Innate immune responses in children and adults with Shigellosis

An array of pro- and anti-inflammatory mediators of the innate immune system was analyzed in stool, urine, and rectal mucosa samples from adults and children with shigellosis to better understand their role in recovery from and in the immunopathogenesis of the disease. Increased concentrations of lactoferrin (Lf), myeloperoxidase (MPO), prostaglandin E(2), and leukotriene B(4) (LTB(4)) in stool during acute shigellosis in both children and adults indicated that activated cells of the innate defense system at the mucosal site were secreting the mediators. Increased concentration of MPO and 8-iso-prostaglandin F(2alpha) and lower levels of superoxide dismutase (SOD) activity in stool during acute Shigella infection suggested increased formation of reactive oxygen species, free radical-catalyzed peroxidation of membrane lipids, and decreased scavenging of the reactive oxygen radicals. In children, lower expression of SOD in tissue with severe inflammation and lower levels of SOD activity in stool for longer periods compared to adults may further worsen the tissue damage and predispose the children to a lowered defense. Both adult and pediatric patients had significantly higher expression of inducible nitric oxide synthase (iNOS) in the rectum with severe inflammation, compared to that seen with mild inflammation, accompanied by persistently up-regulated iNOS mRNA, reflecting increased production of nitric oxide at the local site. However, in contrast to adults, reduced urinary nitrate levels in pediatric patients during acute shigellosis suggested lower production of nitric oxide in the renal compartment. Persistent production of Lf in pediatric patients may contribute to chronic inflammation in the rectum. In addition, increased production of proinflammatory mediators in the rectum of patients with severe histology suggested contribution of these molecules to the immunopathogenesis of severe colitis caused by shigellae.     

Evaluation of the monoclonal antibody-based kit Bengal SMART for rapid detection of Vibrio cholerae O139 synonym Bengal in stool samples.

A monoclonal antibody-based test, Bengal SMART, was developed for rapid detection of Vibrio cholerae O139 synonym Bengal directly from stool specimens. The test, which takes about 15 min to complete, was used to screen 189 diarrheal stool specimens. The results were compared with those of a monoclonal antibody-based coagglutination test (COAT) and the conventional culture methods used as the "gold standard" for detection of V. cholerae O139. The Bengal SMART test showed a sensitivity of 100% and a specificity of 97% in comparison with the gold standard. It also fared better than COAT, which had a sensitivity of 96% for rapid detection of V. cholerae O139 synonym Bengal. These results show that Bengal SMART is suitable for use in field settings for rapid diagnosis of cholera caused by V. cholerae O139.     

Epidemiology and risk factors of asthma-chronic obstructive pulmonary disease overlap in low- and middle-income countries

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Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia).

Ezetimibe [1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone] (Zetia; Schering-Plough, Kenilworth, NJ) is the first in a new class of cholesterol-lowering agents known as cholesterol absorption inhibitors. The objective of this study was to identify the isoform(s) of human liver and intestinal UDP-glucuronosyltransferase (UGT) enzymes responsible for the glucuronidation of ezetimibe. The main circulating metabolite of this drug in human plasma is SCH 60663, the phenolic glucuronide conjugate of ezetimibe. SCH 60663 [m/z = 584 Thompsons (Th)] is also the major in vitro metabolite formed by human liver microsomes supplemented with UDP glucuronic acid (UDPGA). In contrast to the liver, human jejunum microsomes supplemented with UDPGA converted ezetimibe to two glucuronides with the same mass (m/z = 584 Th) by liquid chromatography-mass spectrometry. One corresponds to the phenolic glucuronide (1-O-[4-trans-2S,3R)-1-(4-fluorophenyl)-4-oxo-3-[3(S)-hydroxy-3-(4-fluorophenyl)propyl]-2-azetidinyl]phenyl-beta-D-glucopyranuronic acid; SCH 60663) and the other was identified as the benzylic glucuronide of ezetimibe (1-O-[1(S)-(4-fluorophenyl)-3-[1-(4-fluorophenyl)-2(S)-(4-hydroxyphenyl)-4-oxo-3(R)-azetidinyl]propyl]-beta-D-glucopyranuronic acid; SCH 488128). Recombinant human UGT1A1, UGT1A3, and UGT2B15 all exhibited catalytic activity with respect to the formation of the phenolic glucuronide. However, UGT2B7 exclusively formed SCH 488128, a trace metabolite detected in dog and human plasma samples after oral administration of ezetimibe. In conclusion, the formation of SCH 60663 is mediated via UGT1A1, UGT1A3, and UGT2B15, and the formation SCH 488128 is mediated via UGT2B7.     

Review on carbonaceous materials and metal composites in deformable electrodes for flexible lithium-ion batteries

With the rapid propagation of flexible electronic devices, flexible lithium-ion batteries (FLIBs) are emerging as the most promising energy supplier among all of the energy storage devices owing to their high energy and power densities with good cycling stability. As a key component of FLIBs, to date, researchers have tried to develop newly designed high-performance electrochemically and mechanically stable pliable electrodes. To synthesize better quality flexible electrodes, based on high conductivity and mechanical strength of carbonaceous materials and metals, several research studies have been conducted. Despite both materials-based electrodes demonstrating excellent electrochemical and mechanical performances in the laboratory experimental process, they cannot meet the expected demands of stable flexible electrodes with high energy density. After all, various significant issues associated with them need to be overcome, for instance, poor electrochemical performance, the rapid decay of the electrode architecture during deformation, and complicated as well as costly production processes thus limiting their expansive applications. Herein, the recent progression in the exploration of carbonaceous materials and metals based flexible electrode materials are summarized and discussed, with special focus on determining their relative electrochemical performance and structural stability based on recent advancement. Major factors for the future advancement of FLIBs in this field are also discussed.

With the rapid propagation of flexible electronic devices, flexible lithium-ion batteries are emerging as the most promising energy supplier among all of the energy storage devices due to high energy and power densities with good cycling stability.     

Enhanced X-Ray Detectors Using Polar Dopants for KCD Digital Radiography

The goal of this study is to develop high resolution imaging detectors with applications in digital radiography and computed tomography. A physical treatment aimed at a better understanding of the line-spread function response of kinestatic charge detector (KCD) gas media, using dopants with permanent electric dipoles, is presented. Experimental results were obtained by operating a KCD krypton-filled detector at pressures up to 60 atm and constant electric field-to-gas density ratio doped with small amounts of polar or nonpolar polyatomic molecules with low or high ionization potential. The results clearly indicate that the addition of dopants having both low ionization potential and high dipole moment significantly enhance the imaging signal quality. An analysis of the experimental results aimed at providing a plausible interpretation of the reported observations is offered.     

Impact of Pre-Treatment NLR and Other Hematologic Biomarkers on the Outcomes of Early-Stage Non-Small-Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy

Introduction: We evaluated the association of pre-treatment immunologic biomarkers on the outcomes of early-stage non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). Materials and methods: In this retrospective study, all newly diagnosed early-stage NSCLC treated with SBRT between January 2010 and December 2017 were screened and included for further analysis. The pre-treatment neutrophil-lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were calculated. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan–Meier. Multivariable models were constructed to determine the impact of different biomarkers and the Akaike information criterion (AIC), index of adequacy, and scaled Brier scores were calculated. Results: A total of 72 patients were identified and 61 were included in final analysis. The median neutrophil count at baseline was 5.4 × 10⁹/L (IQR: 4.17–7.05 × 10⁹/L). Median lymphocyte count was 1.63 × 10⁹/L (IQR: 1.29–2.10 × 10⁹/L), median monocyte count was 0.65 × 10⁹/L (IQR: 0.54–0.83 × 10⁹/L), median platelet count was 260.0 × 10⁹/L (IQR: 211.0–302.0 × 10⁹/L). The median NLR was 3.42 (IQR: 2.38–5.04), median MLR was 0.39 (IQR: 0.31–0.53), and median PLR was 156.4 (IQR: 117.2–197.5). On multivariable regression a higher NLR was associated with worse OS (p = 0.01; HR-1.26; 95% CI 1.04–1.53). The delta AIC between the two multivariable models was 3.4, suggesting a moderate impact of NLR on OS. On multivariable analysis, higher NLR was associated with poor RFS (p = 0.001; NLR^1 HR 0.36; 0.17–0.78; NLR^2 HR-1.16; 95% CI 1.06–1.26) with a nonlinear relationship. The delta AIC between the two multivariable models was 16.2, suggesting a strong impact of NLR on RFS. In our cohort, MLR and PLR were not associated with RFS or OS in multivariable models. Conclusions: Our study suggests NLR, as a biomarker of systemic inflammation, is an independent prognostic factor for OS and RFS. The nonlinear relationship with RFS may indicate a suitable immunological environment is needed for optimal SBRT action and tumoricidal mechanisms. These findings require further validation in independent cohorts.     

Effect of ATP-sensitive Potassium Channel Openers on Intraocular Pressure in Ocular Hypertensive Animal Models

PurposeTo evaluate the effect of ATP-sensitive potassium channel openers cromakalim prodrug 1 (CKLP1) and diazoxide on IOP in three independent mouse models of ocular hypertension.MethodsBaseline IOP was measured in TGFβ2 overexpression, steroid-induced, and iris dispersion (DBA/2J) ocular hypertension mouse models, followed by once daily eyedrop administration with CKLP1 (5 mM) or diazoxide (5 mM). The IOP was measured in conscious animals with a handheld rebound tonometer. Aqueous humor dynamics were assessed by a constant perfusion method. Effect of treatment on ocular tissues was evaluated by transmission electron microscopy.ResultsCKLP1 decreased the IOP by 20% in TGFβ2 overexpressing mice (n = 6; P < 0.0001), 24% in steroid-induced ocular hypertensive mice (n = 8; P < 0.0001), and 43% in DBA/2J mice (n = 15; P < 0.0001). Diazoxide decreased the IOP by 32% in mice with steroid-induced ocular hypertension (n = 13; P < 0.0001) and by 41% in DBA/2J mice (n = 4; P = 0.005). An analysis of the aqueous humor dynamics revealed that CKLP1 decreased the episcleral venous pressure by 29% in TGFβ2 overexpressing mice (n = 13; P < 0.0001) and by 72% in DBA/2J mice (n = 4 control, 3 treated; P = 0.0002). Diazoxide lowered episcleral venous pressure by 35% in steroid-induced ocular hypertensive mice (n = 3; P = 0.03). Tissue histology and cell morphology appeared normal when compared with controls. Accumulation of extracellular matrix was reduced in CKLP1- and diazoxide-treated eyes in the steroid-induced ocular hypertension model.ConclusionsATP-sensitive potassium channel openers CKLP1 and diazoxide effectively decreased the IOP in ocular hypertensive animal models by decreasing the episcleral venous pressure, supporting a potential therapeutic application of these agents in ocular hypertension and glaucoma.     

Green synthesis of gold nanoparticles using an antiepileptic plant extract: in vitro biological and photo-catalytic activities

Gold nanoparticles are one of the widely used metallic nanoparticle having unique surface plasmon characteristic, offers major utility in biomedical and therapeutic fields. However, chemically synthesized nanoparticle creates toxicity in the living organisms and contradicts the eco-friendly and cost-effective nature. So, developing greener synthetic route for synthesis of gold nanoparticle using natural materials is an enthralling field of research for its effectiveness in synthesizing eco-friendly, non-toxic materials. Moreover, biological components attached as stabilizing agent can exert its own effect along with the advantages of nanoparticle conjugation. In this work, we used for the first time methanolic leaf extract of Moringa oleifera as this fraction of M. oleifera exerts a neuroactive modulation against seizure as evidenced by earlier literature. The green gold nanoparticles synthesized were characterized by different characterization tools, dynamic light scattering and transmission electron microscopy techniques etc. Prepared nanoparticles were biologically (antioxidant, antimicrobial and blood cytotoxicity) characterized to screen their further utility in therapeutic strategies. Characteristics and activities of green gold nanoparticles were compared with conventional citrate stabilized gold nanoparticles. It was observed that green gold nanoparticles prepared using M. oleifera show less cytotoxicity and helps in regeneration of neuronal cells in animal model study. It establishes the fact that conjugation of different plant extract fraction for stabilization of gold nanoparticle may be responsible factor for enhancement of bioactive nature of green gold nanoparticle. In addition, the green gold nanoparticle show efficient photo-catalytic efficiency. Development of such bioactive gold nanoparticles will lead to functional materials for biomedical and therapeutic applications.

Gold nanoparticles are one of the widely used metallic nanoparticle having unique surface plasmon characteristic, offers major utility in biomedical and therapeutic fields.