Humans ; Histamine ; Receptors, Histamine H2 ; Schizophrenia/drug therapy*

Objective The efficacy and safety of pitolisant in the treatment of adult narcolepsy have been confirmed in clinical trials abroad， but there is a lack of data on the application of pitolisant in Chinese patients. The aim of this study is to investigate the efficacy and safety of pitolisant in the treatment of adult narcolepsy in China.Methods A total of 30 subjects were enrolled in this study and were given individualized titration once a day for 8 weeks. Epworth Somnolence Scale （EES） and daily cataplexy rate （DCR） were used as the primary outcome measures，and Clinical Global Impression-Severity scale（CGI-S） and Clinical Global Impression of Change Scale （CGI-C） were used as the secondary outcome measures；safety indicators included adverse event （AE） records and laboratory examination.Results The results showed that there were significant improvements in ESS score and number of cataplexy attacks after medication. At the end of treatment，ESS score was reduced by（7.63±4.79）（P<0.001）. For all subjects， the average daily number of cataplexy attacks was 0.83 at baseline，which was reduced significantly to （0.39±0.82）after 3 weeks of pitolisant treatment and（0.38±0.79）after 5 weeks of pitolisant treatment（P<0.05）. After the treatment ended， the median CGI-S score of excessive daytime sleepiness （EDS） improved from "severe" at baseline to "mild"（P<0.001）， and the CGI-S score of cataplexy improved from "mild" at baseline to "basically normal"（P<0.001）. Most AEs were mild and did not receive any drug treatment， and there were no significant changes in other laboratory markers used to monitor the general condition of the subjects before and after treatment. Conclusion Pitolisant has good efficacy and safety in the treatment of EDS and cataplexy in Chinese adults with narcolepsy.
Narcolepsy ; Histamine ; Cataplexy

OBJECTIVE: To observe the effects of catgut embedding and polyglycolic acid/poly-lactic acid (PGLA) embedding at "Zusanli" (ST 36) on the activation of local skin mast cells (MC), and expression of substance P (SP) and histamine (HA), and to explore the mechanism of the temporal stimulation effect of acupoint catgut embedding and provide a foundation for further research on the initiation mechanism of acupoint catgut embedding. METHODS: One hundred and sixty male SPF-grade SD rats were randomly divided into a blank group (10 rats), a sham-embedding group (50 rats), a catgut group (50 rats), and a PGLA group (50 rats). Each intervention group was further randomly divided into five subgroups according to the time points after intervention: 8 hours, 3 days, 7 days, 14 days, and 21 days, with 10 rats in each subgroup. One-time sham-embedding, catgut embedding and PGLA embedding was given at left "Zusanli" (ST 36) in each intervention group, respectively. The skin and subcutaneous connective tissue of the left "Zusanli" (ST 36) were collected at the corresponding time points after intervention, except for the blank group (only one day before intervention). Toluidine blue staining was used to detect MC count and degranulation, and immunohistochemical staining was used to detect the expression of SP and HA positive cells. RESULTS: There was no significant difference in MC count between the subgroups of each intervention group and the blank group (P>0.05). There was no significant difference in MC count between the subgroups of the catgut group and the PGLA group (P>0.05). The MC count in the 8-hour subgroup of PGLA group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the MC count in the 21-day subgroup of PGLA group was lower than that in the 21-day subgroup of catgut group (P<0.05). Compared with the blank group, the degranulation rates of MC were increased in the 8-hour and 3-day subgroups of sham-embedding group, 8-hour, 3-day, and 7-day subgroups of catgut group, and 8-hour, 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.01, P<0.05, P<0.001). There was no significant difference in the degranulation rate of MC between the subgroups of the catgut group and the PGLA group (P>0.05), and no significant difference in the degranulation rate of MC between the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of SP positive cells was increased in the 8-hour subgroup of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.001, P<0.05). The expression of SP positive cells in the 7-day subgroup of catgut group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.001). The expression of SP positive cells in the 7-day subgroup of PGLA group was higher than that in the 3-day subgroup of PGLA group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.01). There was no significant difference in the expression of SP positive cells between the subgroups of the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of HA positive cells was increased in the 8-hour, 3-day subgroups of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 8-hour, 3-day, 7-day, 14-day, and 21-day subgroups of PGLA group (P<0.001, P<0.01, P<0.05). The expression of HA positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.05), while the expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 8-hour subgroup of PGLA group (P<0.05), and the expression of HA positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.05). The expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 3-day subgroup of catgut group (P<0.05). CONCLUSION Catgut and PGLA embedding at "Zusanli" (ST 36) in healthy rats could induce changes in local skin MC, SP, and HA, which may be one of the mechanisms of the temporal stimulation effect after acupoint embedding. There are certain differences between different suture materials. A moderate inflammatory response in the acupoint area, mediated by MC and involving SP and HA, may be one of the initiating factors for the effect of acupoint catgut embedding.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Mast Cells ; Histamine ; Substance P/genetics* ; Catgut ; Acupuncture Points

Basal Forebrain ; Cholinergic Agents ; Cholinergic Neurons ; Humans ; Receptors, Histamine H1 ; Schizophrenia

β3-adrenergic agonists induce adaptive thermogenesis and promote beiging of white fat. However, it remains unclear which metabolites mediate the stimulatory effects of β3-adrenergic agonists on thermogenesis of brown and beige fat. In this study, adipose tissue was isolated from 8-week-old C57/BL6J male mice by intraperitoneal administration of β3-adrenergic agonist CL316,243 for RNA-Seq, which revealed that histidine decarboxylase, a key enzyme in histamine synthesis, was strongly induced in adipose by CL316,243. Therefore, we speculated that histamine might be involved in the process of thermogenesis in adipose tissue. We determined the physiological role and mechanism by which histamine promotes fat thermogenesis by intravenous administering histamine to C57BL/6J mice fed a normal or a high-fat diet. The results showed that intravenous injection of histamine into C57BL/6J mice fed a normal diet stimulated the expression of thermogenic genes, including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and uncoupling protein 1 (UCP1), in brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT). H&E staining also suggested that histamine treatment decreased the size of lipid droplets in adipocytes. Moreover, histamine treatment also enhanced thermogenesis of fat in high-fat diet induced obese mice, and improved glucose intolerance and fatty liver phenotype. Finally, we demonstrated that the effects of histamine on the thermogenic program were cell autonomous. Our data suggest that histamine may mediate the effects of β3-adrenergic agonists on thermogenesis of fat.
Adipose Tissue, Beige ; Adipose Tissue, Brown ; Animals ; Histamine ; Male ; Mice ; Mice, Inbred C57BL ; Thermogenesis ; Uncoupling Protein 1/genetics*

The aim of this work was to study effects of ketotifen fumarate (KF) on prevention of tissue damage in testes of rats with experimental autoimmune orchitis (EAO) and on the contralateral testis in a model of prolonged testicular cord torsion (TCT). Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution (vehicle group). Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score. Mast cells (MC) were identified by histochemistry and quantified. In EAO model, KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group. KF also reduced the number of testicular MC compared to vehicle group. Similarly, in TCT model, multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium, seminiferous tubule atrophy, and interstitial edema. Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed. In contrast, sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features. A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals. In conclusion, we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models. The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.
Animals ; Autoimmune Diseases/pathology* ; Cell Count ; Epididymis/pathology* ; Epididymitis/pathology* ; Histamine H1 Antagonists/pharmacology* ; Hypersensitivity, Delayed ; Immunity, Cellular/drug effects* ; Ketotifen/pharmacology* ; Male ; Mast Cells/pathology* ; Orchitis/pathology* ; Rats ; Severity of Illness Index ; Spermatic Cord Torsion/pathology* ; Testis/pathology* ; Vaccination

Antipsychotic-induced weight gain (AIWG) is a common adverse effect of this treatment, particularly with second-generation antipsychotics, and it is a major health problem around the world. We aimed to review the progress of pharmacogenetic studies on AIWG in the Chinese population to compare the results for Chinese with other ethnic populations, identify the limitations and problems of current studies, and provide future research directions in China. Both English and Chinese electronic databases were searched to identify eligible studies. We determined that > 25 single-nucleotide polymorphisms in 19 genes have been investigated in association with AIWG in Chinese patients over the past few decades. HTR2C rs3813929 is the most frequently studied single-nucleotide polymorphism, and it seems to be the most strongly associated with AIWG in the Chinese population. However, many genes that have been reported to be associated with AIWG in other ethnic populations have not been included in Chinese studies. To explain the pharmacogenetic reasons for AIWG in the Chinese population, genome-wide association studies and multiple-center, standard, unified, and large samples are needed.
Antipsychotic Agents ; adverse effects ; Asian Continental Ancestry Group ; genetics ; China ; Genome-Wide Association Study ; Genotype ; Humans ; Lipid Metabolism ; genetics ; Neurosecretory Systems ; drug effects ; Pharmacogenomic Testing ; Polymorphism, Single Nucleotide ; Receptors, Adrenergic ; genetics ; Receptors, Dopamine ; genetics ; Receptors, Histamine ; genetics ; Receptors, Serotonin ; genetics ; Weight Gain ; drug effects ; genetics

We previously described a rare case of anaphylaxis presumably induced by carminic acid in cochineal dye used as a food additive. In this study, highly pure carminic acid was added to an albumin-containing buffer at various concentrations, followed by serial dilution. Varying the mixing ratio of carminic acid and albumin affected the extent of histamine release from passively sensitized basophils. Similar basophil histamine release occurred with carminic acid-globulin solutions. These results provide experimental evidence indicating that basophil activation is dependent on hapten (carminic acid) and carrier (protein) interaction.
Anaphylaxis ; Basophils ; Carmine ; Food Additives ; Histamine Release ; Hypersensitivity ; In Vitro Techniques

Scombroid fish poisoning (SFP) is a form of histamine food poisoning caused by the ingestion of improperly stored fish. The term “scombroid” derives from the family name of the fish family first implicated, such as tuna and mackerel. On the other hand, non-scombroid fish species, such as sardine and herring, can also cause histamine poisoning. The histamine is converted from histidine by a bacterial enzyme in the causative fish. Because the symptoms of SFP can easily be confused with food allergies, it is believed to have been significantly under-reported. In 2016, an outbreak of SFP occurred among primary school students who had eaten yellowtail steak in Korea. The most common findings consisted of a rapid onset of flushing of the face and trunk, erythematous and urticarial rash, diarrhea, and headache occurring soon after consuming the spoiled fish. Usually, the course is self-limiting and antihistamines can be used successfully to relieve symptoms, but several life-threatening SFP cases have been reported. Clinical toxicologists should be familiar with SFP and have competency to make a differential diagnosis between fish allergy and histamine poisoning. SFP is a histamine-induced reaction caused by the ingestion of histamine-contaminated fish, whereas a fish allergy is an IgE-mediated reaction. This review discusses the epidemiology, pathophysiology, diagnosis, treatment, and preventive measures of SFP.
Diagnosis ; Diagnosis, Differential ; Diarrhea ; Eating ; Epidemiology ; Exanthema ; Flushing ; Food Hypersensitivity ; Foodborne Diseases ; Hand ; Headache ; Histamine Antagonists ; Histamine ; Histidine ; Humans ; Hypersensitivity ; Korea ; Perciformes ; Poisoning ; Tuna

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