Screen‐printed biosensor for allergens

Allergen levels in indoor environments, leading to many diseases, eg asthma, rhinitis and conjunctivitis, affect a large and increasing fraction of the population. A quite effective and inexpensive method of a rough but very rapid overall assessment of total allergen level in the environment has been developed. The method involved estimation of protein in allergen extracts by screen‐printed electrodes using two different techniques. The biosensor comprised a rhodinised carbon working electrode, a silver/silver chloride reference electrode and a carbon counter electrode. In the first method the enzyme protease reacted with allergen protein to release amino acid, which produced hydrogen peroxide in the presence of amino acid oxidase. This was detected amperometrically. The second method used potassium bromide as electrolyte and the electrode was subjected to dual potential. Bromine, released due to electrolysis at higher potential, was consumed by the allergen protein at lower potential. In the first method, a unique technique was used to microencapsulate the enzyme protease and immobilise it on the surface of the electrode by in‐situ polymerisation to avoid contact with the amino acid oxidase. A total of seven allergens were tested and the results gave a good correlation with the standard protein measurement method. Environmental specimens from indoors, schools and workplaces can be evaluated for the aeroallergens produced by dust mites, animal hairs, cockroach debris, pollens, etc as a means of determining the exposure risk. Copyright © 2005 Society of Chemical Industry     

Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors

Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABA(A) and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA rho1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.     

Continuous infusion of porcine factor VIII in the management of patients with factor VIII inhibitors

Increased detection thresholds for pure tones were observed in a large cohort of children exposed to lead environmentally while smaller studies in lead-exposed workers have reported conflicting results on assessments of auditory function. Pure tone detection thresholds were determined in a group of monkeys (Macaca fascicularis) dosed with 2 mg/kg/day of lead from birth through testing at 13 years of age. Blood lead concentrations were stable at about 30 micrograms/dl until monkeys were 10-11 years of age at which time they increased to between 50 and 70 micrograms/dl. Five age- and rearing-matched monkeys served as controls. Detection thresholds were determined at six frequencies between 0.125 and 31.5 kHz. Ear phones were fit over both ears, and thresholds were determined for each ear separately. The monkey signaled detection of the tone by breaking contact with a stainless steel bar. Three lead-exposed monkeys exhibited normal pure tone detection functions. Three monkeys had thresholds outside of the control range at some frequencies; there was a tendency for higher frequencies to be differentially more affected. These findings are consistent with reports of elevated pure tone thresholds in humans exposed to lead developmentally, although the effect is smaller than might have been predicted given the concurrent blood lead concentrations of these monkeys.     

A monitoring, feedback, and triggering system for reproducible breath-hold MR imaging

OBJECTIVE: To evaluate the diagnostic accuracy and clinical usefulness of high-resolution transvaginal duplex Doppler ultrasound in postpartum and post-abortion patients with excessive hemorrhage who are suspected of having residual trophoblast. METHODS: Forty-eight women with excessive hemorrhage referred for possible residual trophoblastic tissue were evaluated by transvaginal duplex Doppler ultrasonography. Based on two-dimensional imaging, the patients were divided prospectively into groups: women who had an empty uterus with a normal uterine cavity, those with a pure endometrial fluid collection and no echogenic foci, those who had a mixed endometrial fluid collection with foci of echogenicity, and those with intracavitary heterogeneous material with mixed echo patterns of fluid and solid components. In each group, Doppler studies were performed and the resistance index (RI) was calculated. The two-dimensional patterns and Doppler results were correlated with clinical and pathologic follow-up. RESULTS: Twenty-eight subjects had a normal uterine cavity and seven had a pure endometrial fluid collection; all were treated conservatively and none showed later clinical evidence of residual trophoblastic tissue. In 13 women, residual trophoblast was strongly suggested from the images of two-dimensional ultrasonography: Five showed an endometrial fluid collection with some echogenic foci, and eight exhibited intracavitary mixed echogenic material. All underwent curettage, and residual trophoblastic tissue was found in ten of the 13. The mean (+/- standard deviation) RI to flow in the myometrial arteries was 0.54 +/- 0.15 in women without residual trophoblast and 0.35 +/- 0.1 in those with residual trophoblastic tissue (P < .01). CONCLUSION: Our experience suggests that transvaginal duplex Doppler ultrasonography is an effective noninvasive method for evaluating patients with excessive postpartum and post-abortion hemorrhage who are suspected of having residual trophoblastic tissue. Its use enhances the positive preoperative diagnosis of residual trophoblastic tissue and may reduce unnecessary curettage procedures.     

The role of mineralocorticoid receptors in hypothalamic-pituitary-adrenal axis regulation in humans

In rodents, two types of glucocorticoid receptors, the mineralocorticoid (MR; type I) and the glucocorticoid (type II) receptors, have been demonstrated to play a role in hypothalamic-pituitary-adrenal (HPA) axis regulation. Because MR shows a very high affinity for cortisol, it has been suggested that MR plays an important role in restraint of CRH and ACTH secretion during the nadir of the circadian rhythm. Although a number of studies have established the importance of MR in rodents, the functional role of MR in humans has not been determined. These studies evaluated whether spironolactone, an MR antagonist, had a detectable effect on HPA axis regulation in humans, and whether the effect was greatest during the evening, when plasma cortisol concentrations are in the MR range. Compared to the placebo day, after a single dose of spironolactone at either 0800 or 1600 h, there is a significant increase in plasma cortisol, which is preceded by a rise in ACTH and beta-endorphin. A significant effect of spironolactone on cortisol secretion was demonstrated with no differences between the morning and evening. Because the effect of spironolactone on cortisol was short lived, a second experiment was conducted using two doses of spironolactone, again sampling in the morning and evening. After two doses of spironolactone, plasma cortisol levels showed a significant and sustained spironolactone-induced elevation for the entire sampling period. However, neither plasma beta-endorphin nor ACTH was increased compared to levels on the placebo day. These data suggest that MR appear to play a clear role in HPA axis regulation during the time of the circadian peak as well as the trough. Furthermore, MR blockade may affect the sensitivity of the adrenal to ACTH.