Lack of effects of lesions of the dorsal noradrenergic bundle on behavioral vigilance

The effects of 6-hydroxydopamine (6-OHDA)-induced lesions of the dorsal noradrenergic bundle (DNB) were assessed in animals trained in a task designed to measure sustained attention, or vigilance. Infusions of 6-OHDA reduced frontal cortical noradrenaline contents but did not significantly affect striatal and hypothalamic noradrenaline contents. The performance of lesioned animals did not differ significantly from sham-lesioned controls. The performance of both the lesioned and sham-lesioned animals was impaired by the presentation of a visual distractor and by a decrease in the probability for a signal. The results from this study largely coincide with the results from previous studies on the effects of noradrenergic lesions on various aspects of attention. In contrast to the attentional functions assessed in this experiment, the ability to detect and select stimuli that are associated with activation of sympathetic functions is hypothesized to be sensitive to the effects of DNB lesions.     

Successful weight loss in a self-taught, self-administered program

There is little evidence concerning the effectiveness of self-help materials for weight control. The purpose of this research was to evaluate a self-help weight-loss program. Obese (body fat > or = 25.0%, range = 25.0-48.6%, mean +/- SEM = 36.5 +/- 1.3%) men (n = 14) and women (n = 21) were given a workbook detailing a behavior modification approach to weight loss that emphasizes self-monitoring of diet and exercise behaviors, and then sent home for 6 months to learn how to lose weight on their own. A group of 9 controls (CONT) who did not get a workbook were used for comparison. ANOVA showed that the experimental group (EXP) lost 8.1 +/- 0.9 (mean +/- SEM) kg body weight, 6.4 +/- 0.8 kg fat, and 3.9 +/- 0.6% body fat; all significant over time (p < 0.001) and different from the CONT (p < 0.0001) who showed no change in these variables. The EXP also reduced their fat intake (% of joules) from 36.1 +/- 1.0% to 27.9 +/- 1.3% (p < 0.0001), increased their carbohydrate intake from 45.7 +/- 1.2% to 50.0 +/- 1.7% (p < 0.007) and their protein intake from 16.3 +/- 0.05% to 20.7 +/- 0.7% (0 < 0.03), all of which were significantly different (p < 0.03) than the CONT who did not change. Dietary fiber increased in the EXP from 19.8 +/- 1.4 to 27.3 +/- 2.2 g/d (p < 0.001) even with a significant reduction in energy intake (11.3 +/- 0.6 vs. 8.9 +/- 0.5 Mj/d; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Two structural adaptations for regulating transmitter release at lobster neuromuscular synapses

The distal accessory flexor muscle (DAFM) in the lobster (Homarus americanus) walking leg consists of 5 muscle fiber bundles. All five bundles, one proximal, one distal, and 3 medial, are innervated by one excitatory and one inhibitory motor neuron. Both neurons release more transmitter on the distal bundle than on the proximal bundle. The aim of our studies was to investigate the structural basis of this differentiation. Thin sections cut at 50 microns intervals showed a similar number of excitatory synapses on the two bundles. Freeze-fracture views of excitatory synapses showed that synapse size, active zone number per synapse, and intramembrane particle density in the postsynaptic membrane are similar proximally and distally. Active zones at synapses on the distal bundle are larger and contain about 50% more large intramembrane particles, which are thought to include the voltage-gated Ca2+ channels that couple the action potential to transmitter release, than their counterparts on the most proximal bundle. This difference in channel number appears to produce a disproportionate increase in the probability of transmitter release sufficient to account for most of the proximal-distal disparity in the amplitude of the excitatory postsynaptic potential. In contrast, staining the inhibitor for antibodies to the inhibitory neurotransmitter, GABA, showed that it forms more varicosities on the distal bundle than on the proximal bundle. Because most of the synapses are located in the varicosities, differences in synapse number likely regulate the proximal-distal disparity in the amount of inhibitory transmitter released. Therefore, the regional differentiation in the amount of transmitter released in the DAFM appears to be based on two distinct mechanisms. In the inhibitor, transmitter release appears to be regulated differentially by differences in synapse number. In the excitor, transmitter release appears to be regulated differentially from a similar number of synapses by differences in active zone structure.     

Photophysical and redox properties of a series of phthalocyanines: relation with their photodynamic activities on TF-1 and Daudi leukemic cells

The photodynamic therapy (PDT) efficiency of five phthalocyanines, chloroaluminum phthalocyanine (AlPc), dichlorosilicon phthalocyanine (SiPc), bis(tri-n-hexylsiloxy)silicon phthalocyanine (PcHEX), bis(triphenylsiloxy)silicon phthalocyanine (PcPHE) and nickel phthalocyanine (NiPc), was assessed on two leukemic cell lines TF-1 and erythroleukemic and B lymphoblastic cell lines, Daudi, respectively. AlPc showed the best photocytotoxicity leading to 0.008 surviving fraction at 2 x 10(-9) M for TF-1 and 4 x 10(-9) M for Daudi. A1 5 x 10(-7) M, SiPc and PcHEX induced a significant photokilling, whereas NiPc and PcPHE were inactive. Laser flash photolysis and photoredox properties of the phthalocyanines were investigated to try to relate these parameters with the biological effects. AlPc showed the longest triplet life-time: 484 microseconds in dimethyl sulfoxide/H2O. This value was increased up to 820 microseconds when AlPc was complexed with human serum albumin used as a membrane model. Such an enhancement was not observed with the silicon phthalocyanines. Upon irradiation, all the phthalocyanines generated singlet oxygen with 0.29-0.37 quantum yield values. The reduction potentials of the excited states obtained from measurement in the ground state and energy of the excited triplets show that AlPc is the best electron acceptor. The in vitro photocytotoxicity observed and the measured parameters are in agreement with a key role of electron transfer in PDT assays involving these phthalocyanines.     

The effect of growth hormone replacement on cortisol metabolism and glucocorticoid sensitivity in hypopituitary adults

OBJECTIVE: Growth hormone (GH) replacement therapy in hypopituitary adults is associated with sodium and water retention. The underlying mechanisms are incompletely understood and a possible contribution of altered cortisol metabolism or action has not been evaluated. We have investigated the effect of GH replacement therapy on cortisol metabolism, cortisol binding globulin and in-vitro glucocorticoid sensitivity in a group of adult hypopituitary patients. DESIGN AND PATIENTS: We studied 19 adult hypopituitary patients (18 adult onset, M:F, 6:13), who were receiving conventional hydrocortisone (16 patients), thyroxine (14 patients), triiodothyronine (1 patient), sex steroid (9 patients), human chorionic gonadotrophin (1 patient) or desmopressin (6 patients) replacement during a 6-month, double blind controlled trial of GH therapy (active:placebo, 8:11) followed by a 6-month open phase of GH (mean dose: 0.2 IU/kg/week, range 0.051-0.27) and after a 6-week washout phase following discontinuation of GH therapy. MEASUREMENTS: Twenty-four-hour urine free cortisol, cortisol metabolites (CoM), ratio 11-hydroxy/11-oxo CoM (F/E) and ratio 5 alpha/beta tetrahydrocortisol were measured at 6 months, 12 months and after the 6 week washout phase. Serum cortisol binding globulin was measured basally, at 6 months, 12 months and after washout. Glucocorticoid sensitivity was determined in lymphocyte preparations from 8 patients, during GH therapy and after washout, using an in-vitro technique dependent on dexamethasone suppression of phytohaemagglutinin-stimulated thymidine incorporation into DNA. Plasma renin activity and aldosterone were measured after 6-12 months GH therapy and after washout. RESULTS: After 6 months of GH, in patients on hydrocortisone (n = 9), there were significant decreases in CoM (mean decrement 21%, P < 0.01), F/E (mean decreased from 1.27 to 1.0, P = 0.04; reference range 0.33-1.29) and 5 alpha/5 beta tetrahydrocortisol (mean decreased from 0.67 to 0.48, P = 0.01) and a subsequent increase after washout. Patients not on hydrocortisone (n = 2) demonstrated a normal basal F/E falling by 25% on GH therapy but no change in CoM. During 12 months of GH therapy, patients on hydrocortisone (n = 7) demonstrated a further trend to decrement in CoM (P = 0.09) which reversed after washout (P = 0.04). Urine free cortisol tended to fall during GH therapy and increased significantly following washout after 12 months treatment (P < 0.02). Serum cortisol binding globulin decreased by 20% (P < 0.05) during 12 months GH treatment but remained within the reference range. In-vitro studies demonstrated a trend to reduced glucocorticoid sensitivity on GH therapy; the maximum inhibition of phytohaemagglutinin by dexamethasone tended to be less on GH therapy (P = 0.052) and was also lower than in 29 normal volunteers (P < 0.05). There were no significant changes in plasma renin but there was a small increment in aldosterone in recumbent patients (P = 0.04) during the open phase of GH therapy in the placebo arm. CONCLUSIONS: GH therapy in hypopituitary adults is associated with an apparent reduction in availability of administered hydrocortisone as measured by urine cortisol metabolites and urine free cortisol. This effect is unlikely to be clinically significant except possibly in ACTH deficient subjects on suboptimal hydrocortisone replacement. The changes in F/E suggest that GH may directly or indirectly modulate the activity of 11 beta-hydroxysteroid dehydrogenase. The apparent decrease in glucocorticoid sensitivity during GH therapy, demonstrated in vitro, merits further investigation.     

Reversible nephrotic syndrome in Crohn's disease complicated with renal amyloidosis

A 24-year-old woman suffered from ano-rectal Crohn's disease and nephrotic syndrome due to glomerular amyloidosis AA. She received azathioprine and colchicine for two years. Both Crohn's disease and nephrotic syndrome resolved. However amyloid renal lesions were still present. This course is exceptional, and leads to a discussion of the treatment of amyloidosis associated with Crohn's disease.     

Linkage mapping of fifty-eight new rat microsatellite markers

Fifty-eight new anonymous simple sequence repeats (SSR) were generated and mapped to various rat chromosomes. Among them two genes (rat homologs for human cadherin-14 and mouse fibroblast growth factor-related protein) were mapped on Chromosomes (Chrs) 2 and 11 respectively. The majority of markers were generated from a small insert genomic library specific to Chr 11, 13, 14, and 15. Twenty new markers were mapped to Chr 13, which is known to contain a blood pressure quantitative trait locus (QTL). Several approaches to obtain microsatellite markers are described. The protocols and newly generated markers should be useful for ongoing rat genome project.