Worlanyo E. Gato

Investigating Susceptibility to Diabetes Using Features of the Adipose Tissue in Response to In Utero Polycyclic Aromatic Hydrocarbons Exposure

Background In recent times, there has been an increase in the incidence of type 2 diabetes mellitus (T2DM) particularly in children. Adipocyte dysfunction provide a critical link between obesity and insulin resistance resulting in diabetes outcome. Further, environmental chemical exposure during early years of life might be a significant contributing factor to the increase in the incidence of T2DM. This study tests the idea that exposure to environmental contaminants (2-aminoanthracene [2AA]) in utero will show effects in the adipose tissue (AT) that signify T2DM vulnerability. 2AA is a polycyclic aromatic hydrocarbon found in a variety of products. Methods To accomplish the study objective, pregnant dams were fed various amounts of 2AA adulterated diets from gestation through postnatal period. The neonates and older offspring were analyzed for diabetic-like genes in the ATs and analysis of serum glucose. Furthermore, weight monitoring, histopathology and immunohistochemical (IHC) staining for CD68 in AT, adipocyte size determination and adiponectin amounts in serum were undertaken. Results Up-regulation of adiponectin and interleukin-6 genes were noted in the pups and older rats. Combination of intrauterine 2AA toxicity with moderate high fat diet exhibited gene expression patterns similar to those of the neonates. Elevated serum glucose levels were noted in treated groups. IHC of the AT indicated no significant malformations; however, CD68+ cells were greater in the animals treated to 2AA. Similarly, mean sizes of the adipocytes were larger in treated and combined 2AA and moderate high fat animals. Adiponectin was reduced in 2AA groups. Conclusion From the preceding, it appears intrauterine 2AA disturbance, when combined with excess fat accumulation will lead to greater risk for the diabetic condition.

Time-Dependent Regulation of Apoptosis by Aen and Bax in Response to 2-Aminoanthracene Dietary Consumption

Background/Objective: The modulation of the toxic effects of 2-aminoanthracene (2AA) on the liver by apoptosis was investigated. Fisher-344 (F344) rats were exposed to various concentrations of 2AA for 14 and 28 days. The arylamine 2AA is an aromatic hydrocarbon employed in manufacturing chemicals, dyes, inks, and it is also a curing agent in epoxy resins and polyurethanes. 2AA has been detected in tobacco smoke and cooked foods. Methods: Analysis of total messenger ribonucleic acid (mRNA) extracts from liver for apoptosis-related gene expression changes in apoptosis enhancing nuclease (AEN), Bcl2-associated X protein (BAX), CASP3, Jun proto-oncogene (JUN), murine double minute-2 p53 binding protein homolog (MDM2), tumor protein p53 (p53), and GAPDH genes by quantitative real-time polymerase chain reaction (qRT-PCR) was coupled with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase-3 (Casp3) activity assays. Results: Specific apoptosis staining result does not seem to show significant difference between control and treated animals. This may be due to freeze-thaw artifacts observed in the liver samples. However, there appears to be a greater level of apoptosis in medium- and high-dose (MD and HD) 2AA treated animals. Analyses of apoptosis-related genes seem to show AEN and BAX as the main targets in the induction of apoptosis in response to 2AA exposure, though p53, MDM2, and JUN may play supporting roles. Conclusion: Dose-dependent increases in mRNA expression were observed in all genes except Casp3. BAX was very highly expressed in the HD rats belonging to the 2-week exposure group. This trend was not observed in the animals treated for 4 weeks. Instead, AEN was rather very highly expressed in the liver of the MD animals that were treated with 2AA for 28 days.

Evaluating the Cytotoxicity of Tin Dioxide NanoFiber

ABSTRACT Tin dioxide nanofibers (SnDNFs) are small fibers that have many applications. Tin dioxide nanofibers can be used in cosmetics, solar cells, toxic gas release sensors, and air pollution control. To date there have been few studies on the cytotoxicity of SnDNFs. The goal of this research is to determine if electrospun SnDNFs are toxic in a lung cancer cell line (A549). Considering the nano-scale size of the fibers, they can easily be inhaled and enter the pulmonary system and cause toxic effects in the lung. Occupational exposure to SnDNFs has been linked to pulmonary disease, making the A549 cell line important in this study. Nanofiber toxicity can vary based upon the characteristics of the fibers. Smaller nanofibers have been shown to have more toxic effects than their larger counterparts. The synthesized SnDNFs were characterized using SEM, Raman spectroscopy, and powder X-ray diffractometer (PXRD). SEM images showed the fibers to be 200–300 nm in diameter. Raman spectroscopy and PXRD indicated that the fibers were in the rutile phase. After quantifying the SnDNFs, the fibers were introduced to A549 cells at concentrations ranging from 0.02–500 µg mL−1 and incubated at 37°C. These cells were quantified with the MTT assay to measure cell proliferation (IC50 = 0.02 mg mL−1), while lactate dehydrogenase (LDH) leakage was used to determine cytotoxicity, and apoptosis assays to assess the mechanism of cell death. Increasing concentration of SnDNF generated a consequential decrease in cell proliferation and viability. The percent cytotoxicity of SnDNF was not significantly changed at the various concentrations and time frames. In order to gain additional insight about the mechanism of cytotoxicity of SnDNFs, genes with links to inflammation and apoptosis were evaluated and found to be over-expressed in treated cells. At the concentrations of SnDNF examined, SnDNF was mildly toxic to the A549 cells.

Examining the Link Between the Human Microbiome and Antisocial Behavior: Why Criminologists Should Care About Biochemistry, Too

ABSTRACT Objective: The expansion of technology enables closer examination of human biological functioning which has exponentially increased knowledge about how the human organism interacts with surrounding environs to produce certain behaviors. The contemporary biosocial model pushes crime theorists and researchers alike to consider the many biological factors that may be implicated in violent behavior and how those factors are ameliorated or exacerbated by environmental influences (and vice versa). This paper describes the human microbiome and discusses why and how the human microbiome should be incorporated into biosocial investigations of violent behavior. Method: To date, a fairly significant knowledge-base has accumulated regarding the evolutionary, genetic, and sociological bases of violent behavior but has not yet carefully considered other factors related to biochemistry: namely, the microbiome. We review the emerging literature on the role of the microbiome on phenotypes––particularly antisocial behavior––and synthesize the contribution of this literature to the study of antisocial behavior. Results: The microbiome is likely an important contributor to animal and human behavior. Recent studies show that the microbiome holds promise in explaining antisocial behavior among a wide range of species including humans. Conclusion: Criminological theory and public policy can incorporate knowledge about the microbiome in the explanation of violent behavior, and prevention and intervention efforts.

Diabetes in the Cape Coast metropolis of Ghana: an assessment of risk factors, nutritional practices and lifestyle changes

Background Despite the significant increase in the incidence of diabetes in Ghana, research in this area has been lagging. The purpose of the study was to assess the risk factors associated with diabetes in the Cape Coast metropolis of Ghana, and to describe nutritional practices and efforts toward lifestyle change. Methods A convenient sample of 482 adults from the Cape Coast metropolis was surveyed using a self-reported questionnaire. The survey collected information on the demographic, socioeconomic characteristics, health status and routine nutritional practices of respondents. The aims of the study were addressed using multivariable regression analyses. Results A total of 8% of respondents reported that they had been diagnosed with diabetes. Older age and body weight were found to be independently associated with diabetes. Individuals living with diabetes were no more likely than those without diabetes to have taken active steps at reducing their weight. Conclusion The percentage of self-reported diabetes in this population was consistent with what has been reported in previous studies in Ghana. The findings from this study highlight the need for more patient education on physical activity and weight management.

Assessment of the short-term toxicity of TiO2 nanofiber in Sprague Dawley rats: Gato et al.

Synthetic nanomaterials have many unique chemical and physical properties, mainly due to their high specific surface area and quantum confinement effect. Specifically, titanium dioxide (TiO2) nanomaterial has high stability, anticorrosive, and photocatalytic properties. However, there are concerns over adverse biological effects resulting from bioeffects. This study was to investigate adverse effects associated with acute ingestion of TiO2 nanofiber (TDNF). TDNF was fabricated via electrospinning method, followed by dissolution in water. Six‐ to seven‐week‐old male Sprague Dawley rats were exposed to a total of 0, 40, and 60 ppm of TDNF for 2 weeks via oral gavage. Serum total protein and weight gain during the course of this study displayed marginal concentration‐dependent alterations. These findings were followed by a global gene expression analysis to identify which transcripts might be responsive to TNDF toxicity. Differentially expressed mRNA levels were dose‐dependently higher in animals exposed to TNDF. The majority of the affected genes were biochemically involved in immune response and inflammation. We believe this is due to the fact that TNDF is unable to penetrate the cell and forms phagocytosis sites that trigger inflammatory and immune response. All results taken together, short‐term ingestion of TNDF produced marginal effects indicative of inflammation. Finally, the broad gene expression data were validated through quantification of immunoglobulin heavy chain alpha (Igha). Igha gene was upregulated in treated groups, showing similar expression patterns to the global gene expression data.

Response: Investigating Susceptibility to Diabetes Using Features of the Adipose Tissue in Response to In Utero Polycyclic Aromatic Hydrocarbons Exposure (Diabetes Metab J 2016;40:494-508)

We appreciate your interest and comments on our article entitled “Investigating susceptibility to diabetes using features of the adipose tissue in response to in utero polycyclic aromatic hydrocarbons exposure” that was published in Diabetes & Metabolism Journal [1].

Blood pressure control, glycemic control, and dyslipidemia among healthy adults in the Cape Coast metropolis, Ghana

BACKGROUND The World Health Organization recommends the implementation of interventions focused on the early detection of clinical risk factors for cardiovascular disease (CVD) as effective strategies for the control of CVD in low resource settings. However, due to health system resource constraints, surveillance capacity for the identification of high-risk populations for non-communicable diseases, including CVD have been inadequate. The purpose of this study was to describe the prevalence of CVD clinical risk factors among healthy adults residing in the Cape Coast metropolis of Ghana. The clinical risk factors assessed included glycemic control, insulin sensitivity, lipid control and blood pressure. METHODS The study participants included 70 healthy adults without a previous diagnosis of CVD from Cape Coast metropolis. Blood samples, blood pressure and anthropometric measurement were obtained for each participant. Serum glycated hemoglobin (HbA1c), insulin, glucose, triglycerides, and cholesterol levels were measured. RESULTS Approximately four out of ten participants were either overweight or obese. Almost three-quarters of the sample were considered prehypertensive or hypertensive. About three in ten were clinically prediabetic. About a third of the participants had high non-HDL cholesterol levels. Triglyceride concentration levels were found to be high in almost 10 percent of the study sample. Approximately six percent were identified as having metabolic syndrome. CONCLUSION A significant proportion of the study participants were identified to be at risk for CVD. There is the need for adaptive and less resource-intensive CVD risk-factor screening interventions to allow for the timely detection and management of CVD risk factors in low-resource settings.

Investigating the Toxic Effects of 2-Aminoanthracene Ingestion in Pregnant Sprague Dawley Dams

ABSTRACT Polycyclic aromatic hydrocarbons (PAHs) refer to organic compounds that are byproducts of incomplete combustion of fossil fuels and wood. One specific polycyclic aromatic hydrocarbon, 2-aminoanthracene (2AA), is a member of a broader group of compounds known as anthracenes, which have been classified by the United States Agency for Toxic Substances and Disease Registry (ASTDR) as one of a group of PAHs of top concern based on their greater potential risk for exposure and greater harmful effects to humans, compared to other PAHs. Previous research has shown that 2AA affects genes involved in carbohydrate and lipid metabolism, inflammatory stress responses, and immune system responses, among other processes. The objective of the present study was to examine the toxicity of dietary ingestion of 2AA from gestation through the postnatal period. Pregnant dams (Day 1) were purchased from Taconic Hudson, NY, and assigned into dose regimens of 0 mg/kg- (control-C), 50 mg/kg- (low dose-LD) and 100 mg/kg-diet (high dose-HD) 2AA. Dams were fed 2AA contaminated diet during the period of gestation and postpartum. Insulin and H&E immunohistochemical staining were undertaken and indicated no significant changes between control and treated groups. However, percent pancreatic islets (islets within the pancreas) were larger in the exposed groups. The value was 1.5% in the control dams compared to 3.2% and 4.3% low dose and high dose groups respectively. Serum concentrations of albumin and lactate dehydrogenase (LDH) were increased in the exposed groups, with the HD group experiencing the greater increase. Analyses of Fabp4, Mgmt , Fas, Nhej1, Aldh1a1 and Ncam1 were conducted via real-time quantitative polymerase chain reaction (RT-pPCR), using β-Actin as the control gene. There was an up-regulation of the Mgmt and Nhej1 gene transcripts in the exposed groups, with the extent of upregulation being highest in the HD group. Taken together, a link between environmental exposure to 2AA and pancreatic effects appears to exist.

Short-term evaluation of hepatic toxicity of titanium dioxide nanofiber (TDNF)

Abstract Various in vitro and in vivo studies have shown titanium dioxide nanoparticles (TDNPs) increase the production of reactive oxygen species and change the expression of genes and proteins involved in the inflammatory response and cell division. Although, the cytotoxicity of TDNPs has been shown to be largely dependent on the characteristics of the particles including shape and surface area. This present study investigates the effects of titanium dioxide nanofibers (TDNFs) with a diameter of 300–800 nm, on the histopathology of liver tissue, changes in feed efficiency and liver weights, changes in hepatic gene expression, and serum biochemical parameters in male Sprague-Dawley rats. Male Sprague-Dawley rats were fed concentrations of 0 ppm, 40 ppm, and 60 ppm TDNF by oral gavage for two weeks. Selected inflammatory response, oxidative stress, and regulatory cell cycle genes were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Differences in gene expression compared to the 0 ppm group were observed in genes Gnat3, IghA, IL-1β, p21, p53, and TNF-α. Histopathology, body and liver weights, and feed efficiency showed no significant differences. Albumin levels in all groups were not significantly higher than the reference range while ALT levels for all groups were high compared to the reference value. Currently, the results suggest TDNF does not exhibit significant hepatic toxicity. This may be explained by the rutile crystalline structure of the nanofibers, the lower concentration or the short duration of exposure toxic used during experimentation.