Investigation of the phenylalanine hydroxylase gene and tardive dyskinesia.

Phenylketonuria (PKU), an inborn error of phenylalanine metabolism, has been shown to be a risk factor for tardive dyskinesia (TD). In male psychiatric patients there was a significant relationship between TD and measures of plasma phenylalanine following ingestion of a standardized phenylalanine dose that was indicative of higher brain availability of phenylalanine in patients with TD. In addition, a medical food formulation consisting of branched chain amino acids, which compete with phenylalanine for transport across the blood-brain barrier, has been demonstrated to be an efficacious treatment for TD. Cumulatively these findings suggested that TD was related to phenylalanine metabolism and thus that sequence variants in the gene for phenylalanine hydroxylase (PAH), the rate-limiting enzyme in the catabolism of phenylalanine, could be associated with TD susceptibility. Genetic screening of PAH in a group of 123 psychiatric patients revealed ten sequence polymorphisms and two mutations, but none appeared to be a significant risk factor for TD.     

Critical study of hair growth analysis with computer-assisted methods

BACKGROUND: Computer-assisted image analysis has been proposed for human hair growth studies. METHODS: The performances of Trichoscan, a commercially available automated system combining epiluminiscence microscopy with digital image analysis, developed for office-based hair growth measurements, have been evaluated comparatively on the same skin sites using standardized photographic equipment and calibrated processing for contrast-enhanced phototrichogram (CE-PTG) analysis. This reference method has been validated with scalp biopsies and histological examination of serial sectioning. RESULTS: Besides edge effects, hair fibres escaped the Trichoscan analysis for various reasons including, but not limited to, thickness, pigmentation, closeness and crossing. CONCLUSION: Most of these problems have been identified in the late 1980s and remain largely unsolved by the processing software that was evaluated in 2004. Therefore claims promoting the Trichoscan method for accurate hair measurements in clinical trials on scalp and body hair are not supported by the present investigation. The speed at which the analysis is performed is outweighed by the errors in signal detection. Therefore we suggest that improvements must be clearly documented before Trichoscan is established for quantified diagnostic purposes and detailed hair cycle monitoring during hair trials.     

Additive Effects of Sevoflurane and Propofol on γ-Aminobutyric Acid Receptor Function

Background: Previous studies have shown that propofol and sevoflurane enhance the function of [gamma]-aminobutyric acid type A (GABAA) receptors. However, it is not known whether these two drugs modulate the same molecular pathways. In addition, little is known about receptor function in the presence of both propofol and sevoflurane. The aim of this study was to better understand the interactions of propofol and sevoflurane with the GABAA receptor.

Methods: Wild-type [alpha]1, [beta]2, [gamma]2s GABAA receptor subunit complementary DNAs were transfected into human embryonic kidney cells grown on glass coverslips using a calcium phosphate transfection method. After transfection (36-72 h), cells were whole cell patch clamped and exposed to combinations of the following: 0.3-1,000 [mu]m [gamma]-aminobutyric acid (GABA), 0-10 [mu]m propofol, and 0-1,650 [mu]m sevoflurane. Chemicals were delivered to the cells using two 10-channel infusion pumps and a rapid solution exchanger.

Results: Both propofol and sevoflurane alone enhanced the amplitude of GABAA receptor responses to submaximal concentrations of GABA in a dose-dependent manner. The enhancement was underpinned by an increase in the apparent affinity of the receptor for GABA. Coapplication of both anesthetics further enhanced the apparent affinity of the receptor for GABA.     

Posttraumatic stress disorder and associated risk factors in Canadian peacekeeping veterans with health-related disabilities.

OBJECTIVES: This study investigates posttraumatic stress disorder (PTSD) and its associated risk factors in a random, national, Canadian sample of United Nations peacekeeping veterans with service-related disabilities. METHODS: Participants included 1016 male veterans (age < 65 years) who served in the Canadian Forces from 1990 to 1999 and were selected from a larger random sample of 1968 veterans who voluntarily and anonymously completed a general health survey conducted by Veterans Affairs Canada in 1999. Survey instruments included the PTSD Checklist-Military Version (PCL-M), Center for Epidemiological Studies-Depression Scale (CES-D), and questionnaires regarding life events during the past year, current stressors, sociodemographic characteristics, and military history. RESULTS: We found that rates of probable PTSD (PCL-M score > 50) among veterans were 10.92% for veterans deployed once and 14.84% for those deployed more than once. The rates of probable clinical depression (CES-D score > 16) were 30.35% for veterans deployed once and 32.62% for those deployed more than once. We found that, in multivariate analyses, probable PTSD rates and PTSD severity were associated with younger age, single marital status, and deployment frequency. CONCLUSIONS: PTSD is an important health concern in the veteran population. Understanding such risk factors as younger age and unmarried status can help predict morbidity among trauma-exposed veterans.     

A novel hybridoma antibody (PASE/4LJ) to human prostatic acid phosphatase suitable for immunohistochemistry

A murine monoclonal antibody PASE/4LJ to prostatic acid phosphatase (PAP) was used to immunostain a wide variety of sections of benign and malignant tissues (654 blocks). Non-neoplastic adult and fetal prostatic glands, primary and metastatic prostatic carcinomas, and scattered cells in prostatic and penile urethra were positive. Rat, dog and rabbit prostates were negative. Nine of 400 tumours of non-prostatic origin showed some positivity: 6/36 carcinoids, 1/9 islet cell tumours, 1/55 ovarian adenocarcinomas (serous) and one carcinosarcoma of the lung (epithelial portion). Positive staining was seen in islet cells in 4/5 specimens of normal pancreas, and in 4/9 blocks of normal pancreas surrounding a pancreatic tumour. Loops of Henle, maculae densae, and distal tubules in 10/10 fetal and 2/9 adult kidneys were also positive, with proximal tubules and collecting ducts negative. All other 159 blocks of non-neoplastic adult and fetal tissues were negative. The antibody was also affinity purified from ascitic fluid, and shown not to inhibit the enzyme activity of prostatic acid phosphatase.     

双波长紫外分光光度法测定贝母中腺苷和胸苷的含量

将4种贝母的甲醇提取物经薄层色谱法粗分离后,直接用双波长紫外分光光度法测定其含量。结果表明,该方法线性关系好,腺苷和胸苷标准曲线的相关系数均为0.9999,同时也发现平贝、炉贝和伊贝中腺苷都占核苷总量60%以上,而浙贝中仅占约40%,提示贝母生药的抗凝血活性可能与贝母中核苷类化合物的种类和含量的差别有关。     

Pharmacological analysis of the interaction between Bay K 8644 and 5-HT in rabbit aorta

Bay K 8644 potentiated and augmented 5-hydroxytryptamine (5-HT)-induced contractions in the rabbit, isolated aorta preparation, as manifested in leftward shift and increase in the asymptote of 5-HT E/[A] (effect vs concentration) curves. The operational model of agonism (Black & Leff, 1983) was used to analyse this interaction and the concomitant effects of irreversible receptor alkylation by phenoxybenzamine. The competitive effects of spiperone in the presence and absence of Bay K 8644 were also examined. From these analyses it is concluded that Bay K 8644 elicits its potentiating effects by increasing the efficacy of 5-HT at the 5-HT2 receptor with no alteration in affinity. This is consistent with the known effect of Bay K 8644 of causing an increase in the functional concentration of plasmalemmal calcium channels coupled to the 5-HT2 receptors in this preparation. The positively co-operative shape of the 5-HT E/[A] curves obtained in the aorta and the quantitative nature of their potentiation by Bay K 8644 indicated that the coupling of 5-HT2 receptor occupancy to intracellular calcium concentration is linear and that the co-operativity resides in the subsequent relation between intracellular calcium and pharmacological effect. Bay K 8644 may serve as a probe for differentiating between the types of calcium channels that transduce 5-HT receptor-mediated effects in different systems. Such information would be useful in the classification of agonist interactions with 5-HT receptors.     

Resting and total energy expenditure in patients with ischemic heart disease.

Total energy expenditure (TEE) was measured by doubly labeled water in 13 preoperative patients undergoing elective coronary artery surgery and compared to resting energy expenditure (REE) measured by indirect calorimetry (IC) calculated from the Harris-Benedict (HB) formula or from formulas based on midarm circumference and arm muscle circumference. Mean REE measured by IC and calculated from the HB, midarm circumference, arm muscle circumference formulas were 62, 75, 62, and 69%, respectively, of TEE measured by doubly labeled water. REE measured by IC correlated significantly with that predicted by the HB (p = 0.006) but not the anthropometric formulas. The relationship between REE derived from anthropometric predictive formulas and REE measured by IC is altered in ischemic heart disease.