Differences in reactivation of tuberculosis induced from anti-tnf treatments are based on bioavailability in granulomatous tissue

The immune response to Mycobacterium tuberculosis (Mtb) infection is complex. Experimental evidence has revealed that tumor necrosis factor (TNF) plays a major role in host defense against Mtb in both active and latent phases of infection. TNF-neutralizing drugs used to treat inflammatory disorders have been reported to increase the risk of tuberculosis (TB), in accordance with animal studies. The present study takes a computational approach toward characterizing the role of TNF in protection against the tubercle bacillus in both active and latent infection. We extend our previous mathematical models to investigate the roles and production of soluble (sTNF) and transmembrane TNF (tmTNF). We analyze effects of anti-TNF therapy in virtual clinical trials (VCTs) by simulating two of the most commonly used therapies, anti-TNF antibody and TNF receptor fusion, predicting mechanisms that explain observed differences in TB reactivation rates. The major findings from this study are that bioavailability of TNF following anti-TNF therapy is the primary factor for causing reactivation of latent infection and that sTNF-even at very low levels-is essential for control of infection. Using a mathematical model, it is possible to distinguish mechanisms of action of the anti-TNF treatments and gain insights into the role of TNF in TB control and pathology. Our study suggests that a TNF-modulating agent could be developed that could balance the requirement for reduction of inflammation with the necessity to maintain resistance to infection and microbial diseases. Alternatively, the dose and timing of anti-TNF therapy could be modified. Anti-TNF therapy will likely lead to numerous incidents of primary TB if used in areas where exposure is likely. © 2007 Marino et al

Human Resource Role In Work-Life Balance: A Case Of High Technology Knowledge Workers In Taiwan

This case involves the problems that young people in Taiwan are facing in high tech companies. Employees are spending many hours in their jobs and making high salaries as a result, but their social lives are suffering greatly. This paper examines the relationship between the work and social life of young Taiwanese workers in high tech firms. Although salaries and compensation packages are high, the social lives of these workers have diminished greatly. This study provides a comprehensive viewpoint from the perspective of an employee within the Human Resource department of one of these companies

Testosterone and growth hormone normalization: a retrospective study of health outcomes

Enrique Ginzburg1, Alvin Lin2, Michael Sigler1, Denise Olsen2, Nancy Klimas1, Alan Mintz21University of Miami Miller School of Medicine, Miami, Florida, USA; 2Cenegenics® Medical Institute, Las Vegas, Nevada, USABackground: Age-related declines in testosterone and growth hormone (GH) are associated with increased adiposity and decreases in lean mass and bone mineral density (BMD). A long-term retrospective study examined the effects of testosterone and/or GH supplementation on body composition and quality of life (QoL).Methods: A database survey assessed the records of 91 men and 97 women (ages 25–82) in treatment groups based on their hormonal status: dehydroepiandrosterone but no hormonal supplementation (control); testosterone only (Tes); GH only (GH); and testosterone plus GH (Tes+GH). Pre- and post-treatment assessments recorded changes in fat and lean mass, BMD, and QoL.Results: After an average of 3 years of treatment, weight decreased in women in the control and Tes+GH groups but remained stable in men in all groups. Tes and Tes+GH produced statistically significant increases in lean mass, reductions in fat mass, and improvements in BMD in both sexes; GH produced similar changes in women. QoL and mood improved in all groups. Treatments were generally safe and well tolerated.Conclusions: In this retrospective survey, treatment with testosterone and/or GH was associated with favorable effects in men and women across a wide age range.Keywords: testosterone, growth hormone, body composition, quality of lif

Comparison of home range size, habitat use and the influence of resource variations between two species of greater gliders (Petauroides minor and Petauroides volans)

Knowledge of the spatial requirements of a species is fundamental to understanding its environmental requirements. However, this can be challenging as the size of a species’ home range can be influenced by ecological factors such as diet and size-dependent metabolic demands, as well as factors related to the quality of their habitat such as the density and distribution of resources needed for food and shelter. Until recently, the genus Petauroides was thought to include only a single species with a widespread distribution across eastern Australia. However, a recent study has provided genetic and morphological evidence supporting Petauroides minor as a distinct northern species. Previous studies have focused on the ecology of P. volans, but there has been inadequate research on P. minor. Data on home range and habitat use were obtained for both species using a combination of techniques including GPS collar locations, radiotelemetry, and spotlighting and comparisons were made using consistent methodology. Home range sizes of P. minor (4.79 ha ± 0.97 s.d., KUD .95) were significantly larger than those of P. volans (2.0 ha ± 0.42 s.d., KUD .95). There were no significant differences between male and female home range sizes in either species. Both species showed site-specific preferences for tree species and for larger diameter trees for both forage and shelter. Tree size and biomass/ha were significantly greater in the P. volans study sites than the P. minor study sites and there was a negative correlation between home range size and eucalypt biomass. Larger home range size is likely driven by the substantial differences in biomass between northern (tropical) and southern (temperate) eucalypt-dominated habitats affecting the quality and quantity of resources for food and shelter. Understanding landscape use and habitat requirements within each species of Petauroides can provide important information regarding limiting factors and in directing conservation and management planning

Lophira alata suppresses glioblastoma cell growth via inhibition of protein kinase C-α

The root of the plant Lophira alata (Ochnaceae) has been used as a component of traditional herbal decoctions administered to cancer patients in southwestern Nigeria. However, the mechanism of the cytotoxic effects of Lophira alata alone or in the presence of phorbol ester has not been investigated in malignant brain tumor cells. This study was aimed at examining the cytotoxic potential of the methanolic fraction of Lophira alata root on malignant glioma invasive cellular growth and survival. The antiproliferative effects of Lophira alata were assessed using the MTT (3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide) assay. Protein immunoblots were carried out to test the effects of Lophira alata, alone or in the presence of phorbol ester, on survival signaling pathways such as Akt, mTOR, PARP and caspases. The methanolic fraction of Lophira alata (LAM) induced a concentration-dependent and time-dependent decrease in glioma cell viability and cell proliferation. In addition, LAM attenuated phorbol 12-myristate 13-acetate (PMA)-mediated signaling of downstream targets such as Akt/mTOR. Gene silencing using siRNA targeting PKC-alpha abrogated LAM-mediated downregulation of Akt. Our data also revealed that treatment with LAM induced both PARP and caspase cleavage. The HPLC fingerprint of the fraction indicates the presence of the flavonoids luteolin and rutin, which are known to inhibit the proliferation of glioblastoma cells

Correlation Study: Student Success in Biochemistry as a Prerequisite for Integrated Pharmacology and Medicinal Chemistry

Background A rise in new schools of pharmacy has led to implementation of new curriculums. Pharmacy schools must adhere to standards set by the Accreditation Council of Pharmacy Education in order to provide knowledge of foundational sciences and prepare pharmacy students for the future. Prerequisites are typically foundational science courses taken early in the program so that students have the knowledge necessary to be excellent pharmacists. Within the Cedarville University School of Pharmacy, Biochemistry is a prerequisite course for Integrated Medicinal Chemistry and Pharmacology (PCoMedChem). Objectives The goal of this study is to determine if Biochemistry should remain a prerequisite course for Integrated Medicinal Chemistry and Pharmacology at Cedarville University under a TBL setting based on if student success in Biochemistry influences student success in PcoMedChem. Methodology The study will evaluate student individual and overall course grades for both Biochemistry and PcoMedChem. The data will include grades from the 2018-2021 cohorts of pharmacy students. Inclusion criteria consists of completion of Biochemistry and Integrated Medicinal Chemistry and Pharmacology. No exclusion of students exist because all student data will be evaluated. Students will complete a survey through Qualtrics regarding extracurricular commitments as well as perceptions towards the courses to supplement the findings and explain discrepancies. Analysis The demographics and students’ perceptions will be compared in SPSS by analyzing frequency of responses. Using SPSS, the Wilcoxon test and Levene’s test will be conducted followed by a Pearson or Spearman correlation, depending on distribution, in order to determine correlation between grades in Biochemistry and PcoMedChem. Additionally, an ANCOVA test will be used to analyze the data gathered from our survey. A p-value of 0.05 will be indicative of statistical significance

Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

Abstract Background Vaccine protection investigation includes three processes: vaccination, pathogen challenge, and vaccine protection efficacy assessment. Many variables can affect the results of vaccine protection. Brucella, a genus of facultative intracellular bacteria, is the etiologic agent of brucellosis in humans and multiple animal species. Extensive research has been conducted in developing effective live attenuated Brucella vaccines. We hypothesized that some variables play a more important role than others in determining vaccine protective efficacy. Using Brucella vaccines and vaccine candidates as study models, this hypothesis was tested by meta-analysis of Brucella vaccine studies reported in the literature. Results Nineteen variables related to vaccine-induced protection of mice against infection with virulent brucellae were selected based on modeling investigation of the vaccine protection processes. The variable "vaccine protection efficacy" was set as a dependent variable while the other eighteen were set as independent variables. Discrete or continuous values were collected from papers for each variable of each data set. In total, 401 experimental groups were manually annotated from 74 peer-reviewed publications containing mouse protection data for live attenuated Brucella vaccines or vaccine candidates. Our ANOVA analysis indicated that nine variables contributed significantly (P-value 0.05). The protection level of RB51 was sacrificed when the values of several variables (e.g., vaccination route, vaccine viability, and challenge pathogen strain) change. It is suggestive that it is difficult to protect against aerosol challenge. Somewhat counter-intuitively, our results indicate that intraperitoneal and subcutaneous vaccinations are much more effective to protect against aerosol Brucella challenge than intranasal vaccination. Conclusions Literature meta-analysis identified variables that significantly contribute to Brucella vaccine protection efficacy. The results obtained provide critical information for rational vaccine study design. Literature meta-analysis is generic and can be applied to analyze variables critical for vaccine protection against other infectious diseases.http://deepblue.lib.umich.edu/bitstream/2027.42/112497/1/12859_2013_Article_5801.pd