Soluble Epoxide Hydrolase Inhibition Exhibits Antihypertensive Actions Independently of Nitric Oxide in Mice with Renovascular Hypertension

Objective: The present study was performed to examine whether the blood pressure (BP)-lowering effects of soluble epoxide hydrolase (sEH) inhibition in two-kidney, one-clip (2K1C) Goldblatt hypertension are nitric oxide (NO) dependent. Methods: Mice lacking the endothelial NO synthase (eNOS) gene (eNOS-/-) and their wild-type controls (eNOS+/+) underwent clipping of one renal artery. BP was monitored by radiotelemetry and the treatment with the sEH inhibitor cis-4-[4-(3-adamantan-1-yl-ureido)cyclohex-yloxy]-benzoic acid (c-AUCB) was initiated on day 25 after clipping and lasted for 14 days. Renal concentrations of epoxyeicosatrienoic acids (EETs) and their inactive metabolite dihydroxyeicosatrienoic acids (DHETs) were measured in the nonclipped kidney. Renal NO synthase (NOS) activity was determined by measuring the rate of formation of L-[(14)C]citruline from L-[(14)C]arginine. Results: Treatment with the sEH inhibitor elicited similar BP decreases that were associated with increases in daily sodium excretion in 2K1C eNOS+/+ as well as 2K1C eNOS-/- mice. In addition, treatment with the sEH inhibitor increased the ratio of EETs/DHETs in the nonclipped kidney of 2K1C eNOS+/+ as well as 2K1C eNOS-/- mice. Treatment with the sEH inhibitor did not alter renal NOS activity in any of the experimental groups. Conclusions: Collectively, our present data suggest that the BP-lowering effects of chronic sEH inhibition in 2K1C mice are mainly associated with normalization of the reduced availability of biologically active EETs in the nonclipped kidney and their direct natriuretic actions.     

Efficacy and tolerance of tacrolimus and pimecrolimus for atopic dermatitis: a meta-analysis

Tacrolimus ointment and pimecrolimus cream have proved to be suitable for the treatment of atopic dermatitis. We conducted a meta-analysis of the efficacy, adverse events/withdrawal of tacrolimus versus pimecrolimus in the treatment of atopic dermatitis. According to our meta-analysis, 0.1% tacrolimus was more effective than 1% pimecrolimus in the treatment of adult patients and moderate to very severe pediatric patients, and more 0.1% mild pediatric patients treatal with pimecrolimus withdrew from the tria...     

The Brainstem Pathologies of Parkinson's Disease and Dementia with Lewy Bodies

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are among the human synucleinopathies, which show alpha‐synuclein immunoreactive neuronal and/or glial aggregations and progressive neuronal loss in selected brain regions (eg, substantia nigra, ventral tegmental area, pedunculopontine nucleus). Despite several studies about brainstem pathologies in PD and DLB, there is currently no detailed information available regarding the presence of alpha‐synuclein immunoreactive inclusions (i) in the cranial nerve, precerebellar, vestibular and oculomotor brainstem nuclei and (ii) in brainstem fiber tracts and oligodendroctyes. Therefore, we analyzed the inclusion pathologies in the brainstem nuclei (Lewy bodies, LB; Lewy neurites, LN; coiled bodies, CB) and fiber tracts (LN, CB) of PD and DLB patients. As reported in previous studies, LB and LN were most prevalent in the substantia nigra, ventral tegmental area, pedunculopontine and raphe nuclei, periaqueductal gray, locus coeruleus, parabrachial nuclei, reticular formation, prepositus hypoglossal, dorsal motor vagal and solitary nuclei. Additionally we were able to demonstrate LB and LN in all cranial nerve nuclei, premotor oculomotor, precerebellar and vestibular brainstem nuclei, as well as LN in all brainstem fiber tracts. CB were present in nearly all brainstem nuclei and brainstem fiber tracts containing LB and/or LN. These findings can contribute to a large variety of less well‐explained PD and DLB symptoms (eg, gait and postural instability, impaired balance and postural reflexes, falls, ingestive and oculomotor dysfunctions) and point to the occurrence of disturbances of intra‐axonal transport processes and transneuronal spread of the underlying pathological processes of PD and DLB along anatomical pathways.     

Subjects with mild and moderate asthma respond to segmental allergen challenge with similar, reproducible, allergen-specific inflammation

BACKGROUND: The relationship between severity of asthma and bronchial inflammation is poorly understood. OBJECTIVE: We examined acute and subacute inflammatory responses to allergen in subjects with mild and moderate persistent asthma to evaluate whether different cellular and mediator responses to endobronchial allergen challenge are associated with differences in disease severity. METHODS: Segmental allergen challenge was performed in 8 subjects with mild and 10 subjects with moderate allergic asthma to compare baseline airways inflammation and allergen-induced inflammatory responses 24 hours later. This evaluation was repeated after 6 weeks in 9 subjects to investigate the reproducibility of these inflammatory responses. RESULTS: Subjects with mild and moderate asthma had similar decreases in FEV(1) in response to segmental allergen challenge (9.1% +/- 4.2% vs 15.1% +/- 4.6%, P = .35). There was no difference in inflammatory cell counts or cytokine concentrations in the groups with mild and moderate asthma at baseline or after saline or allergen challenge. Repeat segmental allergen challenge 6 weeks later showed that these cellular and cytokine responses were reproducible. CONCLUSION: Segmental allergen challenge in subjects with mild and moderate asthma produces similar allergen-specific physiologic and inflammatory responses that are reproducible 6 weeks later. In this model of allergic asthma, acute responses to allergen do not appear to be related to disease severity.     

A new technique to register proliferation of clonogenic cells from brain tumors

The soft agar technique for culturing human clonogenic tumor cells has been usefully applied for predicting individual clinical responses to chemotherapy, for screening of new antineoplastic drugs, and in basic biological research. The counting of colonies formed by clonogenic cells is, however, a rather time consuming and inaccurate procedure. We here report a method to combine the easy and precise registration of DNA-synthesis by ³H-thymidine incorporation with the ability of soft agar to permit proliferation of clonogenic cells and inhibit proliferation of non-neoplastic cells.The glioma cell lines U 251 MG and T-MG 1, the benignant glia cells T-BG 1, T-BG 2, T-BG 3 and fibroblasts were cultured in Furcellaran gel. Twenty hours before harvesting 3H-thymidine was added. The Furcellaran gel was resolved by 50 mM Lil. The cells were trapped on glass fiber filters and incorporated radioactivity was measured. ³H-thymidine incorporation in malignant cells increased exponentially with time, while 3H-thymidine incorporation in the benignant glia cells and fibroblasts was inhibited. The correlation between number of colonies counted after 16 days and ³H-thymidine incorporation registered after different culture times was very good. The correlation was best when the cultures were harvested after 8 days (r = 0.95), indicating that it is possible to reduce the assay time.The five glioma biopsies tested grew well with a mean plating efficiency of 0.4% (range 0.02–1.8%). The most intense proliferation seemed to take place during the first week in culture. The good correlation between ³H-thymidine incorporation on day 7 and colony number on day 14 (r = 0.93), indicate that reduction of assay time is possible also for the glioma biopsies.     

Chlamydia trachomatis in subfertile couples undergoing an in vitro fertilization program: a prospective study

OBJECTIVES: The objectives were to estimate the prevalence of Chlamydia trachomatis infection in subfertile couples and to study the relationship between markers of C. trachomatis infection and male infertility as well as pregnancy rates after in vitro fertilization (IVF). STUDY DESIGN: All consecutive couples consulting for infertility and IVF in Pellegrin Hospital were screened for C. trachomatis by direct (PCR test) and serological methods. RESULTS: Two hundred and seventy-seven couples were included in the study (mean age in years: 35 for men, 32 for women; mean duration of infertility: 4 years). The most frequent indication for IVF was tubal factor in 33%, endometriosis in 6%, dysovarian function in 12%, male infertility in 36% and others in 13%. C. trachomatis PCR was positive in 1.2% of men, 95% confidence interval (CI95%): (0.2%; 3.3%) and in 2.7% of women, CI95%: (1.1%; 5.5%). When combining all chlamydial markers, 17.3% of men, CI95%: (12.7%; 22.8%) and 20.4% of women, CI95%: (15.6%; 25.9%) had at least one positive marker. The presence of positive markers was not associated with altered semen characteristics. Couples with positive markers had a pregnancy rate of 23.1% (12 out of 52) compared with 20.2% (24 out of 119) among those with negative markers. CONCLUSION: In this population, the presence of past or current C. trachomatis infection was associated with neither semen characteristics nor outcome of IVF in subfertile couples.     

Postoperative Schmerztherapie mit Piritramid und Metamizol

In this randomized study, the efficacy of i.v. patient-controlled analgesia (PCA) was determined for the opioid piritramide (a pure mu-receptor agonist) and the antipyretic analgesic metamizole (Dipyrone) in three groups of patients following abdominal surgery. The doses of piritramide were 1.5 mg (40 patients) and 3 mg (40 patients) on demand. In addition, we studied the effect of 71 mg metamizole in combination with on-demand boluses of 1.5 mg piritramide in 40 patients. During PCA we estimated the degree of analgesia (verbal gain rating scale, visual analog scale) and monitored the ventilation, vigilance, and typical drug side effects over a period of 24 h. The individual demand for analgesic drugs varied markedly. The mean consumption of piritramide during the study was 46.5 mg in the group with 1.5 mg per bolus and 68.6 mg in the group with 3.0 mg. The resulting pain relief was satisfactory in both groups. The combination of piritramide 1.5 mg and metamizole 71 mg per bolus resulted in a reduction of mean Piritramide-consumption to 44.1 mg, and the pain relief was similar to that produced in the group treated with 3 mg piritramide per bolus. The intensity of typical side effects of opioids and antipyretic analgesics (nausea, vomiting, lowering of respiratory frequency, sweating) was low and always easily controlled. The acceptance by patients, nurses, and physicians of PCA was high. PCA with on-demand intravenous injection of the combination of piritramide and metamizole improved the degree of analgesia and concomitantly reduced the opioid dose.     

Intraocular pressure and safety in glaucoma patients switching to latanoprost/timolol maleate fixed combination from mono- and adjunctive therapies.

PURPOSE: The aim of this study was to evaluate the efficacy and safety in ocular hypertensive or open-angle glaucoma patients changed to a latanoprost/timolol fixed combination (LTFC) from previous therapy. METHODS: We employed a retrospective, multicenter, active-controlled study evaluating patients who had a previous therapy substituted with LTFC and had a 3-month follow-up. RESULTS: In the 168 patients included in the trial, LTFC reduced the intraocular pressure (IOP) after switching from previous therapies: timolol (22.8+/-3.5 to 19.0+/-3.9 mmHg, N=49, p<0.001), latanoprost (21.2+/-3.8 to 18.3+/-2.5 mmHg, N=54, p<0.001), and a dorzolamide/timolol fixed combination (20.9+/-2.4 to 20.0+/-2.7 mmHg, N=32, p=0.03). In switching from a latanoprost and timolol unfixed combination, the pressure changed from 18.3+/-3.8 to 18.9+/-3.0 mmHg (N=33, p=0.38). LTFC was persistent in 131 (78%) patients within the 3-month treatment period. The most common adverse event with LTFC was conjunctival hyperemia, which occurred in patients not previously treated with latanoprost therapy (N=16, 10%). CONCLUSIONS: LTFC generally provides reduced IOP and limited side effects when substituted for other common glaucoma therapies, while providing similar pressure when switched from its own individual components.     

磁共振与经阴道超声对卵巢肿瘤的诊断价值

目的探讨磁共振(Magnetic Resonance Imaging,MRI)和经阴道超声(Transvaginal Ultrasonography,TVS)鉴别卵巢肿瘤良恶性的诊断价值和经济价值。方法51例可疑卵巢肿瘤患者行MRI及TVS检查,对比二者检查结果,并对二者医疗费用进行成本一效果分析。结果MRI诊断卵巢恶性肿瘤的敏感性为88.2%,特异性为97.6%,准确性94.9%,阳性预测值93.8%,阴性预测值为95.3%。TVS诊断卵巢恶性肿瘤的敏感性为94.1%,特异性为95.2%,准确性94.9%,阳性预测值88.9%,阴性预测值为97.6%。正确诊断卵巢良恶性肿瘤的单位成本MRI是879/754元(每例,每个),TVS是197/169元(每例/每个)。结论TVS和MRI诊断卵巢良恶性肿瘤价值相同,TVS是鉴别卵巢良恶性肿瘤最经济有效的方法。     

2型糖尿病患者自然步态下赤足足底压力特征分析

目的探讨2型糖尿病患者足底压力分布特点。方法使用比利时RS-SCAN公司生产的Footscan1m压力平板,检测357例2型糖尿病患者自然行走过程的赤足压力,多次测量后取3次数据计算各区域压强的平均值录入SPSS 16.0统计软件。结合足底压力测量软件将足底分为第1趾,第2—第5趾、第1、第2、第3、第4、第5跖骨底、足弓、足跟内侧、足跟外侧共10个解剖区域。检查足外观有无胼胝及拇趾外翻,根据软件计算足弓指数将患者足型分为正常足、扁平足及高弓足,分析指标为患者足底各分区压强、全足压强和双足平均总压强(N/cm2),比较左右足全足压强及不同性别患者左右足全足压强,不同足外观、足型患者双足平均总压强。结果足底各分区前3位排序,左足:第3跖骨底第4跖骨底第2跖骨底,右足第3跖骨底第2跖骨底足跟内侧。左、右足全足压强比较差异有统计学意义,左足右足(P0.01),男性患者左右足全足压强均大于女性患者(P0.05)。357例患者中胼胝者66例,拇趾外翻45例。比较不同足外观患者双足平均总压强,胼胝组最高(P0.05)。不同足型患者比较,3组间足底压强差异无统计意义(P0.05)。结论2型糖尿病患者足底各分区压强最高值双足均为第3跖骨底,全足总压强比较左足右足,男性女性。糖尿病合并胼胝者足底压强最高,不同足型患者间足底压强差别无统计学意义。