[Analysis of the necessity of anticoagulation therapy and influencing factors of stent occlusion after transjugular intrahepatic portosystemic shunt].

Objective: To explore the necessity of anticoagulation therapy and influencing factors of stent occlusion after transjugular intrahepatic portosystemic shunt. Methods: The basic information, laboratory test results, preoperative portal venous pressure, postoperative anticoagulation time, postoperative stent stenosis or occlusion, followed-up and other data of all patients who underwent TIPS surgery in Shandong Provincial Hospital from 2010 to 2019 were retrospectively analyzed. Data were analyzed using t-test, χ2 test, and multivariate analysis (logistic regression and Cox-regression-analysis). Results: A total of 280 cases were finally included in the study, of which 110 (39.3%) had stent stenosis or occlusion, and 170 (60.7%) had stent patency. New or worsening ascites were identified in 194 cases during the follow-up period, including 14 (31.1%) cases in the stent stenosis or occlusion group and 19 (12.8%) cases in the stent patency group. Univariate analysis showed that presence or absence of platelet (P=0.037) and total bilirubin (P=0.038) were correlated with stent stenosis or occlusion. Postoperative continuous anticoagulation was correlated with stent blockage (P=0.029) in patients with partial portal vein thrombosis. Postoperative continuous anticoagulation and stent occlusions were not significantly correlated in patients with preoperative portal cavernoma and preoperative portal vein patency (P=0.848; P=0.744). Multivariate analysis results showed that whether long-term anticoagulation (P=0.017), all-cause rebleeding (P<0.001), postoperative significant hepatic encephalopathy (P<0.012), and postoperative new or worsening ascites (P<0.001) was significantly associated with stent occlusion (P<0.05), while platelets (P=0.134), total bilirubin (P=0.229), international normalized ratio (P=0.436), and portal vein pressure (P=0.230) were not significantly associated with stent occlusion after surgery. Conclusion: In patients with partial portal vein thrombosis before surgery, continuous anticoagulation for 30 days post-TIPS therapy can effectively prevent stent stenosis or occlusion; while in patients with portal vein patency, portal cavernoma and complete portal vein blockage before surgery, postoperative anticoagulation has no significant effect on stent stenosis or occlusion.

Factors affecting the first-born child's attitude toward the second child in Shanghai.

OBJECTIVE: This study aimed to investigate factors associated with the attitude of the first-born child (FBC) towards the birth of the second child in China, in order to provide guidance for the preparation of a multi-child family. SUBJECTS AND METHODS: A questionnaire, including requesting information for gender, age, health, parents' education and household income, was randomly distributed participating FBCs. The anxiety level, psychological, emotional and behavioral manifestations of the FBCs were evaluated. F-test and t-test were performed to identify significant factors associated with the FBC's attitude towards the second child. Out of the 65 surveys distributed, 61 were recovered and analyzed. RESULTS: Our analysis indicated that female FBCs (total score vs. male, 45.38±4.02 vs. 42.95±4.29, p=0.031) with parents of higher education (p=0.020 in psychological and p=0.025 in behavioral manifestations) were in general more receptive to the second child. The FBC's health, school years and household income were not significant factors associated with their attitude towards the second child (p>0.05). Our analysis also found that the FBC's attitude towards the arrival of the second child was largely positive, and older children with parents of higher education were more likely to be receptive to the second child. CONCLUSIONS: The findings of this study could provide guidance for parents to better prepare the psychological, emotional and behavioral states of the FBCs and family, enabling the FBCs with a positive attitude towards the second child. This finding is instrumental to promote a harmonious family atmosphere and growth environment for both the first- and second-born children.

Correlation between carotid atherosclerotic plaque properties and serum levels of lncRNA CCAT2 and miRNA-216b.

OBJECTIVE: The purpose of this study was to uncover the clinical values of serum long non-coding RNA (lncRNA) CCAT2 and miRNA-216b in the properties of carotid atherosclerotic plaques. PATIENTS AND METHODS: Patients with carotid atherosclerotic plaques were assigned into stable plaque group (n=60) and unstable plaque (n=75) group based on their examination results of cervical contrast-enhanced CT examination. Maximal plaque thickness (MAPT) and intima-media thickness (IMT) in each group were determined. Serum levels of lncRNA CCAT2 and miRNA-216b in patients with carotid atherosclerotic plaques were detected by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Moreover, the correlation between serum levels of CCAT2 and miRNA-216b was analyzed by Pearson's correlation analysis. Besides, potential correlations of serum levels of CCAT2 and miRNA-216b with MAPT and IMT in patients with carotid atherosclerotic plaques were assessed as well. RESULTS: Results revealed that MAPT and IMT were markedly higher in unstable plaque group than those in stable plaque group. Serum level of CCAT2 was higher in unstable plaque group, while miRNA-216b was lower than those in stable group. A negative correlation was identified between serum levels of CCAT2 and miRNA-216b. In addition, CCAT2 level was positively correlated with IMT and MAPT in patients with carotid atherosclerotic plaques, while miRNA-216b level was negatively correlated with them. CONCLUSIONS: Detection of serum levels of CCAT2 and miRNA-216b could be applied for predicting the rupture of carotid atherosclerotic plaques. They may be potential biomarkers predicting ischemic stroke.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with lobaplatin and docetaxel to treat synchronous peritoneal carcinomatosis from gastric cancer: Results from a Chinese center.

BACKGROUND: This work was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel to treat peritoneal carcinomatosis (PC) from gastric cancer (GC). METHODS: A total of 50 consecutive GC PC patients treated by 52 CRS+HIPEC procedures with lobaplatin 50 mg/m(2) and docetaxel 60 mg/m(2) in 6000 mL of normal saline at (43 ± 0.5) °C for 60 min. The primary endpoint was overall survival (OS), and the secondary endpoints were perioperative safety profiles. RESULTS: At the median follow-up of 22.5 (range, 5.1-50.7) months, the median OS was 14.3 (95% CI 7.6-21.0) months, and the 1-, 2-, and 3-year survival rates were 58%, 40%, and 32%, respectively. Mortality and serious adverse event (grade 3-5) morbidity rates in postoperative 30 days were 0.0% and 23.1%, respectively. Univariate analysis identified 4 parameters with significant effects on OS: completeness of cytoreduction (CC) 0-1, normal (N) the preoperative tumor markers level (TM), adjuvant chemotherapy ≥6 cycles, and peritoneal cancer index ≤20. However, multivariate analysis identified CC0-1, perioperative TM (N), adjuvant chemotherapy ≥6 cycles as the independent predictor for better survival. CONCLUSIONS: CRS+HIPEC with lobaplatin and docetaxel to treat selected GC PC could improve OS, with acceptable perioperative safety.

Association between ARNTL (BMAL1) rs2278749 polymorphism T >C and susceptibility to Alzheimer disease in a Chinese population.

In the present study, we examined whether the ARNTL (BMAL1) rs2278749 T/C polymorphism was associated with the susceptibility to Alzheimer disease (AD). This case-control study examined the genotypes of apolipoprotein E (APOE e4) and BMAL1 rs2278749 T/C using restriction fragment length polymorphism and the TaqMan assay, respectively. A total of 296 unrelated AD patients and 423 control subjects were included. Both in the entire sample and in APOE e4 non-carriers, the prevalence of T carriers in BMAL1 rs2278749 T/C in AD patients was significantly higher than that in control subjects (entire sample: χ(2) = 12.950, P < 0.0001; APOE e4 non-carriers: χ(2) = 13.094, P < 0.0001). Both in the entire sample and in APOE e4 non-carriers, the prevalence of TT genotypes 2278749 in AD patients was also significantly higher than that in control subjects (entire sample: χ(2) = 7.765, P = 0.024; APOE e4 non-carriers: χ(2) = 13.062, P < 0.0001). However, among APOE e4 carriers, the difference in the prevalence of T carriers or TT genotypes in the BMAL1 rs2278749 T/C between patients and control subjects presents was not significant (T carriers: χ(2) = 0.078, P = 0.851 or TT genotypes: χ(2) = 2.576, P = 0.325). Among APOE e4 non-carriers, T carriers in the BMAL1 rs2278749 T/C were associated with a high susceptibility to AD, but among APOE e4 carriers, the association between AD and BMAL1 rs2278749 T/C was not significant.

Application of SRAP markers in the identification of Stylosanthes guianensis hybrids.

Sequence-related amplified polymorphism (SRAP) is a new molecular marker technology developed based on polymerase chain reaction. The authenticity of 84 progenies of 8 hybrid combinations of Stylosanthes guianensis was identified by SRAP markers to select the true hybrids used in the present study. A total of 35 SRAP primer combinations were selected from the parents of 8 hybrid combinations. The selected polymorphism primer combinations were applied to identify the authenticity of all progenies. The male parents of the primer combinations had specific markers, whereas the female parents did not. 68 progenies exhibited male parent-specific bands, which were identified as true hybrids. The rest of the progenies were considered self-hybrids because of the absence of male parent-specific bands. The results of hybrid identification provided solid evidence for further studies of hybrids and demonstrated SRAP molecular markers as a useful technology for assessing the purity of S. guianensis hybrids.

PD plus error-dependent integral nonlinear controllers for robot manipulators with an uncertain Jacobian matrix.

In framework of traditional PID controllers, there are only three parameters available to tune, as a result, performance of the resulting system is always limited. As for Cartesian regulation of robot manipulators with uncertain Jacobian matrix, a scheme of PID controllers with error-dependent integral action is proposed. Compare with traditional PID controllers, the error-dependent integration is employed in the proposed PID controller, in which more parameters are available to be tuned. It provides additional flexibility for controller characteristics and tuning as well, and hence makes better transient performance. In addition, asymptotic stability of the resulting closed-loop system is guaranteed. All signals in the system are bounded when exogenous disturbances and measurement noises are bounded. Numerical example demonstrates the superior transient performance of the proposed controller over the traditional one via Cartesian space set-point manipulation of two-link robotic manipulator.

Reactive gliosis and neuroinflammation in rats with communicating hydrocephalus.

UNLABELLED: Reactive gliosis has been implicated in injury and recovery patterns associated with hydrocephalus. The roles that these mechanisms play in the pathophysiology of hydrocephalus are still not clear in terms of cytopathology and gene expression. In this paper, we investigated the relationship between reactive gliosis and neuroinflammation of hydrocephalic rats of different severity at both cellular and molecular levels. Therefore 35 adult SD (standard deviation) rats were randomly divided into the normal group (n=5), the sham operation group (n=5) and the model group (n=25). Hydrocephalic rat models were induced by intraventricular injections of 3% kaolin, and the ventricular dilatation was examined by MRI (magnetic resonance imaging) at 2-week postoperation. Then the model group was subdivided into the mild group (n=5), the moderate group (n=7) and the severe group (n=9) according to the degree of ventricular dilatation. While IL-18 (interlukin 18), GFAP (glial fibrillary acidic protein), and Iba-1 (ionized calcium binding adaptor molecule-1) were detected by ELISA (enzyme-linked immunosorbent assay), RT-PCR, immunohistochemistry, Western blot and correlation analysis were conducted at the same time. According to the result comparison between the normal group and the sham operation group, the ventricle of model group was obviously enlarged (P<0.01). The expression of GFAP and Iba-1 was increased (P<0.05) in brain tissue of the model group and IL-18 was also increased in CSF (cerebrosinal fluid) sample of model group. It was revealed by correlation analysis that the increase was positively correlated with the severity of ventricular dilatation. CONCLUSION: These results indicate that gliosis and inflammation continue to rise dramatically in experimental hydrocephalus and can be regarded as the main factors of hydrocephalus. Regulating the level of gliosis and alleviating inflammation may provide new therapeutic methods of hydrocephalus.

Marital status and risk for late life depression: a meta-analysis of the published literature.

This study assessed the relationship between marital status and the risk for depression in people ≥ 55 years old. Using the Medline™, EMBASE™ and Cochrane Library databases, clinical studies that published data on the association between marital status and risk of depression among individuals aged ≥ 55 years were identified. A quantitative meta-analysis of 24 cross-sectional and eight longitudinal studies was performed. Compared with married elderly people, unmarried elderly people had a higher risk for depression (odds ratio [OR], 1.55; relative risk [RR], 1.36). Compared with married elderly people, the widowed elderly people (OR 1.49; RR 1.71), divorced people (RR 2.14) and never-married people (OR 1.32) had a higher risk for depression. Among elderly unmarried people, widowed people had a higher risk for depression than those who never married (OR 1.51). In conclusion, being unmarried was an important risk factor for depression in elderly people.

RNAi-mediated silencing of a novel Ascaris suum gene expression in infective larvae.

In the present study, the potential of RNA interference (RNAi) as a gene silencing tool and the resultant effects on Ascaris suum larval development was examined by targeting a gene (represented by the EST 06G09) specifically expressed in the infective larvae of A. suum. BALB/c mice were infected with RNAi-treated larvae. The results showed that the target gene was silenced after soaking for 72 h, and the survival rate of the RNAi-treated larvae was reduced by 17.25% (P<0.01). A significant difference (P<0.05) was detected in the numbers of larvae collected from the livers and lungs of infected mice 4 days after infection with untreated larvae (164.29 ± 21.51) and RNAi-treated larvae (71.43 ± 14.35). Significant differences (P<0.01) were also found in the body length and width between untreated larvae (480 ± 105.77 µm for length and 23.93 ± 3.72 µm for width) and RNAi-treated larvae (400.57 ± 71.31 µm for length and 20.20 ± 2.43 µm for width). These results show that the gene represented by EST 06G09 may play a role in the development of A. suum larvae.

Seroprevalence of Toxoplasma gondii infection in breeding sows in Western Fujian Province, China.

The objective of the present investigation was to estimate the seroprevalence T. gondii infection in breeding sows in Western Fujian Province, the People's Republic of China. Sera collected from breeding sows during 2006-2007 from 6 different regions in Western Fujian Province were assayed for antibodies to T. gondii by an indirect hemagglutination antibody (IHA) test. Antibodies to T. gondii were detected in 87 (14.38%) of 605 breeding sows. Differences in seroprevalence were observed between sampling regions, ranging from 10.14% to 37.50%. The present investigation demonstrated that the prevalence of T. gondii infection in breeding sows in Fujian Province was high. Integrated control strategies and measures should be implemented to prevent and control T. gondii infection in breeding sows, which in turn will have significant implications for the control of human infection with T. gondii in this province.

Cognitive behavioural therapy and reminiscence techniques for the treatment of depression in the elderly: a systematic review.

Psychotherapy, including cognitive behavioural therapy (CBT), reminiscence and general psychotherapy (GPT), is viewed as effective treatment for depression, but its efficacy in older people is not well defined. This systematic review included 14 randomized controlled trials that assessed the efficacy of psychotherapy for treating depression in elderly people (> or = 55 years). The results of this meta-analysis showed that, compared with placebo, psychotherapy was more effective in reducing depression scores (standardized mean difference -0.92; 95% confidence interval -1.21, -0.36). Subgroup analysis showed that CBT, reminiscence and GPT were all more effective than placebo; psychotherapy as an adjunct to antidepressant medication did not increase effectiveness. There was no significant difference between CBT and reminiscence in improving depression. A higher drop-out rate was observed in studies that did not include psychotherapy versus those that did, although this difference was not statistically significant. Thus, various general formats of psychotherapy are effective for treating depression in older people, although psychotherapy does not significantly increase the effectiveness of anti-depressant medication.

The relationship among renal injury, changed activity of renal 1-alpha hydroxylase and bone loss in elderly rats with insulin resistance or Type 2 diabetes mellitus.

BACKGROUND AND OBJECTIVE: Chronic kidney disease can lead to a decrease in active vitamin D [1,25-(OH)2D], which may be reversed by 1-alpha hydroxyvitamin D [1-alpha(OH)D]. Renal 1-alpha hydroxylase, expressed in renal tubular epithelial cells, is a key enzyme in the synthesis of 1,25-(OH)2D. 1,25- (OH)2D plays an important role in the regulation of calcium and phosphate metabolism, and its deficiency can result in osteoporosis. Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) are associated with renal injury, decrease in 1,25-(OH)2D and bone loss. The study aimed to explore the relationship among renal injury, decrease in 1,25-(OH)2D and bone loss in the presence of IR or T2DM, as well as the role of renal 1-alpha hydroxylase in the process. MATERIALS AND METHODS: Fifty 18-month-old male Wistar rats were randomized into 5 groups: normal control group (Group N), IR group (Group I), T2DM group (Group D), No.1 treatment group (Group T1), and No.2 treatment group (Group T2), 10 in each group. High-fat diet was administered to induce IR, while high-fat diet and low-dose streptozotocin were jointly applied to induce T2DM. Rats in Groups T1 and T2 were treated with vitamin D and 1-alpha(OH)D, respectively. At week 12, IR was determined by the use of euglycemic insulin clamp technique for rats in each group, and then glucose infusion rate (GIR) was calculated. Meanwhile, urinary albumin (UA), serum 25-(OH)D and 1,25-(OH)2D levels were determined by radioimmunoassay. After the rats were sacrificed, bone mineral density (BMD) in femoral bone and lumbar vertebrae was measured by the use of dual energy X-ray absorption. RESULTS: The GIR in Group N was significantly higher than that of the other 4 groups (p<0.01). Compared with Groups N (p<0.01) or I (p<0.05), the UA levels in Groups D, T1, and T2 were obviously higher. The UA level in Group I was higher than that of Group N, but the difference was not significant (p>0.05). In Groups D and I, the UA levels showed a negative correlation with GIR. No significant difference was observed in the levels of 25-hydroxyvitamin D [25-(OH)D]. The levels of 1,25-(OH)2D in Groups D and T1 were markedly lower than that of Groups N or T2 (p<0.01). The 1,25-(OH)2D level in Group I was lower than that of Group N (p<0.05), but higher than that of Group D (p<0.01). The 1,25-(OH)2D level in Group T2 was nearly equivalent to that of Group N. In Groups D and I, the levels of 1,25-(OH)2D were negatively correlated with UA, and positively correlated with GIR. The BMD levels in lumbar vertebrae or femoral bone in Groups D and T1 were similar, but both were lower than that of Groups T2 (p<0.05) and N (p<0.01). The BMD levels were lower in Groups I and T2 compared with that of Group N (p<0.05), but higher than that of Groups D and T1 (p<0.05). The BMD levels in lumbar vertebrae or femoral bone in Groups I and D were positively correlated with GIR. The BMD level in lumbar vertebrae or femoral bone in Group D showed negative correlation with UA. CONCLUSION: In elderly rats with T2DM or IR, renal injury may cause decreased activity of renal 1-alpha hydroxylase, which may result in bone loss and disturbance in VD metabolism, mainly manifesting as a significant reduction in the 1,25-(OH)2D level.

The relationship between renal injury and change in vitamin D metabolism in aged rats with insulin resistance or type 2 diabetes mellitus.

Insulin resistance (IR), IR treated with vitamin D, IR treated with 1alpha-hydroxyvitamin D (1alpha-(OH)D), type 2 diabetes mellitus (T2DM), T2DM treated with vitamin D and T2DM treated with 1alpha-(OH)D were studied in animal models using aged Wistar rats. Glucose infusion rates and levels of urinary albumin (UA), serum 25-hydroxyvitamin D (25-(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured. T2DM rats had higher UA than IR or normal rats, and levels of 25-(OH)D in all models weresimilar. IR rats had higher 1,25-(OH)2D levels than T2DM rats, and had lower 1,25-(OH)2D levels than normal rats. Treating IR or T2DM rats with vitamin D had no effect on 25-(OH)D or 1,25-(OH)2D. Administration of 1alpha-(OH)D significantly increased 1,25-(OH)2D in IR rats to above-normal levels, and significantly increased 1,25-(OH)2D in T2DM rats to normal levels. In IR or T2DM, abnormal vitamin D metabolism is characterized by 1,25-(OH)2D deficiency and is related to renal injury.

Characterization of Fasciola samples from different host species and geographical localities in Spain by sequences of internal transcribed spacers of rDNA.

In the present study, 25 samples representing Fasciola (Platyhelminthes: Trematoda: Digenea) from nine host species and 19 geographical locations in Spain were characterized genetically by sequences of the first (ITS-1) and second (ITS-2) internal transcribed spacers (ITS) of nuclear ribosomal DNA (rDNA). The ITS rDNA was amplified from individual liver flukes by polymerase chain reaction (PCR), and the amplicons were sequenced directly. The lengths of the ITS-1 and ITS-2 sequences were 422 and 362 bp, respectively, for all Spanish liver fluke samples sequenced. Comparison of the ITS sequences of the Spanish Fasciola samples examined in the present study with that of Fasciola hepatica, Fasciola gigantica and the "intermediate Fasciola" revealed that all Spanish Fasciola samples examined represent the single species of F. hepatica, with only slight sequence variation in the ITS-2 (1/362, 0.3%) among the sequenced samples, but the sequence variation was not related to particular host species and/or geographical origins of the samples. The Spanish F. hepatica examined differed from Fasciola from elsewhere by two nucleotides in the ITS-2, which provided genetic marker for the differentiation of Spanish F. hepatica from Fasciola from other geographical localities. These results have implications for studying the population genetic structure of the Spanish F. hepatica and for the diagnosis and control of the disease it causes.

Direct identification of propargyl radical in combustion flames by vacuum ultraviolet photoionization mass spectrometry.

We have developed an effusive laser photodissociation radical source, aiming for the production of vibrationally relaxed radicals. Employing this radical source, we have measured the vacuum ultraviolet (VUV) photoionization efficiency (PIE) spectrum of the propargyl radical (C(3)H(3)) formed by the 193 nm excimer laser photodissociation of propargyl chloride in the energy range of 8.5-9.9 eV using high-resolution (energy bandwidth = 1 meV) multibunch synchrotron radiation. The VUV-PIE spectrum of C(3)H(3) thus obtained is found to exhibit pronounced autoionization features, which are tentatively assigned as members of two vibrational progressions of C(3)H(3) in excited autoionizing Rydberg states. The ionization energy (IE = 8.674 +/- 0.001 eV) of C(3)H(3) determined by a small steplike feature resolved at the photoionization onset of the VUV-PIE spectrum is in excellent agreement with the IE value reported in a previous pulsed field ionization-photoelectron study. We have also calculated the Franck-Condon factors (FCFs) for the photoionization transitions C(3)H(3) (+)(X;nu(i),i = 1-12)<--C(3)H(3)(X). The comparison between the pattern of FCFs and the autoionization peaks resolved in the VUV-PIE spectrum of C(3)H(3) points to the conclusion that the resonance-enhanced autoionization mechanism is most likely responsible for the observation of pronounced autoionization features. We also present here the VUV-PIE spectra for the mass 39 ions observed in the VUV synchrotron-based photoionization mass spectrometric sampling of several premixed flames. The excellent agreement of the IE value and the pattern of autoionizing features of the VUV-PIE spectra observed in the photodissociation and flames studies has provided an unambiguous identification of the propargyl radical as an important intermediate in the premixed combustion flames. The discrepancy found between the PIE spectra obtained in flames and photodissociation at energies above the IE(C(3)H(3)) suggests that the PIE spectra obtained in flames might have contributions from the photoionization of vibrationally excited C(3)H(3) and/or the dissociative photoionization processes involving larger hydrocarbon species formed in flames.

Expression of testis specific ankyrin repeat and SOCS box-containing 17 gene.

Human ASB-17 (Ankyrin Repeat and SOCS Box-containing 17) is a recently identified gene belonging to the ASB family, isolated from testis cDNA library. Human ASB-17 is expressed exclusively in testis among 16 tissues, revealed by Northern blot. Mouse Asb-17 was shown to be expressed from the third week post birth to adult by semi-quantitative RT-PCR analysis. In situ hybridization on frozen sections demonstrated that Asb-17 is expressed in spermatogenic cells in adult mouse, but not in Leydig cell and epididymis in adult mouse. ASB-17 proteins are highly conserved in mammals including human, mouse, rat, Canis familiaris and Macaca fascicularis.

1-Alkyl-3-amino-5-aryl-1H-[1,2,4]triazoles: novel synthesis via cyclization of N-acyl-S-methylisothioureas with alkylhydrazines and their potent corticotropin-releasing factor-1 (CRF(1)) receptor antagonist activities.

Cyclizations of alkylhydrazines with N-acyl-S-methylisothioureas, readily synthesized from acyl chlorides, sodium thioisocyanate, dialkylamines then methyl iodide in a one-pot reaction, gave 1-alkyl-3-dialkylamino-5-phenyltriazoles 7 as major products. The regioisomers were assigned through the use of NOE NMR experiments. While bearing a N-bis(cyclopropyl)methyl-N-propylamino group, this series of compounds shows very good binding affinity on the human CRF(1) receptor. Among them, 1-methyl-3-[N-bis(cyclopropyl)methyl-N-propylamino]-5-(2,4-dichlorophenyl)-1H-[1,2,4]triazole 7a had the best binding affinity for the CRF(1) receptor (K(i)=9 nM).

Stimulus induced pH changes in cochlear implants: an in vitro and in vivo study.

Large pH changes have been shown to be potentially harmful to tissue. The present study was designed to examine stimulus induced changes in pH for a variety of stimulus parameters both in vitro and in vivo, in order to ensure that stimulation strategies for neural prostheses result in minimal pH change. Stimulation using charge balanced biphasic pulses at intensities both within and well above maximum clinical levels for cochlear implants (0.025-0.68 microC per phase), were delivered to platinum electrodes in vitro [saline, phosphate buffered saline (PBS), or saline with human serum albumin (HSA)], and in vivo (scala tympani). Stimulus rates were typically varied from 62.5 to 1000 pulses per second (pps), although rates of up to 14,500 pps were used in some experiments. The pH level was recorded using a pH indicator (Phenol red) or pH microelectrodes. While electrical stimulation at intensities and rates used clinically showed no evidence of a pH shift, intensities significantly above these levels induced pH changes both in vitro and in vivo. The extent of pH change was related to stimulus rate and intensity. In addition, pH change was closely associated with the residual direct current (dc) level. As expected, stimulation with capacitive coupling induced little dc and a minimal pH shift. Moreover, no pH shift was observed using alternating leading phase pulse trains at intensities up to 0.68 microC per phase and 1000 pps. Saline with HSA or buffered solutions dramatically reduced the extent of pH shift observed following stimulation in unbuffered inorganic saline. Reduced pH shift was also observed following in vivo stimulation. These findings provide an insight into mechanisms of safe change injection in neural prostheses.

Reduction in excitability of the auditory nerve following electrical stimulation at high stimulus rates: V. Effects of electrode surface area.

High rate intracochlear electrical stimulation at high intensities can induce significant reductions in the excitability of the auditory nerve as measured by a decrement in the amplitude of the electrically evoked auditory brainstem response (EABR). Such changes are primarily associated with stimulus induced neuronal activity, although direct current (DC) can also contribute. We examined the extent of stimulus induced change in auditory nerve excitability using large surface area platinum electrodes ('high-Q' electrodes). These electrodes have a surface area approximately 70 times greater than standard Pt electrodes of the same geometric area, resulting in lower DC and charge density (charge/electrode surface area) for a common stimulus. Guinea pigs were bilaterally implanted with either high-Q or standard Pt electrodes, and unilaterally stimulated for 2 h using stimulus intensities of 12 dB or 20-30 dB above EABR threshold (0.34 microC/phase) at stimulus rates of 200, 400, or 1000 pulses per second (pps). EABRs were recorded before and following the acute stimulation. While there were significant reductions in EABR amplitudes and elevated EABR thresholds following stimulation at 12 dB above threshold using 400 and 1000 pps delivered to standard Pt electrodes, there were fewer or no significant changes in the post-stimulus EABR amplitude and threshold using high-Q electrodes under equivalent stimulus conditions. At a higher stimulus intensity (20-30 dB above EABR threshold), no reduction in EABR amplitude was observed at 200 pps for both stimulating electrodes. However, EABRs were reduced significantly at 400 and 1000 pps. There was significantly greater EABR recovery following stimulation using high-Q electrodes compared with standard Pt electrodes at 400 (P<0.05) and 1000 pps (P<0.05). These data indicate that large surface area electrodes can significantly reduce stimulus induced changes in auditory nerve excitability, and may therefore have important clinical application.