[Emergency psychological intervention of acute ammonia leakage event].

Objective: To analyze the situation of emergency psychological intervention in an acute ammonia leakage event, and to provide reference for emergency response. Methods: In August 2020, the emergency treatment of 65 patients admitted by Zhangqiu District People's Hospital Affiliated to Jining Medical College of Shandong Province in June 2019 in the ammonia tank car leakage incident was analyzed, the psychological intervention in emergency after the incident was collected, the anxiety and depression were evaluated by symptom checklist 90 (SCL-90) , and targeted psychological intervention was implemented according to the psychological evaluation results, And analyze the intervention efficiency. Results: Among the 65 patients, there were 52 cases of ammonia stimulation reaction, 11 cases of mild poisoning and 2 cases of moderate poisoning. There were 60 cases of chest tightness and dyspnea, 11 cases of bloody sputum, 58 cases of sore throat, 43 cases of hoarseness, 28 cases of photophobia and tears, 13 cases of blurred vision, 18 cases of nausea and vomiting, and 2 cases of dry and wet rales in the lungs. The scores of somatization, depression, anxiety, hostility, phobia, paranoia and negative coping in patients with mild and moderate poisoning were higher than those in patients with stimulus response (P<0.05) . The effective rate of intervention was 98.7%. Conclusion: Emergency psychological evaluation and intervention in mass public health events are helpful to the treatment of patients.

[The role of abnormal mitochondrial fusion and fission in PBDE-47-induced change in mitochondrial mass in PC12 cells].

Objective: To investigate the effect of 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) on the mitochondrial mass in rat adrenal pheochromocytoma (PC12) cells and the potential mechanisms. Methods: Highly differentiated PC12 cells were divided into control, 1, 10 or 20 µmol/L PBDE-47-treated groups and cultured for 24 h. Transmission electron microscopy was employed to observe the changes in mitochondrial morphology and quantity in PC12 cells. Flow cytometry was used to measure the fluorescence intensity of Nonyl Acridine Orange (NAO) , a fluorescent indicator of mitochondrial membrane cardiolipin, to reflect mitochondria mass. Western blotting was used to determine the expression levels of Mitofusion 1 (Mfn1) and Fission 1 (Fis1) proteins. To further explore the role of abnormal mitochondrial fusion and fission in PBDE-47-induced mitochondrial mass changes, PC12 cells were divided into control group, 5 µmol/L M1 treatment group, 20 µmol/L PBDE-47 treatment group and 5 µmol/L M1+20 µmol/L PBDE-47 combined treatment group and cultured for 24 h, then the fluorescence intensity of NAO and expression levels of Mfn1 and Fis1 proteins were detected. Results: The control group showed numerous mitochondria with normal morphology, while the number of mitochondria decreased after PBDE-47 treatment. Especially, the disappeared cristae, swelling and vacuoles of mitochondria and decreased fluorescence intensity of NAO (P<0.05) were observed in 10 and 20 µmol/L PBDE-47-treated groups. Meanwhile, the expression levels of Mfn1 and Fis1 proteins in the 10 and 20 µmol/L PBDE-47-treated groups were significantly decreased compared with control group (P<0.05) . However, 5 µmol/L M1 co-treatment with 20 µmol/L PBDE-47 significantly increased the levels of Mfn1 and Fis1 proteins and fluorescence intensity of NAO compared with the 20 µmol/L PBDE-47 group (P<0.05) . Conclusion: PBDE-47 can inhibit the mitochondrial fusion and fission process, thus leading to damage of mitochondria mass in PC12 cells.

In situ forming oxidised hyaluronic acid/adipic acid dihydrazide hydrogel for prevention of epidural fibrosis after laminectomy.

Post-operative epidural fibrosis is a biological response after laminectomy that may lead to clinical symptoms, such as radicular pain. An ideal material for prevention of epidural fibrosis should be able to inhibit fibroblast adhesions and reduce formation of scar tissue. An injectable hydrogel would be the material of choice for this purpose, since it could fill an irregular surgical defect completely, gelate in situ and be delivered in a minimally-invasive manner. The objective of this study was to evaluate, in vitro and in vivo, the cytocompatibility and anti-adhesive effect of an oxidised hyaluronic acid/adipic acid dihydrazide (oxi-HA/ADH) hydrogel. Different cell types present in the spine were used to test the cytocompatibility of the hydrogel. The hydrogel extraction medium had no deleterious effects on neural cells (PC-12), but reduced fibroblasts viability (NIH/3T3). Although the hydrogel did not change the release of lactate dehydrogenase from myoblasts (C2C12) and Schwann cells (RSC96), the extraction medium concentration slightly affected the mitochondrial activity of these two cell types. qPCR showed that the hydrogel down-regulated S100a and P4hb expression in NIH/3T3 cells, supporting the hypothesis that the hydrogel might inhibit fibroblast activity. The animal study showed a reduction of scar tissue formation as well as severity of adhesion between scar tissue and the dura mater in a rat laminectomy model. Superficially, the peel-off test showed significantly decreased tenacity. In conclusion, the oxi-HA/ADH hydrogel is a promising injectable and thermosensitive material for prevention of post-operative epidural fibrosis.

Cardiac Sodium Channel Mutations: Why so Many Phenotypes?

The cardiac Na(+) channel (Nav1.5) conducts a depolarizing inward Na(+) current that is responsible for the generation of the upstroke Phase 0 of the action potential. In heart tissue, changes in Na(+) currents can affect conduction velocity and impulse propagation. The cardiac Nav1.5 is also involved in determination of the action potential duration, since some channels may reopen during the plateau phase, generating a persistent or late inward current. Mutations of cardiac Nav1.5 can induce gain or loss of channel function because of an increased late current or a decrease of peak current, respectively. Gain-of-function mutations cause Long QT syndrome type 3 and possibly atrial fibrillation, while loss-of-function channel mutations are associated with a wider variety of phenotypes, such as Brugada syndrome, cardiac conduction disease, dilated cardiomyopathy, and sick sinus node syndrome. The penetrance and phenotypes resulting from Nav1.5 mutations also vary with age, gender, body temperature, circadian rhythm, and between regions of the heart. This phenotypic variability makes it difficult to correlate genotype-phenotype. We propose that mutations are only one contributor to the phenotype and additional modifications on Nav1.5 lead to the phenotypic variability. Possible modifiers include other genetic variations and alterations in the life cycle of Nav1.5 such as gene transcription, RNA processing, translation, posttranslational modifications, trafficking, complex assembly, and degradation. In this chapter, we summarize potential modifiers of cardiac Nav1.5 that could help explain the clinically observed phenotypic variability. Consideration of these modifiers could help improve genotype-phenotype correlations and lead to new therapeutic strategies.

Irritable bowel syndrome and the incidence of colorectal neoplasia: a prospective cohort study with community-based screened population in Taiwan.

BACKGROUND: We aim to report the prevalence of irritable bowel syndrome (IBS) and elucidate the influence of IBS on the incidence of colorectal neoplasm through a community-screening-based, longitudinal follow-up study. METHODS: We enroled 39,384 community residents aged 40 years or older who had participated in a community-based colorectal cancer-screening programme with an immunochemical faecal occult test since 1999. We followed a cohort that was free of colorectal neoplasm (excluding colorectal neoplasm at baseline) to ascertain the incident colorectal neoplasm through each round of screening and used a nationwide cancer registry. Information on IBS was obtained by linking this screened cohort with population-based health insurance claim data. Other confounding factors were also collected via questionnaire or biochemical tests. RESULTS: The overall period prevalence of IBS was 23%, increasing from 14.7% for subjects aged 40-49 years to 43.7% for those aged 70 years and more. After controlling for age, gender and family history of colorectal cancer, screenees who had been diagnosed as having IBS exhibited a significantly elevated level (21%; adjusted hazard ratio (HR)=1.21 (95% CI: 1.02-1.42)) of incident colorectal adenoma compared with those who had not been diagnosed with IBS. A similar finding was noted for invasive carcinoma; however, the size of the effect was of borderline statistical significance (adjusted HR=1.20 (95% CI: 0.94-1.53)). CONCLUSIONS: IBS led to an increased risk for incident colorectal neoplasm.

Saturated fatty acid induces cancer stem cell-like properties in human hepatoma cells.

Hepatic steatosis has been reported to be a risk factor for the development of liver cancer. The underlying mechanism for carcinogenesis remains to be elucidated. It has been postulated that cancer stem cells (CSCs) within tumor tissues are a subset of cells with stem cell properties of self-renewal and undifferentiation. The purpose of this study was to investigate the effects of a saturated fatty acid, palmitate (PA), on CSC-like properties of human hepatoma HepG2 cells. We investigated the effects of PA on HepG2 cells and primary rat hepatocytes (PRH) by exposing them to PA to induce lipid accumulation. Significant fat accumulation was observed by Oil Red O staining in cells exposed to PA, and it was accompanied by significant increase in NFκB (p65) nuclear translocation in HepG2 cells. Notably, PA significantly enhanced the sphere forming ability of HepG2 cells, but not PRH. Furthermore, PA significantly increased stemness gene expressions of Sox2 and Oct4, and sonic hedgehog (Shh) production. Notably, NFκB inhibitors, N-Acetyl-L-cysteine and pyrollidine dithiocarbamate, and a NOX inhibitor, diphenyleneiodonium, significantly attenuated PA-induced sphere forming ability of HepG2 cells. Our results suggest that lipid accumulation may not only induce pro-inflammatory responses in hepatocytes but may also activate CSC-like properties of hepatoma cells through NFκB activation.

Transforming growth factor-ß enhances matrix metalloproteinase-2 expression and activity through AKT in fibroblasts derived from angiofibromas in patients with tuberous sclerosis complex.

BACKGROUND: Patients with tuberous sclerosis complex (TSC) develop fibrous tumours in the brain, skin, kidney, heart and lungs due to TSC1/2 mutations. In the skin, patients develop angiofibromas that have vascular and fibrotic components in which transforming growth factor (TGF)-ß and matrix metalloproteinase (MMP)-2 are important. OBJECTIVES: To investigate if the TGF-ß axis and MMP-2 play an important role in the pathogenesis of TSC angiofibromas. METHODS: Samples from TSC angiofibromas and normal skin were measured for expression of TGF-ß and MMP-2 by immunohistochemistry and real-time polymerase chain reaction. Fibroblasts grown from TSC angiofibromas (TSC fibroblasts) were incubated with TGF-ß. Expression of ERK, AKT and S6K was measured by Western blotting, and MMP-2 expression and activity were determined by enzyme-linked immunosorbent assay and gelatin zymography, respectively. RESULTS: There was an increase in the expression of TGF-ß and MMP-2 in TSC tumours compared with those in normal skin. The baseline expression of MMP-2 was increased in conditioned medium from TSC fibroblasts. In addition, TGF-ß enhanced MMP-2 production and activity, which could be abrogated by pretreatment with an AKT inhibitor (LY294002) but not with rapamycin. Finally, there was a significant colocalization of TGF-ß and MMP-2 in the TSC tumours. CONCLUSIONS: There is an increase of MMP-2 as a result of TGF-ß acting through AKT in TSC tumour cells. This regulation of the TGF-ß-AKT-MMP-2 axis is independent of mammalian target of rapamycin (mTOR) signalling. In addition to targeting the mTOR pathway, targeting TGF-ß simultaneously could block dysregulated tissue remodelling in TSC tumours.

The chondroprotective effects of ferulic acid on hydrogen peroxide-stimulated chondrocytes: inhibition of hydrogen peroxide-induced pro-inflammatory cytokines and metalloproteinase gene expression at the mRNA level.

OBJECTIVE: The objective of the study is to evaluate the effect of ferulic acid (FA), an antioxidant from the Chinese herb Dong-Gui [Chinese angelica, Angelica sinensis (Oliv.) Diels], on the regulation of various genes in hydrogen peroxide-stimulated porcine chondrocytes at the mRNA level. METHODS: The effect of FA and the effective concentration of FA on porcine chondrocytes was evaluated by the lactate dehydrogenase, WST-1, crystal violet assay, and a chemical luminescence assay. Gene expression in hydrogen peroxide-stimulated chondrocytes either pre- or post-treated with FA was evaluated by real-time PCR. RESULTS: Chondrocytes pre-treated with 40 microM FA decreased the hydrogen peroxide-induced interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and MMP-1 and partially restored SOX9 gene expression. Post-treatment with 40 microM FA also decreased the expression of MMP-1 and MMP-13. CONCLUSION: FA decreased the hydrogen peroxide-induced IL-1beta, TNF-alpha, MMP-1 and MMP-13 and increased SOX9 gene expression. These findings suggest that FA may prove to be important in the treatment of osteoarthritis. Further research is needed.

[Construction of root library by SSH and preliminary analysis of genes responsible for phosphorus deficiency in maize].

An elite maize inbred line with high tolerance to low phosphorus, 178, was studied for constructing root library and analyzing some genes closely related to phosphorus (P) deficiency using SSH and Semi-quantitative RT-PCR. As a result, 3648 preliminary clones were obtained for root library under stress of P deficiency. By DNA sequencing of 34 random clones, we obtained 23 unique EST sequences which are involved in functions of root cell structure, tolerance and defense, protein modification and composition, transcription regulation, metabolism, and other unknown aspects. Five representative genes were further analyzed for their expression models. The results suggested that the molecular mechanism to adapt P deficiency in maize, performed by multi-genes with different contributions, is similar to rice, Arabidopsis and soybean. The expression order of 5 low P tolerant genes in maize root was PAP, GCS, TOM, PDI and AIP. And it was considered preliminarily that physiological and biochemical changes were prior to morphologic changes in maize root and the essential tolerance to low P may be determined by extending absorption of P to wide soil range through adaption of root architecture and root secretions, which is the greatest difference between tolerant and sensitive maize varieties under low P stress.

A new method for facial epidermoid cyst removal with minimal incision.

BACKGROUND: Facial epidermoid cyst is a common benign epithelial tumour frequently seen in young or middle-aged people and may cause aesthetic disability. Surgical excision is the most frequently used method but may result in obvious scar. OBJECTIVE: To improve cosmetic result of removing facial epidermoid cyst through minimal incision surgery. METHODS: Twenty-two cases of facial epidermoid cysts ranging from 0.5 to 1.4 cm in diameter were treated. The skin above the epidermoid cysts was infiltrated with local 0.1-cc 1% xylocaine anaesthetic by using a 26-gauge needle first, then 3-mm incisions were made with a No.11 surgical blade. The cystic contents and its capsule were then squeezed out through the small incision and the underlying connective tissue was chemically cauterized by 20% trichloroacetic acid. The incision wounds were left unsutured. RESULT: Minimal incision method successfully treated 16 out of the 22 epidermoid cyst cases that ranged from 0.5 to 1 cm in diameter. And only one out of six was successfully treated for diameters greater than 1.1 cm. CONCLUSION: The proposed method can minimize the scar when treating facial epidermal inclusion cysts that are less than 1 cm and obtained better cosmetic results.

Steroid-Refractory Autoimmune Myocarditis after Pembrolizumab Therapy: Failure of Equine Anti-Thymocyte Globulin to Prevent Heart Failure.

While immune checkpoint inhibitors (ICIs) are improving outcomes for many cancers, they can have severe adverse effects. Though cardiac immune-related adverse effects (irAEs) are rare, they have considerable morbidity and mortality. Prior case studies have demonstrated successful treatment of ICI induced autoimmune myocarditis with a variety of immunosuppressive regimens. This case describes steroid-refractory autoimmune myocarditis after treatment with pembrolizumab. Treatment with equine anti-thymocyte globulin, a regimen previously documented to reverse ICI induced autoimmune myocarditis, temporarily improved clinical status and cardiac biomarkers, however eventually failed to prevent progression to heart failure and cardiovascular death. This case highlights the importance of early stress-dose steroids, identifies troponin as a potential marker of treatment response, and underscores the value of collaboration between oncology and cardiology for optimal management.

Bone mineral density as a dose-response predictor for osteoporosis: a propensity score analysis of longitudinal incident study (KCIS no. 39).

BACKGROUND: Osteoporosis is a global disease burden for aging society. The role of quantitative ultrasound (QUS) in the prediction for osteoporosis in a dose-response manner is hardly addressed. AIM: We aimed to show the dose-response of QUS measurement in the prediction for osteoporosis by a community-based study. DESIGN: A prospective cohort study. METHODS: Participants were recruited between 2000 and 2004. Demographic data and heel QUS measurement were collected at baseline. Diagnosis of osteoporosis was ascertained by the follow-up of this cohort over time. In order to reduce the imbalance of baseline characteristics in the observational study, we applied propensity score by using proportional odds regression analysis to match the quintiles of QUS T-score. RESULTS: A total of 44 957 subjects composed of 17 678 men (39.3%) and 27 279 women (69.7%) were recruited. After adjustments for propensity score, an increase in one unit of QUB T-score led to 7% reduction in the risk for osteoporosis [adjusted odds ratio (OR) = 0.93, 95% confidence interval (CI): 0.89-0.96, P < 0.0001]. Higher quintile of QUS T-score yielded a lower risk of osteoporosis with a gradient relationship [OR: 0.82 (95%CI: 0.72-0.92); OR: 0.81 (95%CI: 0.71-0.91); OR: 0.77 (95%CI: 0.68-0.87) and OR: 0.76 (95%CI: 0.67-0.86)] from the second to highest quintile opposed to first quintile (P < 0.0001). The cumulative incidence of osteoporosis was higher in the lower quintile during follow-up (log-rank test, P < 0.001). CONCLUSION: QUS is an independent predictor for osteoporosis in a dose-response manner using a large population-based cohort. Due to the lower cost and portability of QUS measurement, the pre-screening for osteoporosis by QUS can be considered in the area with limited resources can be a feasible and alternative method.

Chitosan/gelatin hydrogel prolonged the function of insulinoma/agarose microspheres in vivo during xenogenic transplantation.

PURPOSE: A chitosan/gelatin solution with glycerol 2-phosphate disodium salt hydrate in liquid phase at room temperature becomes a hydrogel at 37 degrees C. The material can be used as an injectable cell carrier into the human body for gelation in situ. We hoped that the chitosan/gelatin hydrogel provided extra protection for insulinoma/agarose microspheres during xenogenic transplantation. MATERIALS AND METHODS: Mouse insulinoma was microencapsulated in agarose as microspheres, which were macroencapsulated in chitosan/gelatin hydrogel. Insulin secreting profiles were first demonstrated in vitro. Diabetic rats were injected subcutaneously with insulinoma/agarose microspheres or insulinoma/agarose microspheres suspended in chitosan/gelatin solution. The nonfasting blood glucose concentrations (NFBG) of diabetic rats were measured perioperatively. Rats were humanely killed 1 month postoperatively and the hydrogel was retrieved for histological examination. RESULTS: The insulinoma/agarose microspheres continually secreted insulin for 1 month when macroencapsulated in chitosan/gelatin hydrogel in vitro. The NFBG of diabetic rats injected with insulinoma/agarose microspheres decreased to euglycemic status albeit hyperglycemia was restored within 10 days. The NFBG of diabetic rats injected with chitosan/gelatin hydrogel, which contained insulinoma/agarose microspheres, was maintained at less than 200 mg/dL for 25 days. The histological section revealed immune cell infiltration and accumulation within the hydrogel and around the iusulinoma/agarose microspheres that may have contributed to the slowly increasing NFBG after day 25. CONCLUSION: This study showed that chitosan/gelatin hydrogel can be used as a cell carrier for an injectable bioartificial pancreas; the hydrogel prolonged the function of cells encapsulated in agarose microspheres during xenogenic transplantation.

A facile method to functionalize gold nano-tripods with high suspension stability in an aqueous environment.

Here we aim to develop a facile emulsion-based method to prepare tripod gold nanoparticles (AuNPs) with high suspension stability in an aqueous environment. A gyroid-structured polymer template formed by the hydrolysis of a degradable block copolymer, polystyrene (PS)-b-poly(l-lactide), is used for the fabrication of AuNPs. Also, a successful emulsification of dichloromethane (DCM) in the aqueous phase is developed by using thiolated polyethylene glycol (PEG-SH) as the stabilizer. Subsequently, the nanohybrids of PS/Au can be fabricated by templated electroless plating, and then selectively dissolving in the DCM dispersive phase. Most interestingly, a dedicated process for the simultaneous release of the tripod AuNPs from the dissolution of PS associated with PEG-SH at the interface of the emulsion is achieved, giving PEG-SH-functionalized tripod AuNPs dispersed in the aqueous phase, which significantly improves the suspension stabilization of tripod AuNPs. The in situ temperature-programmed electrospray-differential mobility analysis provides a quantitative, statistical analysis of mobility diameter, dynamic shape factor, polydispersity, and colloidal stability.

Prevalence rates of youths diagnosed with and medicated for ADHD in a nationwide survey in Taiwan from 2000 to 2011.

AIMS: Public controversy regarding the potential overdiagnosis and overmedication of children with attention-deficit/hyperactivity disorder (ADHD) has continued for decades. This study used the National Health Insurance Research Database of Taiwan (NHIRD-TW) to explore trends in ADHD diagnosis in youths and the proportion of those receiving medication, with the aim of determining whether ADHD is overdiagnosed and overmedicated in Taiwan. METHOD: Youths (age ≤18 years) who had at least two NHIRD-TW claims records with ADHD diagnosis between January 2000 and December 2011 were selected as the subject cohort. In total, the study sample comprised 145 018 patients with ADHD (mean age at a diagnosis of ADHD: 7.7 ± 3.1 years; 21.4% females). The number of cases of ADHD were calculated annually for each year (from 2000 to 2011), and the number of cases per year who received medication was determined as those with at least one record of pharmacotherapy (immediate-release methylphenidate, osmotic controlled-release formulation of methylphenidate, and atomoxetine) in each year. RESULTS: The prevalence rates of a diagnosis of ADHD in the youths ranged from 0.11% in 2000 to 1.24% in 2011. Compared with children under 6 years of age, the ADHD diagnosis rates in children aged between 7 and 12 years (ratio of prevalence rates = 4.36) and in those aged between 13 and 18 years (ratio of prevalence rates = 1.42) were significantly higher during the study period. The prevalence in males was higher than that in females (ratio of prevalence rates = 4.09). Among the youths with ADHD, 50.2% received medications in 2000 compared with 61.0% in 2011. The probability of receiving ADHD medication increased with age. More male ADHD patients received medications that females patients (ratio of prevalence rates = 1.16). CONCLUSIONS: The rate of ADHD diagnosis was far lower than the prevalence rate (7.5%) identified in a previous community study using face-to-face interviews. Approximately 40-50% of the youths with ADHD did not receive any medications. These findings are not consistent with a systematic public opinion about overdiagnosis or overmedication of ADHD in Taiwan.

Identification of AF17 as a downstream gene of the beta-catenin/T-cell factor pathway and its involvement in colorectal carcinogenesis.

To elucidate the molecular mechanism of colorectal carcinogenesis, we have been attempting to isolate genes involved in the beta-catenin/T-cell factor pathway. In the experiments reported here, analysis by cDNA microarray indicated that AF17, a fusion partner of the MLL gene in acute leukemias with t(11;17)(q23;q21), was transactivated according to accumulation of beta-catenin. Expression of AF17 was significantly enhanced in 8 of the 12 colorectal cancer tissues examined. Introduction of a plasmid designed to express AF17 stimulated growth of NIH3T3 cells, and fluorescence-activated cell sorter analysis indicated that the AF17 regulation of cell-cycle progression was occurring mainly at the G(2)-M transition. Our results suggest that the AF17 gene product is likely to be involved in the beta-catenin-T-cell factor/lymphoid enhancer factor signaling pathway and to function as a growth-promoting, oncogenic protein. These findings should aid development of new strategies for diagnosis, treatment, and prevention of colon cancers and acute leukemias by clarifying the pathogenesis of these conditions.

3 alpha-Hydroxy-3 beta-(phenylethynyl)-5 beta-pregnan-20-ones: synthesis and pharmacological activity of neuroactive steroids with high affinity for GABAA receptors.

Neuroactive steroids that allosterically modulate GABAA receptors have potential uses as anticonvulsants, anxiolytics, and sedative-hypnotic agents. Recently, a series of pregnanes substituted with simple alkyl groups at the 3 beta-position were synthesized and found to be active in vitro. The present report describes the synthesis of a series of substituted 3 alpha-hydroxy-3 beta-(phenylethynyl)pregnan-20-ones and their in vitro structure-activity relationship determined by their potency for inhibition of [35S]TBPS binding in rat brain membranes. Appropriate substitution of the phenyl group results in ligands with particularly high affinity for the neuroactive steroid site on GABAA receptors (e.g., 4-acetyl 28, IC50 10 nM). The potency of selected steroids was confirmed electrophysiologically in oocytes expressing cloned human GABAA alpha 1 beta 2 gamma 2L receptors (e.g., compound 28, EC50 6.6 nM). Consistent with their in vitro activity, some of the 3 beta-(phenylethynyl)-substituted steroids displayed anticonvulsant activity in the pentylenetetrazol (PTZ) and maximal electroshock (MES) tests following ip administration in mice. Notably, the 3 beta-[(4-acetylphenyl)ethynyl]-19-nor derivative 36 demonstrated an attractive anticonvulsant profile (PTZ and MES ED50 values of 2.8 and 9.2 mg/kg, respectively). A new pharmacophore for the neuroactive steroid site of GABAA receptors is proposed based upon the high affinity of certain substituted 3 beta-(phenylethynyl) steroids.

Ultraviolet-induced lenticular fluorescence: intraocular straylight affecting visual function.

Ultraviolet radiation (UVR) excitation of fluorophores within the crystalline lens results in intraocular straylight. These fluorescent emissions are known to increase with age. The visual effect of this increase in fluorescent straylight has not previously been published. In this study, the visual deficit associated with UV-induced lenticular fluorescence was measured for 61 normal subjects between the ages of 21 and 80 yr of age using the Regan visual acuity charts at varying levels of contrast. UVR was shown to decrease low contrast acuity and this loss increased linearly with age.

A multicenter study on eradication of Helicobacter pylori infection in patients with duodenal ulcer by lansoprazole-antibiotics combined therapy.

The aim of this prospective randomized multicenter study was to find out if there is one or several promising regimens containing lansoprazole with various combinations of antibiotics which have a high eradication rate of Helicobacter pylori, few side-effects, good patient compliance, and relative low cost if possible. Two hundred and ninety-seven patients with H. pylori positive duodenal ulcer were enrolled and randomly allocated into one of the five treatment groups: 1) group A: received lansoprazole 30 mg once daily for 2 weeks plus amoxicillin (AM) 500 mg and metronidazole (MZ) 500 mg twice daily for one week in the first week; 2) group B: the AM in group A was replaced by clarithromycin (CM) 250 mg; 3) group C: the MZ in group A was replaced by CM 250 mg; 4) group D: the AM and CM in group C was used for 2 wk; 5) group E: the CM in group D was doubled to 500 mg twice daily. All patients received endoscopies pre- and 4-6 weeks post termination of treatment. H. pylori was detected by culture, histology and rapid urease test (CLO test). 13C-urea breath test was performed if the patients refused the second endoscopy. The E-test was adopted to evaluate the MZ and CM resistance of H. pylori. Totally, 253 patients completed the study. The eradication rate of groups A, B, C, D and E were 75%, 80%, 78%, 92%, and 96%, respectively. The eradication rate of group E was significantly higher than that of groups A, B, or C. There were no significant differences of eradication rates between the groups D and E. Sixty-seven cases (28.8%) were MZ-resistant. The difference of eradication rates between MZ-S and MZ-R patients was significant in group A (85.3% vs. 42.9%) and in the combination of groups A and B (83.8% vs. 59.4%). Good compliance (defined as taking > 90% of medications) was seen in more than 90% of cases in each group. Triple therapy containing lansoprazole 30 mg once daily, AM 500 mg and CM 250 mg twice daily for two weeks is a promising regimen which reaches a high eradication rate, avoids MZ resistance, and has very good patient compliance at an acceptable cost.