Levofloxacin-Ceftriaxone Combination Attenuates Lung Inflammation in a Mouse Model of Bacteremic Pneumonia Caused by Multidrug-Resistant Streptococcus pneumoniae via Inhibition of Cytolytic Activities of Pneumolysin and Autolysin

In this study, our objective was to determine whether a synergistic antimicrobial combination in vitro would be beneficial in the downregulation of pneumococcal virulence genes and whether the associated inflammation of the lung tissue induced by multidrug-resistant Streptococcus pneumoniae infection in vivo needs to be elucidated in order to consider this mode of therapy in case of severe pneumococcal infection. We investigated in vivo changes in the expression of these virulence determinants using an efficacious combination determined in previous studies. BALB/c mice were infected with 10⁶ CFU of bacteria. Intravenous levofloxacin at 150 mg/kg and/or ceftriaxone at 50 mg/kg were initiated 18 h postinfection; the animals were sacrificed 0 to 24 h after the initiation of treatment. The levels of cytokines, chemokines, and C-reactive protein (CRP) in the serum and lungs, along with the levels of myeloperoxidase and nitric oxide the inflammatory cell count in bronchoalveolar lavage fluid (BALF), changes in pneumolysin and autolysin gene expression and COX-2 and inducible nitric oxide synthase (iNOS) protein expression in the lungs were estimated. Combination therapy downregulated inflammation and promoted bacterial clearance. Pneumolysin and autolysin expression was downregulated, with a concomitant decrease in the expression of COX-2 and iNOS in lung tissue. Thus, the combination of levofloxacin and ceftriaxone can be considered for therapeutic use even in cases of pneumonia caused by drug-resistant isolates.     

Computational modeling of blast induced whole-body injury: a review

Blast injuries affect millions of lives across the globe due to its traumatic after effects on the brain and the whole body. To date, military grade armour materials are designed to mitigate ballistic and shrapnel attacks but are less effective in resisting blast impacts. In order to improve blast absorption characteristics of armours, the first key step is thoroughly understands the effects of blasts on the human body itself. In the last decade, a plethora of experimental and computational work has been carried out to investigate the mechanics and pathophysiology of Traumatic Brain Injury (TBI). However, very few attempts have been made so far to study the effect of blasts on the various other parts of the body such as the sensory organs (eyes and ears), nervous system, thorax, extremities, internal organs (such as the lungs) and the skeletal system. While an experimental evaluation of blast effects on such physiological systems is difficult, developing finite element (FE) models could allow the recreation of realistic blast scenarios on full scale human models and simulate the effects. The current article reviews the state-of-the-art in computational research in blast induced whole-body injury modelling, which would not only help in identifying the areas in which further research is required, but would also be indispensable for understanding body location specific armour design criteria for improved blast injury mitigation.     

变黑白头翁提取物降低亚砷酸盐对小鼠精细胞的毒性

目的：研究变黑白头翁提取物降低亚砷酸盐对小鼠精细胞毒性的作用。方法：给予实验小鼠亚砷酸钠（20mg／kg每日），并分别在第30、60、90天对小鼠进行检测。亚砷酸盐中毒小鼠被分为2组，其中一组给予变黑白头翁提取物（35mg／kg），另一组给予85％乙醇。通过检测小鼠精细胞凋亡标志蛋白CYP1A1、p53及caspase3的活性，确定细胞及DNA的损伤情况，并测定睾丸毒性标志物的水平。通过圆二色光谱仪及熔化温度数据检测变黑白头翁提取物与DNA的相互作用情况。结果：亚砷酸盐中毒小鼠的所有细胞凋亡标志蛋白及睾丸毒性标志物的水平均有所上升，而经变黑白头翁提取物治疗的小鼠上述各项指标均降低或恢复至正常水平。变黑白头翁提取物与DNA相互作用，引起了DNA结构和构象的变化。结论：变黑白头翁提取物可作为砷中毒引起的生殖功能损害的治疗药物给予研究和开发。     

Seasonal Variation of Phyto-Constituents of Tea Leaves Affects Antiproliferative Potential

Objective: Tea (Camellia sinensis Linn.; family: Theaceae) is popular as a stimulant beverage across the globe and is also utilized as a functional antioxidant in alternative medicine. This study has evaluated the impact of seasonal variation on phyto-constituents of tea.

Method: The antiproliferative potential of methanolic extracts of tea leaves collected in the rainy season (MECR) was compared with the extract of tea leaves collected in the autumn season (MECA) of the same mother plant. Evaluation of in vivo antitumor activity was carried out in adult female Swiss albino mice groups inoculated with Ehrlich ascites carcinoma (EAC) cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to compare efficacy of MECR with that of MECA in the EAC cell line. Both qualitative and quantitative tests for phytochemical constituents present in MECA and MECR were performed. Antitumor efficacy of both the extracts was determined by evaluating different tumor markers showing dose-dependent cytotoxicity.

Results: Statistically significant reduction in EAC-induced tumor was observed in MECR treated mice compared to MECA treated ones. Cell decimation was significantly higher with MECR treatment, where restoration of different parameters including tissue structures returned to normal. Moreover, gas chromatography–mass spectrometry (GC-MS) study revealed the presence of cyclobarbital and benzazulene derivative in MECR, which is thought to be a novel source of these chemicals.

Conclusions: To our knowledge, there is no report that has attempted to reveal nutritional changes in terms of efficacy and variation in anticancer constituents in tea leaves, plucked in two seasons. This study revealed a novel source of barbital and benzazulene derivative. The unique presence of cyclobarbital and benzazulene, as revealed from GC-MS data, in methanolic extract of tea leaves collected during the rainy season (MECR) may have contributed to its enhanced in vitro (adopting MTT assay) and in vivo (on EAC-infected Swiss albino mice) cytotoxicity vis-à-vis antiproliferative properties compared to methanolic extract of tea leaves collected during the autumn season (MECA). The nature of plucking leaves in the two selected seasons is different.     

Atypical presentation of tuberous sclerosis and obsessive compulsive disorder in an adult male

Tuberous Sclerosis (TSC) is clinically marked by a triad of adenoma sebaceum, epilepsy and mental retardation. It can however manifest as various neuropsychiatric disorders. We report a patient who presented with TSC and co-morbid Obsessive Compulsive Disorder.