Contact dermatitis

In recent years, there has been a dramatic rise in our understanding of contact dermatitis. This paper is a review of our knowledge of the mechanisms involved in contact dermatitis and related phenomena, the investigation of these events and the emergence of significant new allergens during the last 5 years.     

Electrical and physiological changes during short-term and chronic electrical stimulation of the normal cochlea

In the electrical stimulation (ES) of auditory pathways, the type of stimulus and the electrode/tissue interface are critical parameters for the safety and efficacy of the protocol. In this study the influence of alternate pulses, applied between round window and vertex electrodes in chronically implanted guinea pigs, and maintained during 1 and 25 daily periods of 2 h (short-term and long-term experiments, respectively), was investigated. ES consisted of monophasic current pulses of ±70 μA and 300 μs in duration at a rate of 167/s, with alternate polarity. Compound Action Potential (CAP) audiograms, amplitudes and latencies of click-evoked CAPs, amplitudes and latencies of electrically-evoked auditory responses (EARs), and electrode impedances, were measured periodically outside or during the ES periods. Short-term ES induced no change in CAP thresholds, amplitude and latency in response to clicks at 80 dB above normal threshold, but induced a slight latency increase and amplitude decrease of the EAR, correlated with an exponential decay of the electrode impedance. On a long-term basis, CAP audiograms and latencies did not change significantly, whereas CAP amplitudes and electrode impedances increased, in correlation with each other. In control guinea pigs receiving no ES, the same CAP amplitude and impedance changes were observed over the same long-term period. The EAR and CAP changes can be explained by a variation of the electrical impedance of the electrode/tissue interface. This is possibly due to a change in electrotytes around the electrode under the influence of the ES for the short-term variation, and to an electrode encapsulation by fibrous tissue independent of the ES for the long-term change. In itself, and under the conditions of this experiment, the ES demonstrated no adverse effects on the auditory function and can be safely used for inner-ear exploration.     

Comparison of ED, EID, and API Criteria for the Robust Optimization of Sampling Times in Pharmacokinetics

Optimization of the sampling schedule can be used in pharmacokinetic (PK) experiments to increase the accuracy and the precision of parameter estimation or to reduce the number of samples required. Several optimization criteria that formally incorporate prior parameter uncertainty have been proposed earlier. These criteria consist in finding the sampling schedule that maximizes the expectation (over a given parameter distribution) of det F (ED-optimality) or Log(det F) (API-optimality), or minimizes the expectation of 1/det F (EID-optimality), where F is the Fisher information matrix. The precision and the accuracy of parameter estimation after having fitted a PK model to a small number of optimal data points (determined according to D, ED, EID, and API criteria) or to a naive sampling schedule were compared in a Monte Carlo simulation study. A one-compartment model with first-order absorption rate (3 parameters) and a two-compartment model with zero-order infusion rate (4 parameters) were considered. Data were simulated for 300 subjects with both structural models, combined with several residual error models (homoscedastic, heteroscedastic with constant or variable coefficient of variation). Interindividual variabilities in PK parameters ranged from 25–66%. ED-, EID-, and API-optimal sampling times were calculated using the software OSP-Fit. Three or five samples were allowed for parameter estimation by extended least-squares. Performances of each design criterion were evaluated in terms of mean prediction error, root mean squared error, and number of acceptable estimates (i.e., with a SE less than 30%). Compared to the D-optimal design, the EID and API designs reduced the bias and the imprecision of the estimation of the parameters having a large interindividual variability. Moreover, the API design resulted in some cases in a higher number of acceptable estimates.     

Halogenated Anesthetics Reduce Interleukin-1β-induced Cytokine Secretion by Rat Alveolar Type II Cells in Primary Culture

Background: Alveolar epithelial type II (ATII) cells participate in the intraalveolar cytokine network by secreting cytokines and are widely exposed to volatile anesthetics during general anesthesia. The aim of the current study was to evaluate the effects of halothane, enflurane, and isoflurane on rat ATII cell cytokine secretions in ATII primary cell cultures.

Methods: Alveolar epithelial type II primary cell cultures were obtained from adult rat lungs. ATII cells were stimulated by recombinant murine interleukin-1[beta] (rmIL-1[beta]) to mimic an inflammatory response, and immediately exposed for various duration to different concentration of halothane, enflurane, or isoflurane. Interleukin-6, macrophage inflammatory protein-2 (MIP-2), and monocyte chemoattractant protein-1 (MCP-1) protein concentrations were then measured in cell culture supernatants. Recombinant mIL-1[beta]-stimulated ATII cells exposed to air served as control.

Results: Halothane, isoflurane, and enflurane (1 minimum alveolar concentration [MAC], 4 h) decreased rmIL-1[beta]-stimulated ATII cell secretions of interleukin-6, MIP-2, and MCP-1, but did not modify total protein secretion. Halothane exposure decreased rmIL-1[beta]-stimulated ATII cell secretions of interleukin-6, MIP-2, and MCP-1 in a dose- and time-dependent manner. Total protein concentrations remained unchanged except at 1.5 MAC of halothane, and no cytotoxic effect could be evidenced by lactate dehydrogenase release. These effects were transient as rmIL-1[beta]-stimulated ATII cell secretions of interleukin-6 and MIP-2 progressively reached control values between 4 and 24 h after the end of halothane exposure. However, MCP-1 inhibition persisted until 24 h. rmIL-1[beta]-induced MIP-2 and tumor necrosis factor-[alpha] mRNA expression were decreased by 36 and 24%, respectively, after halothane exposure.     

Absence of long-term changes in biochemical markers of monoaminergic systems afferent to the excitotoxically neuron-depleted somatosensory thalamus

In a previous study, it was shown that, one month after kainic acid (KA) injection into the thalamus, afferents deprived of postsynaptic target neurons exhibit structural alteration, including the loss of synaptic vesicles. The present study was undertaken to determine whether these long-term morphological changes were associated with changes in biochemical markers of monoaminergic pathways. In situ injection of KA was performed into the right ventrobasal complex of the rat thalamus (VB). Protein content and total amount of norepinephrine, dopamine, 5-hydroxytryptamine and 5-hydroxyindolacetic acid were analyzed in the lesioned area one, two, three and four months after injection using high-performance liquid chromatography and electrochemical detection. The results were compared to those obtained in an equal volume of tissue dissected out from the opposite (intact) VB. Protein content per unit volume decreased progressively to 50% of control in the neuron-depleted area. In contrast, whatever the amine considered, its total amount remained unaltered up to 4 months after the excitotoxic lesion. 5-hydroxyindolacetic acid was also unchanged 4 months after lesion. This study suggests that (i) the quantity of monoamines in afferents to the rat VB does not depend upon the presence of post-synaptic target neurons, (ii) a non-vesicular storage compartment may compensate the loss of synaptic vesicles in afferent fibers to the lesioned area.     

Muscle reorganization after partial denervation and reinnervation

The normal rat tibialis anterior (TA) muscle was found to be innervated by approximately 154 spinal motor cells of which 95 are alpha motoneurons. Most of these axons ran in the L4 root and connected with glycolytic type 2B muscle fibers. The L5 root supplied 8.4% to 14.7% of the motor axons of TA muscle and innervated type 1 and 2A muscle fibers rich in oxidative enzymes. Two months after section of the peroneal nerve, there was marked fiber-type grouping and compact rearrangement of the L4 and L5 motor units. After section of the L4 radicular nerve, the TA muscle remained atrophic with no evidence of fiber-type grouping until 3 months when the L4 regenerating axons reached the muscle. Similar results were obtained after ligation of the divided ends of the L4 radicular nerve, which delayed but did not prevent reinnervation. These data suggest that, after partial denervation, muscle reinnervation by collateral sprouting is a slowly developing process.