Socio-economic determinants of drugged driving--a register-based study

Aims To examine the associations between socio‐economic characteristics and driving under the influence of drugs (DUID), and to elaborate determinants of drugged driving. Design A register‐based case–control study. Setting Finland. Participants Cases (n = 5859) apprehended by the police and suspected of DUID during 1993–2006 and controls (n = 74 809) drawn from the general Finnish population. Measurements The effects of parents' and own education, urbanization of municipality, socio‐economic position (SEP), main activity, income, marital status and living arrangements on DUID were estimated using logistic regression analysis. The analyses were conducted separately for men and women, age groups of under 45 years and aged 45 or over, and for substance groups of benzodiazepines only, benzodiazepines with alcohol, amphetamines and cannabinoids. Findings Low education, unemployment, disability pension, being divorced and living alone were the strongest individual predictors of DUID in all substance groups. Illicit drug users were more disadvantaged compared to those in the benzodiazepines groups. Contrary to other substance and age groups, higher educational level and higher SEP were associated with DUID among benzodiazepine users aged 45 or over. Conclusions A disadvantaged social background is a significant predictor of driving while under the influence of drugs for all substance use groups in Finland. The gradient is greater for amphetamines and cannabinoids than benzodiazepines.     

扁桃斑鸠菊及非洲印楝叶的提取物对链脲佐菌素致糖尿病大鼠肝脏形态学及肝毒性标志物的影响（英文）

目的：研究扁桃斑鸠菊及非洲印楝叶的提取物对链脲佐菌素致糖尿病大鼠肝脏形态学、肝脏氧化性应激标志物及部分肝脏酶类的影响。方法：大鼠腹腔注射链脲佐菌素致糖尿病。不同治疗组大鼠分别口服扁桃斑鸠菊及非洲印楝叶的提取物（500mg/kg）或二甲双胍（150mg/kg）,疗程8周,每周测量大鼠的血糖水平及体质量变化。8周后麻醉处死大鼠。取肝组织制成切片,希夫染色法染色,并测量肝匀浆中丙二醛和谷胱甘肽过氧化物酶的含量;下腔静脉采血,分离血浆,检测血浆中丙氨酸氨基转移酶和天冬氨酸氨基转移酶的活性。结果：二甲双胍及植物提取物均能显著改善糖尿病大鼠的血糖水平,且与糖尿病模型组相比,治疗组的体质量明显增加（P〈0.05）。光学显微镜下,各组大鼠的肝脏形态学无明显差别。植物提取物治疗组大鼠的血浆丙氨酸氨基转移酶及天冬氨酸氨基转移酶的活性与正常对照组相比无明显变化（P〉0.05）,而丙二醛含量明显下降（P〈0.05）。结论：扁桃斑鸠菊及非洲印楝叶的提取物对糖尿病大鼠有明显的降糖作用,而肝脏形态学及肝毒性标志物没有明显变化。     

Chronic inflammation and risk of lung cancer in older adults in the health,aging and body composition cohort study

Objectives

We examined the association between three inflammatory markers (Interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) and incident lung cancer using baseline, updated, and averaged inflammatory measures in older adults.

Demographic,presentation, and treatment factors and racial disparities in ovarian cancer hospitalization outcomes

Background

This study examines whether racial disparities in hospitalization outcomes persist between African–American and White women with ovarian cancer after matching on demographic, presentation, and treatment factors.

Methods

Using data from the Nationwide Inpatient Sample database, 5,164 African–American ovarian cancer patients were sequentially matched with White patients on demographic (e.g., age, income), presentation (e.g., stage, comorbidities), and treatment (e.g., surgery, radiation) factors. Racial differences in-hospital length of stay, post-operative complications, and in-hospital mortality were evaluated using conditional logistic regression models.

Results

White ovarian cancer patients had relatively higher odds of post-operative complications when matched on demographics (OR 1.35, 95% CI 1.05, 1.74), and presentation (OR 1.28, 95% CI 1.00, 1.65) but not when additionally matched on treatment (OR 1.03, 95% CI 0.78, 1.35). African–American patients had longer in-hospital length of stay (6.96?±?7.21 days) compared with White patients when matched on demographics (6.37?±?7.07 days), presentation (6.48?±?7.16 days), and treatment (6.53?±?7.59 days). Compared with African–American patients, White patients experienced lower odds of in-hospital mortality when matched on demographics (OR 0.78, 95% CI 0.66, 0.92), but this disparity was no longer significant when additionally matched on presentation (OR 0.88, 95% CI 0.75, 1.04) and treatment (OR 0.95, 95% CI 0.81, 1.12).

Conclusion

Racial disparities in ovarian cancer hospitalization outcomes persisted after adjusting for demographic and presentation factors; however these differences were eliminated after additionally accounting for treatment factors. More studies are needed to determine the factors driving racial differences in ovarian cancer treatment in otherwise similar patient populations.

     

Evaluation of Cytotoxicity of Various Ophthalmic Drugs, Eye Drop Excipients and Cyclodextrins in an Immortalized Human Corneal Epithelial Cell Line

Purpose. An immortalized human corneal epithelial cell line (HCE) was tested as a screening tool for prediction of topical ocular irritation/ toxicity by pharmaceuticals. Methods. Effects of various drugs, excipients and cyclodextrins (CDs) on viability of HCE cells were evaluated using two in vitrocytotoxicity tests, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) dye reduction assay and propidium iodide assay. Results. Mitochondrion-based MTT test was a more sensitive indicator of cytotoxicity than the plasma membrane-based propidium iodide test. The tests revealed following cytotoxic rankings for ophthalmic drugs: dipivefrin > timolol > pilocarpine dexamethasone; for excipients: benzalkonium chloride (BAC) > sodium edetate (NA₂EDTA) > poly-vinyl alcohol (PVA) > methylparaben; and for CDs: -CD > dimethyl--cyclodextrin (DM--CD) > sulfobutyl ether (-cyclodextrin ((SBE)_7m--CD) hydroxypropyl--cyclodextrin (HP--CD) > -CD. In consideration of the in vivoclinical situation, the short exposure time (5 min) is more relevant even though toxic effects of some test substances were seen only after longer exposure times (30 and 60 min). Conclusions. Immortalized HCE cells are a promising tool for rapid cytotoxicity assays of ocular medications. The cell line is potentially useful in predicting the in vivocorneal toxicity of ocularly applied compounds.     

Use-dependent shift from inhibitory to excitatory GABAA receptor action in SP-O interneurons in the rat hippocampal CA3 area

Cortical inhibitory interneurons set the pace of synchronous neuronal oscillations implicated in synaptic plasticity and various cognitive functions. The hyperpolarizing nature of inhibitory postsynaptic potentials (IPSPs) in interneurons has been considered crucial for the generation of oscillations at beta (15-30 Hz) and gamma (30-100 Hz) frequency. Hippocampal basket cells and axo-axonic cells in stratum pyramidale-oriens (S-PO) play a central role in the synchronization of the local interneuronal network as well as in pacing of glutamatergic principal cell firing. A lack of conventional forms of plasticity in excitatory synapses onto interneurons facilitates their function as stable neuronal oscillators. We have used gramicidin-perforated and whole cell clamp recordings to study properties of GABAAR-mediated transmission in CA3 SP-O interneurons and in CA3 pyramidal cells in rat hippocampal slices during electrical 5- to 100-Hz stimulation and during spontaneous activity. We show that GABAergic synapses onto SP-O interneurons can easily switch their mode from inhibitory to excitatory during heightened activity. This is based on a depolarizing shift in the GABAA reversal potential (EGABA-A), which is much faster and more pronounced in interneurons than in pyramidal cells. We also found that the shift in interneuronal function was frequency dependent, being most prominent at 20- to 40-Hz activation of the GABAergic synapses. After 40-Hz tetanic stimulation (100 pulses), GABAA responses remained depolarizing for approximately 45 s in the interneurons, promoting bursting in the GABAergic network. Hyperpolarizing EGABA-A was restored >60 s after the stimulus train. Similar but spontaneous GABAergic bursting was induced by application of 4-aminopyridine (100 microM) to slices. A shift to depolarizing IPSPs by the GABAAR permeant weak acid anion formate provoked interneuronal population bursting, supporting the role of GABAergic excitation in burst generation. Furthermore, depolarizing GABAergic potentials and synchronous interneuronal bursting were enhanced by pentobarbital (100 microM), a positive allosteric modulator of GABAARs, and were blocked by picrotoxin (100 microM). Intriguingly, GABAergic bursts displayed short (<1 s) oscillations at 15-40 Hz, even though only depolarizing GABAA responses were seen in the SP-O interneurons. This beta-gamma rhythmicity in the interneuron network was dependent on electrotonic coupling, and was abolished by blockade of gap junctions with carbenoxolone (200 microM). Results here implicate the rapid activity-dependent degradation of hyperpolarizing IPSPs in SP-O interneurons in setting the temporal limits for a given interneuron to participate in beta-gamma oscillations synchronized by GABAergic synapses. Furthermore, they imply that mutual GABAergic excitation provided by interneurons may be an integral part in the function of neuronal networks. We suggest that the use-dependent change in EGABA-A could represent a form of short-term plasticity in interneurons promoting coherent and sustained activation of local GABAergic networks.