Brucellar discitis as a cause of lumbar disc herniation: a case report

Brucellosis is an infectious disease spread by consumption of non-pasteurized milk products or through contact with infected animals. Spinal involvement is one of the most important complications and the lumbar area is the most frequently affected site. Among the neurological consequences, nerve root compression can be a result of epidural abscess, granuloma or discitis secondary to vertebral body involvement. In this case report we present a 50-year-old male patient with brucellar discitis without spondylitis which caused lumbar disc herniation. We want to emphasize that discitis should also be considered in differential diagnosis of nerve root compression in suspected cases.     

Non-linear quantitative electroencephalographic (qEEG) changes during processing of chemo-sensory stimulations: a preliminary study

The present study was to investigate the processing of pleasant smell and taste stimuli by non-linear EEG measures. Point correlation dimension (PD2i) has been used for studying the local, and synchronization likelihood (SL) the global dynamical organization. Nine healthy subjects participated in this study. After a baseline period of 30s the patients were given a perfume cap or a chocolate taste for 30s. The analysis was performed off-line on 16 channels. After smell stimulation an immediate bilateral but short response was seen. First a decrease and afterwards an increase were found in the mean PD2i. In contrast, the taste stimulation resulted in a later reaction mainly on the right side. The SL in the slow alpha band decreased during the first 15s after both stimulations. In the second 15s, however, a remarkable SL increase was seen mainly in the 7-14Hz and in every frequency band. The decreased mean PD2i and SL values could be interpreted by the simplified network preparation to cognitive data processing. The PD2i and SL methods detected subtle dynamical changes during olfactory and gustatory processes suitable for collection normative database to pathological conditions.     

The inhibitory effect of trimethylamine on the anticonvulsant activities of quinine in the pentylenetetrazole model in rats

Quinine specifically blocks connexin 36 (Cx36), one of the proteins that form gap junction channels. Quinine suppressed ictal epileptiform activity in in vitro and in vivo studies without decreasing neuronal excitability. In this study, we considered the possible mechanism of anticonvulsant effects of quinine (1, 250, 500, 1000 and 2000 microM, i.c.v.) in the pentylenetetrazole (PTZ) model of seizure. Thus, we used trimethylamine (TMA) (0.05 microM, 5 microM, 50 microM), a gap junction channel opener, to examine whether it could reverse the effects of quinine in rats. Intracerebroventricular (i.c.v.) injection of quinine affected generalized tonic-clonic seizure (GTCS) induced by PTZ by increments in seizure onset and reducing seizure duration. Additionally, pretreatment with different doses of TMA (i.c.v.) attenuated the anticonvulsant effects of quinine on the latency and duration of GTCS. It can be concluded that quinine possesses anticonvulsant effects via modulation of gap junction channels, which could contribute to the control of GTCS.     

Pharmacological evaluation of the anxiolytic and sedative effects of Tilia americana L. var. mexicana in mice

The anxiolytic and sedative effects of Tilia americana L. var. mexicana (Schltdl.) Hardin inflorescence extracts and its acute toxicity were tested. Sodium pentobarbital (SP)-induced hypnosis potentiation (SPP), as well as ambulatory activity and anti-anxiety response in three different experimental models were evaluated with hexane and methanol extracts in mice. In order to determine the proper timing of assessments and to identify the most active extract, a 100mg/kg dosage of hexane, ethyl acetate and methanol crude extracts were tested on SPP after 15, 30 and 60min of the administration. Then a dose-response curve was made for the hexane (10-1000mg/kg) and methanol (10-300mg/kg) extracts in all experimental models. Both extracts produced a significant and dose-dependent lengthening in the time of SP, with the methanol extract being more potent than the hexane extract at 60min after administration. Moreover, a significant and dose-dependent attenuation in the anxiety-response in the plus-maze test and exploratory cylinder activity, but also a diminution in the ambulatory activity and in the head dipping response were observed resembling the response to diazepam. Acute toxicity was observed with less dose of methanol extract (LD(50)=375mg/kg) in comparison to the hexane extract (LD(50)>2900mg/kg). Results of the present study shows that Tilia americana var. mexicana possesses depressant activity on the CNS similar to the better-studied species of European Tilia and reinforces its use as anxiolytic and sedative in traditional medicine.     

The alternative sigma factor B modulates virulence gene expression in a murine Staphylococcus aureus infection model but does not influence kidney gene expression pattern of the host

Infections caused by Staphylococcus aureus are associated with significant morbidity and mortality and are an increasing threat not only in hospital settings. The expression of the staphylococcal virulence factor repertoire is known to be affected by the alternative sigma factor B (SigB). However, its impact during infection still is a matter of debate. Kidney tissues of controls or mice infected with S. aureus HG001 or its isogenic sigB mutant were analyzed by transcriptome profiling to monitor the host response, and additionally expression of selected S. aureus genes was monitored by RT-qPCR. Direct transcript analysis by RT-qPCR revealed significant SigB activity in all mice infected with the wild-type strain, but not in its isogenic sigB mutant (p < 0.0001). Despite a clear-cut difference in the SigB-dependent transcription pattern of virulence genes (clfA, aur, and hla), the host reaction to infection (either wild type or sigB mutant) was almost identical. Despite its significant activity in vivo, loss of SigB did neither have an effect on the outcome of infection nor on murine kidney gene expression pattern. Thus, these data support the role of SigB as virulence modulator rather than being a virulence determinant by itself.     

靶向Atp6i和T细胞免疫应答cDNA7的小干扰RNA载体构建及其腺相关病毒重组颗粒的制备

目的 构建靶向Atp6i和T细胞免疫应答cDNA7(TIRC7)的RNA干扰重组体,包装成腺相关病毒(AAV)重组颗粒,为使用该干扰重组体进行体内外基因治疗相关疾病提供依据.方法 设计特异性针对Atp6i和TIRC7基因共同区域的小干扰RNA序列,连接到经Xba Ⅰ和BglⅡ酶切线性化的pAAV.H1载体上并转化DH5α菌株,提取质粒行酶切鉴定后进行测序分析.将酶切及测序分析鉴定成功的小干扰RNA序列与pAAV-RC、pHelper采用磷酸钙沉淀法共转染AAV-293细胞,复制、包装组成AAV.H1Atp6i重组病毒颗粒,以磷酸盐缓冲液(PBS)作为空白对照组,AAV.H1Luc作为阴性对照组,荧光显微镜观察转染效率.Western免疫印迹检测AAV.H 1Atp6i重组病毒颗粒对TIRC7蛋白表达的影响.结果 成功构建靶向Atp6i和TIRC7的RNA干扰重组体.重组质粒、pAAV-RC及pHelper成功转染AAV-293细胞,转染效率近100％,成功包装成AAV.H1Atp6i重组病毒颗粒.Western免疫印迹显示TIRC7蛋白在空白对照组、阴性对照组及AAV.H1Atp6i处理组均有表达,相对分子质量为75 000,AAV.H1Atp6i处理组TIRC7蛋白表达较空白对照组和阴性对照组均下降了80％ (0.271 ±0.072比0.988±0.042、0.992±0.053,均P＜0.05).结论 成功获得靶向Atp6i和TIRC7的RNA干扰重组体以及AAV.H1Atp6i重组病毒颗粒,可以干扰TIRC7蛋白的表达.     

Piecing together the puzzle of acetaldehyde as a neuroactive agent

Mainly known for its more famous parent compound, ethanol, acetaldehyde was first studied in the 1940s, but then research interest in this compound waned. However, in the last two decades, research on acetaldehyde has seen a revitalized and uninterrupted interest. Acetaldehyde, per se, and as a product of ethanol metabolism, is responsible for many pharmacological effects which are not clearly distinguishable from those of its parent compound, ethanol. Consequently, the most recent advances in acetaldehyde's psychopharmacology have been inspired by the experimental approach to test the hypothesis that some of the effects of ethanol are mediated by acetaldehyde and, in this regard, the characterization of metabolic pathways for ethanol and the localization within discrete brain regions of these effects have revitalized the interest on the role of acetaldehyde in ethanol's central effects. Here we present and discuss a wealth of experimental evidence that converges to suggest that acetaldehyde is an intrinsically active compound, is metabolically generated in the brain and, finally, mediates many of the psychopharmacological properties of ethanol.     

Celecoxib enhances the effect of reboxetine and fluoxetine on cortical noradrenaline and serotonin output in the rat

A substantial number of patients with major depressive disorder (MDD) do not respond adequately to current antidepressant pharmacological treatments, which are all more or less based on a gradually increased enhancement of monoaminergic neurotransmission. Although a functional deficiency in monoaminergic neurotransmission may contribute to MDD, the etiology and pathophysiology are far from clarified. Recent studies suggest that inflammatory processes may contribute, since increased levels of pro-inflammatory cytokines and prostaglandin E(2) (PGE(2)) have repeatedly been observed in a subset of patients suffering from MDD. Interestingly, adjunct treatment with the anti-inflammatory drug celecoxib, a cyclo-oxygenase-2 (COX-2) inhibitor which blocks the PGE(2)-production, has shown to enhance the efficacy of both reboxetine, a selective noradrenaline reuptake inhibitor, as well as fluoxetine, a selective serotonin reuptake inhibitor, in treatment-resistant depression. To examine the neurobiological underpinnings to the clinical observations, we here studied the acute effects of a combined treatment with celecoxib and reboxetine on noradrenaline and dopamine output, as well as celecoxib and fluoxetine on 5-HT output in the medial prefrontal cortex, using in vivo microdialysis in awake freely moving rats. Celecoxib significantly potentiated the effects of reboxetine and fluoxetine on cortical noradrenaline and 5-HT output, respectively, but not the reboxetine-induced dopamine output. Moreover, celecoxib, when given alone, enhanced 5-HT output. These findings provide, in principle, novel experimental support for the clinical utility of combined treatment with antidepressant and anti-inflammatory drugs, such as COX-2 inhibitors, in MDD.     

Antidiabetic effect of total saponins from Entada phaseoloides (L.) Merr. in type 2 diabetic rats

id="absSec_N5a3ed8c0N597cde68">Ethnopharmacological relevance

The seed of Entada phaseoloides (L.) Merr. (Entada phaseoloides) has been long used as an effective herb for the treatment of Diabetes mellitus by Dai people, one of the Chinese ethnic minorities. Saponin is an abundant type of secondary metabolic products in the seed of this plant. The aim of this study is to evaluate the potential therapeutic effects of total saponins from Entada phaseoloides (TSEP) in experimental type 2 Diabetes mellitus (T2DM) rats.

id="absSec_N5a3ed8c0N597ceca0">Materials and methods

T2DM rats were induced by high-fat diet and low-dose streptozotocin (STZ). Then different oral doses of TSEP (25, 50 and 100 mg/kg) were administrated to T2DM rats for 21 days. For comparison, a standard antidiabetic drug, metformin (200 mg/kg), was used as a positive control drug. Then the relative biochemical analysis and histopathological examination were made to evaluate the antidiabetic effect of TSEP.

id="absSec_N5a3ed8c0N597ced00">Results

TSEP dramatically reduced fasted blood glucose and serum insulin levels and alleviates hyperglycemia associated oxidative stress in T2DM rats. Moreover, a significantly hypolipidemic effect and an improvement in tissue steatosis could be observed after TSEP administration. Further investigations revealed a possible anti-inflammation effect of TSEP by examining serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP). The effects of TSEP exhibited a dose-dependent manner and were comparable to metformin.

id="absSec_N5a3ed8c0N597ced60">Conclusion

Our present study demonstrates both hypoglycemic and hypolipidemic activities of TSEP in T2DM rats, which support its antidiabetic property. This work also implies a possibility that TSEP exerts its therapeutic effect through repressing chronic inflammation responses.     

Effect of clonidine pre-medication on propofol requirements during lower extremity vascular surgery: a randomized controlled trial

Background. Pre-medication with clonidine reduces the requirementfor volatile agents during general anaesthesia. This may alsobe true for anaesthesia with propofol, but the amount of dosereduction has not been measured. Because clonidine also affectscardiac output and thus regional blood flow it could alter thepharmacokinetics of propofol. This randomized, double-blindplacebo-controlled trial aimed to study the effect of clonidinepre-medication on dose requirement for propofol during lowerextremity vascular surgery using the bispectral index (BIS)as a measure of anaesthetic depth. Methods. After oral pre-medication with either clonidine 3 µgkg^–1 or placebo, 39 subjects had lower limb vascular surgeryusing propofol infusion for anaesthesia. Anaesthetic depth wasadjusted to a BIS of 45. Predicted plasma propofol concentrationswere noted every 30 min from a target-controlled propofol infusionpump and arterial samples were taken at the same time for propofolmeasurements. Results. Patients in both groups were anaesthetized to similardepths of anaesthesia as indicated by BIS readings (P=0.44).The groups had comparable mean (95% CI) arterial concentrationsof propofol, 4.8 (3.5–6.1) µg ml^–1 in thepatients given clonidine, and 4.6 (3.4–5.7) µg ml^–1in the patients given placebo (P=0.81). However, the averageplasma concentration predicted by the target-controlled infusionwas less in the clonidine group [3.2 (2.9–3.5)] than inthe group given placebo [3.6 (3.3–3.9)] µg ml^–1(P<0.05). Conclusions. Pre-medication with clonidine reduces the requirementfor propofol, which is a pharmacokinetic effect and not a pharmacodynamiccentral sedative effect.