[Two cases of dichlorvos poisoning complicated with gastric perforation].

Severe acute dichlorvos poisoning is characterized by rapid onset, swift disease progression and serious complications. It frequently involves multiple organ failure (central, respiratory and circulatory systems), severe acidosis, and rare occurrences of gastric perforation. When secondary gastric perforation occurs, treatment becomes difficult and the prognosis of patients is poor. Thus, early and sufficient gastrointestinal decontamination is crucial. This article presented two cases of gastric perforation secondary to dichlorvos poisoning and discussed the causes of gastric perforation, as well is clinical diagnostic and treatment methods.

[Two case report of death from acute compound chlorfenapyr poisoning].

Chlorfenapyr is a moderately dangerous insecticide widely used in agriculture. The mortality of acute poisoning patients is high, and there is no effective treatment. This paper retrospectively analyzes the clinical data of two cases of compound chlorfenapyr poisoning. The main symptoms of the patients were high fever, sweating, gradual coma, increased creatine kinase and myoglobin, with delayed poisoning symptoms. Despite comprehensive treatment, both patients died eventually. It indicated that chlorfenapyr was highly toxic and had a high mortality. In addition to routine symptomatic treatment for patients with acute poisoning, blood purification treatment should be actively carried out in the early stage.

Ubiquitous defect-induced density wave instability in monolayer graphene.

Quantum materials are notoriously sensitive to their environments, where small perturbations can tip a system toward one of several competing ground states. Graphene hosts a rich assortment of such competing phases, including a bond density wave instability ("Kekulé distortion") that couples electrons at the K/K' valleys and breaks the lattice symmetry. Here, we report observations of a ubiquitous Kekulé distortion across multiple graphene systems. We show that extremely dilute concentrations of surface atoms (less than three adsorbed atoms every 1000 graphene unit cells) can self-assemble and trigger the onset of a global Kekulé density wave phase. Combining complementary momentum-sensitive angle-resolved photoemission spectroscopy (ARPES) and low-energy electron diffraction (LEED) measurements, we confirm the presence of this density wave phase and observe the opening of an energy gap. Our results reveal an unexpected sensitivity of the graphene lattice to dilute surface disorder and show that adsorbed atoms offer an attractive route toward designing novel phases in two-dimensional materials.

Expression level of miRNA-210-3p in cervical cancer and its prognostic potential.

OBJECTIVE: The purpose of this study was to detect the expression level of microRNA-210-3p (miRNA-210-3p) in cervical cancer (CC) tissues and its clinical significance. PATIENTS AND METHODS: Expression levels of miRNA-210-3p in collected CC tissues, normal cervical tissues and cervical intraepithelial neoplasia (CIN) tissues (CIN I, CIN II, and CIN III) were tested by reverse transcriptase-polymerase chain reaction (RT-PCR). The relationship between miRNA-210-3p level and clinical data of CC patients was analyzed. Moreover, the receiver operating characteristic (ROC) was introduced for assessing the diagnostic potential of miRNA-210-3p in CC. RESULTS: Results revealed that miRNA-210-3p level was higher in CC tissues relative to normal cervical tissues and CIN tissues. Its expression was not correlated with age, pathological subtype, and tumor size of CC patients. However, miRNA-210-3p level was closely linked to FIGO stage, tumor differentiation, and lymphatic metastasis in CC. Based on depicted ROC, miRNA-210-3p was able to distinguish CC from normal cervical tissues and CIN tissues. CONCLUSIONS: MiRNA-210-3p is upregulated in CC, and its level is closely correlated with FIGO stage, tumor differentiation, and lymphatic metastasis in CC patients. Besides, miRNA-210-3p produces a pronounced diagnostic efficacy, so it can be utilized as a novel hallmark for diagnosing CC and predicting the disease progression.

LncRNA SNHG1 promotes cell progression and metastasis via sponging miR-377-3p in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most famous fatal malignancies in the world. LncRNA SNHG1 has been shown to play roles in the development and progression of various tumors, including HCC. The present study aims to investigate the deeper molecular mechanisms of SNHG1 in HCC. The expression levels of SNHG1 and miR-377-3p were detected by qRT-PCR in HCC tissues and cells. MTT assay was used to examine cell proliferation. Cell apoptosis was evaluated by detecting the apoptotic rate and the protein level of C-caspase 3 using flow cytometry and western blot assays. The protein levels of EMT-related proteins (E-cadherin, N-cadherin, and Vimentin) were measured by western blot. Cell migration and invasion were examined by transwell assay. Xenograft analysis was performed to explore the tumor growth in vivo. The binding sites of SNHG1 and miR-377-3p were predicted by the online software and confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay. We found that SNHG1 was markedly upregulated in HCC tissues and cells. Knockdown of SNHG1 induced apoptosis and inhibited proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) of HCC cells. SNHG1 knockdown suppressed the tumor growth of HCC in vivo. SNHG1 directly bound to miR-377-3p. Knockdown of miR-377-3p attenuated the effect of SNHG1 knockdown on proliferation, apoptosis, migration, invasion, and EMT of HCC cells. In conclusion, SNHG1 inhibited apoptosis and induced proliferation, migration, invasion, and EMT by sponging miR-377-3p in HCC, which indicated that SNHG1 may be a potential biomarker and therapeutic target for HCC treatment.

Room temperature strain-induced Landau levels in graphene on a wafer-scale platform.

Graphene is a powerful playground for studying a plethora of quantum phenomena. One of the remarkable properties of graphene arises when it is strained in particular geometries and the electrons behave as if they were under the influence of a magnetic field. Previously, these strain-induced pseudomagnetic fields have been explored on the nano- and micrometer-scale using scanning probe and transport measurements. Heteroepitaxial strain, in contrast, is a wafer-scale engineering method. Here, we show that pseudomagnetic fields can be generated in graphene through wafer-scale epitaxial growth. Shallow triangular nanoprisms in the SiC substrate generate strain-induced uniform fields of 41 T, enabling the observation of strain-induced Landau levels at room temperature, as detected by angle-resolved photoemission spectroscopy, and confirmed by model calculations and scanning tunneling microscopy measurements. Our work demonstrates the feasibility of exploiting strain-induced quantum phases in two-dimensional Dirac materials on a wafer-scale platform, opening the field to new applications.

[Comparison of preoperative planning of radioactive seed implantation for pelvic wall recurrent gynecological malignant tumors between 3D-printing non-coplanar template and 3D-printing coplanar template].

Objective: To compare the difference of preoperative planning parameters between 3D-printing non-coplanar template (3D-PNCT) and 3D-printing coplanar template (3D-PCT) in the treatment of pelvic wall recurrent gynecological malignant tumor with radioactive seeds implantation, and to guide the clinical application. Methods: From January 2016 to March 2018, 33 patients with pelvic wall recurrent gynecological malignant tumor were treated with radioactive seeds implantation assisted by 3D-printing template and in Peking University Third Hospital. All patients underwent 3D-PNCT and 3D-PCT preoperative planning. The D(90) of target remained similar for the same patient. The parameters were compared with Wilcoxon test or Kruskal-Wallis test. Results: D(90) was similar between the two groups (P>0.05). The number of inserting needles through intestine and bone in 3D-PNCT group was less than that in 3D-PCT group (0 (0-13), 0 (0-25), Z=-2.941, P<0.05;0 (0-3), 0 (0-25), Z=-2.232, P<0.05). Conclusion: For patients with gynecological malignancies with pelvic recurrence, both of the two peroperative plans could achieve prescription dose, but 3D-PNCT is more safer.

[Efficacy and dosimetric analysis of (125)I seeds implantation for pelvic recurrent cervical cancer after radiotherapy under CT guidance].

Objective: To evaluate the relationship of dosimetry parameters and efficacy of (125)I seeds implantation for pelvic recurrent cervical cancer (PRCC) after external beam radiotherapy(EBRT) under CT guidance. Methods: A retrospective analysis was made on 30 PRCC patients after EBRT in Peking University Third Hospital with (125)I seeds implantation under CT guidance. Postoperative plans were made to evaluate the dosimetric parameters. Kaplan-Meier method was used to calculate local progression free survival (LPFS) rate and overall survival (OS) rate, and Log-rank test and Cox regression were used for univariate and multivariate analysis. Results: The 1-year and 2-year LPFS rate was 39.4% and 22.5%, respectively. The 1-year and 2-year OS rate was 57.3% and 27.4%, respectively. On postoperative plan, D(90) was (132±47) Gy, D(100) was (51±24) Gy, V(100) was 88%±10%, V(150)was 69%±15%, V(200) was 51%±18%.LPFS time would be longer while D(90) ≥105 Gy or D(100) ≥ 55 Gy or V(100) ≥ 91% (all P<0.05). D(100) was significantly related to LPFS (P<0.05). But these dosimetry parameters got no effect on OS. Conclusions: LPFS time of (125)I seeds implantation for PRCC after EBRT under CT guidance would be longer when D(90)≥105 Gy or D(100)≥ 55 Gy, or V(100)≥ 91%. D(100) is an independent factor related to LPFS.

Characterization of a novel capsaicin/heat ongoing pain model.

BACKGROUND: Human experimental pain models provide an important translational link between pre-clinical models and clinical pain. Using topical capsaicin and continuous heat application, the novel capsaicin/heat ongoing pain (CHOP) model induces long-lasting experimental pain of which the perceived intensity can be individually adjusted. METHODS: In the CHOP model, capsaicin or control cream is applied to a 10 × 10 cm skin area and a heating pad is applied over the area after cream removal. Two experiments in healthy participants were performed for model characterization. In Experiment 1, a constant temperature was applied for 60 min; in Experiment 2, temperature was adjusted to maintain a constant perceived intensity for 60 min. RESULTS: Experiment 1: across participants, constant temperature induced initial habituation followed by an increase in sensation back to baseline. Cluster analysis revealed that half the participants sensitized to the constant temperature, while the other half did not. The degree of sensitization was related to the baseline pain unpleasantness, relative to pain intensity. Experiment 2: constant perceived intensity was achieved in the painful and a non-painful control condition. The two conditions did not differ regarding possibly confounding variables, including blood pressure, heart rate, inflammation or physiological stress as measured by surrogate markers. Secondary allodynia and hyperalgesia were reported more following painful compared to control stimulation. Sensitizers as determined in Experiment 1 were also more pain sensitive in Experiment 2. CONCLUSION: The CHOP model reproduces some aspects of clinical pain, such as longer duration, sensitization, secondary allodynia and hyperalgesia. SIGNIFICANCE: Here we demonstrate a novel pain model that can be applied for up to an hour without tissue damage. The CHOP model allows for investigation of primary and secondary hyperalgesia as well as top-down influences on sensitization, thereby providing an experimental model that can be used to assess clinically-oriented questions.

[Clinical effect of alanyl glutamine in the treatment of patients with gastrointestinal function obstacle caused by severe phorate poisoning].

Objective: To observe the therapeutic efficacy of alanyl glutamine injection on patients with gastrointestinal function obstacle caused by severe phorate poisoning. Methods: A total of 80 eligible patients with gastrointestinal function obstacle caused by severe phorate poisoning were randomly divided into the control group (n=40) and treatment group (n=40) . The control group was treated with the conventional therapy, which included forbidden diet, atropine, pralidoxime iodide, anti-inflammatory, albumin infusion, ω-3 fish oil fat emulsion, protection of organs function, blood perfusion, and Fat Emulsion, Amino Acids (17) and Glucose Injection. The treatment group was treated with alanyl glutamine injection plus the conventional therapy. To observe the time of recovering to normal of gastrointestinal function between the two groups, compared the AChE activity and changes of prealbumin, albumin and total protein of the two groups respectively. Furthermore, the total atropine dosage, the total pralidoxime iodide dosage and ICU stay time between the two groups were also compared. Results: The gastrointestinal function recovery time of patients in the treatment group was less than the control group, the difference was statistically significant (P<0.05) . From the third day of treatment, the serum cholinesterase activity of the treatment group was higher than the control group, the difference was statistically significant (P<0.05) . On the 5th day and 10th day of the treatment, the prealbumin, albumin and total protein of the treatment group were significantly higher than these indexes of the control group in the same period, the difference were statistically significant (P<0.05) . The total atropine dosage, the total pralidoxime iodide dosage and ICU stay time in the treatment group were lower than the control group, the difference were statistically significant (P<0.05) . Conclusion: Alanyl glutamine injection has a great therapeutic effect for gastrointestinal function obstacle patients caused by severe phorate poisoning.

Circulating miR-210 as a diagnostic and prognostic biomarker for colorectal cancer.

microRNA-210 (miR-210), the master hypoxamir, is overexpressed and generally exhibits oncogenic properties in most human solid tumours, including colorectal cancer (CRC). However, the status of circulating miR-210 in CRC is still unknown. This study aims to assess the clinical significance of circulating miR-210 in CRC. Using (reverse transcription quantitative PCR) RT-qPCR analysis, we compared the expression levels of circulating miR-210 in serum of 268 CRC patients and 102 healthy controls, and found that serum miR-210 was significantly higher in CRC than in healthy controls (P < 0.001). The area under the receiver operating characteristic curve (AUC) of circulating miR-210 to detect CRC was 0.821, with a sensitivity of 74.6% and a specificity of 73.5%. The AUC of circulating miR-210 showed significantly higher detection capability than that of carcinoembryogenic antigen (P < 0.05). Kaplan-Meier analysis demonstrated that increased serum miR-210 level correlated with reduced overall survival (OS) and disease-free survival (DFS) (P = 0.008 and P = 0.008 respectively). Cox analysis indicated circulating miR-210 was an independent prognostic factor for OS and DFS. Taken together, our data suggested that circulating miR-210 could be a potential non-invasive marker for diagnosis and prognosis of CRC.

Impact of the number of prior lines of therapy and prior perioperative chemotherapy in patients receiving salvage therapy for advanced urothelial carcinoma: implications for trial design.

BACKGROUND: The differential impact of the number of prior lines of therapy and the setting of prior therapy (perioperative or metastatic) is unclear in advanced urothelial carcinoma. PATIENTS AND METHODS: Ten phase II trials of salvage chemotherapy, biologic agent therapy, or both, enrolling 731 patients, were available. Data on the number of prior lines of therapy and the setting of prior therapy were required in addition to known previously recognized prognostic factors: time from prior chemotherapy, hemoglobin level, performance status, and liver metastasis status. Cox proportional hazards regression was used to evaluate the association of the number of prior lines and prior perioperative therapy with overall survival (OS) as the primary clinical endpoint. Trial was a stratification factor. RESULTS: A total of 711 patients were evaluable. The overall median progression-free survival and OS were 2.7 and 6.8 months, respectively. The number of prior lines was 1 in 559 patients (78.6%), 2 in 111 (15.6%), 3 in 29 (4.1%), 4 in 10 (1.4%), and 5 in 2 (0.3%). Prior perioperative chemotherapy was given to 277 (39.1%) and chemotherapy for metastatic disease to 454 (64.1%). The number of prior lines was not independently associated with OS (hazard ratio, 0.99; 95% CI, 0.86-1.14). Prior perioperative chemotherapy was a favorable factor for OS on univariate but not multivariate analysis. CONCLUSION: The number of prior lines of therapy and prior perioperative chemotherapy were not independently prognostic in patients with urothelial carcinoma receiving salvage therapy. Adoption of these data in salvage therapy trials should enhance accrual, the interpretability of results, and drug development.

A calcitonin receptor (CALCR) single nucleotide polymorphism is associated with growth performance and bone integrity in response to dietary phosphorus deficiency.

Although concerns over the environmental impact of excess P in the excreta from pig production and governmental regulations have driven research toward reducing dietary supplementation of P to swine diets for over a decade, recent dramatic increases in feed costs have further motivated researchers to identify means to further reduce dietary P supplementation. We have demonstrated that genetic background impacts P utilization in young pigs and have identified genetic polymorphisms in several target genes related to mineral utilization. In this study, we examined the impact of a SNP in the calcitonin receptor gene (CALCR) on P utilization in growing pigs. In Exp. 1, 36 gilts representing the 3 genotypes identified by this CALCR SNP (11, 12, and 22) were fed a P-adequate (PA) or a marginally P-deficient (approximately 20% less available P; PD) diet for 14 wk. As expected, P deficiency reduced plasma P concentration, bone strength, and mineral content (P < 0.05). However, the dietary P deficiency was mild enough to not affect the growth performance of these pigs. A genotype x dietary P interaction (P < 0.05) was observed in measures of bone integrity and mineral content, with the greatest reduction in bone strength and mineral content due to dietary P deficiency being associated with the allele 1. In Exp. 2, 168 pigs from a control line and low residual feed intake (RFI) line were genotyped for the CALCR SNP and fed a PA diet. As expected, pigs from the low RFI line consumed less feed but also gained less BW when compared with the control line (P < 0.05). Although ADFI did not differ between genotypes, pigs having the 11 genotype gained less BW (P < 0.05) than pigs having the 12 or 22 genotypes. Pigs of the 11 and 12 genotypes had bones that tolerated greater load when compared with animals having the 22 genotype (P < 0.05). A similar trend was observed in bone modulus and ash % (P < 0.10). These data are supportive of the association of this CALCR SNP with bone integrity and its response to dietary P restriction. Although the allele 1 is associated with greater bone integrity and mineral content during adequate P nutrition, it is also associated with the greatest loss in bone integrity and mineral content in response to dietary P restriction. Understanding the underlying genetic mechanisms that regulate P utilization may lead to novel strategies to produce more environmentally friendly pigs.

Incorporating correlation for multivariate failure time data when cluster size is large.

We propose a new estimation method for multivariate failure time data using the quadratic inference function (QIF) approach. The proposed method efficiently incorporates within-cluster correlations. Therefore, it is more efficient than those that ignore within-cluster correlation. Furthermore, the proposed method is easy to implement. Unlike the weighted estimating equations in Cai and Prentice (1995, Biometrika 82, 151-164), it is not necessary to explicitly estimate the correlation parameters. This simplification is particularly useful in analyzing data with large cluster size where it is difficult to estimate intracluster correlation. Under certain regularity conditions, we show the consistency and asymptotic normality of the proposed QIF estimators. A chi-squared test is also developed for hypothesis testing. We conduct extensive Monte Carlo simulation studies to assess the finite sample performance of the proposed methods. We also illustrate the proposed methods by analyzing primary biliary cirrhosis (PBC) data.

Response to dietary phosphorus deficiency is affected by genetic background in growing pigs.

Concern over the environmental effect of P excretion from pig production has led to reduced dietary P supplementation. To examine how genetics influence P utilization, 94 gilts sired by 2 genetic lines (PIC337 and PIC280) were housed individually and fed either a P-adequate diet (PA) or a 20% P-deficient diet (PD) for 14 wk. Initially and monthly, blood samples were collected and BW recorded after an overnight fast. Growth performance and plasma indicators of P status were determined monthly. At the end of the trial, carcass traits, meat quality, bone strength, and ash percentage were determined. Pigs fed the PD diet had decreased (P < 0.05) plasma P concentrations and poorer G:F (P < 0.05) over the length of the trial. After 4 wk on trial, pigs fed the PD diet had increased (P < 0.05) plasma 1,25(OH)(2)D(3) and decreased (P < 0.05) plasma parathyroid hormone compared with those fed the PA diet. At the end of the trial, pigs fed the PD diet had decreased (P < 0.05) BW, HCW, and percentage fat-free lean and tended to have decreased LM area (P = 0.06) and marbling (P = 0.09) and greater (P = 0.12) 10th-rib backfat than pigs fed the PA diet. Additionally, animals fed the PD diet had weaker bones and also decreased (P < 0.05) ash percentage and increased (P < 0.05) concentrations of 1alpha-hydroxylase and parathyroid hormone receptor mRNA in kidney tissue. Regardless of dietary treatment, PIC337-sired pigs consumed more feed and gained more BW than their PIC280-sired counterparts (P < 0.05) during the study. The PIC337-sired pigs also had greater (P < 0.05) HCW, larger (P < 0.01) LM area, and tended to have (P = 0.07) greater dressing percentage. Meat from the PIC337-sired pigs also tended to have greater (P = 0.12) concentrations of lactate but decreased (P = 0.07) concentrations of total glucose units 24 h postslaughter. Although plasma 1,25(OH)(2)D(3) concentrations were elevated (P < 0.05) in all the animals fed the PD diet, this elevation due to P deficiency tended (P = 0.09) to be greater in the PIC337-sired pigs after 12 wk on the treatment. The PIC337-sired pigs had stronger (P < 0.01) bones with greater ash percentage than the PIC280-sired pigs. The difference in the strength of the radii between the PIC337-sired pigs fed the PA and PD diets was greater than their PIC280-sired counterparts, which resulted in sire line x treatment interactions (P < 0.05). These data indicate differing mechanisms of P utilization between these genetic lines. Elucidating these mechanisms may lead to strategies to increase efficiency of growth in a more environmentally friendly manner.

Effect of dietary phosphorus and its interaction with genetic background on global gene expression in porcine muscle.

Environmental concerns and costs associated with dietary phosphorus (P) supplementation have lead to attempts to minimize the amount of P added to swine diets. In addition to its requirement for bone growth, dietary P is also necessary for muscular growth. To examine the effects of genetic background and dietary P on global gene expression in the muscle of young pigs, we utilized muscle tissue from 36 gilts sired from two different sire lines. These animals were fed either a P adequate, P deficient or P repletion diets for 14 days and showed differences in growth performance and bone integrity in response to the interaction of genetic background and dietary P. Total RNA from the loin muscle of these animals was obtained for microarray analysis. Significant differences (p<0.01) in gene expression were seen based on the effect of sire line (339 genes), dietary P (18 genes) and the interaction between sire line and dietary P (31 genes). The microarray data were validated by semi-quantitative real-time PCR. These results support our hypothesis that genetic background and dietary P treatment can affect the homeorhetic control of P metabolism in pigs. Genes identified as differentially expressed in this study may be excellent candidate genes for additional work to elucidate genotype specific P requirements as well as to identify a genetic background that can maintain superior growth in a more environmentally friendly manner.

Repeat induced abortions and contraceptive practices among unmarried young women seeking an abortion in China.

OBJECTIVE: To determine the rates of repeated abortion and contraceptive use among unmarried young women seeking an abortion in China. METHODS: We used an anonymous self-administered questionnaire at abortion clinics in Beijing, Changsha, and Dalian from January to September 2000. RESULTS: Of 4547 unmarried young women seeking an abortion, 33.0% reported having had one previous induced abortion. Of those who had had more than one abortion, only 29.7% used a contraceptive method at their first sexual intercourse after the procedure; and of the 446 women who chose contraception, 41.3% used the traditional methods of withdrawal or rhythm. Although 65.0% of the young women had used condoms at least once, only 9.6% did so consistently and correctly; 47.7% of the current pregnancies were associated with nonuse of any contraceptive, and 52.3% were related to contraceptive failure. CONCLUSION: The rate of unmarried young women seeking repeated abortions was high in China on 2000. The rate of consistent condom use was low, and the rate of contraceptive failure was higher.

Simultaneous stimulation of Fas-mediated apoptosis and blockade of costimulation prevent autoimmune diabetes in mice induced by multiple low-dose streptozotocin.

Type I diabetes is the result of a selective destruction of insulin-producing beta cells in pancreatic islets by autoreactive T cells. Depletion of autoreactive T cells through apoptosis may be a potential strategy for the prevention of autoimmune diabetes. Simultaneous stimulation of the Fas-mediated pathway and blockade of costimulation by a CTLA4-Fas ligand (FasL) fusion protein has been reported to lead to enhanced in vitro apoptosis of peripheral lymphocytes. To test the feasibility of CTLA4-FasL-based gene therapy to prevent autoimmune diabetes, we developed a recombinant adenovirus containing the human CTLA4-FasL gene (AdCTLA4-FasL). A single injection of 2 x 10(8) plaque-forming units of AdCTLA4-FasL via the tail vein of mice greatly reduced the incidence of autoimmune diabetes (13%, n=15) induced by multiple low-dose streptozotocin. AdCTLA4-FasL administration abrogated pancreatic insulitis, significantly increased apoptosis of pancreatic T-lymphocytes, and altered splenocyte response to mitogenic and antigenic stimulation. These results indicate the therapeutic potential of simultaneous stimulation of the Fas-mediated pathway and blockade of costimulation by adenovirus-mediated CTLA4-FasL gene transfer in the prevention of autoimmune diabetes.

Evaluation of beta-amyloid peptide 25-35 on calcium homeostasis in cultured rat dorsal root ganglion neurons.

Accumulation of beta-amyloid (Abeta) protein in brain is an important characteristic for the etiology of Alzheimer's disease. Of all the possible processes generating the neurotoxic effects by Abeta, disruption of intracellular Ca(2+) homeostasis is the primary event. In this process, various intracellular Ca(2+) regulatory mechanisms are reported to be involved. Using patch-clamp techniques, both low and high voltage activated Ca(2+) channel currents were recorded in the cultured dorsal root ganglion (DRG) neurons. Application of Abeta protein fragment, Abeta(25-35) (2 microM), for 30 s increased the amplitude in both currents. The Abeta-triggered facilitation effect of Ca(2+) channel was found in all the depolarized potentials tested, as shown in the current-voltage relationship. Furthermore, after applying single cell Ca(2+) microfluorometric method, it was found that Abeta(25-35) alone could trigger elevations of intracellular Ca(2+) concentration ([Ca(2+)](i)) level in 90% of the cells tested. The elevation diminished completely by cumulatively adding CdCl(2), NiCl(2), thapsigargin (TG), FCCP and Zn(2+) in the normal bath solution. Combining pharmacological approaches, we found that voltage-dependent Ca(2+) channels, Ca(2+) stores and a putative Zn(2+)-sensitive extracellular Ca(2+) entry, respectively, makes 61.0, 25.1, and 13.9% contribution to the [Ca(2+)](i) increase caused by Abeta. When tested in a Ca(2+)-free buffer, mitochondria was found to contribute 41.3% of Abeta produced [Ca(2+)](i) elevation and the remaining 58.7% was attributed to endoplasmic reticulum (ER) release.

Enhanced cyclosporine-itraconazole interaction with cola in lung transplant recipients.

BACKGROUND: Invasive aspergillosis is a major cause of morbidity and mortality in lung transplant recipients (LTR), occurring in up to 15% of patients post-transplant. The 14% aspergillus incidence at the Cleveland Clinic Foundation prompted institution of universal prophylaxis with oral itraconazole (ICZ) in 1997. We report our experience with two protocols of ICZ administration in non-cystic fibrosis LTR and the interaction with cyclosporine (CSA). METHODS: Group 1 patients (n=12) were administered ICZ capsules in a fasting or fed state, with or without a histamine-2 (H-2) receptor antagonist or proton pump inhibitor. Group 2 patients (n=12) received the same protocol as group I, but in a fed state with a carbonated beverage (cola) to increase acidity in the stomach to enhance absorption of ICZ. The ICZ dose was 200 mg/d, given as one daily dose. A historical control group (n=10) did not receive chemoprophylaxis with ICZ. CSA daily doses, dose intervals, concentration, cost, and random ICZ levels were documented over a 4-month period of time and compared using generalized estimating equations. RESULTS: The daily CSA mg/kg/d dose decreased over time in all three groups, but no differences were found between the three groups. The CSA dosing interval over time was significantly prolonged in group 2 compared to group 1 or the control group (p< or =0.003). Over time, there was no difference in CSA concentration between all groups. There was no difference in cost over time between the three groups; however, the mean cost of CSA therapy was significantly lower in group 2 compared to the control group (p=0.025). Group 2 administered ICZ with cola had greater random blood concentrations of ICZ (p=0.019). CONCLUSIONS: ICZ capsules administered in a fed state with a cola resulted in greater random levels of ICZ, a decrease in cost/d of CSA, and a prolongation of CSA dosing interval. Although daily CSA dosage trended lower in group 2, it did not reach statistical significance. We believe these changes in CSA dosing over time reflect increased absorption of ICZ and recommend verifying ICZ absorption with an itraconazole level, especially when CSA intervals are not prolonged.