Effects of meta-chlorophenylpiperazine infusions in patients with seasonal affective disorder and healthy control subjects. Diurnal responses and nocturnal regulatory mechanisms

BACKGROUND: Multiple lines of evidence suggest that brain serotonergic systems may be disturbed in seasonal affective disorder (SAD). Previously, we found that the serotonergic agent meta-chlorophenylpiperazine (m-CPP) produced increases in activation and euphoria in depressed patients with SAD, but not in patients with SAD following light treatment or in the summer, nor in healthy control subjects in any condition. In the present study, we attempted to replicate and extend this finding using better methods. METHODS: Seventeen outpatients with SAD and 15 control subjects underwent successive 3-week periods of bright light treatment and light avoidance in a randomized order. During the third week of each condition, on 2 different occasions, subjects were admitted to the hospital for a night of sleep (core temperatures were recorded), followed by infusions of m-CPP (0.08 mg/kg) or placebo the next morning. Dependent measures included the 24-item National Institute of Mental Health Self-Rating Scale, plasma corticotropin, cortisol, prolactin, growth hormone, and norepinephrine concentrations, and core temperatures. RESULTS: Meta-chlorophenylpiperazine produced (1) significant increases in "activation-euphoria" ratings only in depressed patients with SAD in the untreated condition and (2) blunted corticotropin and norepinephrine responses in patients with SAD compared with controls across both light treatment conditions. In both groups, light treatment was associated with significant reductions in nocturnal core temperatures, which were correlated with similarly significant reductions in mean diurnal growth hormone concentrations. In patients with SAD, (1) the reductions in nocturnal core temperatures also were correlated with the reductions in baseline depression ratings and (2) the reductions in mean growth hormone concentrations were significantly smaller compared with controls. CONCLUSIONS: The abnormal m-CPP-induced activation-euphoria responses represent a replicated state marker of winter depression in patients with SAD. The blunted m-CPP-induced responsiveness of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system may represent traitlike abnormalities. The improvements in mood following light treatment in patients with SAD seem to be associated with the lowering of nocturnal core temperatures. The findings, although not easily explained based on a uniform abnormality of serotonin receptors, are nonetheless compatible with the notion that selected regions of the central nervous system are deficient in serotonin transmission during winter depression.     

Psychosocial, behavioral, and health factors related to menopause symptomatology

California Proposition 65 (Prop65) provides a mechanism by which the manufacturer may perform a quantitative risk assessment to be used in determining the need for cancer warning labels. This paper presents a risk assessment under this regulation for professional and do-it-yourself insulation installers. It determines the level of insulation glass fiber exposure (specifically Owens Corning's R-25 PinkPlus with Miraflex) that, assuming a working lifetime exposure, poses no significant cancer risk under Prop65's regulations. "No significant risk" is defined under Prop65 as a lifetime risk of no more than one additional cancer case per 100,000 exposed persons, and nonsignificant exposure is defined as a working lifetime exposure associated with "no significant risk." This determination can be carried out despite the fact that the relevant underlying studies (i.e., chronic inhalation bioassays) of comparable glass wool fibers do not show tumorigenic activity. Nonsignificant exposures are estimated from (1) the most recent RCC chronic inhalation bioassay of nondurable fiberglass in rats; (2) intraperitoneal fiberglass injection studies in rats; (3) a distributional, decision analysis approach applied to four chronic inhalation rat bioassays of conventional fiberglass; (4) an extrapolation from the RCC chronic rat inhalation bioassay of durable refractory ceramic fibers; and (5) an extrapolation from the IOM chronic rat inhalation bioassay of durable E glass microfibers. When the EPA linear nonthreshold model is used, central estimates of nonsignificant exposure range from 0.36 fibers/cc (for the RCC chronic inhalation bioassay of fiberglass) through 21 fibers/cc (for the i.p. fiberglass injection studies). Lower 95% confidence bounds on these estimates vary from 0.17 fibers/cc through 13 fibers/cc. Estimates derived from the distributional approach or from applying the EPA linear nonthreshold model to chronic bioassays of durable fibers such as refractory ceramic fiber or E glass microfibers are intermediate to the other approaches. Estimates based on the Weibull 1.5-hit nonthreshold and 2-hit threshold models exceed by at least a factor of 10 the corresponding EPA linear nonthreshold estimates. The lowest nonsignificant exposures derived in this assessment are at least a factor of two higher than field exposures measured for professionals installing the R-25 fiberglass insulation product and are orders of magnitude higher than the estimated lifetime exposures for do-it-yourselfers.     

Path-dependency in public–private partnership in French urban renewal

Public–private partnership in urban renewal in France concerns mainly housing, transport infrastructure and large public facilities. The distinction between public, private and civil actors does not concern social and economic development. This situation tends to limit the integration of different issues and approaches in renewal projects. Also, French urban renewal projects do not produce a new type of partnership between public and private actors and the regulatory framework. These projects remain publicly dominated policy-making procedures because of the uneven distribution of resources and assets and despite a policy discourse emphasising the need for a new division of work between state, market and civil society. The current French situation cannot be understood without bearing in mind the history of urban planning policies in France. Using a historical analysis and the path-dependence approach, we highlight the resilience of inherited structures of interaction between public and private actors.     

Effects of nicotine and stress on startle amplitude and sensory gating depend on rat strain and sex

We recently reported that 14 days of nicotine administration (12 mg/kg/day) reduced acoustic startle reflex amplitude and impaired prepulse inhibition (PPI) of startle in male and female Long-Evans rats. These findings contrasted with reports of nicotine-induced enhancement of startle and PPI in Sprague-Dawley (a different strain) male rats. The present experiment administered 0, 6, or 12 mg/kg/day nicotine via osmotic minipump for 14 days to 120 Sprague-Dawley rats (male and female) and to 120 Long-Evans rats (male and female) and examined ASR and PPI. Half of the subjects also were stressed by immobilization once each day to examine nicotine-stress interactions. Nicotine enhanced ASR and PPI responses of Sprague-Dawley rats but impaired these responses in Long-Evans rats, regardless of sex. Effects of stress were complex and depended on strain, sex, and drug dose. These findings indicate that effects of nicotine on measures of reactivity (ASR) and sensory gating (PPI) depend on genotype and that nicotine stress interactions depend on genotype, sex, and nicotine dosage.     

Osteopathy and resistance to vitamin D toxicity in mice null for vitamin D binding protein

A line of mice deficient in vitamin D binding protein (DBP) was generated by targeted mutagenesis to establish a model for analysis of DBP's biological functions in vitamin D metabolism and action. On vitamin D-replete diets, DBP-/- mice had low levels of total serum vitamin D metabolites but were otherwise normal. When maintained on vitamin D-deficient diets for a brief period, the DBP-/-, but not DBP+/+, mice developed secondary hyperparathyroidism and the accompanying bone changes associated with vitamin D deficiency. DBP markedly prolonged the serum half-life of 25(OH)D and less dramatically prolonged the half-life of vitamin D by slowing its hepatic uptake and increasing the efficiency of its conversion to 25(OH)D in the liver. After an overload of vitamin D, DBP-/- mice were unexpectedly less susceptible to hypercalcemia and its toxic effects. Peak steady-state mRNA levels of the vitamin D-dependent calbindin-D9K gene were induced by 1,25(OH)2D more rapidly in the DBP-/- mice. Thus, the role of DBP is to maintain stable serum stores of vitamin D metabolites and modulate the rates of its bioavailability, activation, and end-organ responsiveness. These properties may have evolved to stabilize and maintain serum levels of vitamin D in environments with variable vitamin D availability.     

The neuropathy of Dejerine and Sottas: report of an Indian family

We report a case of metastatic insular carcinoma of the thyroid evaluated with 201TI, 99mTc-MIBI, 99mTc-(V)DMSA, 99mTc-MDP and 131I whole-body scans, which were obtained after total thyroidectomy. For the majority of lesions detected in the skeleton and soft tissue, 131I images were generally available, although most were visualized easier with 99mTc-(V)DMSA. Technetium-99m-MDP images were considered better than 99mTc-(V)DMSA images in showing bone lesions but not soft-tissue lesions. Both 201TI and 99mTc-MIBI scans provided sufficient advantage to exhibit neck and mediastinal metastases, but they did not surpass 99mTc-(V)DMSA in detecting abdominal or bony lesions. In this patient with various metastases from insular carcinoma of the thyroid, 99mTc-(V)DMSA seemed to be the tracer of choice for whole-body imaging.