Amygdalar atrophy in panic disorder patients detected by volumetric magnetic resonance imaging

It has been suggested that the pathophysiology of panic disorder (PD) may involve abnormalities in several brain structures, including the amygdala. To date, however, no study has used quantitative structural neuroimaging techniques to examine amygdalar anatomy in this disorder. Volumetric magnetic resonance imaging (MRI) studies of the amygdalas, hippocampi, and temporal lobes were conducted in 12 drug-free, symptomatic PD patients (six females and six males), and 12 case-matched healthy comparison subjects. Volumetric MRI data were normalized for brain size. PD patients were found to have smaller left-sided and right-sided amygdalar volumes than controls. No differences were found in either hippocampi or temporal lobes. These findings provide new evidence of changes in amygdalar structure in PD and warrant further anatomical and MRI brain studies of patients with this disorder.     

Human pharmacology of ayahuasca: subjective and cardiovascular effects,monoamine metabolite excretion,and pharmacokinetics

The effects of the South American psychotropic beverage ayahuasca on subjective and cardiovascular variables and urine monoamine metabolite excretion were evaluated, together with the drug's pharmacokinetic profile, in a double-blind placebo-controlled clinical trial. This pharmacologically complex tea, commonly obtained from Banisteriopsis caapi and Psychotria viridis, combines N,N-dimethyltryptamine (DMT), an orally labile psychedelic agent showing 5-hydroxytryptamine2A agonist activity, with monoamine oxidase (MAO)-inhibiting beta-carboline alkaloids (harmine, harmaline, and tetrahydroharmine). Eighteen volunteers with prior experience in the use of psychedelics received single oral doses of encapsulated freeze-dried ayahuasca (0.6 and 0.85 mg of DMT/kg of body weight) and placebo. Ayahuasca produced significant subjective effects, peaking between 1.5 and 2 h, involving perceptual modifications and increases in ratings of positive mood and activation. Diastolic blood pressure showed a significant increase at the high dose (9 mm Hg at 75 min), whereas systolic blood pressure and heart rate were moderately and nonsignificantly increased. Cmax values for DMT after the low and high ayahuasca doses were 12.14 ng/ml and 17.44 ng/ml, respectively. Tmax (median) was observed at 1.5 h after both doses. The Tmax for DMT coincided with the peak of subjective effects. Drug administration increased urinary normetanephrine excretion, but, contrary to the typical MAO-inhibitor effect profile, deaminated monoamine metabolite levels were not decreased. This and the negligible harmine plasma levels found suggest a predominantly peripheral (gastrointestinal and liver) site of action for harmine. MAO inhibition at this level would suffice to prevent first-pass metabolism of DMT and allow its access to systemic circulation and the central nervous system.     

Estradiol enhances endothelial cell interactions with extracellular matrix proteins via an increase in integrin expression and function

Premenopausal women have a lower cardiovascular risk and a higher incidence of several autoimmune diseases involving blood vessels than men. Although the precise effects of estrogens on the cardiovascular system are largely unknown, recent data suggest that estrogens can exert direct regulatory effects on endothelial cells. In the present study, we show that 17β-estradiol increases human umbilical vein endothelial cell attachment to the extracellular matrix proteins laminin-1, type IV collagen, type I collagen, and fibronectin. Estradiol enhanced adhesion most significantly to laminin-1 and to fibronectin-derived synthetic peptides containing an RGD sequence. Upon exposure to estradiol, an increase in β1, α5 and α6 integrin mRNA was observed in subconfluent cells which was abrogated by treatment with cycloheximide. This increase was followed by a later enhancement in surface expression of the above integrins. In addition, integrin-mediated signaling was also enhanced by estrogens since an increase in tyrosine-phosphorylation of focal adhesion kinase induced by cell attachment was observed in estrogen-treated endothelial cells. Since integrins have an important role in mediating endothelial cell attachment, migration and differentiation, the increase in integrin expression and function induced by estradiol may be an important mechanism through which estrogens can promote neovascularization and vessel repair. This revised version was published online in June 2006 with corrections to the Cover Date.     

Genetic polymorphism of glutathione S-transferase P1 gene and lung cancer risk

Objectives: The human GSTTP1 gene is polymorphic with an A G transition in exon 5 causing a replacement 105 IleVal in the GSTP1 protein. The two isoforms, encoded by the alleles GSTP1*A and GSTP1*B, respectively, show different catalytic efficiencies towards some carcinogenic epoxides. In this study we have addressed the possible role of the Ile105Val GSTP1 polymorphism in lung cancer susceptibility.Methods: The polymorphic site was genotyped by RFLP in a group of lung cancer patients (n=164) and in two control groups (healthy smokers, n=132; general population, n=200). All patients and controls were Northwestern Mediterranean Caucasians of the same ethnic origin.Results and Conclusions: The cancer patients showed frequencies of GSTP1*A/A; GSTP1*A/B and GSTP1*B/B (50%, 38%, 11%, respectively) very similar to those of both control groups (healthy smokers: 48%, 41%, 11%). After adjusting for age, sex and smoking status, no association was found between the GSTP1*B allele and lung cancer risk (OR: 1.18; 95% CI: 0.67–2.07). The Ile105val GSTP1 polymorphism was also analysed in combination with the GSTM1 and GSTT1 genes. The results showed that allelism at GSTP1 did not increase the risk associated with the GSTM1 or GSTT1 deletions.     

Rapid Determination of the Chemical Composition of Ethylene/Butadiene Copolymers Using FTIR Spectroscopy and Chemometrics

Fourier transform infrared spectroscopy by attenuated total reflection (ATR‐FTIR), combined with the partial least square (PLS) method provides a fast characterization of ethylene/butadiene copolymers' intricate composition. The PLS regression method is constructed to quantify ethylene, 1,2‐butadiene (vinyl), trans‐1,4‐butadiene, and 1,2‐cyclohexane units in the copolymer. These rings are formed by intramolecular cyclization during polymerization. The performance of PLS models is evaluated by comparing the result obtained by ¹³C NMR and the model for three unknown samples. It is shown that the proposed method allows to accurately estimate the chemical composition of ethylene/butadiene copolymers in a much shorter time than NMR.     

Mortality in healthy elderly patients after ICU admission

Purpose  The aim of this study was to assess mortality in healthy elderly patients after non-elective medical ICU admission and to identify predictive factors of mortality in these patients. Methods  Patients ≥65 years living at home and with full-autonomy (Barthel index, BI > 60), without cognitive impairment, and non-electively admitted to a medical ICU were prospectively recruited. A full comprehensive geriatric assessment was made with validated scales. Results  A total of 230 patients were included, 110 (48%) between 65 and 74 years and 120 (52%) ≥75 years. No significant differences were observed between the two groups in premorbid functional and cognitive status, main diagnosis at ICU admission, APACHE II and SOFA scores, use of mechanical ventilation or haemodialysis or length of ICU stay. Over a mean follow-up of 522 days (range 20–1,170 days) the cumulative mortality of the whole group was 55%, being significantly higher in older subjects (62 vs. 47%; P = 0.024). On multivariate analysis, only parameters related to quality of life (QOL) and functional status were independent predictors of cumulated mortality (P < 0.01, both). Thus, in patients with EQ-5D_vas (<70) or baseline Lawton index (LI) (<5) the hazard ratio for cumulated mortality was 2.45 (95% CI: 1.15–5.25; P = 0.03) and 4.10 (95% CI: 1.53–10.99; P = 0.006), respectively, compared to those with better scores. Conclusions  Healthy elderly non-elective medical patients admitted to the ICU have a high mortality rate related to premorbid QOL. The LI and/or EQ-5D_vas may be useful tools to identify patients with the best chance of survival.