Examination of the exposome in an animal model: The impact of high fat diet and rat strain on local and systemic immune markers following occupational welding fume exposure.

The goal of this study was to investigate the impact of multiple exposomal factors (genetics, lifestyle factors, environmental/occupational exposures) on pulmonary inflammation and corresponding alterations in local/systemic immune parameters. Accordingly, male Sprague-Dawley (SD) and Brown Norway (BN) rats were maintained on either regular (Reg) or high fat (HF) diets for 24wk. Welding fume (WF) exposure (inhalation) occurred between 7 and 12wk. Rats were euthanized at 7, 12, and 24wk to evaluate local and systemic immune markers corresponding to the baseline, exposure, and recovery phases of the study, respectively. At 7wk, HF-fed animals exhibited several immune alterations (blood leukocyte/neutrophil number, lymph node B-cell proportionality)-effects which were more pronounced in SD rats. Indices of lung injury/inflammation were elevated in all WF-exposed animals at 12wk; however, diet appeared to preferentially impact SD rats at this time point, as several inflammatory markers (lymph node cellularity, lung neutrophils) were further elevated in HF over Reg animals. Overall, SD rats exhibited the greatest capacity for recovery by 24wk. In BN rats, resolution of immune alterations was further compromised by HF diet, as many exposure-induced alterations in local/systemic immune markers were still evident in HF/WF animals at 24wk. Collectively, HF diet appeared to have a greater impact on global immune status and exposure-induced lung injury in SD rats, but a more pronounced effect on inflammation resolution in BN rats. These results illustrate the combined impact of genetic, lifestyle, and environmental factors in modulating immunological responsivity and emphasize the importance of the exposome in shaping biological responses.

Scaffold of Selenium Nanovectors and Honey Phytochemicals for Inhibition of Pseudomonas aeruginosa Quorum Sensing and Biofilm Formation.

Honey is an excellent source of polyphenolic compounds that are effective in attenuating quorum sensing (QS), a chemical process of cell-to-cell communication system used by the opportunistic pathogen Pseudomonas aeruginosa to regulate virulence and biofilm formation. However, lower water solubility and inadequate bioavailability remains major concerns of these therapeutic polyphenols. Its therapeutic index can be improved by using nano-carrier systems to target QS signaling potently. In the present study, we fabricated a unique drug delivery system comprising selenium nanoparticles (SeNPs; non-viral vectors) and polyphenols of honey (HP) for enhancement of anti-QS activity of HP against P. aeruginosa PAO1. The developed selenium nano-scaffold showed superior anti-QS activity, anti-biofilm efficacy, and anti-virulence potential in both in-vitro and in-vivo over its individual components, SeNPs and HP. LasR is inhibited by selenium nano-scaffold in-vitro. Using computational molecular docking studies, we have also demonstrated that the anti-virulence activity of selenium nano-scaffold is reliant on molecular binding that occurs between HP and the QS receptor LasR through hydrogen bonding and hydrophobic interactions. Our preliminary investigations with selenium-based nano-carriers hold significant promise to improve anti-virulence effectiveness of phytochemicals by enhancing effective intracellular delivery.

Fibrinolytic Activity of Blood and its Determinants in Healthy Medical Students.

BACKGROUND: Decreased fibrinolytic activity results in longer fibrinolysis time of blood and an increased propensity for hypercoagulable states of blood. Subjects with less fibrinolytic activity are prone to coronary artery disease, stroke and thromboembolic phenomena. AIM: The study aims to identify the impact of gender, dietary habits, body mass index, physical activity level and menstrual cycle on fibrinolytic activity in healthy subjects. SETTINGS AND DESIGN: Cross-sectional study on randomly selected 206 healthy medical students aged 17 to 23 years. MATERIALS AND METHODS: Anthropometric measurements, dietary habits, physical activity level and menstrual history were obtained. Fibrinolysis time of fasting venous blood sample was determined by Euglobulin Lysis Time (ELT) method. RESULTS: Highly significant gender difference was noted in mean fibrinolytic activity (p=0.002). Mean fibrinolytic activity also showed a significant relationship with BMI (p=0.001) and with different phases of menstrual cycle in females (p=0.004). However, such relationship was not observed with diet and physical activity (p>0.05) in boys and girls. CONCLUSION: Gender difference, body mass index and menstrual cycle phases have influences on the fibrinolytic activity of blood. This might be due to cyclical changes in the sex hormones levels, endometrium-derived plasmin and plasminogen activators and excess production of plasminogen activator inhibitor type-1 (PAI-I) in visceral adipocytes.

Metal chelator combined with permeability enhancer ameliorates oxidative stress-associated neurodegeneration in rat eyes with elevated intraocular pressure.

Because as many as half of glaucoma patients on intraocular pressure (IOP)-lowering therapy continue to experience optic nerve toxicity, it is imperative to find other effective therapies. Iron and calcium ions play key roles in oxidative stress, a hallmark of glaucoma. Therefore, we tested metal chelation by means of ethylenediaminetetraacetic acid (EDTA) combined with the permeability enhancer methylsulfonylmethane (MSM) applied topically on the eye to determine if this noninvasive treatment is neuroprotective in rat optic nerve and retinal ganglion cells exposed to oxidative stress induced by elevated IOP. Hyaluronic acid (HA) was injected into the anterior chamber of the rat eye to elevate the IOP. EDTA-MSM was applied topically to the eye for 3 months. Eyeballs and optic nerves were processed for histological assessment of cytoarchitecture. Protein-lipid aldehyde adducts and cyclooxygenase-2 (COX-2) were detected immunohistochemically. HA administration increased IOP and associated oxidative stress and inflammation. Elevated IOP was not affected by EDTA-MSM treatment. However, oxidative damage and inflammation were ameliorated as reflected by a decrease in formation of protein-lipid aldehyde adducts and COX-2 expression, respectively. Furthermore, EDTA-MSM treatment increased retinal ganglion cell survival and decreased demyelination of optic nerve compared with untreated eyes. Chelation treatment with EDTA-MSM ameliorates sequelae of IOP-induced toxicity without affecting IOP. Because most current therapies aim at reducing IOP and damage occurs even in the absence of elevated IOP, EDTA-MSM has the potential to work in conjunction with pressure-reducing therapies to alleviate damage to the optic nerve and retinal ganglion cells.

An extended role for CT in the emergency diagnosis of malignant spinal cord compression.

AIM: To evaluate the usefulness of computed tomography (CT) for triaging between urgent transfer to a neurosurgical unit and delayed magnetic resonance imaging (MRI) in the local hospital. MATERIALS AND METHODS: Radiologists blinded to the MRI findings scored CT images from 1-5 using a novel grading system based on the degree of cord compression observed in 44 patients. Seventy separate levels were scored. The observers' CT scores were compared with the MRI findings. All scoring radiologists were specialist registrars at different stages of training. RESULTS: Agreement between CT and MRI scores for metastatic spinal cord compression (MSCC) were high with Cohen's weighted Kappa score 0.70 (p<0.001, 95% CI 0.65 to 0.75). CT has a sensitivity of 89% and specificity of 92% for MSCC. Half the false-positive and false-negative results came from a single junior radiologist who would not normally report CT or MRI studies unsupervised. The best CT-MRI agreement was from the most senior trainee radiologist. CONCLUSIONS: Spinal findings on routine staging whole-body CT combined with clinical findings are sufficient to determine which patients with MSCC can safely wait for MRI the next working day at the local hospital and those who need emergency transfer to a neurosurgical unit for MRI and possible surgical decompression.

Progesterone-induced reorganisation of NOX-2 components in membrane rafts is critical for sperm functioning in Capra hircus.

Spermatozoa produce increasing levels of reactive oxygen species (ROS) during development. We examined the functional organisation of NOX-2 subunits in developing spermatozoa and its involvement in ROS generation. We found NOX-2 components associated predominantly with caveolin-rich microdomains of sperm head and mid piece membranes. Capacitation in vitro enriched NOX-2 components within the caveolin-positive sperm membrane rafts. Progesterone, but not 17ß-oestradiol, brought about loss of caveolin and extensive reorganisations in NOX-2 distribution on sperm head microdomains and accompanying activation in the levels of superoxide. The sensitivity of superoxide production by spermatozoa to methyl-ß-cyclodextrin confirms that NOX-2 function in spermatozoa is tightly dependent on raft organisation. We conclude that progesterone-induced reorganisation of NOX-2 components in sperm membrane rafts is critical for sperm functioning.

Overexpression of aldehyde dehydrogenase 1A1 reduces oxidation-induced toxicity in SH-SY5Y neuroblastoma cells.

Oxidative stress leading to lipid peroxidation is a problem in neurodegenerative diseases, because the brain is rich in polyunsaturated fatty acids and low in endogenous antioxidants. One of the most toxic byproducts of lipid peroxidation, 4-hydroxynonenal (HNE), is implicated in oxidative stress-induced damage in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). In this study, the human neuroblastoma cell line SH-SY5Y was used to test the protective effects of increasing the detoxification of HNE by overexpressing the HNE-detoxifying enzyme aldehyde dehydrogenase 1A1 (ALDH1). Overexpression of ALDH1 in the SH-SY5Y cells acts to reduce production of protein-HNE adducts and activation of caspase-3. Our data suggest that detoxification of HNE could be therapeutic in preventing some of the toxic disruptions of the brain's redox systems found in many neurodegenerative diseases.

Acute sensorineural hearing loss immediately following a local anaesthetic dental procedure.

Acute sensorineural hearing loss is an uncommon phenomenon. We describe the first case of a 42-year-old lady who presented with acute sensorineural hearing loss occurring immediately after a dental procedure. Possible mechanisms are discussed. She was treated with high dose oral steroids, low molecular weight dextran and vasodilators with benefit.

Bioactividad de los extractos y aislamiento de los lignanos de las semillas de Centaurea dealbata / Bioactivity of the extracts and the isolation of lignans from the seeds of Centaurea dealbata

La Centaurea dealbata Willd. (familia: Asteraceae) pertenece al género Centaurea, que comprende unas 500 especies. Para evaluar la actividad antioxidante y la toxicidad general de los extractos de n-hexano, diclorometano (DCM) y metanol (MeOH) de las semillas de C. dealbata se han utilizado, respectivamente, el ensayo DPPH y el ensayo de letalidad de gambas en salmuera. Tanto el extracto de DCM como el de MeOH presentaron niveles signifi cativos de actividad antioxidante, con valores de RC50 de 6,8 x 10-2 y 4,7 x 10-2 mg/mL, respectivamente. Ninguno de los extractos presentó una toxicidad general signifi cativa (LD50 = >1000 mg/mL). Se observó que los tres principales componentes bioactivos del extracto de MeOH fueron los lignanos arctigenina, arctiina y matairesinosida. Las estructuras de estos lignanos se dilucidaron mediante análisis espectroscópicos exhaustivos y comparación directa con los datos respectivos publicados. Éste es el primer informe sobre la ocurrencia de arctiina y matairesinol en C. dealbata. También se presenta la distribución de estos lignanos dentro del género Centaurea

Centaurea dealbata Willd. (Family: Asteraceae) belongs to the big genus Centaurea that comprises ca. 500 species. The n-hexane, dichloromethane (DCM) and methanol (MeOH) extracts of the seeds of C. dealbata have been assessed for antioxidant activity and general toxicity using, respectively, the DPPH assay, and the brine shrimp lethality assay. Both the DCM and the MeOH extract showed signifi cant levels of antioxidant activities with an RC50 value 6.8 x 10-2 and 4.7 x 10-2 mg/mL, respectively. None of the extracts exhibited any signifi cant general toxicity (LD50 = >1000 mg/mL). Three major bioactive components of the MeOH extract were found to be the lignans, arctigenin, arctiin and matairesinoside. The structures of these lignans were elucidated by comprehensive spectroscopic analyses, and also by direct comparison with the respective published data. This is the fi rst report on the occurrence of arctiin and matairesionl in C. dealbata. The distribution of these lignans within the genus Centaurea has also been presented

Identification of lymphocyte subsets in pregnancy gingivitis.

The percentage of gingival tissue and peripheral T, T Subsets and B lymphocytes were assessed in ten pregnant women during the first, second and third trimesters. Clinically the gingival index (GI) was found to be higher during pregnancy than in the control group. The percentage of the T3, T4 and B cells appeared to decrease in peripheral blood and gingival tissues during pregnancy as compared to control group.

Prepubertal periodontitis: a genetic analysis.

Genetic factors were recognized as possible predisposing factors in the etiopathogenesis of prepubertal periodontitis (PP). Consequently, the present work was carried out to determine the possible mode of inheritance and if there were any associated chromosomal aberrations in cases with PP. The study included 3 families with probands manifesting PP (the families included 18 individuals). Pedigree analysis was carried out as well as chromosomal analysis. The results pointed out to the possibility of new mutations arising due to various environmental factors (including the use of pesticides and their handling), in addition to a possible autosomal recessive inheritance. Chromosomal analysis showed no association between a certain chromosomal aberration and PP. An interesting finding was that a girl proband proved to be Xo female, i.e. a case of Turner's syndrome. This could be considered the first report of Turner's syndrome with PP.