cAMP-Epac1 signaling is activated in DDAVP-induced endolymphatic hydrops of guinea pigs

Abstract Objective To explore whether Cyclic Adenosine Monophosphate (cAMP)-Epac1 signaling is activated in 1-Desamino-8-D-arginine-Vasopressin-induced Endolymphatic Hydrops (DDAVP-induced EH) and to provide new insight for further in-depth study of DDAVP-induced EH. Methods Eighteen healthy, red-eyed guinea pigs (36 ears) weighing 200-350 g were randomly divided into three groups: the control group, which received intraperitoneal injection of sterile saline (same volume as that in the other two groups) for 7 consecutive days; the DDAVP-7d group, which received intraperitoneal injection of 10 mg/mL/kg DDAVP for 7 consecutive days; and the DDAVP-14d group, which received intraperitoneal injection of 10 μg/mL/kg DDAVP for 14 consecutive days. After successful modeling, all animals were sacrificed, and cochlea tissues were collected to detect the mRNA and protein expression of the exchange protein directly activated by cAMP-1 and 2 (Epac1, Epac2), and Repressor Activator Protein-1 (Rap1) by Reverse Transcription (RT)-PCR and western blotting, respectively. Results Compared to the control group, the relative mRNA expression of Epac1, Epac2, Rap1A, and Rap1B in the cochlea tissue of the DDAVP-7d group was significantly higher (p< 0.05), while no significant difference in Rap1 GTPase activating protein (Rap1gap) mRNA expression was found between the two groups. The relative mRNA expression of Epac1, Rap1A, Rap1B, and Rap1gap in the cochlea tissue of the DDAVP-14d group was significantly higher than that of the control group (p< 0.05), while no significant difference in Epac2 mRNA expression was found between the DDAVP-14d and control groups. Comparison between the DDAVP-14d and DDAVP-7d groups showed that the DDAVP-14d group had significantly lower Epac2 and Rap1A (p< 0.05) and higher Rap1gap (p < 0.05) mRNA expression in the cochlea tissue than that of the DDAVP-7d group, while no significant differences in Epac1 and Rap1B mRNA expression were found between the two groups. Western blotting showed that Epac1 protein expression in the cochlea tissue was the highest in the DDAVP-14d group, followed by that in the DDAVP-7d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); Rap1 protein expression in the cochlea tissue was the highest in the DDAVP-7d group, followed by the DDAVP-14d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); no significant differences in Epac2 protein expression in the cochlea tissue were found among the three groups. Conclusion DDAVP upregulated Epac1 protein expression in the guinea pig cochlea, leading to activation of the inner ear cAMP-Epac1 signaling pathway. This may be an important mechanism by which DDAVP regulates endolymphatic metabolism to induce EH and affect inner ear function. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 5.

Congenital renal diabetes insipidus caused by aquaporin 2 gene mutation in siblings: 2 cases report and literature review / 中国综合临床

Objective:To improve clinicians' understanding of congenital nephrogenital diabetes insipidus (CNDI) and to reduce missed and misdiagnosis. Methords 　Based on the literature, the clinical data and gene mutation of 2 patients with CNDI who were admitted to the Department of Endocrinology and Metabolism of the First Affiliated Hospital of Henan University of Science and Technology on July 30, 2020 were analyzed retrospectively. Results:(1) The presentee, 4 years old, had irritable thirst, polydipsia and polyuria for more than 3 years. The sister, 2.5 years old, had irritable thirst, polydipsia and polyuria for more than 2 years. The clinical diagnosis was “CNDI”, and the symptoms improved after treatment with hydrochlorothiazide. (2) The genetic test revealed that the congenital nephrogenic uremia and her sister had a heterozygous mutation of c.170A>C (p.Q57P) and c.211G>A (p.Vl71M) in the aquaporin-2 gene, and the mother carried the AQP2 gene. c.170A>C(p.Q57P) mutation.Conclusion:CNDI is a rare disease. Early diagnosis and treatment can improve the prognosis of patients to the greatest extent, and prenatal diagnosis can guide eugenics.

Idiopathic partial central diabetes insipidus

ABSTRACT Diabetes insipidus is a rare disorder characterized by the inability to concentrate urine, which results in hypotonic urine and increased urinary volume. It may occur because of antidiuretic hormone deficiency or resistance to its action in the renal tubules. When there is a deficiency in the synthesis of antidiuretic hormones, diabetes insipidus is called central; when there is resistance to its action in the renal tubules, it is said to be nephrogenic. We report a case of idiopathic partial central diabetes insipidus and highlight the management and treatment of the disease.

Evaluation of aversive behavior in Rattus norvegicus experimentally infected by two distinct strains of Toxoplasma gondii (ME49 and VEG): study of epigenetic markers

ABSTRACT Background: Behavioral changes in Rattus norvegicus infected with two strains of Toxoplasma gondii (ME49 and VEG) were investigated. Methods: Rats were evaluated for motor activity and aversion or attraction to cat urine 60 days after infection. After euthanasia, arginine-vasopressin gene methylation in the central nervous system was evaluated. Results: A significant difference was observed in the methylation of the arginine-vasopressin promoter gene between rats infected with the ME49 and VEG strains. Conclusions: Although differences were not observed in many parameters, significant differences were observed in the methylation of the arginine-vasopressin promoter gene in rats infected with the two studied strains.

Otorhinolaryngological adverse effects of urological drugs

ABSTRACT Purpose: To describe the otorhinolaryngological adverse effects of the main drugs used in urological practice. Materials and Methods: A review of the scientific literature was performed using a combination of specific descriptors (side effect, adverse effect, scopolamine, sildenafil, tadalafil, vardenafil, oxybutynin, tolterodine, spironolactone, furosemide, hydrochlorothiazide, doxazosin, alfuzosin, terazosin, prazosin, tamsulosin, desmopressin) contained in publications until April 2020. Manuscripts written in English, Portuguese, and Spanish were manually selected from the title and abstract. The main drugs used in Urology were divided into five groups to describe their possible adverse effects: alpha-blockers, anticholinergics, diuretics, hormones, and phosphodiesterase inhibitors. Results: The main drugs used in Urology may cause several otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported and varies among drug classes. Conclusions: Most of the drugs used in urological practice have otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported. Therefore, doctors must be aware of these adverse effects to improve adherence to the treatment and to minimize damage to the health of patients.

Mechanism of Suoquanwan on Enuresis Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

Objective:To explore the targets and relevant signaling pathways of Suoquanwan in the treatment of enuresis using network pharmacology，and animal expriments are applied to further define its mechanism of action. Method:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） database was used to screen out active chemical components of Suoquanwan，varieties of systematic biological databases were integrated to construct the "active component-disease-target" network relationship，and the common protein protein interaction network（PPI） network genes were functionally enriched. Quantitative real time polymerase chain reaction（Real-time PCR） and Western blot were used to verify the effect of Suoquanwan on AVPR2 and DRD2 gene. Result:A total of 32 active ingredients were screened from Suoquanwan. These active ingredients were interacted with 131 potential targets relating to Enuresis，which contained 14 core target genes，namely arginine vasopressin receptor 2 （AVPR2）， neurotrophic receptor tyrosine kinase 1（NTRK1）， dopamine receptor D2（DRD2）， opioid receptor mu 1（OPRM1）， 5-hydroxytryptamine receptor 1A（HTR1A）， 5-hydroxytryptamine receptor 1B（HTR1B），solute carrier family 6 member 4（SLC6A4），Adrenoceptor Alpha 2A（ADRA2A）， prostaglandin-endoperoxide synthase 2（PTGS2）， cholinergic receptor muscarinic 2（CHRM2）， solute carrier family 6 member 3 （SLC6A3）， 5-hydroxytryptamine receptor 6（HTR6）， solute carrier family 6 member 2（SLC6A2）， cytochrome P450 family 2 subfamily C member 19（CYP2C19）. Gene enrichments mainly involved to G protein-coupled receptor signaling pathway，regulation of trans-synaptic signaling，regulation of neurotransmitter transport and neuroactive ligand-receptor interaction. Real-time PCR and Western blot results showed that Suoquanwan could enhance the expression of AVPR2 in rat kidney，and weaken the expression of DRD2 in rat adrenal. Conclusion:The main chemical constituents in Suoquanwan may alleviate enuresis by regulating AVPR2 and DRD2 and then participating in the G protein-coupled receptor signaling pathway，regulation of trans-synaptic signaling，regulation of neurotransmitter transport and other biological processes.

Effects of the ice popsicle on vasopressin, osmolality, thirst intensity, and thirst discomfort / Efectos del picolé de hielo sobre vasopresina, osmolaridad, intensidad y malestar de la sed / Efeitos do picolé de gelo sobre vasopressina, osmolaridade, intensidade e desconforto da sede

ABSTRACT Objective: To analyze the effects of the ice popsicle on vasopressin, osmolality, thirst intensity, and thirst discomfort. Method: This is a quasi-experimental, pre- and post-test study conducted in a laboratory. The sample consisted of nine healthy male volunteers, who received 2% hypertonic saline solution. Results: Popsicle intake did not result in a statistically significant reduction in vasopressin levels (F=0.876 and p=0.428). However, there was a reduction in the hormonal physiological profile of vasopressin from 7.1 pg/ml to 5.8 pg/ml after the first two interventions. Osmolality concentration changed from 270.65 to 286.51 mOsm/kg, with no statistical difference (F=2.207; p=0.09). Ice popsicles significantly reduced thirst intensity (F=10.00; p=0.001) and thirst discomfort (F=10.528; p <0.001). Conclusion: There was a reduction in thirst intensity and discomfort after the use of the 20 ml ice popsicle. There was no statistical difference for vasopressin and osmolality. However, there was a reduction in the hormonal physiological profile of vasopressin during 30 minutes of intervention.

RESUMEN Objetivo: Evaluar los efectos del picolé de hielo sobre el perfil hormonal de la vasopresina, la osmolaridad, y la intensidad y el malestar de la sed. Método: Estudio casi-experimental pre- y pos-test, realizado en laboratorio. Nueve varones voluntarios sanos recibieron solución salina endovenosa al 2% y un picolé de hielo de 20 ml cada 15 minutos. Resultados: Ingerir el picolé no derivó en una caída estadísticamente significativa del nivel de vasopresina (F=0,876 y p=0,428). Entretanto, se registró una reducción en el perfil hormonal de la vasopresina de 7,1 pg/ml a 5,8 pg/ml después de las dos intervenciones. La osmolaridad plasmática se modificó de 270,65 a 286,51 mOsm/kg sin diferencia estadística (F=2,207; p=0,09). Se registraron reducciones en la intensidad (F=10,00 y p= 0,001) y en el malestar de la sed (F= 10,528; p<0,001). Conclusión: Se registraron reducciones en la intensidad y el malestar de la sed después de la intervención. No hubo diferencia estadística para la vasopresina y la osmolaridad. De esta manera, se observa la reducción en el perfil fisiológico de la vasopresina durante los 30 minutos de la intervención.

RESUMO Objetivo: Avaliar efeitos do picolé de gelo sobre perfil hormonal de vasopressina, osmolaridade, intensidade e desconforto da sede. Método: Quase-experimental, pré e pós-teste, realizado em laboratório. Nove voluntários saudáveis receberam solução salina endovenosa 2% e um picolé de gelo 20 ml a cada 15 minutos. As variáveis foram coletadas em cinco momentos. Resultados: Ingestão do picolé não resultou queda estatisticamente significativa da vasopressina (F = 0,876 e p = 0,428). Houve redução no perfil hormonal da vasopressina de 7,1 pg/ml para 5,8 pg/ml após duas intervenções. Osmolaridade plasmática alterou de 270,65 para 286,51 mOsm/kg, sem diferença estatística (F=2,207; p= 0,09). Houve redução da intensidade (F=10,00 e p= 0,001) e desconforto da sede (F=10,528; p < 0,001). Conclusão: Houve redução na intensidade e desconforto da sede. Não houve diferença estatística para vasopressina e osmolaridade. Observou-se redução no perfil fisiológico da vasopressina durante 30 minutos de intervenção.

Predictive value of plasma copeptin level for diagnosis and mortality of pulmonary embolism

SUMMARY OBJECTIVE: Early diagnosis and risk stratification may provide a better prognosis in pulmonary embolism (PE). Copeptin has emerged as a valuable predictive biomarker in various cardiovascular diseases. The aim of this study was to determine the levels of copeptin in patients with acute PE and to evaluate its relationship with disease severity and PE-related death. METHODS: Fifty-four patients and 60 healthy individuals were included in this study. Copeptin concentrations and right ventricular dysfunction were analyzed. The correlation between copeptin levels and hemodynamic and echocardiographic parameters was examined. After these first measurements, patients were evaluated with PE-related mortality at the one-year follow-up. RESULTS: The copeptin levels were higher in PE patients than in the control group (8.3 ng/mL vs 3.8 ng/mL, p<0.001). Copeptin levels were found to be significantly higher in patients with PE-related death and right ventricular dysfunction (10.2 vs 7.5 ng/ml, p=0.001; 10.5 vs 7.5 ng/ml, p=0.002, respectively). When the cut-off value of copeptin was ≥5.85, its sensitivity and specificity for predicting PE were 71.9% and 85.0%, respectively (AUC=0.762, 95% CI=0.635-0.889, p<0.001). CONCLUSIONS: The copeptin measurement had moderate sensitivity and specificity in predicting the diagnosis of PE, and the copeptin level was significantly higher in patients with PE-related death at the one-year follow-up. Copeptin may be a useful new biomarker in predicting diagnosis, risk stratification, and prognosis of PE.

RESUMO OBJETIVO: O diagnóstico precoce e a estratificação de risco podem proporcionar um melhor prognóstico em casos de embolia pulmonar (EP). A copeptina surgiu como um valioso biomarcador preditivo de várias doenças cardiovasculares. O objetivo deste estudo é determinar os níveis de copeptina em pacientes com EP aguda e avaliar a sua relação com a severidade da doença e mortes relacionadas à EP. MÉTODOS: Um total de 54 pacientes e 60 indivíduos saudáveis foram incluídos neste estudo. As concentrações de copeptina e disfunções ventriculares direitas foram analisadas. A correlação entre os níveis de copeptina e parâmetros ecocardiográficos e hemodinâmicos foi examinada. Após essas primeiras medições, os pacientes foram avaliados em relação à mortalidade relacionada à EP após um ano. RESULTADOS: Os níveis de copeptina foram maiores em pacientes com EP do que no grupo de controle (8,3 ng/mL vs 3,8 ng/mL, p<0,001). Os níveis de copeptina eram significativamente maiores em pacientes com mortes relacionadas à EP e disfunção ventricular direita (10,2 vs 7,5 ng/ml, p=0,001; 10,5 vs 7,5 ng/ml, p=0,002, respectivamente). Com um valor de corte ≥5,85 para a copeptina, sua sensibilidade e especificidade preditivas para EP foram 71,9% e 85,0%, respectivamente (AUC=0,762, 95% IC=0,635 - 0,889, p<0,001). CONCLUSÃO: A medição da copeptina teve sensibilidade e especificidade preditivas moderadas para o diagnóstico de EP, e o nível de copeptina foi significativamente maior em pacientes com mortes relacionadas à EP após um ano. A copeptina pode ser um novo biomarcador preditivo útil para o diagnóstico, a estratificação de risco e o prognóstico de PE.

Perpendicular and transverse needling of "Sanyinjiao" (SP6) relieves abdominal pain by regulating arginine vasopressin and its receptor expression levels in uterus and hypothalamus in cold-stasis type dysmenorrhea rats / 针刺研究

OBJECTIVE: To observe the effect of perpendicular and subcutaneous transverse needling at "Sanyinjiao" (SP6) on visceral pain behavior, arginine vasopressin (AVP) content in the serum, uterine tissues, spinal cord and hypothalamus and expression of AVP receptors AVPR1A and AVPR1B in the uterine tissues, spinal cord and hypothalamus in cold-stasis (stasis due to pathogenic cold) type dysmenorrhea rats, so as to explore their mechanisms underlying pain relief. METHODS: Forty female SD rats were randomly divided into blank control, model, perpendicular needling and transverse needling groups, with 10 rats in each group. The cold-stasis dysmenorrhea rat model was established by exposure in a freezer (-25 ℃) for 4 h, once daily for 5 days, and subcutaneous injection of estradiol benzoate (once daily for 10 days) and intra-abdominal injection of oxytocin injection (once). For rats of the two acupuncture groups, acupuncture needles were inserted into the bilateral SP6 perpendicularly or transversely to a depth of about 4-5 mm, and retained for 20 min. The abdominal pain behavior was assessed by recording the writhing latency and scaling the rats' writhing reactions after modeling. The contents of AVP in the serum, uterus, spinal cord and hypothalamus tissues were assayed using ELISA and the expression of AVPR1A and AVPR1B in the uterus, spinal cord and hypothalamus was measured by using Western blot and quantitative real time-PCR, respectively. RESULTS: After mode-ling and compared with the blank control group, the writhing latency was significantly shortened (P0.05). CONCLUSION: Both perpendicular and subcutaneous transverse needling at SP6 have an immediate analgesic effect in cold-stasis type dysmenorrhea rats, which may be related to their effects in regulating AVP levels and its receptor expression in the uterine and hypothalamus.

New insights into the transcriptional regulation of aquaporin-2 and the treatment of X-linked hereditary nephrogenic diabetes insipidus

The kidney collecting duct (CD) is a tubular segment of the kidney where the osmolality and final flow rate of urine are established, enabling urine concentration and body water homeostasis. Water reabsorption in the CD depends on the action of arginine vasopressin (AVP) and a transepithelial osmotic gradient between the luminal fluid and surrounding interstitium. AVP induces transcellular water reabsorption across CD principal cells through associated signaling pathways after binding to arginine vasopressin receptor 2 (AVPR2). This signaling cascade regulates the water channel protein aquaporin-2 (AQP2). AQP2 is exclusively localized in kidney connecting tubules and CDs. Specifically, AVP stimulates the intracellular translocation of AQP2-containing vesicles to the apical plasma membrane, increasing the osmotic water permeability of CD cells. Moreover, AVP induces transcription of the Aqp2 gene, increasing AQP2 protein abundance. This review provides new insights into the transcriptional regulation of the Aqp2 gene in the kidney CD with an overview of AVP and AQP2. It summarizes current therapeutic approaches for X-linked nephrogenic diabetes insipidus caused by AVPR2 gene mutations.

Arginine Vasopressin-Aquaporin-2 Pathway-Mediated Dehydration Effects of Electroacupuncture in Guinea Pig Model of AVP-Induced Eendolymphatic Hydrops / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of electroacupuncture (EA) on endolymphatic hydrops (EH) and the regulation of arginine vasopressin (AVP)-aquaporin-2 (AQP2) pathway in guinea pigs.@*METHODS@#EH was induced in male guinea pigs by an intraperitoneal injection of AVP. For the treatment, EA was delivered to Baihui (GV 20) and Tinggong (SI 19) acupoints, once per day for 10 consecutive days. In histomorphological studies, cochlear hydrops degree was evaluated by hematoxylin-eosin (HE) staining, and then the ratio of scala media (SM) area to SM + scala vestibuli (SV) area (R value) was calculated. In mechanical studies, a comparison of plasma AVP (p-AVP) concentrations, cyclic adenosine monophosphate (cAMP) levels, vasopressin type 2 receptor (V2R) and AQP2 mRNA expressions in the cochlea were compared among groups.@*RESULTS@#EA significantly reduced cochlear hydrops in guinea pigs (P=0.001). EA significantly attenuated the AVPinduced up-regulation of p-AVP concentrations (P=0.006), cochlear cAMP levels (P=0.003) and AQP2 mRNA expression (P=0.016), and up-regulated the expression of V2R mRNA (P=0.004) in the cochlea.@*CONCLUSIONS@#The dehydrating effect of EA might be associated with its inhibition of AVP-AQP2 pathway activation.

JNK/c-Jun signaling pathway mediates arginine vasopressin neuron regeneration by promoting cytoskeleton reconstruction in rats with electrical lesions of the pituitary stalk / 南方医科大学学报

OBJECTIVE@#To investigate the mechanism by which doublecortin promotes the recovery of cytoskeleton in arginine vasopressin (AVP) neurons in rats with electrical lesions of the pituitary stalk (PEL).@*METHODS@#Thirty-two SD rats were randomized into PEL group with electrical lesions of the pituitary stalk through the floor of the skull base (=25) and sham operation group (=7), and the daily water consumption (DWC), daily urine volume (DUV) and urine specific gravity (USG) of the rats were recorded. Four rats on day 1 and 7 rats on each of days 3, 7 and 14 after PEL as well as the sham-operated rats were sacrificed for detection of the expressions of β-Tubulin (Tuj1), doublecortin and caspase- 3 in the AVP neurons of the supraoptic nucleus using immunofluorescence assay and Western blotting.@*RESULTS@#After PEL, the rats exhibited a typical triphasic pattern of diabetes insipidus, with the postoperative days 1-2 as the phase one, days 3-5 as the phase two, and days 6-14 as the phase three. Immunofluorescent results indicated the repair of the AVP neurons evidenced by significantly increased doublecortin expressions in the AVP neurons following PEL; similarly, the expression of Tuj1 also increased progressively after PEL, reaching the peak level on day 7 after PEL. The apoptotic rates of the AVP neurons exhibited a reverse pattern of variation, peaking on postoperative day 3 followed by progressive reduction till day 14. Western blotting showed that the expressions of c-Jun and p-c-Jun were up-regulated significantly on day 3 ( < 0.05) and 7 ( < 0.01) after PEL, while an upregulated p-JNK expression was detected only on day 3 ( < 0.05), as was consistent with the time-courses of neuronal recovery and apoptosis after PEL.@*CONCLUSIONS@#JNK/c-Jun pathway is activated after PEL to induce apoptosis of AVP neurons in the acute phase and to promote the repair of neuronal cytoskeleton by up-regulation of doublecortin and Tuj1 expressions.

Effects and mechanism of injection of glutamate into hypothalamic paraventricular nucleus on visceral pain in chronic visceral hypersensitivity rats / 中华行为医学与脑科学杂志

Objective@#To investigate the effects of glutamate (Glu) injected into hypothalamic paraventricular nucleus (PVN) on visceral pain of chronic visceral hypersensitivity (CVH) rats and its possible mechanism.@*Methods@#Newborn SD rats were given CVH rat model by colorectal distension (CRD) on the 8th, 10th and 12th day after birth. Thirty rats with successful CVH model were randomly divided into CVH model group (CVH group), CVH + injection of saline into PVN group (NS group), CVH+ injection of Glu into PVN (3, 6, and 12 μg Glu, namely G3, G6, and G12, respectively), 6 rats in each group, and 6 SD rats with matching body mass were taken as sham operation group (Sham group). The pain behavior of the rats was evaluated by pain threshold, abdominal withdrawal reflex (AWR) score, and abdominal external oblique muscle electromyography (EMG). The expression of arginine vasopressin (AVP) and the proliferation of colon tissue were detected by immunohistochemical staining. The apoptosis of colon tissue was detected by TUNEL.@*Results@#Compared with the NS group, the pain thresholds of the G3, G6 and G12 groups increased, and the AWR scores and EMG amplitudes decreased. The differences were statistically significant(Pain threshold: t=7.65, 16.31, 24.78, both P<0.05; AWR scores: t=-2.98, -4.77, -7.29, both P<0.05; EMG amplitudes: t=-3.06, -5.75, -8.92, both P<0.05). Compared with the Sham group, the expression of AVP in PVN of the CVH group and NS group decreased ((42.63±5.20) %, (18.67±2.94) %, (17.53±2.47) %; t=6.95, t=7.56, both P<0.05). The expression of AVP was increased after different doses of Glu into PVN, and the AVP level in G12 group ((18.15±6.49)%) was higher than that of NS group, the difference was statistically significant (t=-4.21, P<0.05). Compared with the Sham group, the expression of PCNA in colonic mucosal cells of the CVH group and NS group decreased ((65.48±1.68) %, (18.39±1.67) %, (17.69±1.68) %; t=34.35, t=34.80, both P<0.05). The expression of PCNA was increased after different doses of Glu injected into PVN, and the PCNA level in G12 group ((59.91±5.63)%) was higher than that of NS group, the difference was statistically significant (t=-12.44, P<0.05). Compared with the Sham group, the expression of apoptotic cells in colonic mucosal cells of the CVH group and NS group increased ((23.38±11.40)%, (83.79±3.57)%, (80.91±2.47)%; t=-8.77, t=-8.54, both P<0.05). The expression of apoptotic cells was decreased after different doses of Glu into PVN, and the G12 group was ((18.15±6.49) %). Compared with NS group, the difference was statistically significant (t=15.65, P<0.05).@*Conclusion@#Injection of Glu into hypothalamic PVN can alleviate the visceral pain behaviors in CVH rats, and its mechanism may be related to arginine vasopressin.

Effects and mechanism of injection of glutamate into hypothalamic paraventricular nucleus on viscer-al pain in chronic visceral hypersensitivity rats / 中华行为医学与脑科学杂志

Objective To investigate the effects of glutamate (Glu) injected into hypothalamic pa-raventricular nucleus (PVN) on visceral pain of chronic visceral hypersensitivity (CVH) rats and its possi-ble mechanism. Methods Newborn SD rats were given CVH rat model by colorectal distension (CRD) on the 8th,10th and 12th day after birth. Thirty rats with successful CVH model were randomly divided into CVH model group (CVH group),CVH + injection of saline into PVN group (NS group),CVH+ injection of Glu into PVN (3,6,and 12 μg Glu,namely G3,G6,and G12,respectively),6 rats in each group,and 6 SD rats with matching body mass were taken as sham operation group (Sham group). The pain behavior of the rats was evaluated by pain threshold,abdominal withdrawal reflex (AWR) score,and abdominal external ob-lique muscle electromyography (EMG). The expression of arginine vasopressin (AVP) and the proliferation of colon tissue were detected by immunohistochemical staining. The apoptosis of colon tissue was detected by TUNEL. Results Compared with the NS group, the pain thresholds of the G3, G6 and G12 groups in-creased,and the AWR scores and EMG amplitudes decreased. The differences were statistically significant (Pain threshold:t=7. 65,16. 31,24. 78,both P<0. 05;AWR scores:t=-2. 98,-4. 77,-7. 29,both P<0. 05;EMG amplitudes:t=-3. 06,-5. 75,-8. 92,both P<0. 05). Compared with the Sham group,the expression of AVP in PVN of the CVH group and NS group decreased ((42. 63±5. 20) %,(18. 67±2. 94) %,(17. 53± 2. 47) %; t=6. 95,t=7. 56,both P<0. 05). The expression of AVP was increased after different doses of Glu into PVN,and the AVP level in G12 group ((18. 15±6. 49)%) was higher than that of NS group,the difference was statistically significant (t=-4. 21,P<0. 05). Compared with the Sham group,the expression of PCNA in colonic mucosal cells of the CVH group and NS group decreased ((65. 48±1. 68) %,(18. 39± 1. 67) %,(17. 69±1. 68) %;t=34. 35,t=34. 80,both P<0. 05). The expression of PCNA was increased after different doses of Glu injected into PVN,and the PCNA level in G12 group ((59. 91±5. 63)%) was higher than that of NS group,the difference was statistically significant (t=-12. 44,P<0. 05). Compared with the Sham group,the expression of apoptotic cells in colonic mucosal cells of the CVH group and NS group increased ((23. 38±11. 40)%,(83. 79± 3. 57)%,(80. 91± 2. 47)%;t=-8. 77,t=-8. 54,both P<0. 05). The expression of apoptotic cells was decreased after different doses of Glu into PVN,and the G12 group was ((18. 15±6. 49) %). Compared with NS group,the difference was statistically significant ( t=15. 65,P<0. 05). Conclusion Injection of Glu into hypothalamic PVN can alleviate the visceral pain be-haviors in CVH rats,and its mechanism may be related to arginine vasopressin.

Effects of Androgen on Social Behavior of Mice and Underlying Mechanisms / 中国药学杂志

OBJECTIVE: To investigate the effect of androgen on social behavior of male mice and underlying mechanisms. METHODS: After sham or gonadectomy (GDX) operation under deep anesthesia, adolescent (4-week-old) ICR male mice were divided into sham operation group (Sham), gonadectomy group (GDX), and gonadectomy with testosterone propionate (TP, 0.5, 1 mg•kg-1•d-1) supplementation group (GDX+TP)(TP supplementation was continued until the end of the experiment). By 13-week-old, social behaviors were tested. Testosterone levels in serum and the brain as well as arginine vasopressin (AVP) level in the brain were analyzed by ELISA. Androgen receptor (AR) level in the brain was analyzed by Western blot. Morphology of accessory olfactory bulb was detected by paraffin section. AVP expression in amygdala was detected by immunofluorescence. RESULTS: TP supplementation reversed GDX-induced inhibition of sexual behavior and invasive aggressive behavior. TP improved the social recognition ability rather than the general sense of smell of GDX mice. TP supplementation increased the level of testosterone in the brain and in serum and the expression of AR in the brain of GDX mice. TP increased the cell density of mitral cell layer, a projecting neuron in accessory olfactory bulb and elevated the level of AVP in the amygdala brain area. CONCLUSION: Androgen promotes social recognition by increasing the expression of AR in the brain, cell density in the mitral cell layer in accessory olfactory bulb, and AVP level in the amygdala, thus affecting social behavior of adult male mice.

The predictive analysis of action mechanism for classic TCM excellent prescriptions of Danggui Buxue decoction on diabetes with TCMIP / 中国药理学通报

To explore the pharmacodynamic material basis and mechanism of the classic TCM excellent prescriptions(cTCMep) Danggui Buxue decoction, so as to provide more choices for the prevention and treatment of diabetes mellitus (DM). Methods With the integrative pharmacology of traditional Chinese medicine (TCMIP) , we predicted the pharmacodynamic material basis and mechanisms of the cTCMep Danggui Buxue decoction for treatment of DM. Results The 50 " Astragalus-Angelica" components in the cTCMep Danggui Buxue decoction directly or indirectly acted on 60 key drug targets. These drug targets restored the disease imbalance network of DM and its complications by acting on 30 major regulatory pathways such as nervous-endocrine system, gap junction, hormone signaling pathways, and cardiovascular circulatory system. The main components of Astragalus membranaceus membranaceus involved in the prevention and treatment of DM were astragalosides, astragalosides and alavonoids. The main components involved in the prevention and treatment of DM in Angelica sinensis were organic acids such as ferulic acid, oil components such as (3-sweet myrrh, stigmasterol-|3-D-glucoside, smbelliferol and scopolamine. Conclusions The 50 " Astragalus-Angelica" components in the cTCMep Danggui Buxue decoction may play a role in preventing and treating DM through the AVPR1A, AVPR1B and AVPR2 (AVPR: Arginine vasopressin receptor, three subtypes), of which Astragalus membranaceu is the key component.

Effects of Tianxiang capsule on neurotransmitters and hormone level in rats with motion sickness / 国际中医中药杂志

Objective To investigate the effects of Tianxiang capsule on Neurotransmitters and Hormone Level of rats with motion sickness. Methods Male SD rats were randomly divided into six groups, including blank control group, model control group, positive drug control group, low-dose, mid-dose and high-dose Tianxiang capsule groups with the method of random digital table, and every group had 10 mice. Except the normal group, the rats in the other groups were intragastrically pre-administered for 1 hour, and the low, medium and high doses of Tianxiang capsule were 0.91, 1.82, 3.64 g/kg, the positive drug control group was given scopolamine 1 mg/kg, and then the rat motion sickness model was induced by a rotary stimulation device. After the modeling, the feces, urine, standing hair, trembling were immediately observed and recorded, and the halo response index of the rats was calculated. The blood from the heart puncture was taken and the vestibular nucleus were put on the ice. Then, the content of histamine (HIS) in the vestibular nucleus and plasma was detected by ELISA. The expression of plasma cortisol (Cort) and arginine vasopressin (AVP) were measured by radioimmunoassay. Results Compared with the model control group, the motion sickness index of rats with low, medium and high doses of Tianxiang capsule (6.56 ± 2.16, 6.10 ± 1.35, 4.46 ± 2.50 vs. 8.90 ± 2.61) significantly decreased (P<0.05 or P<0.01). The HIS content in the vestibular nucleus (12.70 ± 3.86 μg/L, 11.45 ± 1.57 μg/L, 10.02 ± 1.30 μg/L vs. 17.50 ± 4.82 μg/L) significantly decreased (P<0.05 or P<0.01). The plasma content of HIS (4.24 ± 1.75 μg/L vs. 7.69 ± 3.06 μg/L), Cort (286.90 ± 8.72 ng/ml vs. 329.26 ± 29.04 ng/ml) and AVP (16.54 ± 2.48 pg/ml vs. 22.35 ± 3.08 pg/ml) in the high doses of Tianxiang capsule significantly decreased (P<0.05 or P<0.01). Conclusions The Tianxiang capsule could effectively reduce the motion sickness index of rats with motion sicknes, which might be related to the down-regulation of HIS in Vestibule Nucleus and HIS, Cort and AVP in plasma.

The clinical application of arginine vasopressin in pediatric disease / 中国小儿急救医学

Arginine vasopressin (AVP),a peptide hormone produced in the supraoptic nucleus and paraventricular nucleus of hypothalamus,mainly used in treating gastrointestinal bleeding and central diabetes insipidus in the past.Recent years,low-dose AVP infusion can help stabilize hemodynamics,fluid manage-ment and decrease the dosage of catecholamine use,also decrease complication occurrence of catecholamine. Now,the clinical use of AVP in vasodilatory shock,cardiopulmonary resuscitation and cardiovascular surgery has been increasingly emphasized.

Arginine vasopressin reverses fever induced by lipopolysaccharide in rats and its effect on hyperalgesia / 中国病理生理杂志

AIM: To investigate the effect of peripheral administration of arginine vasopressin (AVP) on lipopolysaccharide (LPS)-induced fever and hyperalgesia in rats and its relationship with interleukine-1β (IL-1β) and prostaglandin E2 (PGE2).METHODS: The core temperature (Tc), brown adipose tissue (BAT) temperature and activity were measured by telemetry in adult male Sprague-Dawley rats at an ambient temperature of 23 ℃ during a 12 h light/12 h dark photoperiod (lights on at 06:00 and lights off at 18:00).The rats were intraperitoneally injected with LPS (50 μg/kg), AVP (10 μg/kg) or V1a vasopressin receptor antagonist (V1a antagonist, 30 μg/kg) at 10:00 or 11:30.Hyperalgesia was assessed by measuring the latency to withdraw a hindpaw from radiant heat (Hargreaves test).The concentrations of IL-1β and PGE2 in the serum were tested by ELISA.RESULTS: Intraperitoneal administration of LPS induced periods of biphasic fever accompanied by hyperalgesia.AVP reversed LPS-induced fever, and decreased the hyperalgesia and BAT thermogenesis.Peripheral administration of V1a antagonist enhanced the fever produced by LPS, but did not affect the hyperalgesia.AVP significantly attenuated LPS-induced IL-1β and PGE2 production.CONCLUSION: Peripheral administration of AVP reverses LPS-induced fever and decreases hyperalgesia by reduction of BAT thermogenesis and inhibition of IL-1β and PGE2.Endogenous AVP attenuates the fever induced by LPS, but does not affect the nociceptive thresholds.

Change of serum sST2 and copeptin levels in patients with chronic heart failure and their correlation / 心血管康复医学杂志

Objective:To observe change of peripheral serum levels of soluble ST 2 (sST2 ) and copeptin in patients with chronic heart disease (CHF) ,and explore their diagnostic value for heart failure . Methods :A total of 80 CHF patients ,who hospitalized in our department of cardiology from Jun 1st ,2015 to Dec 1st ,2015 ,were selected as CHF group .Meanwhile ,another 30 patients with cardiac neurosis or arrhythmia were regarded as normal cardiac function group .According to NYHA classification ,CHF group was further divided into class II group (n= 22 ) , class III group (n=32) and class IV group (n=26) .Serum sST2 and copeptin levels were measured and compared a‐mong all groups ,and their correlation was analyzed .Results:Compared with normal cardiac function group ,there were significant rise in serum levels of sST2 [(0.27 ± 0.09) ng/ml vs .(1.18 ± 0.81) ng/ml] and copeptin [(1239.64 ± 229.98) pg/ml vs .(1987.16 ± 426.84) pg/ml] in CHF group , P< 0.01 both .Compared with class II group , there were significant rise in serum levels of sST2 [ (0.46 ± 0.17) ng/ml vs .(0.77 ± 0.18) ng/ml vs .(2.31 ± 0.29) ng/ml] and copeptin [ (1625.61 ± 522.13) pg/ml vs .(2103.15 ± 340.74) pg/ml vs .(2194.31 ± 332.97) pg/ml] in class III and class IV group ,and those of class IV group were significantly higher than those of class III group , P<0.05 or <0.01 .Pearson product‐moment correlation analysis indicated that serum sST2 level was significant posi‐tively correlated with serum copeptin level in CHF group (r=0.66 ,P=0.005) .Conclusion:Serum sST2 and copep‐tin levels are closely associated with severity of heart failure .They can be used as markers for heart failure ,which is worth extending .