis ofthe regulation of the basal expression of CYP1A2, a key enzymeIn procarcinogen activation.     

Comparative behavioral characterization of the neuroactive steroids 3α-OH,5α-pregnan-20-one and 3α-OH,5β-pregnan-20-one in rodents

Pregnan steroids have been shown to possess anesthetic, hypnotic, anticonvulsant and anxiolytic properties. In this study, two endogenous neuroactive steroid isomers, 3-hydroxy-5-pregnan-20-one (3,5-P) and 3-hydroxy-5-pregnan-20-one 3,5-P), were studied for differences in their pharmacological properties using behavioral assays. 3,5-P and 3,5-P were similar in their potencies and efficacies in blocking pentylenetetrazol-induced seizures in mice (ED₅₀: 3,5-P=2.8 mg/kg and 3,5-P=3.0 mg/kg). Similarly, both neuroactive steroids produced roto-rod deficits within the same range of potency (TD₅₀:3,5-P=18.8 mg/kg and 3,5-P=21.2 mg/kg). However, in animal models of anxiety, subtle differences were observed between the two isomers. In both the light/dark transition test and elevated plus-maze, 3,5-P was more efficacious than 3,5-P, though both compounds had similar potencies. In the Geller-Seifter test, 3,5-P was more potent and efficacious than 3,5-P. Neither compound had significant effects on unpunished responding within the dose range tested. Both compounds produced similar biphasic curves in the locomotor test. All together, the data indicate that 3,5-P and 3,5-P have similar anticonvulsant activity, but the 5-isomer possesses more potent and efficacious anxiolytic properties than the 5-isomer.     

On the road to collaborative treatment planning: Consumer and provider perspectives

Although consumers have made significant gains in having their voices heard in several areas within mental health, they have made less progress in being able to collaborate with their own treaters in setting treatment goals. On the basis of several years of groundwork by staff at the Connecticut Mental Health Center (CMHC), the Patient Care Committee conducted a needs assessment of providers and consumers to assess both groups' current involvement, interest in, and attitudes toward collaborative treatment planning. The results indicate that providers tend to place much of the responsibility for the difficulties in implementing collaborative treatment planning on consumers. Also, providers tend to underestimate consumers' interest in participating in this process. Implications of these findings for the development of an agency-wide training to enhance the collaborative nature of treatment planning are discussed.     

Age but not sex affects motor recovery after unilateral sensorimotor cortex suction-ablation in the rat

Both age and sex can influence recovery after brain injury. To determine the impact of these variables on motor recovery, young (2 month old) and older (5-6 months old) male and female rats were first trained to traverse a narrow elevated beam. Rats then underwent suction-ablation of right sensorimotor cortex or sham operation. Motor recovery was measured by repeated testing on the beam over 3 weeks. Shamoperated rats performed perfectly regardless of age or sex throughout testing. There was no difference in beam-walking scores among the groups of lesioned rats on the first trial 24 hrs. after injury (Kruskal-Wallis H = 0.18, p = 0.98). There was a significant effect of age (two-way ANOVA F1,32 = 29.58, p < 0.0001) but not sex (ANOVA F1,32 = 0.78, p = 0.38) on subsequent recovery. These data show that motor recovery after unilateral injury to the sensorimotor cortex varies with age, but not sex.     

Therapeutic Agents of Assertive Community Treatment

The goal of this study was to learn how assertive community treatment (ACT) contributes to the improvement of those with serious mental illness in order to contribute to the growing clinical literature regarding the therapeutic agents of ACT teams. Methods included reviewing the case records of three ACT clients who have improved significantly, as well as interviewing the clients themselves and their clinicians. The results indicated that there was significant agreement among the case records, the clients, and their clinicians in identifying the most useful aspects of assertive community treatment. Primary among these factors were the persistence demonstrated by ACT clinicians in engaging their clients, the trust that clients developed in their clinicians, and as a result, the process by which their clinicians became guides to the world of psychiatric and social services that further facilitated their clients' community adjustment. In closing, we consider implications from these findings both for staff development for ACT team members, and for suggestions toward the development of a model of recovery from serious mental illness.     

Motion discrimination of single targets: comparison of preliminary findings in normal subjects and patients with glaucoma

Background: Luminance, global motion and flicker sensitivities are affected in patients with primary open-angle glaucoma. Although no theoretical model has been put forward to explain the observed reduction in sensitivity in this patient group, these findings have often been attributed to diffuse and selective loss of large optic nerve fibres. Methods: Movement processing was investigated using an optical projection system that generates smooth, continuous motion with control of speed, displacement and motion direction. Motion-displacement and direction-discrimination thresholds were measured in eight normal subjects and in three patients with diagnosed glaucoma. At each speed tested, targets were presented for a range of displacements and thresholds were extracted after probit analysis. The measurements were carried out both foveally and at 19° in the periphery and provided the data necessary to develop and optimise a model of motion perception based on multiple time delays for the correlation of signals that map progressively more distant parts of the visual field. Results: Our preliminary findings show that direction discrimination can be at chance level even for large displacements when motion is detected 80% of the time. Model simulations show that specific changes in the spatial sampling interval and the speed of transmission of the motion signals involved can cause the observed reduction in motion sensitivity and direction discrimination in patients with glaucoma. Conclusions: A model for motion detection and direction discrimination of single targets has been proposed to account for the measured functional relationship between motion displacement thresholds and target speed in normal subjects. Tested patients with glaucoma show reduced motion sensitivity and poor discrimination of motion direction. The type of degraded performance observed experimentally in glaucoma patients is also predicted by the model. Such predictions require specific changes in model parameters that may be indicative of changes in the retina caused by the disease.     

Semen Parameters Before and After Transurethral Surgery for Ejaculatory Duct Obstruction

Purpose

We examined how transurethral resection of the ejaculatory ducts, performed for infertility, affects semen quality in patients with azoospermia and oligo-asthenospermia.

Materials and Methods

A retrospective review was done of 46 cases of transurethral resection of the ejaculatory ducts for ejaculatory duct obstruction, confirmed by transrectal ultrasound. Clinical course and semen quality were assessed by semen parameter indications.

Results

In 65 percent of the patients transurethral resection of the ejaculatory ducts improved semen quality (greater than a 50 percent increase in total motile sperm count) and 20 percent initiated a pregnancy an average of 6.1 months postoperatively. Statistically significant increases in total motile sperm count were achieved in men with azoospermia and those treated for oligo-asthenospermic indications; the improvement also was shown to be sustainable. Complications occurred in 20 percent of the men.

Conclusions

Significant and durable semen quality improvement can be achieved after transurethral resection of the ejaculatory ducts for all surgical indications. In most unsuccessful cases the reason for failure is unclear.