Platelet activation in depression and effects of sertraline treatment: An open-label study.

OBJECTIVE: The authors' goal was to determine whether sertraline attenuates the increased platelet activation seen among depressed patients. METHOD: They tested 21 otherwise healthy patients with untreated major depressive episode who were 25-52 years old and 21 age- and sex-matched comparison subjects. Patients received 6 weeks of sertraline treatment, and 17 returned for retesting. RESULTS: At baseline, the depressed patients had greater platelet secretion than the comparison subjects in response to collagen. Depressed patients with a family history of coronary disease had nonsignificantly greater wound-induced fibrinogen receptor binding than the other subjects. Platelet secretion in response to collagen was significantly reduced after treatment with sertraline. CONCLUSIONS: Sertraline diminished the increased platelet secretion found among depressed patients, although the findings are limited by a lack of a placebo control group.

A spectral unfolding method to determine source depth distribution.

The depth distribution in tissue of a gamma-emitting isotope can be estimated by observing the energy spectrum of photons emerging from the body. Monte Carlo methods were used to compute surface energy spectra for 99Tcm point sources at various depths. From these noise-free results a discrete response matrix was constructed to relate the input source depth to the corresponding output spectrum. Observed spectra with noise were then simulated independently by Monte Carlo calculations assuming various measurement times and source strengths. The source distribution was determined by solving the discrete inverse unfolding problem by the Method of Regularisation. The effective depth resolution is seen to depend strongly upon measurement time. The results show that limited depth resolution can be obtained from a single view of the object region.

The role of dopaminergic transmission through D1-like and D2-like receptors in amphetamine-induced rat ultrasonic vocalizations.

RATIONALE: Systemic amphetamine (AMPH) administration increases the rate of 50-kHz ultrasonic vocalizations (USVs) in adult rats and preferentially enhances the 'trill' subtype; these effects of AMPH critically depend on noradrenergic transmission, but the possible contributions of dopamine are unclear. OBJECTIVE: To assess the role of dopamine in 50-kHz USVs emitted drug-free and following systemic AMPH administration. METHODS: Adult male Long-Evans rats pre-selected for high AMPH-induced calling rates were tested with AMPH (1 mg/kg, intraperitoneal (IP)) and saline following pretreatment with the following dopamine receptor antagonists: SCH 23390 (0.005-0.02 mg/kg, subcutaneous (SC)), SCH 39166 (0.03-0.3 mg/kg, SC), haloperidol (0.1, 0.2 mg/kg, IP), sulpiride (20-80 mg/kg, SC), raclopride (0.1-0.5 mg/kg, SC), clozapine (4 mg/kg, SC), risperidone (0.5 mg/kg, SC), and pimozide (1 mg/kg, IP). The dopamine and noradrenaline reuptake inhibitors (GBR 12909 and nisoxetine, respectively) were also tested, alone and in combination. RESULTS: SCH 23390, SCH 39166, haloperidol, and raclopride dose-dependently inhibited vocalizations under AMPH and suppressed the proportion of trill calls. Sulpiride, however, had no discernable effect on call rate or profile, even at a high dose that reduced locomotor activity. Single doses of clozapine, risperidone, and pimozide all markedly decreased calling under saline and AMPH. Finally, GBR 12909 and nisoxetine failed to promote 50-kHz USVs detectably or alter the subtype profile, when tested alone or in combination. CONCLUSIONS: The rate of 50-kHz USVs and the call subtype profile following systemic AMPH administration depends on dopaminergic neurotransmission through D1-like and D2-like receptors. However, inhibiting dopamine and/or noradrenaline reuptake appears insufficient to induce calling.

α- and ß-Adrenergic receptors differentially modulate the emission of spontaneous and amphetamine-induced 50-kHz ultrasonic vocalizations in adult rats.

Amphetamine (AMPH) increases adult rat 50-kHz ultrasonic vocalizations, preferentially promoting frequency-modulated (FM) calls that have been proposed to reflect positive affect. The main objective of this study was to investigate a possible noradrenergic contribution to AMPH-induced calling. Adult male Long-Evans rats were tested with AMPH (1 mg/kg intraperitoneal) or saline combined with various systemic pretreatments: clonidine (α2 adrenergic agonist), prazosin (α1 antagonist), atipamezole (α2 antagonist), propranolol, betaxolol, and/or ICI 118,551 (ß1/ß2, ß1, and ß2 antagonists, respectively), nadolol (ß1/ß2 antagonist, peripheral only), or NAD-299 (5HT(1A) antagonist). In addition, effects of cirazoline (α1 adrenergic agonist) and cocaine (0.25-1.5 mg/kg intravenous) were studied alone. AMPH-induced calling was suppressed by low-dose clonidine and prazosin. Cirazoline and atipamezole did not significantly affect calling rate. Propranolol, without affecting the call rate, dose dependently promoted 'flat' calls under AMPH while suppressing 'trills,' thus reversing the effects of AMPH on the 'call subtype profile.' This effect of propranolol seemed to be mediated by simultaneous inhibition of CNS ß1 and ß2 rather than by 5HT(1A) receptors. Finally, cocaine elicited fewer calls than did AMPH, but produced the same shift in the call subtype profile. Taken together, these results reveal differential drug effects on flat vs trill vs other FM 50-kHz calls. These findings highlight the value of detailed call subtype analyses, and show that 50-kHz calls are associated with adrenergic α1- and ß-receptor mechanisms. These preclinical findings suggest that noradrenergic contributions to psychostimulant subjective effects may warrant further investigation.

Heritability of functioning in families with schizophrenia in relation to neurocognition.

UNLABELLED: The role of daily functioning is an integral part of the schizophrenia (SZ) phenotype and deficits in this trait appear to be present in both affected persons and some unaffected relatives; hence we have examined its heritability in our cohort of African American schizophrenia families. There is now ample evidence that deficits in cognitive function can impact family members who are not themselves diagnosed with SZ; there is some, but less evidence that role function behaves likewise. We evaluate whether role function tends to "run in families" who were ascertained because they contain an African American proband diagnosed with SZ. METHODS: We analyzed heritability for selected traits related to daily function, employment, living situation, marital status, and Global Assessment Scale (GAS) score; modeling age, gender, along with neurocognition and diagnosis as covariates in a family based African-American sample (N=2488 individuals including 979 probands). RESULTS: Measures of role function were heritable in models including neurocognitive domains and factor analytically derived neurocognitive summary scores and demographics as covariates; the most heritable estimate was obtained from the current GAS scores (h2=0.72). Neurocognition was not a significant contributor to heritability of role function. CONCLUSIONS: Commonly assessed demographic and clinical indicators of functioning are heritable with a global rating of functioning being the most heritable. Measures of neurocognition had little impact on heritability of functioning overall. The family covariance for functioning, reflected in its heritability, supports the concept that interventions at the family level, such as evidenced-based family psychoeducation may be beneficial in schizophrenia.

N-formimidoyl thienamycin (MK0787): in vitro study.

N-Formimidoyl thienamycin (MK0787) was compared in vitro with three other beta-lactam and two aminoglycoside antibiotics. It was second in activity only to cefotaxime against members of the Enterobacteriaceae and to amikacin against Pseudomonas species. It was the most active antibiotic against Staphylococcus aureus. Resistance (minimal inhibitory concentration, greater than 128 microgram/ml) to N-formimidoyl thienamycin was not observed.

Gamma-ray imaging with stochastic apertures.

The spatial distribution of a radioactive fluid can be measured indirectly by observing the emerging gamma rays. A method is proposed and analyzed for gamma-ray imaging by stochastic time modulation and cross-correlation. Theoretical comparison is made to collimation and coded aperture techniques in gamma-ray image formation. Computed results are presented that illustrate the mean response and statistical error characteristics of this technique. Monte Carlo simulations are performed as a further verification. Because it relies upon a point-by-point reconstruction, rather than upon the integral properties of any particular aperture, the time modulation approach is seen to provide a theoretical basis for obtaining a smooth three-dimensional point response.

Effect of bupropion-SR on orgasmic dysfunction in nondepressed subjects: a pilot study.

UNLABELLED: The objective of this study was to determine whether the aminoketone antidepressant bupropion has beneficial effects in orgasmic dysfunction. DESIGN: Single-blind, sequential treatment order of three weeks each: placebo, bupropion-SR 150 mg/day, bupropion-SR 300 mg/day. SUBJECTS: Nondepressed women (n = 20) and men (n = 10) having nonphysiologic orgasmic delay or inhibition. MAIN OUTCOME MEASURES: Reported difficulty or delay in achieving orgasm, satisfaction with orgasm and erectile function, and subjective impressions of drug effect. RESULTS: In the women, there were significant improvements relative to baseline (p < .01) on both doses of bupropion-SR in all measured aspects of sexual function, and significant improvements relative to placebo (p < .05) in overall sexual satisfaction on both doses and satisfaction with intensity of orgasm on 150 mg/day (300 mg/day, p = .10). In the men, significant improvements over baseline (p < .01) were observed with both doses in overall sexual satisfaction, ability to achieve an erection, and delay in reaching orgasm/ejaculation; significant improvements relative to placebo (p < .05) were observed in overall sexual satisfaction on both doses, ability to achieve erection on 150 mg/day, and delay in orgasm/ejaculation on 150 mg/day. Seventy percent of subjects reported improvement in libido, arousal, or orgasmic function during bupropion administration. CONCLUSIONS: Bupropion-SR may be a useful agent for treating orgasmic delay and inhibition, and possibly disorders of sexual arousal. The results argue against bupropion's apparent prosexual effect in depressed patients being simply a result of its antidepressant activity.