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Objective To investigate the clinical values of the leukocyte count,D-dimer,histidine decarboxylase (HDC) and intestinal fatty acid binding protein (I-FABP) for diagnosing acute intestinal obstruction.Methods Sixty patients who treated in China-Japan Union Hospital of Jilin University from January 2017 to January 2018 were collected prospectively,and were divided into strangulated intestinal obstruction (STR-IO) group (n =20),simple intestinal obstruction (SIM-IO) group (n =20) and peritonitis group (n =20).Twenty healthy volunteers were collected as control group.Automatic blood cell analyzer was used to detecting the leukocyte count.The concentration of plasma D-dimer was detected by immune turbidimetry method.The concentration of serum HDC and I-FABP were measured by enzyme linked immunosorbent assay (ELISA) method.Compared the above indicators of four groups of samples.The measurement data are expressed as mean ± standard deviation (Mean ± SD).Tamhane's T2 and Dunnett's T3 methods were used to comparison between groups.Estimation of receiver operating characteristic curve(ROC) and area under curve (AUC) used logistic regressive model.Results The leukocyte count in control group,SIM-IO group,peritonitis group,and STR-IO group were (6.97 ± 1.68) × 109/L,(8.24 ± 2.78) × 109/L,(11.33 ±4.75) × 109/L,and(12.53 ± 5.96) × 109/L respectively.STR-IO group and peritonitis group were significantly higher than those of control group(F =12.74,P =0.01),but there was no significant difference between SIM-IO group and control group(P ＞ 0.05).The concentration of plasma D-dimer in control group,SIM-IO group,peritonitis group,and STR-IO group were (0.44± 0.30) μg/ml,(1.17 ± 0.67) μg/ml,(1.20 ± 0.72) μg/ml,and (1.67 ± 0.67) μg/ml respectively.The concentration of D-dimer in STR-IO group was significantly higher than those of control group (F =57.08,P =0.00),and there was no significant difference among other group (P ＞ 0.05).The concentration of serum HDC in control group,SIM-IO group,peritonitis group,and STR-IO group were (5.51 ±4.30) ng/ml,(14.33 ± 3.71) ng/ml,(11.53 ± 4.67) ng/ml,and (35.65 ± 21.15) ng/ml respectively.The concentration of HDC in STR-IO group was significantly higher than those of other three groups (F =39.03,P =0.00).The concentration of serum I-FABP in control group,SIM-IO group,peritonitis group,and STR-IO group were (0.20 ± 0.06) ng/m],(0.31 ± 0.17) ng/ml,(0.22 ±0.03)ng/ml,and (0.81 ±0.56) ng/ml respectively.The concentration of I-FABP in STR-IO group was significantly higher than those of other three groups (F =23.07,P =0.01).The AUC of HDC,I-FABP,D-dimer,and leukocyte count were 0.998,0.868,0.730,and 0.704 respactively.Conclusion Leukocyte count,D-dimer,and HDC or I-FABP combined detection may be a more effective index for diagnosing acute intestinal obstruction.
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Resumen Los tumores de células de Leydig (TCL) son tumores endócrinos del intersticio testicular, cuya incidencia se encuentra en aumento. Los síntomas incluyen feminización o virilización en pacientes prepuberales, y pérdida de libido, disfunción eréctil, infertilidad y/o ginecomastia en adultos. Si bien son usualmente benignos, cuando malignizan en adultos no responden a radio y quimioterapia. Múltiples trabajos han reportado que la histidina decarboxilasa (HDC), enzima que cataliza la conversión de L-histidina en histamina (HA), tiene un rol importante en el desarrollo de tumores. A su vez, en nuestro laboratorio demostramos que la HA induce la proliferación de células de Leydig tumorales (CLT) murinas, mientras que la inhibición de HDC disminuye su proliferación y capacidad esteroidogénica. Además, observamos elevada expresión de HDC en TCL pediátricos vs. controles de distintos estadios de madurez sexual; y se ha descrito que ratones knock out para HDC poseen una angiogénesis incompleta. Para evaluar el rol de HDC en la modulación de la angiogénesis se empleó la línea de CLT de rata R2C, principal modelo utilizado en estudios de Leydigioma. También se realizaron estudios en TCL pediátricos. Los medios condicionados por las CLT R2C estimularon la angiogénesis tanto in vitro como in vivo (empleando HUVEC y analizando el grado de vascularización de membranas corioalantoideas de codorniz, respectivamente). El efecto in vitro se revirtió al tratar previamente las CLT R2C con α-metil-DL-histidinadihidrocloruro, inhibidor específico de HDC. A su vez, tanto la HA como los medios condicionados provenientes de TCL pediátricos, produjeron un aumento en la proliferación de las HUVEC. Nuestros resultados sugieren que las CLT producen HA y otros factores proangiogénicos, y que la inhibición selectiva de HDC atenúa la capacidad proangiogénica de las CLT. En base a estos resultados y evidencias previas del laboratorio, inhibidores específicos de HDC podrían ser utilizados como potencial terapia neoadyuvante en TCL.
ABSTRACT Leydig Cell tumors (LCT) are a rare group of endocrine tumors in the testicular interstitium. Between 1 and 3% of testicular malignances in adults and 4% in prepubertal children belong to LCT. An increasing incidence of this type of neoplasia has been reported recently all around the world. Particularly, a strong relationship between LCT and the use of anabolic steroids (which are commonly used nowadays) has been reported recently. In prepubertal boys, symptoms include feminization or virilization, depending on the major circulating steroid (estradiol or testosterone respectively). Adult patients show loss of libido, penile dysfunction, infertility and/or gynecomastia. Although the etiology still is unknown, several studies indicate that tumoral Leydig cells have an excessive production of insulin-like growth factor (IGF-1), as well as aromatase (CYP19) overexpression, which causes an enormous amount of estrogens (particularly estradiol, E2), and both factors play an important role in tumorigenesis. While usually benign, when LCT became malignant in adults they respond poorly to radio and chemotherapy. Likewise, it has been reported that both therapies increase the incidence of several tumors. All these data imply the need of new therapeutic targets to avoid the chirurgical dissection of the testes and the consequences of the hormonal therapies associated, which implicate not only the loss in reproductive function, but also psychological disorders. Several publications have reported that histidine decarboxylase (HDC), the only enzyme capable of catalyzing the conversion from L-histidine to histamine (HA) in mammals, has an important role in the development of several types of tumors, such as colorectal, breast and melanoma. At the same time, in our laboratory we have reported that HA induces cell proliferation of murine Leydig cells, and complementary, this cell proliferation decreases when inhibiting selectively HDC, as well as steroid synthesis (progesterone and E2). Also, we observed a higher expression of HDC in pediatric LCT (n = 3) than normal controls corresponding to different stages of sexual maturation (n = 9). It has been described that HDC knock out mice have an incomplete angiogenesis, and also that MA-10 Leydig cells HDC expression correlates with vascular endothelial growth factor (VEGF). The aim of this study is to improve our knowledge about the role of HDC in LCT biology, particularly, the angiogenesis modulation. We used the R2C Leydig cell line, the most used model for in vitro studies of Leydigioma, because it overexpresses CYP19 and constitutively produces high levels of IGF-1 and E2, as well as human LCT. R2C and pediatric LCT angiogenic capability was evaluated in vitro by measuring proliferation of human umbilical vein endothelial cells (HUVEC). In addition, we verified R2C cells angiogenic capability in vivo, using quail embryo vasculature (chorioallantoic membrane assay). Both models have been validated for the study of angiogenesis. Conditioned medium obtained from R2C cell culture stimulated angiogenesis in vitro (p <0.001) as well as in vivo (p <0.001). The in vitro effect was reverted with a previous treatment on the R2C cell culture using α-methyl-DL-histidine hydrochloride (α-MHD, 10 µM), a specific HDC activity inhibitor (p <0.001). Finally, human conditioned medium from pediatric LCT increased HUVEC proliferation (p <0.01). In the same way, the analyzed patients showed higher testosterone and estradiol levels than normal serum concentrations, which was in concordance to phenotypical features observed in presence of LCT. Our results indicate that tumoral Leydig cells (TLC) produce HA, as well as other angiogenic factors, and it could be stimulating the vascular endothelium. The selective inhibition of HDC attenuates the pro-angiogenic capability in TLC. Considering all these results and previous observations of our laboratory, specific inhibitors of HDC could be used, in the future, as a potential therapeutic target for the treatment of LCT.
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Abstract Growth of Enterobacter aerogenes and accumulation of histamine in chub mackerel (Scomber japonicus) were investigated through measuring bacterial count, histidine decarboxylase (HDC) activity and histamine content in fish samples stored at various temperatures from 4 to 37 °C. Results showed that bacterial count and HDC activity rapidly increased in chub mackerel inoculated with E. aerogenes at storage temperature above 20 °C and reached the highest values (8.64 log CFU/g and 31.68 U/g) at 37 °C. Meanwhile, fish samples stored at 25 and 37 °C for 18 h, formed histamine at above 50 mg/100 g of the potential hazard level. In contrast, bacterial growth and histamine formation were controlled for 36 h by cold storage at low temperature (4 °C). Therefore, strict temperature control was necessary for preservation and processing of chub mackerel in order to assure this marine fish safety.
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Objective:To discuss the effects of recombinant IFN-α-IL-18 fusion protein on chicken lymphocyte histamine induced and the NF-κB p65 activation and nucleo-cytoplasmic transport.Methods: The healthy chickens blood was sterile adopted with anticoagulant,then separation of the chicken peripheral blood lymphocyte and divided into 10 groups:The yeast expression and purification protein IFN-α-IL-18,IL-18,IFN-α were added with 250 ng/ml,500 ng/ml and 1 000 ng/ml respectively while the control was only added RPMI1640 with 3 repetitions for each group.Then the histidine decarboxylase activity,histamine,IFN-γ,PI3K,MAPK and NF-κB p65 in cell nucleus were detected.Results: The recombinant IFN-α-IL-18 and IL-18 could significantly promote the activity of histidine decarboxylase (P<0.01),increase the contents of histamine (P<0.01),induce IFN-γ (P<0.01),improve the contents of PI3K (P<0.01) and the NF-κB p65 levels in nucleus (P<0.01),and the higher concentration of IFN-α had a similar effect to lymphocytes.The effects of IFN-α-IL-18,IL-18 and IFN-α on MAPK was acratia.Conclusion: IFN-α-IL-18 and IL-18 can stimulate chicken peripheral blood lymphocyte populations increased histamine contents significantly and promote the induction of IFN-γ.IFN-α-IL-18,IL-18 and IFN-α increase PI3K expression in lymphocyte associated with the NF-κB activation and NF-κB p65 nucleo-cytoplasmic transport.The study built foundation for the function of IFN-α-IL-18 and the exploration of the mechanism of controlling epidemic diseases.
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Objective To investigate the expression and significance of Histidine decarboxylase (HDC) in liver and intestinal tissue for early diagnosis of strangulated intestinal obstruction.Methods Ten male Wistar rats for the control group and 20 ones for the test group which was divided into A,B groups.Group A (n =10) was made by using ligating ileum for 1 h and group B (n =10) was for 3 h.When intestinal ob struction models were built,the changes of pathology in liver and intestine tissue were observed by light microscope.Real time quantitative PCR was used to detect the expression of HDC in liver and intestinal tissue.Results Under light microscopic level,the injury score of intestine in test group was increased in comparison with that in control group.At 3 h after strangulated intestinal obstruction,RT-PCR showed that brightness of HDC band in intestine tissue was significantly higher than the control.Real time quantitative PCR also showed that the expression of HDC in liver tissue in group A and group B increased 1.34 fold(P ＞0.05) and 2.21 fold (P ＜ 0.05) respectively,when compared with the control group.The expression of HDC in intestine tissue in group A and group B increased 1.81 fold(P ＞ 0.05) and 8.02 fold (P ＜ 0.01) respectively,when compared with the control group.Conclusion Expression of HDC can be used for early diagnosis of strangulated intestinal obstruction.
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Early diagnosis is one of the difficulties in strangulated intestinal obstruction.Serological markers for the early diagnosis of intestinal obstruction has become a hot spot resently.Studies have shown that histidine decarboxylase had a high sensitivity and specificity in the diagnosis of gastric mucosal injury of intestinal obstruction,which would be expected to become an effective serological marker for the early diagnosis of strangulated intestinal obstruction.In this review,the author will describe the advance of serum histidine decarboxylase level for diagnosis of strangulated intestinal obstruction.
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Objective To investigate the clinical values of serum histidine decarboxylase(HDC),intestinal fatty acid binding protein(I-FABP),and diamine oxidase(DAO)for diagnosing intestinal mucosal injury (IMI)in patients with intestinal obstruction.Methods The expression levels of serum HDC,I-FABP,and DAO in 28 patients with strangulated intestinal obstruction,19 patients with simple intestinal obstruction,17 patients with acute simple appendicitis,and 20 healthy control were determined by enzyme-linked immunosorbent assay (ELISA)before clinical treatment,and then the areaa under receiver operating characteristic curves(AUC)of these diagnostic indicators were compared.In addition,the incidences of systemic inflammatory response syndrome (SIRS)and infectious complications were closely observed.The difference of the expressions of HDC,I-FABP,and DAO and their relationship with SIRS and infectious complications were compared among these patients and controls.Results The expression levels of serum HDC, I-FABP, and DAO were the highest in patients with strangulated intestinal obstruction (all P < 0.001), and the expression levels of these three indicators were significantly higher in patients with simple intestinal obstruction than in those with acute simple appendicitis or healthy controls (all P<0.05).The AUC of HDC (0.913) was significantly larger than that of I-FABP (0.877, P =0.000) and DAO (0.873, P = 0.000).When the cut-off value of HDC ≥31.00 ng/ml, the sensitivity, specificity, false negative rate, and false positive rate of HDC were 74.5% , 94.6% , 25.5% , and 5.4% , respectively,which were all better than those of I-FABP and DAO.There were significant differences of the incidence of SIRS ( P = 0.046) and abdominal infection (P = 0.027) among patients with strangulated intestinal obstruction, patients with simple intestinal obstruction, and patients with acute simple appendicitis, while lung infection showed no such significant difference (P = 0.728).The expression level of serum HDC was significantly higher in patients with strangulated intestinal obstruction who were also suffered from SIRS ( P = 0.000) or abdominal infection ( P =0.002) than that of uninfected patients.Meanwhile, the expression levels of serum I-FABP and DAO were significantly higher in the SIRS patients with strangulated intestinal obstruction than that of uninfected patients ( P = 0.027, P=0.017, respectively).The expression levels of HDC, I-FABP, and DAO were significantly correlated with the incideces of SIRS and abdominal infection ( all P < 0.05 ) , among which the level of HDC and the incidence of SIRS had the highest correlation (R = 0.608, P = 0.001).Conclusion HDC can be an effective indicator for diagnosing IMI in patients with intestinal obstruction.
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Objective To investigate the expression changes of histidine decarboxylase(HDC)and H+,K+-ATPase in gastric mucosa during the healing of experimental gastric ulcer in rats.Methods The ulcers were caused by applying acetic acid to the serosal surface of the anterior face of the rat gastric body.At different time points during ulcer healing,HDC and H+,K+-ATPase mRNA and protein expressions were studied by using reverse transcription-polymerase chain reaction and Western blot respectively.Results An ulcer crater developed on the anterior face of the gastric body on day 1 after the induction of ulcers,and the ulcer area was biggest on day 3.On day 12,most of the gastric ulcers had healed.Compared with the control group,the HDC and H+,K+-ATPase mRNA expression in the gastric mucosa of ulcer rats showed a decrease on day 1,and increased back to initial level on day 9.The protein expression of HDC and H+,K+-ATPase in gastric mucosa of ulcer rats decreased immediately on day 1,more on day 6,and returned to the initial levels on day 12.Conclusion The mRNA and protein expressions of HDC and H+,K+-ATPase decrease in the healing process of gastric ulcers,resulting in accelerated ulcer healing through inhibiting gastric acid secretion.