Plasma Histamine Research Articles

A Histamine-Free Diet Is Helpful for Treatment of Adult Patients with Chronic Spontaneous Urticaria.

BackgroundIn adult patients with chronic urticaria (CU), the prevalence of food allergy is low compared to childhood patients. However, there are many patients who report food-related aggravation of CU, and some of them may have histamine intolerance.ObjectiveThe aim of this study was to evaluate the role of ingested histamine and to investigate the effect of a histamine-free diet in adult patients with CU.MethodsTwenty-two adult patients with CU were enrolled. Foods with high amounts of histamine were prohibited to all patients for four weeks. The degree of severity of the urticaria was evaluated using the urticaria severity score (USS) and urticaria activity score (UAS). Plasma histamine levels and diamine oxidase (DAO) activity were determined and compared before (baseline) and after the histamine-free diet.ResultsTwenty-two adult patients were recruited and completed four weeks of histamine-free diet. The USS and UAS scores each showed significant differences before and after the histamine-free diet (p=0.010, p=0.006). There was a significant reduction in plasma histamine level after the histamine free-diet, compared with baseline (p=0.010). However, DAO activity did not change after the histamine-free diet (p=0.165).ConclusionOur study suggested that ingested histamine might be related to CU severity and that a histamine-free diet is helpful for treatment of adult patients with CU.

Antihistaminic and cardiorespiratory effects of diphenhydramine hydrochloride in anesthetized dogs undergoing excision of mast cell tumors.

OBJECTIVE To evaluate the effects of IV diphenhydramine hydrochloride administration on cardiorespiratory variables in anesthetized dogs undergoing mast cell tumor (MCT) excision. DESIGN Randomized, blinded clinical trial. ANIMALS 16 client-owned dogs with MCTs. PROCEDURES In a standardized isoflurane anesthesia session that included mechanical ventilation, dogs received diphenhydramine hydrochloride (1 mg/kg [0.45 mg/lb], IV; n = 8) or an equivalent volume of saline (0.9% NaCl) solution (IV; control treatment; 8) 10 minutes after induction. Cardiorespiratory variables were recorded throughout anesthesia and MCT excision, and blood samples for determination of plasma diphenhydramine and histamine concentrations were collected prior to premedication (baseline), throughout anesthesia, and 2 hours after extubation. RESULTS Cardiorespiratory values in both treatment groups were acceptable for anesthetized dogs. Mean ± SD diastolic arterial blood pressure was significantly lower in the diphenhydramine versus control group during tumor dissection (52 ± 10 mm Hg vs 62 ± 9 mm Hg) and surgical closure (51 ± 10 mm Hg vs 65 ± 9 mm Hg). Mean arterial blood pressure was significantly lower in the diphenhydramine versus control group during surgical closure (65 ± 12 mm Hg vs 78 ± 11 mm Hg), despite a higher cardiac index value. Plasma histamine concentrations were nonsignificantly higher than baseline during maximal manipulation of the tumor and surgical preparation in the diphenhydramine group and during surgical dissection in the control group. CONCLUSIONS AND CLINICAL RELEVANCE IV administration of diphenhydramine prior to MCT excision had no clear clinical cardiorespiratory benefits over placebo in isoflurane-anesthetized dogs.

Sinomenine-induced histamine release-like anaphylactoid reactions are blocked by tranilast via inhibiting NF-κB signaling

Zhengqing Fengtongning (ZQFTN), the pharmaceutical preparation of sinomenine (SIN) derived from the medicinal plant Sinmenium acutum, is well-known in China as an effective treatment for rheumatoid arthritis (RA). However, its histamine-release anaphylactoid reactions (HRARs) occur often in some patients. Therefore, it is desirable to establish effective clinical protocols to manage such HRARs. In the study, rat models with systemic HRARs and local HRARs of the skin were established. The level of vascular permeability and mast cell numbers was determined by quantitative analysis using Evans blue dye and histological assays. The levels of histamine, leukotriene B4 (LTB4) and IL-33 in plasma were detected by UHPLC–SPE–MS, ELISA and immunohistochemistry assays, respectively. The results demonstrated that SIN significantly induced both systemic and local HRARs in rats, showing significant decrease of body temperature, increases in vascular permeability in skin, injury of lung tissues and mast cell infiltration and IL-33 expression in skin and lung tissues. Mechanistic study showed that tranilast could prevent SIN-triggered HRARs via inhibition of H1 receptor gene expression and NF-κB signaling. Our findings provide evidence that mast cell membrane stabilizers and H1 receptor blockers effectively prevent SIN-induced HRARs, and cromolyn, cetirizine and tranilast can be used in the clinic for the management of HRARs induced by ZQFTN.

Effect of compound glycyrrhizin combined with fexofenadine hydrochloride in the treatment of chronic urticaria and its influence on plasma histamine

Objective To investigate the effect of compound glycyrrhizin combined with fexofenadine hydrochloride in the treatment of chronic urticaria and its effect on plasma histamine. Methods 100 patients with chronic urticaria were selected as study objects, and they were divided into the control group(50 cases) and observation group(50 cases) according to the random number table method.The control group was treated with fexofenadine hydrochloride, while the observation group was treated with compound glycyrrhizin on the basis of the control group.The clinical effect and plasma histamine level were compared between the two groups. Results The effective rate of the observation group was 96.0%, which was significantly higher than 84.0% of the control group(χ2=7.951, P<0.05). After treatment, the plasma histamine content of the observation group was (2.38±0.26)ng/mL, which was lower than (3.10±0.29)ng/mL of the control group, and the difference between the two groups was statistically significant(t=6.084, P<0.05). Conclusion The compound glycyrrhizin combined with fexofenadine hydrochloride in the treatment of chronic urticaria can reduce the symptoms of the patients, reduce the number and size of the patients and effectively control the clinical symptoms of the patients.And it can effectively reduce the level of plasma histamine in patients with good clinical effect and application value, it is worth to be promoted in clinical. Key words: Urticaria; Histamine; Compound glycyrrhizin; Fexofenadine hydrochloride

Mast cell activation disorder masquerading as a nervous breakdown

While mast cells have been implicated in human disease since the early 1900s, mast cell activation syndrome (MCAS) was only recently discovered and recognized as a disorder caused by aberrant release of mast cell mediator enzymes. These mediators trigger a wide variety of symptoms ranging from headache, pruritis and gastrointestinal discomfort to life-threatening anaphylaxis. MCAS is frequently unrecognized and misdiagnosed because symptoms associated with MCAS are often present in other medical conditions and are highly variable among patients. We describe a case of a 62-year-old male who presented to the emergency department (ED) with three days of recurrent flushing, diarrhea, mild edema of his hands bilaterally, and severe emotional lability with recurrent crying. In the ED, he was misdiagnosed with severe anxiety and directly sent to a mental health clinic for assistance. However, he was previously seen in allergy clinic for suspected MCAS. Fortuitously standing labs including plasma histamine, tryptase, and urine studies that were ordered in allergy clinic were drawn concurrently with the initial ED workup. He was found to have elevated histamine level during his ED episode and treatment for MCAS was initiated. In subsequent visits, his symptoms, except for episodes of “brain fog” and emotional lability, improved significantly on a combination of antihistamines, oral cromolyn sodium, and montelukast. Additionally every other day prednisone has substantially cleared the neurocognitive symptoms. This case highlights the difficulty of MCAS diagnosis and the importance of assessing for MCAS, especially in patients who have multisystem complaints.

Drug-induced anaphylaxis in the emergency room.

Anaphylaxis is a life‐threatening, systemic allergic reaction that presents unique challenges for emergency care practitioners. Anaphylaxis occurs more frequently than previously believed. Therefore, proper knowledge regarding the epidemiology, mechanisms, symptoms, diagnosis, and treatment of anaphylaxis is essential. In particular, the initial treatment strategy, followed by correct diagnosis, in the emergency room is critical for preventing fatal anaphylaxis, although making a diagnosis is not easy because of the broad and often atypical presentation of anaphylaxis. To this end, the clinical criteria proposed by the National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network are useful, which, together with a differential diagnosis, could enable a more accurate diagnosis. Additional in vitro tests, such as plasma histamine and tryptase measurements, are also helpful. It should be emphasized that adrenaline is the only drug recommended as first‐line therapy in all published national anaphylaxis guidelines. Most international anaphylaxis guidelines recommend injecting adrenaline by the intramuscular route in the mid‐anterolateral thigh, whereas i.v. adrenaline is an option for patients with severe hypotension or cardiac arrest unresponsive to intramuscular adrenaline and fluid resuscitation. In addition to the route of administration, choosing the appropriate dose of adrenaline is essential, because serious adverse effects can potentially occur after an overdose of adrenaline. Furthermore, to avoid future recurrence of anaphylaxis, providing adrenaline auto‐injectors and making an etiological diagnosis, including confirmation of the offending trigger, are recommended for patients at risk of anaphylaxis before their discharge from the emergency room.

B-FAHF-2 plus oral immunotherapy (OIT) is safer and more effective than OIT alone in a murine model of concurrent peanut/tree nut allergy.

Concurrent sensitization to peanut (PN) and tree nuts (TN), the most dangerous food allergies, is common. Current oral immunotherapy (OIT) is not fully satisfactory. To determine whether the herbal formula B-FAHF-2 (BF2) ameliorates PN/TN OIT adverse reactions and enhances persistence of a tolerant state. Concurrently sensitized PN-, walnut- (WN) and cashew (CSH)-allergic mice received 1-day PN/WN/CSH rush OIT plus 3weeks of maintenance dosing, with or without 3weeks prior and 3weeks BF2 co-treatment. Anaphylactic symptom scores, core body temperatures, plasma histamine levels, basophil numbers, antigen-specific IgE, cytokine levels, and IL-4, INF-γ and Foxp3 gene promoter DNA methylation status, and their correlation with final challenge symptom scores were determined. BF2+OIT-treated mice experienced significantly fewer and less severe adverse reactions than OIT-only-treated mice (P<.01) during the 1-day rush OIT build-up dose phase. Both OIT-only and BF2+OIT mice showed significant desensitization (P<.01 and .001, respectively) at 1week post-therapy challenge, being greater in BF2+OIT mice. All sham-treated and 91% of OIT-treated mice experienced anaphylaxis whereas only 21% of BF2+OIT-treated mice exhibited reactions during 5-6weeks of dose escalation single PN and TN challenges. Greater and more persistent protection in BF2+OIT mice was associated with significantly lower plasma histamine and IgE levels, increased IFN-γ/IL-4 and IL-10/IL-4 ratios, DNA remethylation at the IL-4 promoter and demethylation at IFN-γ and Foxp3 promoters. Final challenge symptom scores were inversely correlated with IL-4 DNA methylation levels (P<.0002) and positively correlated with IFN-γ and Foxp3 gene promoter methylation levels (P<.0011) (P<.0165). Combined BF2/OIT therapy was safer and produced longer post-treatment protection and more tolerance-prone immunological and epigenetic modifications than OIT alone. BF2/OIT may provide an additional OIT option for patients with concurrent PN/TN and other food allergies.

Anti‑allergic action of bacillus Calmette‑Guerin extract in experimental mast cell‑mediated anaphylactic models.

Allergy is an acquired hypersensitivity reaction of the immune system mediated by IgE‑induced mast cell degranulation. In China, bacillus Calmette‑Guerin extract (BCGE) has been shown to be clinically effective for regulating immunity, which enhances the resistance of the body to anaphylactic disease, infectious diseases and cancer. However, the mechanisms remain to be fully elucidated. The present study investigated the potential anti‑allergic effects of BCGE in animal models of mast cell‑dependent anaphylaxis and mechanisms of BCGE in mast cells. Anti‑allergic actions of BCGE were evaluated in passive cutaneous anaphylaxis, dextran T40‑induced scratching behavior mouse models, and in ovalbumin (OVA)‑induced contraction of intestinal tube isolated from OVA‑sensitized guinea pigs. Direct mast cell‑stabilizing effects of BCGE were examined in mast cells from the abdominal cavity of OVA‑sensitized rats. Anti‑allergic signaling mechanisms of BCGE in mast cells were investigated by detection of cyclic adenosine monophosphate levels and protein kinase A expression in mast cells. It was observed that BCGE prevented OVA‑induced cutaneous vascular hyperpermeability, skin itching, elevation in plasma histamine levels and abdominal cavity fluid mast cell degranulation in animal models, in a dose‑dependent manner. BCGE also suppressed OVA‑mediated guinea pig intestinal tube contraction invitro. In addition, BCGE was found to increase the levels of interferon‑γ, and reduce the levels of interleukin‑4 and OVA‑sIg E levels in OVA‑sensitized rats. BCGE also increased levels of cyclic adenosine monophosphate and the expression of protein kinase A in mast cells separated from the abdominal cavity fluid of OVA‑sensitized rats. In conclusion, the results suggested that BCGE possesses anti‑allergic activity by inhibiting IgE‑induced mast cell degranulation, providing a foundation for the development of BCGE for the treatment of mast cell‑mediated allergic disorders.

The efficacy and safety of mivacurium in pediatric patients

BackgroundMivacurium is the shortest acting nondepolarizing muscle relaxant currently available; however, the effect of different dosages and injection times of intravenous mivacurium administration in children of different ages has rarely been reported. This study was aimed to evaluate the muscle relaxant effects and safety of different mivacurium dosages administered over different injection times in pediatric patients.MethodsSix hundred forty cases of pediatric patients, aged 2 m-14 years, ASA I or II, were divided into four groups (Groups A, B, C, D) according to the age class (2–12 m, 13–35 m, 3–6 years and 7–14 years) respectively, also each group were divided into four subgroups by induction dose (0.15, 0.2 mg/kg in 2–12 m age class; 0.2, 0.25 mg/kg in other three age classes), and mivacurium injection time (20 s, 40 s), totally 16 subgroups. Neuromuscular transmission was monitored with supramaximal train-of-four stimulation of the ulnar nerve. Radial artery blood (1 ml) was sampled to quantify plasma histamine concentrations before and 1, 4, and 7 min after mivacurium injection (P0, P1, P2 and P3).ResultsFive hundred sixty-two cases completed the study. There were no demographic differences within the four groups. The onset time of 0.2 mg/kg groups in 2–12 m aged patients were shorter than those of 0.15 mg/kg groups (189 ± 64 s vs. 220 ± 73 s, 181 ± 60 s vs. 213 ± 71 s, P <0.05), and the recovery times were no statistical differences. The T1 25% recovery time of 0.2 mg/kg in 3–6 years aged patients was shorter than that of 0.25 mg/kg group (693 ± 188 s vs. 800 ± 206 s, P <0.05). The onset and recovery times of mivacurium were not different in 13–35 m and 7–14 years aged patients. The plasma concentrations of histamine at P0, P1, P2 and P3 were not different within four groups.ConclusionsThe induction dose and injection time of mivacurium had mostly insignificant effects on onset and recovery times. The main exception to this was that in 2–12 m aged patients, increasing the dose of mivacurium from 0.15 to 0.2 mg/kg accelerated the onset time by about 30 s. Mivacurium produced no significant release of histamine in any age group at the doses studied.Trial registrationClinicalTrials.gov Identifier-NCT02117401, July 14, 2014. (Retrospectively registered)

Nonclinical Profile of BLZ-100, a Tumor-Targeting Fluorescent Imaging Agent.

BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. It is composed of a chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green. BLZ-100 is in clinical development for intraoperative visualization of human tumors. The nonclinical safety and pharmacokinetic (PK) profile of BLZ-100 was evaluated in mice, rats, canines, and nonhuman primates (NHP). Single bolus intravenous administration of BLZ-100 was well tolerated, and no adverse changes were observed in cardiovascular safety pharmacology, PK, and toxicology studies in rats and NHP. The single-dose no-observed-adverse-effect-levels (NOAELs) were 7 mg (28 mg/kg) in rats and 60 mg (20 mg/kg) in NHP, corresponding to peak concentration values of 89 400 and 436 000 ng/mL and area-under-the-curve exposure values of 130 000 and 1 240 000 h·ng/mL, respectively. Based on a human imaging dose of 3 mg, dose safety margins are >100 for rat and monkey. BLZ-100 produced hypersensitivity reactions in canine imaging studies (lethargy, pruritus, swollen muzzle, etc). The severity of the reactions was not dose related. In a follow-up study in dogs, plasma histamine concentrations were increased 5 to 60 minutes after BLZ-100 injection; this coincided with signs of hypersensitivity, supporting the conclusion that the reactions were histamine based. Hypersensitivity reactions were not observed in other species or in BLZ-100 human clinical studies conducted to date. The combined imaging, safety pharmacology, PK, and toxicology studies contributed to an extensive initial nonclinical profile for BLZ-100, supporting first-in-human clinical trials.

Feeding a High Concentration Diet Induces Unhealthy Alterations in the Composition and Metabolism of Ruminal Microbiota and Host Response in a Goat Model.

There is limited knowledge about the impact of long-term feeding a high-concentrate (HC) diet on rumen microbiota, metabolome, and host cell functions. In this study, a combination of mass spectrometry-based metabolomics techniques, 454 pyrosequencing of 16S rDNA genes, and RT-PCR was applied to evaluate the changes of ruminal microbiota composition, ruminal metabolites, and related genes expression in rumen epithelial cells of lactating goats received either a 35% concentrate diet or a 65% concentrate diet for 4 or 19 weeks, respectively. Results show that feeding a HC diet reduced the microbiota diversity and led to the disorders of metabolism in the rumen. The concentrations of lactate, phosphorus, NH3-N and endotoxin Lipopolysaccharide in ruminal fluids, and plasma histamine, lactate and urine N (UN) were increased significantly in goats fed with a HC diet. A significant increase of genes expression related to volatile fatty acids transport, cell apoptosis, and inflammatory responses were also observed in goats fed with a HC diet. Correlation analysis revealed some potential relationships between bacteria abundance and metabolites concentrations. Our findings indicate that a HC diet can induce ruminal microbiota dysbiosis and metabolic disorders, thus increasing risks to host health and potential harm to the environment.

Muscle relaxation effect and safety of mivacurium in patients with early hepatocirrhosis

Objective To observe muscle relaxation effect and safety of mivacurium in hepatocirrhosis patients, and provide a guidance in its clinical application. Methods Candidates for elective laparoscopic surgery were divided into a hepatocirrhosis group(group C, n=32) and a non hepatocirrhosis group (group N, n=25). Muscular relaxation monitor was applied with a train of four stimulation(TOF). The intubation dosage was 0.2 mg/kg. Tracheal intubation was performed when train of four stimulation ratio(TOFr, T4∶T1) was 0, and pump infusion of mivacurium was started when muscle relaxation began to recover (TOFr>0) with a velocity of 0.6 mg·kg-1·h-1, which was switched to 0.3 mg·kg-1·h-1 and then stopped in 30 min and 20 min prior to end of suturing in group C and group N respectively. The key parameter included plasma cholinesterase(PchE) activity, histamine concentration, variation of MAP, HR, onset time of mivacurium, acting duration of the first dose, time of TOFr recovery, time from drug withdrawal to extubation, and recovery index. Results The PchE activity were(4 304±901) U/L and (6 227±1 289) U/L in two groups (P 0.05). The mean histamine concentrations of all patients were (0.196±0.020), (0.238±0.021), (0.278±0.024) μg/L prior to intravenous injection of mivacurium and in 5 min and 10 min post to injection, there were significant differences between the three times points(P 0.05). The duration of the first dose were(20±4) min and (16±3) min respectively, the recovery of TOFr to 75% were (35±10) min and (24±5) min, time from drug withdrawal to extubation were (35±9) min and (24±7) min, and there were significant differences between the two groups (P<0.05). Conclusions The plasma histamine concentration increase slightly without significant influence on MAP and HR, with satisfactory intubation conditions, good muscle relaxation and fast recovery from muscle relaxation when mivacurium was applied in patients with early hepatic cirrhosis. Compared with non hepatic cirrhosis patients, the time of muscle relaxation recovery induced by mivacurium was longer in hepatic cirrhosis patients, but compared with other muscle relaxant, it still had obvious advantages. Because mivacurium didn't directly depend on the liver to metabolize, so it could reduce the burden of liver on drug metabolism. It is recommended to be applied in patients with early hepatic cirrhosis. Key words: Cirrhosis of liver; Mivacurium chloride; Histamine; Cholinesterase; Monitoring of muscle relaxation

Regulation of plasma histamine levels by the mast cell clock and its modulation by stress

At steady state, plasma histamine levels exhibit circadian variations with nocturnal peaks, which is implicated in the nighttime exacerbation of allergic symptoms. However, the regulatory mechanisms are largely unexplored. This study determined how steady-state plasma histamine levels are regulated and affected by environmental factors. We found that plasma histamine levels decreased in mast cell–deficient mice and their circadian variations were lost in mast cell–deficient mice reconstituted with bone marrow–derived mast cells (BMMCs) harboring a mutation in the circadian gene Clock. Clock temporally regulates expression of organic cation transporter 3 (OCT3), which is involved in histamine transport, in mast cells; OCT inhibition abolished circadian variations in plasma histamine levels. Mice housed under aberrant light/dark conditions or suffering from restraint stress exhibited de-synchronization of the mast cell clockwork, concomitant with the loss of circadian variations in OCT3 expression and plasma histamine levels. The degree of compound 48/80–induced plasma extravasation in mice was correlated with plasma histamine levels. Collectively, the mast cell clock mediates circadian regulation of plasma histamine levels at steady state, in part by controlling OCT3 expression, which can be modulated by stress. Additionally, we propose that plasma histamine levels potentiate mast cell–mediated allergic reactions.

Anaphylaxis as a Manifestation of Systemic Mastocytosis: A Case Report and Review of Literature

Introduction: Anaphylaxis is defined as “a serious, life-threatening generalized or systemic hypersensitivity reaction” and “a serious allergic reaction that is rapid in onset and might cause death”. The determination of different mast cells (MC) mediators, such as serum and/or plasma histamine and tryptase, is proposed for the diagnosis of anaphylaxis. There are differences in the clinical presentation of anaphylaxis in patients with indolent systemic mastocytosis versus idiopathic anaphylaxis. Case presentation: This is the case of a 72-year-old female patient presenting with acute bacterial pyelonephritis treated with intra venous antibiotics. She developed a facial flush then a diffuse flush with hypoxia and respiratory arrest. The patient recovered with non-invasive ventilation without the need for intubation. A full blood panel returned normal and two bone marrows biopsies were performed. The second one showed the presence of a perivascular infiltrate mast cell, consistent with systemic mastocytosis. Discussion: All aspects of systemic mastocyosis including the classification and the main clinical manifestations as well as the diagnosis were concisely reviewed. Then supportive and immunomodulator treatment were differentiated. Conclusion: Patients suffering of systemic mastocytosis typically present anaphylactic symptoms primarily involving the cardiovascular system in the absence of urticaria and/or angioedema, which makes such clinical presentation highly suspicious. Patients suffering of c-MCD (Cutaneous-mast cell disease) need assistance in identifying their triggers and education on proper avoidance.

Preventive effects of royal jelly against anaphylactic response in a murine model of cow’s milk allergy

Context: Royal jelly (RJ) has long been used to promote human health. Objective: The current study investigated the preventive effects of RJ against the development of a systemic and intestinal immune response in mice allergic to cow’s milk proteins. Materials and methods: Balb/c mice treated orally for seven days with RJ at doses of 0.5, 1 and 1.5 g/kg were sensitized intraperitoneally with β-lactoglobulin (β-Lg). Serum IgG and IgE anti-β-Lg were determined by an enzyme-linked immunosorbent assay (ELISA). Plasma histamine levels, symptom scores and body temperature were determined after in vivo challenge to β-Lg. Jejunums were used for assessment of local anaphylactic responses by an ex vivo study in Ussing chambers and morphologic changes by histological analysis. Results: RJ significantly decreased serum IgG (31.15–43.78%) and IgE (64.28–66.6%) anti-β-Lg and effectively reduced plasma histamine level (66.62–67.36%) (p < 0.001) at all the doses tested. Additionally, no clinical symptoms or body temperature drops were observed in RJ-pretreated mice. Interestingly, RJ significantly reduced (p < 0.001) intestinal dysfunction by abolishing the secretory response (70.73–72.23%) induced by sensitization and prevented length aberrations of jejunal villi by 44.32–59.01% (p < 0.001). Discussion and conclusions: We speculate that using RJ may help prevent systemic and anaphylactic response in allergic mice. These effects may be related to its inhibitory effects on the degranulation of mast cells.

Baicalein, wogonin, and Scutellaria baicalensis ethanol extract alleviate ovalbumin-induced allergic airway inflammation and mast cell-mediated anaphylactic shock by regulation of Th1/Th2 imbalance and histamine release.

Asthma is characterized by chronic inflammation, goblet cell hyperplasia, the aberrant production of the Th2 cytokines, and eosinophil infiltration into the lungs. In this study, we examined the effects of baicalein, wogonin, and Scutellaria baicalensis ethanol extract on ovalbumin (OVA)-induced asthma by evaluating Th1/Th2 cytokine levels, histopathologic analysis, and compound 48/80-induced systemic anaphylaxis and mast cell activation, focusing on the histamine release from rat peritoneal mast cells. Baicalein, wogonin, and S. baicalensis ethanol extract also decreased the number of inflammatory cells especially eosinophils and downregulated peribronchial and perivascular inflammation in the lungs of mice challenged by OVA. Baicalein, wogonin, and S. baicalensis ethanol extract significantly reduced the levels of tumor necrosis factor α, interleukin (IL)-1β, IL-4, IL-5 and the production of OVA-specific IgE and IgG1, and upregulated the level of interferon-γ and OVA-specific IgG2a. In addition, oral administration of baicalein, wogonin, and S. baicalensis ethanol extract inhibited compound 48/80-induced systemic anaphylaxis and plasma histamine release in mice. Moreover, baicalein, wogonin, and S. baicalensis ethanol extract suppressed compound 48/80-induced mast cell degranulation and histamine release from rat peritoneal mast cells. Conclusively, baicalein and wogonin as major flavonoids of S. baicalensis may have therapeutic potential for allergic asthma through modulation of Th1/Th2 cytokine imbalance and histamine release from mast cells.

Flavonoids from whole plant of Euphorbia hirta and their evaluation against experimentally induced gastroesophageal reflux disease in rats

Background:Euphorbia hirta possesses antibacterial, anti-inflammatory, galactogenic, antidiarrheal, antioxidant, hypoglycemic, antiasthmatic, antiamebic, antifungal, and antimalarial activities.Objective:The overall objective of the current study was the investigation of the whole plant extract of E. hirta and flavonoids from E. hirta on gastroesophageal reflux disease (GERD) in rats.Materials and Methods:The whole plant extract of E. hirta was characterized by analysis of flavonoids (HPLC: HPLC, UV, IR, MS and 1HNMR). GERD model was induced surgically in Wistar rats under pentobarbitone sodium anesthesia (50 mg/kg, i.p.) and the tissue esophagus and stomach were removed. The tissues were washed with physiological saline and were examined for GERD. The whole plant extract of E. hirta in doses of 50, 100, and 200 mg/kg were administered orally twice daily at 10:00 and 16:00 hours, respectively, for 5 days and kaempferol (100 mg/kg) or omeprazole (OMZ) in the dose of 30 mg/kg 1 hour prior to the induction of GERD. Control groups received suspension of 1% carboxymethyl cellulose in distilled water (10 mL/kg).Results:The levels of gastric wall mucus increased and of plasma histamine and H+, K+ ATPase significantly decreased in groups treated by both the plant extract and flavonoids. Both the plant extract and flavonoids reduced the lipid peroxidation and superoxide dismutase and increased the levels of catalase and reduced glutathione.Conclusions:The whole plant extract of E. hirta is attributed to its antisecretory, gastroprotective, and antioxidant potential as that of quercetin, rutin, kaempferol, and proton pump blocker (omeprazole) to treat GERD.SUMMARY The aqueous extract of whole plant of Euphorbia hirta revealed the presence of kaempferol (0.0256%), quercetin (0.0557%), and rutin (0.0151%), and the ethyl acetate fraction of whole plant of E. hirta possesses kaempferol (0.0487%), quercetin (0.0789%), and rutin (0.0184%).The levels of gastric wall mucus increased and of plasma histamine and H+-K+-ATPase significantly decreased in rats groups treated by both the whole plant extract of E. hirta and flavonoids.Both the whole plant extract of E. hirta and flavonoids reduced the lipid peroxidation and superoxide dismutase and increased the levels of catalase and reduced glutathione in rats groups. Abbreviation used: 1HNMR: Proton Nuclear Magnetic Resonance Spectroscopy, CAT: Catalase, EHAE: Aqueous extract of Euphorbia hirta, EHEF: Ethyl Acetate Fractions of Euphorbia hirta, GERD: Gastroesophageal reflux disease, GSH: Reduced Glutathione, HPLC: High performance liquid chromatography, IR: Infrared spectroscopy, LPO: Lipid Peroxidase, MDA: Malondialdehyde, MS: Mass Spectroscopy, OMZ: Omeprazole, ROS: Reactive Oxygen Species, SOD: Superoxide dismutase, TBHQ: tert-Butylhydroquinone, TLC: Thin Layer Chromatography, UV: Ultraviolet, UV: Ultraviolet–Visible Spectroscopy

The Pathogenesis of Alcohol-Induced Airflow Limitation in Acetaldehyde Dehydrogenase 2-Deficient Mice

Background: In Japanese patients, alcohol-induced asthma is attributed to elevated plasma concentrations of acetaldehyde following alcohol consumption because of an acetaldehyde dehydrogenase 2 gene (ALDH2) polymorphism. The resulting increase in plasma histamine concentrations seems to trigger the onset of asthma symptoms. However, the specific pathogenic mechanism underlying this response remains unclear. ALDH2-deficient mice were therefore generated to investigate the pathogenesis of alcohol-induced asthma. Methods: ALDH2-deficient mice were generated using embryonic stem cells that were derived from C57BL/6 mice. The resulting mice were backcrossed into the BALB/c mice background. Exon 1 of ALDH2 was replaced with the Neo cassette. Pure ethanol was orally administered to ALDH2-deficient and wild-type mice, and the plasma concentrations of ethanol, acetaldehyde, and histamine, in addition to enhanced pause (Penh) values, were determined and compared between the 2 groups. Results: We established an ALDH2-deficient mouse line to compare responses between wild-type and ALDH2-deficient mice receiving orally administered ethanol. The results showed that the plasma concentrations of acetaldehyde (p < 0.0001) and histamine (p < 0.005) were significantly higher, and the Penh values (p < 0.01) were significantly greater in the ALDH2-deficient mice, although plasma ethanol levels were not different. Conclusions: We studied the pathogenesis of alcohol-induced asthma using ALDH2-deficient mice. The results demonstrated that alcohol intake resulted in an increase in acetaldehyde levels, and a subsequent increase in histamine levels, which induced airway constriction. Alcohol consumption is known to be an important factor that exacerbates bronchial asthma, and studies investigating this factor are useful for the treatment of patients with alcohol-induced asthma.

Incidence of anaphylactic reactions after propofol administration in dogs.

Propofol is an anesthetic agent suspended in an emulsion system that includes egg yolk lecithin and soybean oil, because of which, there is concern about the use of propofol in patients allergic to these substances. We examined the association between propofol administration and incidence of adverse events in dogs with allergy to egg yolk lecithin and soybean oil. On the basis of the findings of an allergen-specific immunoglobulin E (IgE) test, 14 dogs with high levels (high-IgE group) and 7 dogs with low levels (normal-IgE group) of IgE were selected. Following intravenous administration of propofol, the incidence of anaphylactic reactions and plasma histamine concentrations under general anesthesia maintained with isoflurane throughout surgery were compared between the two groups. The frequency of anaphylactic reactions and plasma histamine concentrations were compared by the chi-square test and Student t-test, respectively. The statistical significance for both tests was set at P<0.05. In the high- and normal-IgE groups, the average frequencies of anaphylactic reactions after propofol administration were 21.4 and 14.3%, and the mean plasma histamine concentrations were 167.9 ± 94.5 nM and 65.7 ± 40.3 nM, respectively. Animals of neither groups experienced shock-like symptoms. These results revealed that propofol might be relatively safe, although careful perioperative anesthesia monitoring and standby protocols are required when using propofol in dogs with a history of allergic diseases or high chicken- or soybean-specific IgE levels.

Efficacy of clemastine fumarate in antagonizing atracurium-induced release of histamine in patients undergoing surgery under general anesthesia

Objective To evaluate the efficacy of clemastine fumarate in antagonizing atracurium-induced release of histamine in the patients undergoing surgery under general anesthesia. Methods Eighty American Society of Anesthesiologists physical statusⅠ or Ⅱ patients, aged 21-59 yr, with body mass index of 17-26 kg/m2, scheduled for elective modified radical mastectomy, were divided into 2 groups (n=40 each) using a random number table: control group (group C) and clemastine fumarat group (group CF). Clemastine fumarate 2 mg was injected intramuscularly at 20 min before induction of anesthesia.Anesthesia was induced with iv midazolam 0.1 mg/kg, etomidate 0.3 mg/kg, fentanyl 4-6μg/kg and atracurium 0.8 mg/kg.The patients were mechanically ventilated after insertion of the larygeal mask airway.Anesthesia was maintained with inhalation of 2% sevoflurane.Before administration of clemastine fumarate, at 20 min after administration, immediately before administration of atracurium, and at 2, 5, 10 and 20 min after administration of atracurium, arterial blood samples were taken for determination of plasma histamine concentrations, and the peak airway pressure and degree of cutaneous color were recorded.The development of histaminemia and adverse cardiovascular events was assessed.Steward recovery scores and Ramsay sedation scores were recorded at 10 min after removal of the laryngeal mask airway. Results The incidence of histaminemia was 60% and 8% in C and CF groups, respectively.Compared with group C, the plasma histamine concentrations, incidence of histaminemia, degree of cutaneous color, and incidence of hypotension and tachycardia were significantly decreased (P 0.05). Conclusion For atracurium-induced release of histamine in the patients undergoing surgery under general anesthesia, clemastine fumarate 2 mg injected intramuscularly before operation can not only antagonize histamine at H1 level, but also reduce histamine release, and exerts no influence on recovery from anesthesia and produces good antihistamine efficacy. Key words: Histamine H1 antagonists; Atracurium; Histamine release; Anesthesia, general