Skin Prick Test Reactivity to Common Allergens in Finnish Adolescents

We studied 708 adolescents aged 15–17 years in the 9th grade of school in Imatra. Of the eligible population born in 1962 77% were included. All were skin prick tested with 16 extracts from two manufacturers with 12 common allergens, which included pollens, epithelia, mite, house dust and fish. At least one positive, immediate reaction (weal diameter 3 mm or larger) occurred in 49% and at least two positive reactions in 43% of those studied. The boys were observed to be significantly more reactive than the girls. The allergen preparations to which positive reactions were most prevalent were house dust, cat and horse epithelium, and mite extract. Large differences in the prevalence of positive reactions were observed with different preparations of the same allergen. Pollen allergens tended to cause the largest positive weal reactions, and the weal size distribution with some pollens was distinctly bimodal. A scheme for calculating allergen potency in histamine-equivalent-prick (HEP) units is presented. It is noted that the result is greatly dependent on the population group chosen for testing.     

Tolerability and Kinetics of a Solvent-Detergent-Treated Intravenous Immunoglobulin Preparation in Hypogammaglobulinaemia Patients

The tolerability and kinetics of a solvent-detergent-treated 6% intravenous immunoglobulin (IVIG) preparation were studied in 15 hypogammaglobulinaemia patients during 3–4 regular substitution infusions of 9–18 g, the mean dose being 359 mg/kg. The infusions were well tolerated, and the trough serum IgG levels achieved were comparable to two commercial IVIG preparations. The stepwise increase of the infusion rate up to 5 mg/kg/min and the use of this IVIG as a 12% solution were possible without serious adverse events in all the 6 studied hypogammaglobulinaemia patients. This greatly reduced the time needed for the infusions.     

Performance of a novel real-time respirator seal integrity monitor on firefighters: Simulated workplace pilot study

Millions of workers, including firefighters, use respiratory protective device. The key aspect in assuring the intended protection level of a respirator is its fit. However, even if the respirator originally fits well, the faceseal may be breached during its use. Until now, there have been no practically viable, inexpensive means to monitor the performance of a respirator during actual use. A novel Respirator Seal Integrity Monitor (ReSIM) was developed and recently evaluated on manikins by our team. The objective of this study was to evaluate the ReSIM effectiveness on respirator-wearing firefighters exposed to aerosols while performing simulated routine operational activities. Initially, 15 subjects were recruited for the study. Following a preliminary investigation that resulted in modifications in the ReSIM prototype and testing protocol, a subset of nine firefighters was chosen for a full-scale evaluation. The testing was conducted in a 24.3-m³ exposure chamber using NaCl as the challenge aerosol. Controlled faceseal leaks were established by opening a solenoid valve for 10, 15, or 20?sec. Leaks were also established as the tested firefighter slightly repositioned the respirator on his/her face. During the testing, the ReSIM measured particles inside a full-face elastomeric respirator with a 72.7% leak detection sensitivity (probability of correct leak identification) and an 84.2% specificity (probability of correct identification of the intervals which are absent of any leak). After adjusting for false negatives and persistent false positives, sensitivity and specificity increased to 83.6% and 92.2%, respectively. The factors causing minor limitations in leak detection sensitivity and specificity can be attributed to variability among subjects, moisture’s effect on the particle sensor, and some in-mask sampling bias. In conclusion, the ReSIM can promptly detect the breach in a respirator faceseal with high sensitivity and specificity. Due to its capability to alert the wearer of possible overexposure to hazardous aerosols, the ReSIM concept has a remarkable potential to be applied in various working environments, where respirators are used.     

The cognition-enhancing activity of E1R,a novel positive allosteric modulator of sigma-1 receptors

Background and Purpose

Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors.

Experimental Approach

E1R was tested for sigma receptor binding activity in a [³H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca²⁺ concentration ([Ca²⁺]_i) assays and in an electrically stimulated rat vas deferens model. E1R''s effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test was used to detect the effects of E1R on locomotion.

Key Results

Pretreatment with E1R enhanced the selective sigma-1 receptor agonist PRE-084''s stimulating effect during a model study employing electrically stimulated rat vasa deferentia and an assay measuring the BK-induced [Ca²⁺]_i increase. Pretreatment with E1R facilitated PA retention in a dose-related manner. Furthermore, E1R alleviated the scopolamine-induced cognitive impairment during the PA and Y-maze tests in mice. The in vivo and in vitro effects of E1R were blocked by treatment with the selective sigma-1 receptor antagonist NE-100. E1R did not affect locomotor activity.

Conclusion and Implications

E1R is a novel 4,5-disubstituted derivative of piracetam that enhances cognition and demonstrates efficacy against scopolamine-induced cholinergic dysfunction in mice. These effects are attributed to its positive modulatory action on the sigma-1 receptor and this activity may be relevant when developing new drugs for treating cognitive symptoms related to neurodegenerative diseases.     

High l-carnitine concentrations do not prevent late diabetic complications in type 1 and 2 diabetic patients

Increased intake of l-carnitine, a cofactor in cellular energy metabolism, is recommended for diabetic patients with late complications. However, its clinical benefits remain controversial. We hypothesized that patients with low l-carnitine levels would have an increased rate of diabetic complications. To test this hypothesis, we evaluated the relationship of l-carnitine concentrations in blood with the prevalence and severity of late diabetic complications in type 1 and 2 diabetic patients. Human blood samples were collected from 93 and 87 patients diagnosed as having type 1 or type 2 diabetes, respectively, and 122 nondiabetic individuals. The determination of free l-carnitine concentrations in whole blood lysates was performed using ultra-performance liquid chromatography with tandem mass spectrometry. In diabetic patients, diabetic complications such as neuropathy, retinopathy, nephropathy, or hypertension were recorded. The average l-carnitine concentration in the blood of control subjects was 33 ± 8 nmol/mL, which was not significantly different from subgroups of patients with type 1 (32 ± 10 nmol/mL) or type 2 diabetes (36 ± 11 nmol/mL). Patients with low (<20 nmol/mL) l-carnitine levels did not have increased occurrences of late diabetic complications. In addition, patient subgroups with higher l-carnitine concentrations did not have decreased prevalence of late diabetic complications. Our results provide evidence that higher l-carnitine concentrations do not prevent late diabetic complications in type 1 and 2 diabetic patients.     

BDNF regulates the expression of fragile X mental retardation protein mRNA in the hippocampus

Both fragile X mental retardation protein (FMRP) and brain-derived neurotrophic factor (BDNF) are implicated in the maturation of neurons and in the higher cognitive functions. We have investigated whether FMRP and BDNF are reciprocally regulated in neurons. Exposure of cultured hippocampal neurons to BDNF, but not to NT-3, reduced FMR1 mRNA levels to 84.8% of control at 4 h and the levels were back to baseline by 24 h or 4 days. Furthermore, expression of FMR1 mRNA was reduced (82.4% of control) in vivo in the hippocampus of transgenic mice overexpressing TrkB receptors, and a small but significant (5.1%) decrease was also detected in FMRP protein levels. In contrast, the expression patterns of BDNF and TrkB mRNAs were not altered in FMRP-deficient mice compared to wild-type mice. Our data provide evidence that BDNF via TrkB signaling decreases FMRP expression and suggest a role for FMRP in BDNF-induced synaptic plasticity.     

Color vision and contrast sensitivity in epilepsy patients treated with initial tiagabine monotherapy

The purpose of the study was to determine whether the use of a GABAergic antiepileptic drug (AED), tiagabine, affects color vision and contrast sensitivity. Twenty newly diagnosed patients with partial epilepsy (aged 19-72 years), receiving tiagabine as their initial monotherapy for 5-41 months were examined. Color vision was examined with the Standard Pseudoisochromatic Plates 2 (SPP2), with the Farnsworth-Munsell 100 Hue Test (FM100) and with the Color Vision Meter 712 (CVM) anomaloscope. Contrast sensitivity was measured with the Pelli-Robson letter chart. Three patients excluded from the color vision evaluation for congenital red-green color vision defects. Seven out of 17 patients (41%) had acquired color vision deficit examined with the FM100. The CVM anomaloscope revealed minor defects in two patients. Contrast sensitivity function was within normal ranges. The present study suggests that AED therapy with tiagabine, like with other established and newer AEDs may interfere with color perception.     

Altered auditory processing in acutely psychotic never-medicated first-episode patients

Individuals with psychosis fail to differentiate external impulses and suffer from distortions of reality testing. Schizophrenia group illnesses are also associated with deficits in working memory and perception. We examined the manifestations of a very early phase of psychotic illness to automatic auditory deviance detection to clarify the basic mechanisms underlying misinterpretations of perception. METHODS: Twenty-five never-medicated patients admitted for hospital evaluation of acute psychosis were studied. Fifty-eight EEG channels were recorded during an auditory oddball paradigm. Event-related potentials (ERPs) time-locked to non-attended deviant auditory stimuli were studied in patients and compared with healthy controls. Auditory processing was examined both at the level of the measured biosignals (standard and deviant responses) and with subtraction waveforms. Topographical differences were characterized using global field power (GFP) and minimum norm estimates. RESULTS: The maximum GFP amplitudes and mean amplitudes of the 58 channels within the time windows corresponding to the previously known 'N2b', 'P3a' and 'P3b' components were clearly reduced in patients when compared to healthy controls. However, the groups did not differ during attention-independent automatic processing corresponding to the 'N1' and 'MMN' components, or with respect to the peak latencies of the GFP maxima. CONCLUSIONS: Impairment of the processing of a deviance in simple auditory input in acutely ill drug-naive first-episode psychotic patients only appears in attention-dependent processing after about 250 ms. The alterations in auditory processing differed between stimulus types, suggesting at least two mechanisms underlying the auditory discrimination impairments in acute psychosis. After 250 ms there was a linear and gradually increasing difference in magnitude between the groups in their responses to deviant stimuli, probably related to arousal. In addition, however, there was a striking difference between the groups in the processing of standard stimuli. The early processing was similar in patients and controls, but the striking difference appeared in later processing. The sensory memory deficits associated with psychosis may be explained by an abnormality in sensory model formation rather than by impaired deviant detection.     

Glucuronidation of Entacapone, Nitecapone, Tolcapone, and Some Other Nitrocatechols by Rat Liver Microsomes

Purpose. Nitrocatechol COMT inhibitors are a new class of bioactive compounds, for which glucuronidation is the most important metabolic pathway. The objective was to characterize the enzyme kinetics of nitrocatechol glucuronidation to improve the understanding and predicting of the pharmacokinetic behavior of this class of compounds. Methods. The glucuronidation kinetics of seven nitrocatechols and 4-nitrophenol, the reference substrate for phenol UDP-glucuronosyltrans-ferase activity, was measured in liver microsomes from creosote-treated rats and determined by non-linear fitting of the experimental data to the Michaelis-Menten equation. A new method that combined densitometric and radioactivity measurement of the glucuronides separated by HPTLC was developed for the quantification. Results. Apparent K_m values for the nitrocatechols varied greatly depending on substitution pattern being comparable with 4-nitrophenol (0.11 mM) only in the case of 4-nitrocatechol (0.19 mM). Simple nitrocatechols showed two-fold V_max values compared with 4-nitrophenol (68.6 nmol min^–1 mg^–1), while all disubstituted catechols exhibited much lower glucuronidation rate. V_max/K_m values were about 10 times higher for monosubstituted catechols compared to disubstituted ones. The kinetic parameters for COMT inhibitors were in the following order: K_m nitecapone >> entacapone > tolcapone; V_max nitecapone > entacapone > tolcapone; V_max/K_m tolcapone > nitecapone > entacapone. Conclusions. Nitrocatechols can in principle be good substrates of UGTs. However, substituents may have a remarkable effect on the enzyme kinetic parameters. The different behaviour of nitecapone compared to the other COMT inhibitors may be due to its hydrophilic 5-substituent. The longer elimination half-life of tolcapone in vivo compared to entacapone could not be explained by glucuronidation kinetics in vitro.