OBJECTIVETo investigate the relationship between specific immunocyte and pseudoanaphylactoid reactions (PR) induced by Shuanghuanglian injection (SHLI).

METHODICR mice, SCID mice and BALB/C athymic mouse were divided into different test groups, the mice were intravenously injected with solutions of different concentration of SHLI, positive control Compound 48/80 and normal sodium. All test substances were mixed with 0. 4% Evans blue. The reaction and vascular permeability of the ears were observed and measured 30 min after SHLI injected.

RESULTSHLI of 300, 600 mg x kg(-1) caused obvious vascular hyperpermeability in ICR mice, but the same dose of SHLI didn't cause vascular hyperpermeability in SCID mice and BALB/C athymic mouse.

CONCLUSIONSHLI in equivalent and 2 times the clinical dose can cause PR in ICR mice, but the same dose of SHLI can't cause PR in SCID mice and BALB/C athymic mouse, so specific immunocyte maybe take part in the SHLI-induced PR.

Anaphylaxis ; chemically induced ; immunology ; Animals ; Drugs, Chinese Herbal ; toxicity ; Immune System ; drug effects ; Injections ; methods ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Mice, SCID

OBJECTIVETo develop animal models and methodologies for assay of pseudoallergy induced by injectable drugs.

METHODRats cutaneous anaphylactoid reaction model was developed by intravenous injection of 0. 6% Evans blue(EB) followed by intracutaneous injection of test substance solutions 50 microL. Diameters of subcutaneous blue spots and EB exudation were assayed.

RESULTRat anaphylactoid reaction was characterized as vascular hyperpermeability which was measured by diameters of blue spots inside the skin and the EB exudation of the blue spots. Compound 48/80 caused severe bluing and EB exudation in the skin by inducing obvious vascular hyperpermeability which indicated that it can induce rat skin pseudoallergy. Normal saline or 5% glucose injection showed no obvious reactions. The rat pseudoallergy model was validated by intracutaneous injections of western drug injections and Chinese medicine.

CONCLUSIONRats could be developed into skin pseudoallergy model for preclinical safety evaluation of injectable drugs. The pseudoallergy reaction in this model is of high clinic consistency, sensitivity, reproducibility, and maneuverability. The model is suitable for the evaluation for pseudoallergy induced by injectable products prepared from Chinese materia medica This model can also be used for safety assay and quality control in manufacturing process, spot checking of marketed products, screening of allergen as well as studying of pseudoallergy mechanism.

Animals ; Disease Models, Animal ; Drug Evaluation, Preclinical ; methods ; Drug Hypersensitivity ; Female ; Injections, Subcutaneous ; methods ; Male ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects

OBJECTIVETo develop animal models and methodologies for assay of pseudoallergy induced by injectable drugs.

METHODMouse anaphylactoid reaction model was developed by intravenous injection of test substance solutions containing Evans blue (EB). Scores of ear blue staining and quantitation of ear EB exudation were the parameters for the pseudoallergy reaction.

RESULTMouse anaphylactoid reaction was characterized as vascular hyperpermeability which was detectable in ears by quantitation of blue staining score and EB exudation. Compound 48/80 and histamine caused severe ear bluing and EB exudation by inducing obvious vascular hyperpermeability which indicated that they can induce mouse pseudoallergy. Intravenous injection of either normal saline or 5% glucose injection showed no ear bluing. The mouse pseudoallergy model was validated by intravenous injections of western drugs and Chinese medicine.

CONCLUSIONMice could be developed into pseudoallergy model for preclinical safety evaluation of injectable drugs. The pseudoallergy reaction in this model is of high clinic consistency, sensitivity, reproducibility, and maneuverability. The model is suitable for the evaluation for pseudoallergy induced by injectable products prepared from Chinese materia medica This model can also be used for safety assay and quality control in manufacturing process, spot checking of marketed products, screening of allergen as well as studying of pseudoallergy mechanism.

Animals ; Disease Models, Animal ; Drug Evaluation, Preclinical ; methods ; Drug Hypersensitivity ; Injections, Intravenous ; Mice ; Mice, Inbred ICR

Objective To evaluate the efficacy and safety of omalizumab on the treatment of chronic spontaneous urticaria (CSU) by systemic review and meta-analysis.Methods Electronic databases,such as PubMed,Clinicaltrials.gov,the Cochrane Database of Systematic Reviews,and the Cochrane Central Register of Controlled Trials,were searched to collect randomized controlled trials (RCTs) about the efficacy and safety of omalizumab in the treatment of CSU.Two reviewers independently screened RCTs according to the inclusion and exclusion criteria,extracted data,and assessed the quality of the included RCTs.And then,a meta-analysis was carried out by using RevMan 5.3 software for comparisons of the efficacy and safety of the 75-,150-,300-,600-mg omalizumab groups versus the placebo group after 1-month treatment,as well as the total omalizumab group versus the placebo group.Results A total of 7 RCTs involving 1 365 patients were included in this meta-analysis.The results showed that the total omalizumab group and different omalizumab subgroups were superior in improving the urticaria activity score of 7 days (UAS7) and wheal number score of 7 days to the placebo group (all P ＜ 0.05).For the improvement in the itch severity score (ISS) of 7 days and complete response rate for main symptoms (UAS7 =0),the total omalizumab group,75-,150-and 300-mg omalizumab groups were superior to the placebo group (all P ＜ 0.05),but there were no significant differences between the 600-mg omalizumab group and the placebo group (P =0.07).The dermatology life quality index (DLQI) was better in the total omalizumab group,150-and 300-mg omalizumab groups than in the placebo group (all P ＜ 0.05),but no significant difference was observed between the 75-mg omalizumab group and the placebo group (P =0.50).There were no significant differences in the incidence of common adverse events or serious adverse events between the total omalizumab group as well as the 75-,150-and 300-mg omalizumab subgroups and the placebo subgroup (all P ＞ 0.05).Conclusions Omalizumab can improve clinical symptoms and life quality of patients with CSU,and is effective in improving the UAS,ISS,wheal number score,DLQI and complete response rate for main symptoms (UAS =0) with high safety.Subcutaneous injection of omalizumab at a dose of 150 or 300 mg/month shows the best efficacy in improving the clinical symptoms and life quality of patients with CSU.

OBJECTIVETo investigate the safety of different level of tween 80 by comparing the degree of pseudoanaphylactoid reactions (PR) induced by medicinal tween 80 and injectable tween 80.

METHODThe analysis of vascular permeability of the mice ears: ICR mouse were divided into different test groups, the mice were intravenously injected with solutions of medicinal tween 80 and injectable tween 80 with 0.2%, 1% and 5% concentration, positive control Compound 48/80 and 5% glucose injection. All test substances were mixed with 0.4% Evans blue. The reaction and vascular permeability of the ears were observed and measured 30 min after injection. The analysis of vascular permeability of the rat's skin: the rats were intravenous injected with 0. 6% Evans blue normal saline solution first, 10 minutes later, the same substances were intradermal administrated into the back of rats. The rats were sacrificed and the diameter of locus ceruleus and the content of Evans blue leak out were measured 20 min after injection.

RESULTMedicinal tween 80 and injectable tween 80 with 5% concentration caused obvious vascular hyper permeability in ICR mice, but the degree of vascular hyperpermeability caused by injectable tween 80 was lighter than by medicinal tween 80. Other tween 80 didn't cause obvious vascular hyper permeability in the ears of mouse. The solution of different concentration of tween 80 caused obvious locus ceruleus reaction in rat's back. As for the content Evans blue leak out, there was no statistical significance between each group except positive control Compound 48/80 group.

CONCLUSIONTween 80 can cause obvious vascular hyper permeability and the effect is dose dependent, which indicated that tween 80 can cause PR. On the other hand, injectable tween 80 is more security than medicinal tween 80, the dosage of tween 80 should be still controlled strictly so that to decrease the incidence of PR.

Anaphylaxis ; chemically induced ; Animals ; Injections ; methods ; Male ; Mice ; Mice, Inbred ICR ; Polysorbates ; toxicity ; Rats ; Rats, Wistar

OBJECTIVETo investigate a possibility to improve the security of pulse-activating injection by comparing the difference of pseudoanaphylactoid reactions (PR) induced by pulse-activating injection before and after improving technology.

METHODThe analysis of vascular permeability of the mice's ears: ICR mouse were divided into different test groups, and intravenously injected with solutions of different concentration of pulse-activating injection before and after improving technology, positive control Compound 48/80 and 5% glucose injection. All test substances were mixed with 0. 4% Evans blue. The reaction and vascular permeability of the ears were observed and measured 30 min after injection. The vascular permeability of the rat's skin: the rats were intravenous injected with 0. 6% Evans blue normal saline solution first, 10 minutes later, the same test substances were intradermal injected into the back of rats, there are 16 injected spots in the back of rat. The rats were sacrificed and the diameter of locus ceruleus and the content of Evans blue leaked out were measured 20 min after injection.

RESULTPulse-activating injection before improving technology with dose of 16.7 mL x kg(-1) ( in 1.67 times the clinical dose ) caused obvious vascular hyperpermeability in ICR mice. In the group of pulse-activating injection before improving technology with dose of 10 mL x kg(-1) (in clinic equivalent dose), no obvious vascular hyperpermeability in the ears were observed. The degrees of vascular hyperpermeability in the group of pulse-activating injection after improving technology with dose of 16.7 mL x kg(-1) were more lessen than the same dose of injection before improving technology. Pulse-activating injection before improving technology caused obvious exudation, oedema locus ceruleus in the injection site of rat's back, and it showed a certain dose-effect relation. Pulse-activating injection after improving technology caused locus ceruleus in the injection site too, but the diameters of the locus ceruleus were shorter than the diameters in the group of pulse-activating injection before improving technology, and the contents of leaked out Evans blue were fewer. All of these showed that PR of skin induced by pulse-activating injection after improving technology is alleviated.

CONCLUSIONPulse-activating injection before improving technology cause obvious vascular hyperpermeability, but the same dose of pulse-activating injection after improving technology can't cause obvious vascular hyperpermeability. The result indicated that the pulse-activating injection before improving technology can cause PR, improving technology can lessen the degree of PR induced by the injection.

Anaphylaxis ; chemically induced ; Animals ; Capillary Permeability ; drug effects ; Injections, Intravenous ; methods ; Male ; Mice ; Mice, Inbred ICR ; Rats ; Skin ; drug effects

To investigate the clinical manifestations, molecular genetics and gonadal pathology characteristics of patients with disorders of sex development (DSD), and to summarize the clinical experience of identifying rare diseases from common symptoms.

The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children′s Medical Center from May 2018 to August 2023 were retrospectively analyzed, summarized and discussed.

According to chromosome karyotype, 416 cases of DSD were classified into three types: 92 cases(22.1%) of abnormal sex chromosome karyotype, 285 cases(68.5%) of 46, XY karyotype and 39 cases(9.4%) of 46, XX karyotype. Among the 92 patients with abnormal sex chromosome karyotype, 59 cases were raised as males, 18 cases (30.5%) complained of short penis with hypospadias and cryptorchidism. The most common karyotype was 45, X/46, XY(58 cases, 63.0%).Among the 285 patients with 46, XY karyotype, 238 cases were raised as males, and 63 cases(26.5%)complained of short penis and hypospadias; 47 cases were raised as females, and 13 cases(27.7%) complained of inguinal mass. A total of 216 patients with 46, XY karyotype were subjected to whole exome gene detection, and 155 cases(71.8%) were found to have molecular pathogenesis with the clinical phenotype. Among the 39 patients with 46, XX karyotype, 19 cases were raised as males, and 8 cases(42.1%) complained of short penis and hypospadias. In the 18 cases of gonad biopsy, 17 cases showed testicular tissue in gonads. Whole exome sequencing was performed in 14 cases. NR5A1 gene heterozygous mutation, SRY gene mutation and SOX3 gene mutation were found in 2 cases, respectively(14.3%). Twenty cases were raised as females, and 14 cases(70.0%) complained of clitoral hypertrophy. Gonad biopsy was performed in 8 cases, with 7 cases of ovotestis(87.5%) and 1 case of NR5A1 gene heterozygous mutation(14.3%).

The etiologies of DSD are complex and diverse, and the clinical manifestations are various, which can be manifested as hypospadias, micropenis, cryptorchidism and other common symptoms of the urinary system. Different etiologies have different treatment options. Therefore, chromosome karyotype, molecular genetic testing and gonadal pathology can be used to clarify the cause of disease, especially for rare diseases, improve the detection rate, reduce the rate of missed diagnosis, and ensure reasonable treatment, especially sex selection.