Major depressive disorder (MDD) is the most common nonfatal disease burden worldwide. Systemic chronic low-grade inflammation has been reported to be associated with MDD progression by affecting monoaminergic and glutamatergic neurotransmission. However, whether various proinflammatory cytokines are abnormally elevated before the first episode of depression is still largely unclear. Here, we evaluated 184 adolescent patients who were experiencing their first episode of depressive disorder, and the same number of healthy individuals was included as controls. We tested the serum levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), IgE, 14 different types of food antigen-specific IgG, histamine, homocysteine, S100 calcium-binding protein B, and diamine oxidase. We were not able to find any significant differences in the serum levels of hs-CRP or TNF-α between the two groups. However, the histamine level of the patients (12.35 μM) was significantly higher than that of the controls (9.73 μM, P < 0.001, Mann-Whitney U test). Moreover, significantly higher serum food antigen-specific IgG positive rates were also found in the patient group. Furthermore, over 80% of patients exhibited prolonged food intolerance with elevated levels of serum histamine, leading to hyperpermeability of the blood-brain barrier, which has previously been implicated in the pathogenesis of MDD. Hence, prolonged high levels of serum histamine could be a risk factor for depressive disorders, and antihistamine release might represent a novel therapeutic strategy for depression treatment.
Adolescent ; Biomarkers ; blood ; C-Reactive Protein ; Chronic Disease ; Cytokines ; Depressive Disorder, Major ; blood ; epidemiology ; etiology ; Female ; Food Hypersensitivity ; blood ; complications ; Histamine ; blood ; Homocysteine ; blood ; Humans ; Immunoglobulin E ; blood ; Immunoglobulin G ; blood ; immunology ; Inflammation Mediators ; blood ; Male ; Risk Factors ; S100 Calcium Binding Protein beta Subunit ; blood ; Young Adult

This paper was aimed to establish screening methods of anaphylactoid reaction caused by safflower yellow for injection based on RBL-2 H3 cell degranulation model and mice model for acute anaphylactoid reaction,and evaluate the hypersensitivity caused by safflower yellow for injection from different batches. An in vitro cell model was used to keep the cells stimulated for an hour with different batches of safflower yellow for injection as the drug group,serum-free MEM medium as negative control group and 30 mg·L-1 C48/80 as positive control group respectively. The supernatant was then absorbed,and neutral red staining technique was used to detect the effect of safflower yellow injection on the degranulation of RBL-2 H3 cells with the positive cell rate of degranulation as the indicator.An in vivo model was established to validate the experimental results,and mice model for acute anaphylactoid reaction and ELISA method were adopted to detect the plasma histamine content,and screen the hypersensitivity caused by safflower yellow for injection at the animal level by using plasma histamine content as a test index. The results of the neutral red staining experiments showed that the positive control C48/80 could cause cell degranulation,and most of the cells were deeply stained. There was significant difference in positive cell rate between different batches of safflower yellow and positive control group. In the mice model for acute anaphylactoid reaction,it was found that the positive control C48/80 significantly increased the histamine content in the plasma of mice,while the safflower yellow in each batch did not cause a significant increase in plasma histamine( P<0. 000 1). The mechanism of anaphylactoid reaction is relatively complicated. This study was mainly based on the release of histamine and other active substances by degranulation of mast cells. No significant degranulation reaction of RBL-2 H3 cells induced by safflower yellow for injection was detected,nor was the plasma histamine level significantly increased in mice from the in vitro and in vivo aspects.
Anaphylaxis ; chemically induced ; Animals ; Cell Degranulation ; drug effects ; Cells, Cultured ; Chalcone ; adverse effects ; analogs & derivatives ; Histamine ; blood ; Mast Cells ; drug effects ; Mice

The detection of drug-induced anaphylactoid reactions remains a global challenge,still lacking mature and reliable animal models or test methods. Therefore,the purpose of this paper is to explore and establish the test methods and evaluation standards for anaphylactoid reactions that apply to injection drugs. Based on the anaphylactoid reaction symptoms of mice induced by intravenous injection drugs C48/40 and Tween 80,a list of systemic anaphylactoid reaction symptoms in mice was sorted out and an evaluation standard of anaphylactoid reactions symptoms was established by applying symptom intensity coefficient K( that can represent these verity of anaphylactoid reaction symptoms) and its calculation formula Accordingly,histamine,tryptase,and Ig E were selected as blood indicators of anaphylactoid reactions,so that a test method combining symptoms evaluation and blood makers detection was established.This test method could be used to evaluate the characteristics of anaphylactoid reactions: coefficient K,blood histamine levels were highly and positively correlated with C48/80 and Tween 80 dose; The log value of histamine was highly and positively correlated with K; tryptase level may rise,or remain steady,or drop,possibly associated with the characteristics of the tested object and time for blood taking; and Ig E level would drop or remain steady,but it would not rise,which can be clearly distinguished from type I allergic reactions. On this basis,tiohexol,iopromide,paclitaxel,Xuesaitong Injection,Shuanghuanglian Injection and Shengmai Injection were used to investigate the applicability. The testing results showed a high degree of consistency with the actual clinical situation. The results suggest that the method of systemic anaphylaxis test in mice has high sensitivity,specificity and good consistency with clinical practice.It is suggested to be further validated and popularized.
Anaphylaxis ; chemically induced ; diagnosis ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; toxicity ; Histamine ; blood ; Immunoglobulin E ; blood ; Injections, Intravenous ; Mice ; Shock ; chemically induced ; diagnosis ; Toxicity Tests ; Tryptases ; blood

BACKGROUND: Acute urticaria sometimes accompanies severe systemic reactions that can be potentially life-threatening. Some patients do not achieve sufficient responses to conventional treatments. There has been no previous study on the effect of continuous intravenous infusion of epinephrine in patients with severe acute urticaria. OBJECTIVE: This study investigated the efficacy and safety of continuous intravenous infusion of low-dose epinephrine in patients with severe acute urticaria who did not achieve a sufficient response to conventional treatments. METHODS: We retrospectively reviewed the medical records of 74 patients with severe acute urticaria who were treated with continuous intravenous infusion of low-dose epinephrine between November 2008 and December 2016. One milligram (1 mL) of 1:1000 epinephrine was diluted in 1 L of saline to yield a concentration of 1 µg/mL. The solution was infused at 0.67 µg/min (40 mL/h). Vital signs were checked at 0, 30, 60, and 90 minutes after infusion of epinephrine. Epinephrine was discontinued after one symptom-free day. RESULTS: Clinical symptoms initially resolved within 24.8 hours on average and symptoms were completely resolved within 73.4 hours on average. Twenty-four adverse events, including palpitation, chest discomfort, hand tremor, increased blood pressure, and elevated cardiac markers, were observed in 19 patients (25.7%). Most adverse events were mild and regressed spontaneously without further management. Four patients (5.4%) stopped the infusion due to adverse events, but all events regressed spontaneously after stopping epinephrine. Six weeks after completion of intravenous infusion of epinephrine, 68 patients (91.9%) were symptom-free and six patients required antihistamines. CONCLUSION: This study suggests that continuous intravenous infusion of low-dose epinephrine is a safe and effective treatment in patients with severe acute urticaria who do not achieve a sufficient response to conventional treatments.
Blood Pressure ; Epinephrine* ; Hand ; Histamine Antagonists ; Humans ; Infusions, Intravenous* ; Medical Records ; Retrospective Studies* ; Thorax ; Tremor ; Urticaria* ; Vital Signs

The treatment of chronic spontaneous urticaria begins with antihistamines; however, the dose required typically exceeds that recommended for allergic rhinitis. Second-generation, relatively non-sedating H1-receptor blockers are typically employed up to 4 times a day. First-generation antihistamines, such as hydroxyzine or diphenhydramine (Atarax or Benadryl), were employed similarly in the past. Should high-dose antihistamines fail to control symptoms (at least 50%), omalizumab at 300 mg/month is the next step. This is effective in 70% of antihistamine-refractory patients. H₂-receptor blockers and leukotriene antagonists are no longer recommended; they add little and the literature does not support significant efficacy. For those patients who are unresponsive to both antihistamines and omalizumab, cyclosporine is recommended next. This is similarly effective in 65%–70% of patients; however, care is needed regarding possible side-effects on blood pressure and renal function. Corticosteroids should not be employed chronically due to cumulative toxicity that is dose and time dependent. Brief courses of steroid e.g., 3–10 days can be employed for severe exacerbations, but should be an infrequent occurrence. Finally, other agents, such as dapsone or sulfasalazine, can be tried for those patients unresponsive to antihistamines, omalizumab, and cyclosporine.
Adrenal Cortex Hormones ; Blood Pressure ; Cyclosporine ; Dapsone ; Diphenhydramine ; Histamine Antagonists ; Humans ; Hydroxyzine ; Leukotriene Antagonists ; Omalizumab ; Rhinitis, Allergic ; Sulfasalazine ; Urticaria*

Many sedatives are used clinically and include benzodiazepines, barbiturates, antihistamines, propofol, and alpha-2-agonist. Benzodiazepines activate GABA neuronal receptors in the brain and present sedating, hypnotic, anxiolytic, amnestic, and anticonvulsant effects, but low analgesic effects. Propofol induce sedative, anxiolytic, and amnestic effects but no analgesic effects. However, risks such as cardiopulmonary instability and hypotension must be considered during administration. Dexmedetomidine is a high selective alpha-2 agonist and has many advantages as a sedative. Patients under dexmedetomidine sedation awaken easily and are more likely to be cooperative. Risk of respiratory depression and cardiopulmonary instability is low as well. Additionally, dexmedetomidine decreases amount of analgesic needed during and after surgery, presenting analgesic effects. Dexmedetomidine also decreases risk of delirium. However, bradycardia may occur and biphasic effects on blood pressure may be observed during beginning of administration. Because of lengthy symptom onset and offset time, physicians should carefully control administration at the beginning and end of dexmedetomidine administration. The purpose of this review is to evaluate the efficacy and availability of dexmedetomidine in various clinical fields including sedation for critically ill patients, regional anesthesia, monitored anesthesia care for some invasive procedures, stabilization of heart in cardiac surgery or endoscopic procedures.
Anesthesia* ; Anesthesia, Conduction ; Barbiturates ; Benzodiazepines ; Blood Pressure ; Bradycardia ; Brain ; Critical Illness ; Delirium ; Dexmedetomidine* ; GABAergic Neurons ; Heart ; Histamine Antagonists ; Humans ; Hypnotics and Sedatives ; Hypotension ; Propofol ; Respiratory Insufficiency ; Thoracic Surgery

Many sedatives are used clinically and include benzodiazepines, barbiturates, antihistamines, propofol, and alpha-2-agonist. Benzodiazepines activate GABA neuronal receptors in the brain and present sedating, hypnotic, anxiolytic, amnestic, and anticonvulsant effects, but low analgesic effects. Propofol induce sedative, anxiolytic, and amnestic effects but no analgesic effects. However, risks such as cardiopulmonary instability and hypotension must be considered during administration. Dexmedetomidine is a high selective alpha-2 agonist and has many advantages as a sedative. Patients under dexmedetomidine sedation awaken easily and are more likely to be cooperative. Risk of respiratory depression and cardiopulmonary instability is low as well. Additionally, dexmedetomidine decreases amount of analgesic needed during and after surgery, presenting analgesic effects. Dexmedetomidine also decreases risk of delirium. However, bradycardia may occur and biphasic effects on blood pressure may be observed during beginning of administration. Because of lengthy symptom onset and offset time, physicians should carefully control administration at the beginning and end of dexmedetomidine administration. The purpose of this review is to evaluate the efficacy and availability of dexmedetomidine in various clinical fields including sedation for critically ill patients, regional anesthesia, monitored anesthesia care for some invasive procedures, stabilization of heart in cardiac surgery or endoscopic procedures.
Anesthesia* ; Anesthesia, Conduction ; Barbiturates ; Benzodiazepines ; Blood Pressure ; Bradycardia ; Brain ; Critical Illness ; Delirium ; Dexmedetomidine* ; GABAergic Neurons ; Heart ; Histamine Antagonists ; Humans ; Hypnotics and Sedatives ; Hypotension ; Propofol ; Respiratory Insufficiency ; Thoracic Surgery

OBJECTIVETo establish a food allergy model in Brown Norway (BN) rats by gavage of ovalbumin (OVA) without any adjuvant, and to evaluate this model.

METHODSA total of 20 male BN rats aged 3 weeks were randomly divided into allergy group and control group (n=10 each). BN rats in the allergy group were given OVA 1 mg per day by gavage, and all the rats were treated for 41 days continuously. On day 42, the rats in the allergy group were given OVA 100 mg by gavage for challenge. The rats in the control group were given normal saline of the same volume by gavage. Differences in body length, body weight, and food intake were compared between the two groups on days 7, 14, 21, 28, 35, and 42. ELISA was used to measure the serum OVA-IgE level and plasma histamine level after challenge on day 42, and the changes in rats' appearance and fecal properties were observed. The model of food allergy was considered successful when the serum OVA-IgE level in the allergy group was no less than the mean serum OVA-IgE level + 3 standard deviation in the control group.

RESULTSThere were no significant differences in body length, body weight or food intake between the allergy and control groups at all time points (P>0.05). On day 21, the control group had a significantly higher food intake than the allergy group (P<0.05). On day 42 after challenge, the allergy group showed significantly higher serum OVA-IgE and plasma histamine levels than the control group (P<0.05). The sensitization rate (rate of successful modeling) was 90%. The fecal properties showed no significant differences between the two groups.

CONCLUSIONSOVA by gavage without any adjuvant can successfully establish the model of food allergy in BN rats and has a high success rate. Food allergy induced by OVA may reduce food intake within a short period of time, but no influence on rats' body length or body weight has been observed.

Animals ; Disease Models, Animal ; Food Hypersensitivity ; etiology ; immunology ; Histamine ; blood ; Immunoglobulin E ; blood ; Male ; Ovalbumin ; immunology ; Rats ; Rats, Inbred BN

The objective of the present study was to elucidate the effect of bisphosphonates, anti-osteoporosis agents, on glucose uptake in retinal capillary endothelial cells under normal and high glucose conditions. The change of glucose uptake by pre-treatment of bisphosphonates at the inner blood-retinal barrier (iBRB) was determined by measuring cellular uptake of [3H]3-O-methyl glucose (3-OMG) using a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB cells) under normal and high glucose conditions. [3H]3-OMG uptake was inhibited by simultaneous treatment of unlabeled D-glucose and 3-OMG as well as glucose transport inhibitor, cytochalasin B. On the other hand, simultaneous treatment of alendronate or pamidronate had no significant inhibitory effect on [3H]3-OMG uptake by TR-iBRB cells. Under high glucose condition of TR-iBRB cells, [3H]3-OMG uptake was increased at 48 h. However, [3H]3-OMG uptake was decreased significantly by pre-treatment of alendronate or pamidronate compared with the values for normal and high glucose conditions. Moreover, geranylgeraniol (GGOH), a mevalonate pathway intermediate, increased the uptake of [3H]3-OMG reduced by bisphosphonates pre-treatment. But, pre-treatment of histamine did not show significant inhibition of [3H]3-OMG uptake. The glucose uptake may be down regulated by inhibiting the mevalonate pathway with pre-treatment of bisphosphonates in TR-iBRB cells at high glucose condition.
Alendronate ; Animals ; Blood-Retinal Barrier ; Capillaries* ; Cytochalasin B ; Diphosphonates* ; Endothelial Cells* ; Glucose* ; Hand ; Histamine ; Mevalonic Acid ; Rats* ; Retinaldehyde*

Interleukin (IL) 33, a member of the IL-1 superfamily, is an "alarmin" protein and is secreted in its active form from damaged cells undergoing necrotic cell death. Mast cells are one of the main effector cell types in allergic disorders. They secrete a variety of mediators, including T helper 2 cytokines. As mast cells have high-affinity IgE receptors (FcepsilonRI) on their surface, they can capture circulating IgE. IgE-bound mast cells degranulate large amounts of histamine, heparin, and proteases when they encounter antigens. As IL-33 is an important mediator of innate immunity and mast cells play an important role in adaptive immune responses, interactions between the two could link innate and adaptive immunity. IL-33 promotes the adhesion of mast cells to laminin, fibronectin, and vitronectin. IL-33 increases the expression of adhesion molecules, such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1, in endothelial cells, thus enhancing mast cell adhesion to blood vessel walls. IL-33 stimulates mast cell proliferation by activating the ST2/Myd88 pathway; increases mast cell survival by the activation of survival proteins such as Bcl-XL; and promotes the growth, development, and maturation of mast cell progenitors. IL-33 is also involved in the activation of mature mast cells and production of different proinflammatory cytokines. The interaction of IL-33 and mast cells could have important clinical implications in the field of clinical urology. Epithelial dysfunction and mast cells could play an important role in the pathogenesis of interstitial cystitis. Urinary levels of IL-33 significantly increase in patients with interstitial cystitis. In addition, the number of mast cells significantly increase in the urinary bladders of patients with interstitial cystitis. Therefore, inhibition of mast cell activation and degranulation in response to increase in IL-33 is a potential therapeutic target in the treatment of interstitial cystitis.
Adaptive Immunity* ; Allergy and Immunology ; Blood Vessels ; Cell Death ; Cystitis, Interstitial ; Cytokines ; Endothelial Cells ; Fibronectins ; Heparin ; Histamine ; Humans ; Immunity, Innate ; Immunoglobulin E ; Interleukin-1 ; Interleukins ; Laminin ; Mast Cells* ; Peptide Hydrolases ; Receptors, IgE ; Urinary Bladder ; Urology ; Vascular Cell Adhesion Molecule-1 ; Vitronectin