Mg Of Histamine Research Articles

Novel Archaeal Histamine Oxidase from Natronobeatus ordinarius: Insights into Histamine Degradation for Enhancing Food Safety.

Histamine, found abundantly in salt-fermented foods, poses a risk of food poisoning. Natronobeatus ordinarius, a halophilic archaeon isolated from a salt lake, displayed a strong histamine degradation ability. Its histamine oxidase (HOD) gene was identified (hodNbs). This is the first report of an archaeal HOD. The HODNbs protein was determined to be a tetramer with a molecular weight of 307 kDa. HODNbs displayed optimum activity at 60-65 °C, 1.5-2.0 M NaCl, and pH 6.5. Notably, within the broad NaCl range between 0.5 and 2.5 M, HODNbs retained above 50% of its maximum activity. HODNbs exhibited good thermal stability, pH stability, and salinity tolerance. HODNbs was able to degrade various biogenic amines. The Vmax of HODNbs for histamine was 0.29 μmol/min/mg, and the Km was 0.56 mM. HODNbs exhibited high efficiency in histamine removal from fish sauce, namely, 100 μg of HODNbs degraded 5.63 mg of histamine (37.9%) in 10 g of fish sauce within 24 h at 50 °C. This study showed that HODNbs with excellent enzymatic properties has promising application potentials to degrade histamine in high-salt foods.

Effects of the immunoglobulin/histamine complex on panic disorder concurrent with chronic spontaneous urticaria: a case report

BackgroundPanic disorder and panic attacks are two of the most common problems in psychiatry. A psychoimmunological correlation between allergic diseases and panic disorder has been strongly suggested. Histamine H1 receptor antagonists have been suggested as alternative drugs for the treatment of panic disorder. Chronic spontaneous urticaria (CSU) and panic disorder improved simultaneously with selective serotonin reuptake inhibitor antidepressants. Panic disorder has also been treated with the antihistamine chlorpheniramine. The immunoglobulin/histamine complex is a histamine-fixed immunoglobulin preparation that was reported to be effective in treating CSU. This case report describes the successful treatment of a patient with concomitant panic disorder and CSU for 23 years using immunoglobulin/histamine complex therapy.Case presentationThis report describes a 52-year-old female Korean patient who suffered from CSU with panic disorder for 23 years. Basic allergy tests (blood tests and skin prick tests) were conducted before and after treatment for the evaluation of allergic conditions. A multiple allergosorbent test (MAST) for the detection of allergen-specific IgE levels was also performed. The clinical severity of CSU was evaluated using the urticaria severity score system. Diagnostic interviews systematically assessed the diagnostic criteria outlined by the DSM-V, and the patient was evaluated before, during and after treatment using the Beck Depression Inventory (BDI-2) for depression, the State-Trait Anxiety Inventory (STAI) for anxiety and the Beck Hopelessness Score (BHS) for hopelessness. The patient received 2 ml of Histobulin™ (12 mg human immunoglobulin/0.15 µg histamine complex) once a week by subcutaneous injection for the treatment of CSU. Initial improvement of CSU was achieved after the third injection. After the twenty-seventh injection of Histobulin™, she showed no symptoms or signs and ceased allergic medication use. With the remission of CSU, allergic rhinitis was also completely resolved. The frequency of the common cold was significantly decreased during and after treatment. The medication frequency and development of clinical manifestations of panic disorder changed in parallel with the clinical severity of CSU. Moreover, the patient exhibited no clinical manifestations and ceased medication for panic disorder and sleeping pills for insomnia simultaneously with the remission of CSU. In the psychological evaluation, the BDI, STAI and BHS scores improved accordingly.ConclusionsThe immunoglobulin/histamine complex was effective in treating CSU and concomitant panic disorder in this patient and could be effective in treating some types of panic disorder. Considering the mechanisms of action of histamine and the immunoglobulin/histamine complex together with the patient’s clinical progress, histamine seemed to be related to panic disorder in this case. The concept of histamine-mediated syndromes, including allergies and psychiatric disorders, shows that a wider disease identity may be needed. Further studies on the immunopathogenesis of panic disorder and the mechanisms of action of the immunoglobulin/histamine complex are necessary.

Efficacy and Safety of Honey Bee Venom (Apis mellifera) Dermal Injections to Treat Osteoarthritis Knee Pain and Physical Disability: A Randomized Controlled Trial.

Objectives: To evaluate purified honey bee (Apis mellifera) venom (HBV) biotherapy for the treatment of osteoarthritis (OA) knee pain and physical function. Design and Patients: Five hundred and thirty-eight patients with Kellgren/Lawrence grade 1-3 radiographic knee OA and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score ≥2 were randomized 1:2 to either control ("histamine") or HBV in this double-blind study. Interventions: After a dose escalation period, patients received 12 weekly dermal injections of control ("histamine") or HBV. At each of the 12 weekly visits, a set of 15 dermal injections (each containing 2.75 μg histamine or 100 μg HBV) were administered at prespecified acupuncture points (5 on each knee: knee top, eye-1 medial, eye-2 lateral, ST 34, BL 40 and 5 near the spinous processes: BL 19, 21, 23, 25, and 27). Outcome Measures: Assessments included WOMAC pain and physical function subscales, visual analog scale (VAS), patient global assessment (PGA), and physician global assessment (PhGA). Rescue medication use (acetaminophen) and routine safety parameters were monitored. Results: HBV biotherapy demonstrated a highly significant improvement over control in WOMAC pain score after 12 weeks (1.1 U mean difference; confidence interval [95% CI]: 0.3-2.0; analysis of covariance [ANCOVA] p = 0.0010 with baseline as covariate) that was also sustained 4 weeks post-treatment. Furthermore, WOMAC physical function was significantly improved over control with HBV (3.1 U mean difference; 95% CI: 0.3-5.9; ANCOVA p = 0.0046), and sustained 4 weeks post-treatment. VAS scores were significantly improved with HBV versus control, as well as PGA and PhGA evaluations, which showed that patients responded more favorably ("very good/good") to their overall OA condition (82.0% vs. 62.4% [p = 0.0001] and 82.1% vs. 54.9% [p = 0.0015], respectively). Use of rescue acetaminophen was similar between the groups (77%-78% of patients). HBV was associated with higher incidence of injection site reactions (<5%); however, the overall safety profiles were comparable between the treatment groups. Conclusions: This phase 3 trial demonstrated that HBV biotherapy resulted in significant improvements in knee OA pain and physical function.

Impairment in the aversive memory of mice in the inhibitory avoidance task but not in the elevated plus maze through intra-amygdala injections of histamine

RationaleEvidence indicates that histamine (HA) modulates learning and memory in different types of behavioral tasks; however, the exact nature of this modulation and its mechanisms are controversial. Furthermore, emotions are able to influence memory processing in a crucial way through the involvement of the amygdala. Our research aims to contribute to the neurobiological body of knowledge on acquisition and retrieval of emotional memory via the histaminergic amygdaloid system in mice. ObjectivesThe present study investigated whether exogenous HA infused into the amygdala differentially modulates the anxiety- and fear-related memory of mice assessed by unconditioned and conditioned tasks. MethodsOver two consecutive days, animals received bilateral microinjections of either vehicle or HA (0.1, 0.5 and 1.0μg by 0.1μl/side volume) into the amygdala before behavioral tests were performed. Mice were examined under two paradigms: an exposure/re-exposure procedure in the elevated plus-maze (EPM) or in the inhibitory avoidance (IA) with electric foot shock trials 1 and 2 and retention test (without foot shock). ResultsPre-test intra-amygdala microinjection of 0.5μg HA induced anxiolytic-like responses, but none of the three doses interfered in mnemonic processing examined in the EPM. Concerning the IA task, step-through retention latencies increased in all groups compared with their respective trials, except in the animals microinjected with 0.5 or 1.0μg HA before the retention test. Thus, HA caused statistically significant amnesia during the session repeated 24h after training without drugs. Retention latency was not modified by microinjections of HA both pre-trial and pre-test or by pre-trial infusion in mice subjected to IA. ConclusionsOur data indicate that the amygdaloid histaminergic system could modulate anxiety-related behaviors in the EPM and impair the retrieval process in fear conditioning with a strong aversive stimulus. These results contribute further evidence of the distinct histaminergic influence on different emotional pathways.

A double-blind, randomized clinical study to determine the efficacy of benzocaine 10% on histamine-induced pruritus and UVB-light induced slight sunburn pain

Introduction: This study aims to explore the efficacy of the topical application of 10% benzocaine for treating pruritus and pain as compared to vehicle ointment. Methods: Twenty male subjects were treated in a randomized double-blind fashion with the investigational medicinal product (IMPD) and vehicle. Immediately after the injection of 100 µg histamine on both arms, subjects received topical treatment and pruritus was subsequently assessed with visual analogue scale (VASpruritus) and Eppendorfer questionnaire. Ultraviolet B radiation (UVB) was administered on the back to induce slight sunburn. Twelve hours after UVB application again the IMPD was applied on the right or left upper back and vehicle on the other side and pain related to sunburn was measured with VASpain and pressure algometry. Results: A trend towards better reduction of pruritus was shown for benzocaine in VASpruritus. For the VASpain significant differences in group comparison (p = 0.02) were observed. Algometer measurements showed onset of pain reduction in the verum group after 20 min whereas in the vehicle-treated area pain relief occurred only after 60 min after application. Conclusions: The topically administered ointment containing 10% benzocaine was found superior over vehicle for treating pain, but not pruritus.

Pruritic and Vascular Responses Induced by Serotonin in Patients with Atopic Dermatitis and in Healthy Controls

Atopic dermatitis (AD) is a chronic inflammatory skin disease with often severe itch. The aim of this study was to determine the pruritogenic and vascular effect of serotonin (5-hydroxytryptamine; 5-HT) in patients with AD and in healthy controls. A 50 µg dose of 5-HT was injected intradermally into non-lesional skin of 25 patients with AD and 25 healthy control individuals, and the effect compared with 0.2 µg histamine as a positive control, and buffer as a negative control. Pruritus was recorded by the subjects, using a computerized visual analogue scale, while flare and wheal were recorded by the investigator. There was no qualitative or quantitative difference in 5-HT-induced itch between patients and control subjects, or between males and females. However, reduced flare and wheal were found in the patient group for 5-HT. There were no correlations between clinical findings (i.e. eczema severity, clinical pruritus) and recorded experimental itch, or flare or wheal responses for 5-HT, in the patients with AD. In both groups a shorter itch latency was found for 5-HT compared with histamine. Through the use of intradermal injections, making it possible to calculate the dose of substance delivered, a lower vascular response to 5-HT was shown in patients with AD compared with healthy controls. In addition to confirming a pruritogenic role of 5-HT in both patients with AD and healthy controls, we found a shorter itch latency for 5-HT compared with histamine in both groups. The short itch latency time may indicate a direct effect of 5-HT on itch receptors.

Cutaneous vascular permeability factors (histamine, 5-hydroxytryptamine, bradykinin) and passive cutaneous anaphylaxis in sheep

Abstract The cutaneous blood vessels of sheep are more sensitive to histamine than those of laboratory rodents. The threshold dose in sheep was 0·0025 μg histamine. The ovine vessels are 70 to 100 times less sensitive to 5-hydroxytryptamine (5-HT) than to histamine, but only four times less sensitive to bradykinin than to histamine. The effects of compound 48/80 are antagonized both by the antihistamine agent mepyramine and by the anti-5-HT agent methysergide, which suggests that compound 48/80 may release 5-HT in addition to histamine in sheep. The capillary-damaging effects of passive cutaneous anaphylaxis in sheep are antagonized by methysergide and by sodium meclofenamate—an agent which antagonizes kinins and slow-reacting substance. The antihistamine agent mepyramine has a small anti-anaphylactic effect, whereas promethazine—a less specific antihistamine—offers more protection to the blood vessels against local anaphylaxis. It is concluded that in the complex interaction of chemical mediators of anaphylaxis in the cutaneous blood vessels of sheep, 5-HT and kinin (and/or SRS-A) may be more important than histamine.

Evaluación del contenido de histamina en atún (Thunnus sp) "in natura" y en sashimi procesado a partir de esta materia prima

With the purpose of assessing the histamine contents in tuna fish (Thunnus sp) "in nature", received in a restaurant located at Niterói city, Rio de Janeiro state, Brazil, and the formation of this compound in sashimi elaborated from this raw material, 123 samples were analyzed by thin layer chromatogra­phy, 30 samples were collected in January, 37 in February and 56 from August until November The results obtained for the samples analyzed during January showed contents between 0,0 and 5,0 mg/ 100 g, both ',pon receipt of the specimen and in the product already elaborated and exposed in the cooled counter. For the samples analyzed during the months of February, the results ranged from 0,0 to 5,0 mg of histamine by 100 g of sample, and the content showed for the elaborated product in the same previous conditions obtained lower values for some samples, showing that the histamine formation is not even in muscular tissue. All samples analyzed during the months comprised from August through November did not indicate presence of histamine. It can be concluded that the product manufacturing and storage were good and did not increased the levels of the toxin.

Photobacterium phosphoreum caused a histamine fish poisoning incident

An incident of histamine fish poisoning (HFP) occurred due to the consumption of iwashi maruboshi (dried sardine) in Osaka, Japan in March 2002. A histamine-producing bacterial strain, YS4-7, was isolated from iwashi maruboshi that contained 1700 mg of histamine per kilogram. This strain was identified as Photobacterium phosphoreum by biochemical examinations and partial sequencing of 16S rDNA. P. phosphoreum YS4-7 showed greater capability as a histamine producer at 4 and 12 °C than Morganella morganii JCM 1672. Strain YS4-7 produced 546 mg of histamine per kilogram in a sardine homogenate stored for 12 h at 20 °C. M. morganii, Raoultella planticola and Hafnia alvei have been isolated from fish implicated in HFP incidents, whereas this is the first report of P. phosphoreum being the causative bacterium in a sporadic case of histamine food poisoning.

Screening Topical Antipruritics: A Histamine-Induced Itch Human Model

Itch is a subjective symptom; its magnitude (intensity) may be only estimated by the reports of patients or volunteers. We utilized a comparative screening method to identify and quantify the efficacy of topical antipruritics with a histamine-induced itch human model. Ten individuals responsive to histamine-induced itch sensation were enrolled. Both forearms served as test sites. Each test site was treated randomly either by histamine injection only or pretreated with a coded candidate formula for 30 min and then a histamine injection. Itch was experimentally induced in each test site by the intracutaneous injection of 100 µg histamine dihydrochloride dissolved in 1 ml normal saline. Itch magnitude was measured each minute after histamine injection for 20 min with a magnitude visual analogue scale. Itch duration was also recorded. Formulation D significantly (p < 0.05) decreased itch magnitude (within a 20-min test period), from 2.6 ± 2.1 cm (mean ± SD) to 2.2 ± 2.1 cm (mean ± SD) when compared to its vehicle control; it also significantly (p < 0.05) shortened itch duration (15.0 ± 7.4 min; mean ± SD) in comparison with its vehicle control (20.3 ± 7.0 min; mean ± SD). Of all the formulations tested, formulation D was the most effective antipruritic in decreasing histamine-induced itch. This method may act as a simple and robust screening procedure when evaluating potential antipruritics and allow a comparison among products. Until validated with disease-induced itch, e.g., atopic dermatitis, the model should be considered screening in nature.

Selective down-regulation of high-affinity IgE receptor (FcεRI) α-chain messenger RNA among transcriptome in cord blood–derived versus adult peripheral blood–derived cultured human mast cells

AbstractSubstantial numbers of human mast cells (MCs) were generated from umbilical cord blood (CB) and from adult peripheral blood (PB). A single CB progenitor produced 15 436 MCs, whereas a single PB progenitor produced 807 MCs on average. However, PB-derived MCs were far more active than CB-derived MCs in terms of high-affinity IgE receptor (FcεRI)-mediated reactions. One million sensitized PB-derived MCs released 3.6 μg histamine, 215 pg IL-5, and 14 ng granulocyte macrophage–colony-stimulating factor (GM-CSF), whereas 106 sensitized CB-derived MCs released only 0.8 μg histamine, 31 pg IL-5, and 0.58 ng GM-CSF on anti-IgE challenge. However, ionophore A23 187 released similar levels of histamine from the 2 MC types. PB-derived MCs highly expressed surface FcεRI α chain, and CB-derived MCs almost lacked it in the absence of IgE. PB-derived MCs expressed approximately 5 times higher levels of messenger RNA (mRNA) for FcεRI α chain than CB-derived MCs, but mRNAs for β and γ chains of the receptors were equally expressed. Among the approximately 5600 kinds of full-length human genes examined by using the high-density oligonucleotide probe-array system, FcεRIα was ranked the fifth most increased transcript in PB-derived MCs. The 4 other increased transcripts were unrelated to MC function. These results suggest that IgE-mediated reactions may be restricted during early infancy through the selective inhibition of FcεRIα transcription, which is probably committed at progenitor stages and is, at least in part, cytokine-insensitive.

Prevention of histamine formation in cheese by bacteriocin-producing lactic Acid bacteria

The susceptibility of 13 amine-forming lactobacilli to several bacteriocins was investigated by an agar diffusion assay. All strains were susceptible to nisin and to five bacteriocins of enterococcal origin. Pediocin PA-1, bavaricin A, lactococcin A, and a bacteriocin from Enterococcus faecalis 1061 did not show inhibitory activity. Two bacteriocin-producing enterococci and a nisin-producing Lactococcus lactis strain were employed as starters in separate cheese-making experiments. Outgrowth of histamine producer Lactobacillus buchneri St2A, which was added to the milk at levels of up to 190 CFU/ml, was almost completely inhibited. No histamine formation was detected in the cheeses made with bacteriocin-producing starters. In the control cheese without bacteriocin, St2A reached levels of 1.1 x 10(sup8) CFU/g, and 200 mg of histamine per kg was found after 4 months of ripening. To our knowledge, this is the first report of bacteriocin-mediated inhibition of histamine formation in foods.

Changes in regional lung impedance after intravenous histamine bolus in dogs: effects of lung volume.

We measured the effect of lung volume on the time course of regional lung input impedance (ZA) after bolus intravenous administration of 2 mg of histamine in seven open-chest dogs using alveolar capsule oscillators. ZA (24-200 Hz) was obtained during apnea at constant lung volume every 2 s for 80 s at lung inflation pressures of 0.1, 0.2, 0.3, 0.5, 0.7, and 1.0 kPa. Local airway resistance (RA) and elastance of the local lung region were calculated by fitting a four-parameter model to the measured ZA. Total lung resistance and lung elastance were also calculated from tracheal pressure and flow measured during mechanical ventilation (0.3 Hz) just before and after each set of ZA measurements. We found the histamine-induced changes in both lung resistance and lung elastance to decrease with increasing lung volume. RA also showed a large negative dependency on lung volume, and the variation between different RA measurements became markedly increased as lung volume decreased. In contrast, local airway elastance was essentially unaffected by lung volume. These results support the idea that parenchymal tethering of the very distal airways impedes their narrowing during bronchoconstriction. They also indicate that reduced parenchymal tethering causes airway narrowing to become markedly more inhomogeneous.

Acute pulmonary response to intravenous histamine using forced oscillations through alveolar capsules in dogs

We measured the time course of alveolar input impedance using two alveolar capsule oscillators after intravenous bolus administration of 20 mg of histamine in open-chest dogs. Impedances (24-200 Hz) were obtained every 2 s after an injection for 100 s. Each impedance was fit with a model consisting of a pathway (with resistance and inertance) leading from the alveolar capsule into a subpleural region (with elastance EA) that, in turn, was connected to the lung compartment (consisting of the remainder of the lung and positive end expiratory pressure system) via another pathway (with resistance RA). In all cases (6 dogs, 2 capsules each), the resistance and inertance leading from the alveolar capsules were negligible. The correlation of the relative increases in RA obtained from the two capsule oscillators in each dog was not significant. The correlation for EA also was not significant. The times at which RA achieved values of 20% greater than baseline were not significantly correlated between the two capsules, as was the case for EA. However, the baseline values of EA and RA from a given capsule were significantly correlated, as were their fractional increases with histamine. These results show that both the magnitude and timing of changes in local lung resistance and elastance are spatially extremely heterogeneous.

The effects of histamine administered in fish samples to healthy volunteers.

The effects of histamine administered in samples of fish to eight healthy volunteers (4 females and 4 males), aged 21-30 years, were studied. The subjects were given 0, 45 and 90 mg of histamine that had been metabolized from histidine by photobacteria in the fish and 90 mg of histamine added to fresh fish, for breakfast. The subjects were observed during 6 h after breakfast. Special attention was paid to clinical symptoms, blood pressure and ECG. The pH of the gastric contents was recorded continuously from 5 min before to 6 h after the meal. Blood samples to measure the histamine concentration were taken at intervals during 24 h after breakfast. Two of the subjects showed effects (facial flushing, headache) that could be attributed to the ingestion of histamine. No significant changes were observed in the blood pressure and ECG. The pH of the gastric fluids did not decrease significantly. The histamine concentration in plasma correlated closely with the histamine dose ingested (p < 0.001, r = 0.996). The Cmax of the dose of 90 mg did not differ statistically significant from the Cmax of the dose of 90 mg histamine added to unspoiled fish.

Early and late effects of prolonged topical capsaicin on cutaneous sensibility and neurogenic vasodilatation in humans

Cutaneous sensibility and neurogenic vasodilatation (flare) were measured before, during and after long-term topical application of capsaicin in humans. Each subject applied a vehicle cream containing 0.075% capsaicin (Axsain, GalenPharma Inc.) to a 4 cm 2 area of skin on one volar forearm and vehicle alone to an identical treatment area on the other forearm, according to a double-blind procedure. Each substances was applied 4 times/day for 6 weeks. Psychophysical measurements of sensory detection thresholds, magnitude of suprathreshold heat pain, magnitude and duration of histamine-induced itch and flare area were obtained before, at 1, 3 and 7 days after the first application, and once a week thereafter for a total of 8 weeks. Capsaicin produced mild burning in all subjects which diminished in magnitude and duration over several weeks. Capsaicin significantly altered detection thresholds for heat pain and the magnitude of pain produced by suprathreshold painful stimuli. Mean detection threshold for heat pain was lowered 1.6°C following 1 day of capsaicin application but subsequently increased to become elevated 3.5°C after 6 weeks of application. In addition, mean magnitude of suprathreshold heat pain diminished progressively after 1 week. Heat pain thresholds returned to or near pretreatment values within 2 weeks after discontinuing application. Detection thresholds for touch, cold sensation and pain induced by low temperature and by mechanical stimulation were not altered by capsaicin. Similarly, capsaicin did not alter the magnitude or duration of itch produced by intradermal injection of 1 μg histamine. However, the area of flare produced by histamine was significantly reduced in capsaicin-treated skin. These studies demonstrate that prolonged application of capsaicin at low concentration selectively diminishes sensations of heat pain and neurogenic vasodilatation, presumably via desensitization of heat-sensitive nociceptors. It is also shown that the decrease in heat pain is temporary and is maintained with repeated capsaicin application. There appears to be a therapeutic role for capsaicin in cutaneous painful syndromes mediated, at least in part, by activity of heat-sensitive nociceptors.

Comparison of methods for intestinal histamine application: histamine in enterosoluble capsules or via a duodeno‐jenunal tube

The study was conducted to investigate whether introduction of histamine in enterosoluble capsules produced the same amount of urinary histamine metabolites as that found after application of histamine through a duodeno-jejunal tube. Secondly, to examine whether a histamine-restrictive or a fast diet affected the amount of urinary metabolites. Fifteen healthy subjects were challenged four times with 100 mg of histamine. Results were monitored by the urinary recovery of 1,4-methylimidazole acetic acid (MIAA) from 24 h before to 72 h after challenge. Urine was collected in 24-h samples except on the first day after challenge when separation into 0-2h-, 2-4 h- and 4-24 h-fractions was made. MIAA was measured by high performance liquid chromatography (HPLC). The results showed that during the first 2 h after challenge the recovery of MIAA was higher with tubes than with capsules. Measurements from all other intervals did not differ significantly between the two challenge regimens. Fast (water only) and histamine-restrictive diet versus non-restrictive diet did not affect the urinary MIAA. MIAA was significantly higher overall during the first 24 h after challenge than in any other fraction. We conclude that oral administration of enterosoluble capsules is an easy and appropriate method for intestinal histamine challenge. Fast and histamine-restrictive diets are not necessary, but subjects should record unexpected responses in a food and symptom diary.

Abnormal nasal glandular secretion in recurrent sinusitis

Recurrent sinusitis (RS) is a very common clinical problem for which no underlying cause can generally be ascertained. We examined nasal mucosal responses in 14 patients with RS to determine if a relative deficiency in secretion of glandular antimicrobial factors might play a role. Twenty-four subjects with no history of sinusitis were studied concurrently as normal control (NC) subjects. RS was defined by two or more episodes of acute sinusitis per year for 2 or more years. After provocation with 25 mg of methacholine or 1 mg of histamine, nasal washings were analyzed for total proteins: the plasma protein albumin, IgG, and nonsecretory IgA (nsIgA), and the glandular proteins secretory IgA (sIgA), lactoferrin (LFN), and lysozyme (LZM). Although baseline secretions in patients with RS were relatively enriched with LFN and LZM as compared to that of secretions in NC subjects, patients with RS had a blunted cholinergic response with decreased secretion of albumin, IgG, nsIgA, sIgA, and LZM. Histamine responses were equivalent in both patients with RS and NC subjects. After 4 to 12 months of medical treatment, the abnormal cholinergic responses improved on repeat methacholine challenge in all eight subjects with RS rechallenged. Thus, patients with RS have a reversible reduction in nasal mucosal secretory responses to cholinergic stimulation. Since glandular secretions are rich in antimicrobial factors, such as LFN, LZM, and sIgA, it appears possible that the inability to secrete glandular proteins normally may predispose to recurrent infections.

Effect of diet on Heinz body formation in kittens

SUMMARY Heinz body formation was examined in kittens, in response to consumption of a variety of diets. A commercial salmon-based diet containing 16.5 mg of nitrite, 39 mg of histamine, and 210,000 IU of vitamin A/kg of diet (dry-matter basis) was found to induce Heinz body formation. Purified experimental diets—containing nitrite up to 405 mg/kg; histamine, 50 mg/kg; histamine, 50 mg/kg plus nitrite, 45 mg/kg; or vitamin A, 250,000 IU/kg—failed to induce Heinz body formation. The effect of propylene glycol (pg) on Heinz body formation was examined by giving groups of 6 kittens purified diets containing 5 or 10% pg for 12 weeks. Two additional kittens were fed a commercial soft-moist diet containing pg for 12 weeks. All kittens fed pg developed Heinz bodies, with peak values for erythrocytes containing Heinz bodies being: 28% for kittens of the 10% pg group; 20% for kittens of the 5% pg group; and 36% for kittens of the soft-moist diet group. Kittens did not develop anemia or methemoglobinemia. Heinz body percentage required 6 to 8 weeks to decrease to the pretreatment value of &lt; 1% after diets containing pg were discontinued. 51Chromium-labeled erythrocytes were used to evaluate erythrocyte survival in 4 kittens of the 10% pg-fed group and in 4 control kittens. Kittens with Heinz body formation induced by 10% pg had significantly (P &lt; 0.001) decreased erythrocyte survival, compared with that for controls, with half-life of 8.3 days for kittens of the pg group, compared with 12.6 days for kittens of the control group.

Pharmacologic modulation by cetirizine 2 HCl and loratadine of the histamine‐induced skin reaction in mice and in humans

AbstractIn mice, the histamine‐induced cutaneous reaction is inhibited by cetirizine with an approached ED50 of 0.04 mg/kg and by loratadine with an approached ED50 of 0.38 mg/kg, both drugsadministered intraperitoneally. At these doses, cetirizine' s onset of activity seems to be more rapid, although both compounds show the same duration for at least 7 hr. Nine healthy volunteers received orally either cetirizine or loratadine (10 mg single dose) or placebo in a double‐blind randomized and cross‐over study design. Both drugswere significantly more effective than placebo (except loratadine at the 2nd and 24th hr for the wheal with 1 and 10 μg histamine, and at the 2nd hr for the flare with 1 μg histamine). At all times and withboth agonists' concentrations, cetirizine was significantly more potent than loratadine (except at the 24th hr for the wheal with 1 μghistamine). Neither numerous nor marked side effects were found.