3H-Ro 15-1788, a benzodiazepine receptor antagonist, was injected IV into male and pregnant mice. Autoradiograms were prepared from sagittal sections of animals killed after 30 s to 48 h. In the adult animal there was a rapid and high initial accumulation of radioactivity in the brain as compared to other organs and tissues. The highest accumulation was found in cortical brain areas, such as the olfactory bulb and the frontal cortex. Cerebellar cortex, globus pallidus, amygdala, substantia nigra, colliculus, hippocampus and pons followed in rank order. The rate of decline of radioactivity was highest in the pons and lowest in the olfactory bulb. The initial disappearance of radioactivity from the cerebellum was higher than from the other brain regions. Ro 15-1788 was rapidly eliminated; 4 h after drug administration there was an almost complete clearance of radioactivity from all tissues. After 24 h no trace of activity remained in the animal. The distribution of radioactivity at later time points indicates that metabolites of Ro 15-1788 are eliminated by fecal, urinary and nasal secretion. In the fetus also there was an early accumulation of radioactivity in the central nervous system. The radioactivity in fetal organs was lower than in the mother at all time intervals.

We undertook a genomewide linkage study in a total of 353 affected sib pairs (ASPs) with schizophrenia. Our sample consisted of 179 ASPs from the United Kingdom, 134 from Sweden, and 40 from the United States. We typed 372 microsatellite markers at approximately 10-cM intervals. Our strongest finding was a LOD score of 3.87 on chromosome 10q25.3-q26.3, with positive results being contributed by all three samples and a LOD-1 interval of 15 cM. This finding achieved genomewide significance (P<.05), on the basis of simulation studies. We also found two regions, 17p11.2-q25.1 (maximum LOD score [MLS] = 3.35) and 22q11 (MLS = 2.29), in which the evidence for linkage was highly suggestive. Linkage to all of these regions has been supported by other studies. Moreover, we found strong evidence for linkage (genomewide P<.02) to 17p11.2-q25.1 in a single pedigree with schizophrenia. In our view, the evidence is now sufficiently compelling to undertake detailed mapping studies of these three regions.

A common subset of genetic risk factors for Parkinson's disease (PD) and essential tremor (ET) has been postulated. Recently, an association between the dopamine D3 receptor (DRD3) Ser9Gly polymorphism and ET has been reported. We studied whether PD tremor is influenced by Ser9Gly in a genetic association study based on the gene bank of the German Competence Network on Parkinson's disease. The study included analyses of motor predominance (mixed, hypokinetic, and tremor), and tremor type (resting, postural, and action). We did not identify any effect of DRD3 Ser9Gly on tremor in PD, even when regarding various symptom combinations to avoid missing a weak effect on the phenotype. Additional studies incorporating symptoms at disease onset, and grading of tremor response to dopaminergic therapy, are warranted.

Multiple sclerosis (MS) affects both white matter and gray matter (GM). Measurement of GM volumes is a particularly useful method to estimate the total extent of GM tissue damage because it can be done with conventional magnetic resonance images (MRI). Many algorithms exist for segmentation of GM, but none were specifically designed to handle issues associated with MS, such as atrophy and the effects that MS lesions may have on the classification of GM. A new GM segmentation algorithm has been developed specifically for calculation of GM volumes in MS patients. The new algorithm uses a combination of intensity, anatomical, and morphological probability maps. Several validation tests were performed to evaluate the algorithm in terms of accuracy, reproducibility, and sensitivity to MS lesions. The accuracy tests resulted in error rates of 1.2% and 3.1% for comparisons to BrainWeb and manual tracings, respectively. Similarity indices indicated excellent agreement with the BrainWeb segmentation (0.858–0.975, for various levels of noise and rf inhomogeneity). The scan-rescan reproducibility test resulted in a mean coefficient of variation of 1.1% for GM fraction. Tests of the effects of varying the size of MS lesions revealed a moderate and consistent dependence of GM volumes on T2 lesion volume, which suggests that GM volumes should be corrected for T2 lesion volumes using a simple scale factor in order to eliminate this technical artifact. The new segmentation algorithm can be used for improved measurement of GM volumes in MS patients, and is particularly applicable to retrospective datasets.

Experimental studies showed that dopamine influences pain perception in healthy volunteers. Dopamine dysfunctions have been linked to the physiopathology of fibromyalgia (FM), which is associated with hyperalgesia and deficient pain inhibition. We sought to investigate the relationships between catecholamine-related polymorphisms [dopamine-D3 receptor (DRD3) Ser9Gly and catechol-O-methyltransferase (COMT) Val158Met] and thermal pain measures in healthy subjects and FM patients. Seventy-three subjects (37 FM patients and 36 controls) participated in this study. Thermal pain thresholds (TPTs) were measured using a Peltier thermode. Inhibitory systems were elicited using a thermal tonic pain stimulation administered before and after activation of the diffuse noxious inhibitory controls (DNIC) by means of a cold-pressor test. Genetic analyses were performed using polymerase chain reaction. Regression analyses were performed across and within groups. FM was associated with lower TPTs and deficient pain inhibition. DRD3 Ser9Gly polymorphism predicted (1) DNIC efficacy across groups and (2) thermal TPTs in FM patients. COMT Val158Met and thermal pain measures were not related. These preliminary results suggest that the DRD3 Ser9Gly polymorphism influences DNIC efficacy and TPTs and that this latter relationship is present only in FM patients. Two core psychophysical features of FM appear to be significantly influenced by limbic dopamine functioning.This experimental study is the first to relate DNIC and TPTs to a functional polymorphism of limbic dopamine-D3 receptors. As lowered pain thresholds and deficient pain inhibition are 2 core features of fibromyalgia, these preliminary results may help identify a subgroup of FM patients who require closer medical attention.

Culinary culture has been an area that has been ignored until recently. However, culinary culture is always the longest-surviving part of a culture and tradition. To put it in a different way, cuisines where many different identities of a society merge together and national feelings are felt most are a mirror of daily life styles, religious beliefs, habits, traditions and customs. Changes of eating style in societies and rising the value of eating socially have been one of the reasons for movements in tourism activities. Gastronomy tourism has become major and has become a rapidly growing component of the attractiveness of tourism destination in recent years. The marketing opportunities to gastronomy tourism are being developed by the countries given importance to that issue. Tourists’ wishes to experience the local tastes in the destinations and accommodation facilities have prepared the ground for the development of gastronomy tourism. Tourism businesses that realized the importance to gastronomy tourism given by local and foreign tourists have featured the gastronomic factors in their facilities. Therefore, it is ensured that to take attention for gastronomy, tourism should be managed in coordination with all tourism- related foundations and civil society organizations and with the encouragement of relevant ministries. In addition, the promotional activities are required to be taken in measurable ways by gastronomic tourism developers.

As demand for advanced logistics services grows, third-party logistics providers (3PLs) are being requested to provide more environmentally sustainable services. This development presents 3PLs with opportunities but also challenges and concerns about how to translate green efforts into practice. The purpose of this paper is to analyse environmental sustainability initiatives undertaken by 3PLs and the factors influencing them, both positively and negatively. The research methodology used in this paper is based on two-phase approach. In the first phase, a systematic literature review on the adoption of green initiatives by 3PLs has been carried out and two research questions have been identified. In the second phase, the research questions have been addressed by a case study analysis conducted on 13 Italian transport and logistics service providers. The research has distinguished three groups of companies with slightly different environmental profiles in terms of the green initiatives implemented and the main drivers and inhibitors. The surveyed companies show a differing degree of involvement in green initiatives due to variations in the breadth of service offered and the importance attributed to environmental issues. The paper concludes with a discussion of the managerial implications of the research, particularly for the development of 3PL's green strategies.

Cerebellar structures were measured in 30 chronic schizophrenic men and 18 healthy men using high resolution MRI. The volume of the posterior superior vermis was found to be significantly smaller in the schizophrenic men, but there was no difference in other cerebellar regions or the intracranial volume. The findings support the view that within the cerebellum the posterior superior vermis may be selectively reduced in men with chronic schizophrenia.

OBJECTIVEPostmortem studies and a positron emission tomography (PET) study have suggested that there is a disturbance of central D(1) dopamine receptor function in schizophrenia. The objective of the present PET study was to compare D(1) receptor binding in first-admission, neuroleptic-naive patients with schizophrenia and in healthy subjects.METHODTen healthy comparison subjects and 10 neuroleptic-naive patients with schizophrenia (diagnosed according to DSM-III-R) were examined twice by PET using (11)C-labeled SCH 23390 ([(11)C]SCH 23390) with high and low specific radioactivity, respectively. The binding potential, receptor density (B(max)), and affinity (K(d)) were determined for the caudate nucleus, the putamen, and several neocortical regions during both PET examinations. Scatchard plots from the two measurements were used to calculate regional D(1) B(max) and K(d). The regional binding values were tested for hemispheric asymmetry and for correlation to clinical symptoms measured by the Brief Psychiatric Rating Scale (BPRS).RESULTS[(11)C]SCH 23390 binding to D(1) receptors did not differ significantly between subjects with schizophrenia and healthy subjects in any of the brain regions or for any of the binding measures studied. Asymmetry of the regional binding values did not differ significantly between the two groups. Scores on the BPRS negative symptom subscale correlated significantly with the B(max) in the right frontal cortex.CONCLUSIONSThese results do not replicate previous postmortem and PET findings of altered central dopamine D(1) receptor binding in schizophrenia. The finding of a positive correlation between frontal D(1) binding and scores on the negative symptom subscale of the BPRS is contrary to a previously reported finding of a negative correlation. These discrepancies motivate further studies using D(1) ligands with higher signals for cortical regions.

Among theories of biological underpinnings to personality traits, different mechanisms of the serotonergic system are perhaps the most common factors suggested to influence individual differences in personality traits. We have investigated two frequent variants in the serotonin 2A receptor gene (5-HT2A) and personality traits. Healthy Swedish subjects (n = 304) were assessed with the Karolinska Scales of Personality (KSP) inventory. After correction for multiple testing, no significant differences were found. We conclude that the investigated 5-HT2A gene variants do not significantly influence personality as assessed by the KSP in the present population.

The distribution of 5-HT(1B) and 5-HT(1D) receptors in the human post mortem brain was examined using whole hemisphere autoradiography and the radioligand [(3)H]GR 125743. [(3)H]GR 125743 binding was highest in the substantia nigra and the globus pallidus. Lower levels were detected in the striatum, with the highest densities in the ventromedial parts. In the amygdala, the hippocampus, the septal region and the hypothalamus, lower [(3)H]GR 125743 binding was observed, reflecting low densities of 5-HT(1B/1D) receptors. In the cerebral cortex, binding was similar in most regions, although restricted parts of the medial occipital cortex were markedly more densely labeled. Binding densities were very low in the cerebellar cortex and in the thalamus. Two methods were used to distinguish between the two receptor subtypes, the first using ketanserin to block 5-HT(1D) receptors and the second using SB 224289 to inhibit 5-HT(1B) receptor binding. The autoradiograms indicated that in the human brain, the 5-HT(1B) receptor is much more abundant than the 5-HT(1D) receptor, which seemed to occur only in low amounts mainly in the ventral pallidum. Although [(3)H]GR 125743 is a suitable radioligand to examine the distribution of 5-HT(1B) receptors in the human brain in vitro, the selectivities of ketanserin and SB 224289 are not sufficiently high to give definite evidence for the occurrence of the 5-HT(1D) receptor in the human brain.