Reciprocal effects of age and clinical allergy: is there more to be learned?
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Biomedical subjects
Publications and source records attributed to I L Bernstein.
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Motivated behaviors, including sodium (Na) appetite, are correlated with increased dopamine (DA) transmission in the nucleus accumbens (NAc). DA transporter (DAT) modulation affects DA transmission and may play a role in motivated behaviors. In vivo Na depletion, which reliably induces Na appetite, was correlated with robust decreases in DA uptake via the DAT in the rat NAc with rotating disk electrode voltammetry [1,277 +/- 162 vs. 575 +/- 89 pmol. s-1. g-1; Vmax of transport for control vs. Na-depleted tissue]. Plasma aldosterone (Aldo) levels increase after in vivo Na depletion and contribute to Na appetite. Decreased DAT activity in the NAc was observed after in vitro Aldo treatment (428 +/- 28 vs. 300 +/- 25 pmol. s-1. g-1). Neither treatment affected DAT activity in the striatum. These results suggest that a direct action of Aldo is one possible mechanism by which Na depletion induces a reduction in DAT activity in the NAc. Reduced DAT activity may play a role in generating increased NAc DA transmission during Na appetite, which may underlie the motivating properties of Na for the Na-depleted rat.
In the rat, the ionic specificity of Na+ appetite is thought to rely on amiloride-sensitive Na+ signals conveyed by the chorda tympani (CT) nerve. We evaluated whether robust Na+ appetite relies exclusively on CT-mediated amiloride-sensitive Na+ signals. Amiloride dramatically reduced sham drinking of NaCl (41.9 +/- 9.0 vs. 6.9 +/- 3.7 ml, 0.1 M NaCl without vs. with 100 microM amiloride), which resulted in intake that was not different from intake of a non-Na+ salt solution (8.8 +/- 2.3 ml, 0.15 M KCl). In addition, intake of 0.1 M NaCl in CT-transected (CTX) rats was reduced (35.8 +/- 13.3 vs. 8.67 +/- 3.4 ml, sham-operated vs. CTX rats), but the addition of amiloride (100 microM) further reduced intake in CTX rats (0.5 +/- 0.29 ml). These data support the idea that amiloride-sensitive Na+ channels are the critical gustatory substrate for Na+ identification during Na+ appetite in the rat. However, the data indicate that these amiloride-sensitive signals are not conveyed exclusively by the CT nerve but by an additional afferent pathway.
Although health risks to pesticides containing Bacillus thuringiensis (Bt) have been minimal, the potential allergenicity of these organisms has not been evaluated. Therefore, a health survey was conducted in farm workers before and after exposure to Bt pesticides. Farm workers who picked vegetables that required Bt pesticide spraying were evaluated before the initial spraying operation (n = 48) and 1 and 4 months after (n = 32 and 20, respectively). Two groups of low- (n = 44) and medium- (n = 34) exposure workers not directly exposed to Bt spraying were also assessed. The investigation included questionnaires, nasal/mouth lavages, ventilatory function assessment, and skin tests to indigenous aeroallergens and to a variety of Bt spore and vegetative preparations. To authenticate exposure to the organism present in the commercial preparation, isolates from lavage specimens were tested for Bt genes by DNA-DNA hybridization. Humoral immunoglobulin G (IgG) and immunoglobulin E (IgE) antibody responses to spore and vegetative Bt extracts were assayed. There was no evidence of occupationally related respiratory symptoms. Positive skin-prick tests to several spore extracts were seen chiefly in exposed workers. In particular, there was a significant (p < 0.05) increase in the number of positive skin tests to spore extracts 1 and 4 months after exposure to Bt spray. The number of positive skin test responses was also significantly higher in high (p < 0.05) than in low- or medium-exposure workers. The majority of nasal lavage cultures from exposed workers was positive for the commercial Bt organism, as demonstrated by specific molecular genetic probes. Specific IgE antibodies were present in more high-exposure workers (p < 0.05) than in the low and medium groups. Specific IgG antibodies occurred more in the high (p < 0.05) than in the low-exposure group. Specific IgG and IgE antibodies to vegetative organisms were present in all groups of workers. Exposure to Bt sprays may lead to allergic skin sensitization and induction of IgE and IgG antibodies, or both.
Genetic linkage analysis of rats that were selectively bred for alcohol preference identified a chromosomal region that includes the neuropeptide Y (NPY) gene. Alcohol-preferring rats have lower levels of NPY in several brain regions compared with alcohol-non-preferring rats. We therefore studied alcohol consumption by mice that completely lack NPY as a result of targeted gene disruption. Here we report that NPY-deficient mice show increased consumption, compared with wild-type mice, of solutions containing 6%, 10% and 20% (v/v) ethanol. NPY-deficient mice are also less sensitive to the sedative/hypnotic effects of ethanol, as shown by more rapid recovery from ethanol-induced sleep, even though plasma ethanol concentrations do not differ significantly from those of controls. In contrast, transgenic mice that overexpress a marked NPY gene in neurons that usually express it have a lower preference for ethanol and are more sensitive to the sedative/hypnotic effects of this drug than controls. These data are direct evidence that alcohol consumption and resistance are inversely related to NPY levels in the brain.
Central infusion of glucagon-like peptide-1-(7-36) amide (GLP-1) and intraperitoneal (i.p.) injection of lithium chloride (LiCl) produce similar patterns of c-Fos induction in the rat brain. These similarities led us to assess the hypothesis that neuronal activity caused by i.p. injection of LiCl involves activation of central GLP-1 pathways. We therefore determined if third-ventricular (i3vt) infusion of a GLP-1 receptor antagonist would block LiCl-induced c-Fos expression in the brainstem. Relative to rats pretreated with i3vt infusion of vehicle, pretreatment with the potent GLP-1 receptor antagonist, des His1 Glu9 exendin-4 (10.0 microgram), significantly attenuated LiCl-induced (76 mg/kg; i.p.) c-Fos expression in several brainstem regions, including the area postrema, the nucleus of the solitary tract, and the lateral parabrachial nucleus. While central infusion of des His1 Glu9 exendin-4 also blocked GLP-1-induced (10.0 microgram) anorexia and c-Fos expression, the antagonist produced no independent effects on food intake or c-Fos expression. These results suggest that LiCl-induced c-Fos expression in the rat brainstem is mediated, at least in part, by GLP-1 receptor signaling.
The induction of c-Fos-like immunoreactivity (c-FLI) in the intermediate division of the nucleus of the solitary tract (iNTS) has been shown to be a cellular correlate of the behavioral expression of a conditioned taste aversion (CTA). To further define neuroanatomical structures and pathways that contribute to this cellular response and to CTA learning in general, electrolytic lesions of insular (gustatory) cortex (IC) were combined with immunostaining for c-FLI. Rats were given either unilateral or bilateral electrolytic lesions of insular cortex or 'sham' operations. Following surgery, 'paired' animals were given a single conditioning trial consisting of intraoral infusion of 5-ml 0.15% sodium-saccharin followed by injection with LiCl (0.15 M, 20 ml/kg, i.p.) while 'unpaired' controls received a non-contingent saccharin-LiCl presentation. Rats with bilateral lesions showed no behavioral evidence of having acquired a CTA. Increases in c-FLI in iNTS were evident, but reduced, relative to 'sham' animals. Rats with unilateral-lesions displayed a CTA by rejecting the saccharin, although increases in c-FLI on the side of the iNTS ipsilateral to the lesion were reduced relative to that seen in 'sham' animals. A comparison of these results with those obtained after amygdala lesions supports the conclusion that amygdala and insular cortex are necessary, but not sufficient, for the behavioral expression of a CTA.
Evidence for an association between early pregnancy sickness and offspring salt (NaCl) preference has been obtained from studying offspring as young adults. To determine whether effects on NaCl preference are expressed in infancy, the present study examined 16-week-old infants whose mothers reported either little or no vomiting (N = 15) or frequent moderate to severe vomiting (N = 14) during the first 14 weeks of their pregnancy. The infants' oral-motor facial reactions to each solution and their relative intakes of distilled water and 0.1m and 0.2m NaCl were used as measures of preference. Infants of mothers who reported no or mild symptoms had a significantly lower relative intake of salt solutions than infants whose mothers reported moderate to severe symptoms (p < 0.01). The former infants also showed a greater number of aversive facial responses when given 0.2m NaCl (p < 0.05). Taken together, these findings support the hypothesis that maternal dehydration, induced by moderate to severe vomiting during pregnancy, can lead to enhanced salt preference in offspring. They also provide a potential explanation for some of the variability encountered when human infants are tested for their salt preference.
Food deprivation increases the rewarding effects of self-administered drugs such as psychomotor stimulants and benzodiazepines. These drugs also possess aversive properties and can produce conditioned taste aversions (CTA). Because drug-seeking behavior is most likely affected by both the rewarding and aversive properties of drugs, we hypothesize that food deprivation might also attenuate a drug's aversive consequences. The CTAs induced by three different drugs (amphetamine, chlordiazepoxide, and LiCl) were assessed separately. Male Long-Evans rats were assigned to one of two feeding conditions: restricted (maintained at 80% of free-feeding body weight), or nonrestricted (with ad lib food). Both groups received CTA training, consisting of an intraoral infusion of a novel saccharin solution (10 min) followed immediately by one of two i.p. injections: paired rats received drug, and unpaired rats received a similar volume of saline. After 10 days of ad lib food access, saccharin was presented to all rats again, and the latency to reject the tastant was used as an index of CTA learning. The rats that had been food restricted at the time of conditioning exhibited attenuated CTAs relative to those that had not been deprived. These differences were seen only when a rewarding drug (amphetamine or chlordiazepoxide) and not when a nonrewarding drug (LiCl) was used as the unconditioned stimulus. In a separate experiment, we established that this effect is apparent only when the deprivation period precedes conditioning rather than precedes testing. The present results indicate that food deprivation modulates the acquisition of a CTA induced by amphetamine or chlordiazepoxide, but not LiCl.
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This algorithm on the diagnosis and treatment of asthma is intended to complement and update the previously published Practice Parameters for the Diagnosis and Treatment of Asthma. Both documents were developed by the Joint Task Force on Practice Parameters, representing the AAAAI, ACAAI, and the JCAAI. The authors of this asthma algorithm have attempted to include all the elements essential for the diagnosis and care of patients with asthma. Every effort was made to keep the algorithm clear and concise, yet thorough and complete (Fig 1). Each component of the algorithm is elaborated further in a brief annotation. For further discussion, the reader is referred to the more extensive Practice Parameters for the Diagnosis and Treatment of Asthma.
The algorithm and text annotations in this document are intended to assist clinical decision making about patients who present with symptoms of rhinitis. This document complements the Executive Summary of Joint Task Force Practice Parameters for Diagnosis and Management of Rhinitis (Ann Allergy, Asthma, Immunol 1998; 81:463-468) and Diagnosis and Management of Rhinitis: Complete Guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology (Ann Allergy, Asthma, Immunol 1998;81:478-578). The Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology is co-sponsored by the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology and the Joint Council of Allergy, Asthma and Immunology.
This document contains complete guidelines for diagnosis and management of rhinitis developed by the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology, representing the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology and the Joint Council on Allergy, Asthma and Immunology. The guidelines are comprehensive and begin with statements on clinical characteristics and diagnosis of different forms of rhinitis (allergic, non-allergic, occupational rhinitis, hormonal rhinitis [pregnancy and hypothyroidism], drug-induced rhinitis, rhinitis from food ingestion), and other conditions that may be confused with rhinitis. Recommendations on patient evaluation discuss appropriate use of history, physical examination, and diagnostic testing, as well as unproven or inappropriate techniques that should not be used. Parameters on management include use of environmental control measures, pharmacologic therapy including recently introduced therapies and allergen immunotherapy. Because of the risks to patients and society from sedation and performance impairment caused by first generation antihistamines, second generation antihistamines that reduce or eliminate these side effects should usually be considered before first generation antihistamines for the treatment of allergic rhinitis. The document emphasizes the importance of rhinitis management for comorbid conditions (asthma, sinusitis, otitis media). Guidelines are also presented on special considerations in patients subsets (children, the elderly, pregnancy, athletes and patients with rhinitis medicamentosa); and when consultation with an allergist-immunologist should be considered.
With c-Fos immunoreactivity as a marker for neural activity, we examined whether environmental cues associated with ethanol injection influence the expression of tolerance to ethanol-induced c-Fos activation. Over 24 training days, male Long-Evans rats received ethanol injection (2.5 g/kg) in one environment and saline injection in a different environment. Relative to rats that received ethanol for the first time, ethanol-induced c-Fos expression in the paraventricular nucleus of the hypothalamus (PVN) and the locus coeruleus (LC) was significantly reduced in rats that had received multiple prior ethanol administrations. However, tolerance was partially reversed when ethanol was given in the saline-paired, rather than the ethanol-paired, environment. Results suggest that tolerance to ethanol, as indexed by c-Fos expression in the PVN and the LC, is mediated in part by Pavlovian conditioned responses to cues that predict ethanol administration.
OBJECTIVE: To determine the ability of budesonide via an inhaler (Pulmicort Turbuhaler; Astra Draco AB) to replace oral glucocorticosteroids (GCSs) in adult subjects with moderate-to-severe asthma. DESIGN: Double-blind, randomized, and placebo-controlled study, with parallel groups. SETTING: Multicenter study in outpatient setting. PARTICIPANTS: Eighty men and 79 women, aged 20 to 69 years, with moderate-to-severe asthma and a mean FEV1 of 58.3% predicted normal. All subjects were receiving oral GCS treatment and 79% of subjects were also receiving inhaled beclomethasone dipropionate (BDP). The mean daily doses of prednisone at baseline, including converted dose of BDP, for the placebo, budesonide 400 microg, and budesonide 800 microg, respectively, were 19.7 mg, 19.5 mg, and 18.7 mg. MEASUREMENTS AND INTERVENTIONS: After a 2-week baseline period, subjects entered a 20-week treatment period, during which the oral dose of prednisone was reduced by forced down-titration at 2-weekly intervals. RESULTS: Subjects receiving 400 microg or 800 microg bid of budesonide achieved a significantly greater reduction (82.9% and 79.0% respectively) in oral GCS dose compared with placebo-treated subjects (27%; p<0.001). Two thirds of the subjects receiving budesonide were able to achieve sustained oral corticosteroid cessation, compared with 8% in the placebo group. Additionally, both doses of budesonide resulted in significant improvement in results of pulmonary function tests and asthma symptoms scores, and a significant decrease in the use of bronchodilator therapy. The mean plasma cortisol levels before and after adrenocorticotropic hormone stimulation increased most toward the normal range in the budesonide-treated groups compared with placebo-treated subjects. CONCLUSION: Budesonide administered via Turbuhaler has a significant oral GCS-sparing capacity with maintained or improved asthma control in adult subjects with moderate-to-severe asthma.
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Selectively bred rat lines, developed to model genetic contributions to alcohol abuse, include the Indiana alcohol-preferring (P) and alcohol-nonpreferring (NP) lines, and the Alko-Alcohol (AA) and Alko-Nonalcohol (ANA) lines. Preferring and nonpreferring lines were compared in their response to intraperitoneal injection of either ethanol or isotonic saline using c-Fos expression as a marker of neuronal activity. Although line differences were noted in several brain regions, the principal finding was that alcohol-nonpreferring lines (NP and ANA) displayed greater c-Fos expression in the locus coeruleus (LC) relative to the alcohol-preferring lines (P and AA) following injection of 3.0 g ethanol/kg. These data point to the LC as an area which may play a role in the differences in voluntary ethanol consumption between rat lines genetically bred for low and high ethanol preference.
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