Papers by Aramandla Ramesh
Environmental Toxicology and Pharmacology, Sep 1, 2013
Our environment is contaminated with a diverse array of chemicals; one of which is polycyclic aro... more Our environment is contaminated with a diverse array of chemicals; one of which is polycyclic aromatic hydrocarbons (PAHs). While some PAHs are potent by nature, others undergo interactions such as additivity, synergism, antagonism or potentiation to manifest their toxicity. Therefore, the objective of this study was to investigate whether exposure to benzo(a)pyrene (BaP), a PAH compound influences the cytotoxicity and metabolism of fluoranthene (FLA; another PAH compound) using HT-29 cells. Cells cultured in Dulbecco's Modified Eagle Medium were treated with 1, 5, 10, 25 μM BaP and FLA (0.01% dimethylsulfoxide as vehicle) individually and in combination over the course of 0-96 h. At the end of exposure, cells were stained with propidium iodide and the changes in cell cycle were analyzed using FACS analysis. Apoptosis was determined by caspase-3 assay. Post-incubation, samples were extracted and analyzed for FLA metabolites by reverse-phase HPLC with fluorescence detection. Cells exposed to BaP + FLA showed a marginal decrease in growth as compared to FLA alone and vehicle controls. Also, a decline in the percentage of cells in the S and G2 phases compared to G1 phase of cell cycle was noted when cells were treated with BaP and FLA together, compared to individual FLA treatment. The rate of FLA metabolism was more when cells were exposed to FLA in combination with BaP, compared to FLA alone. The enhanced biotransformation of FLA as a result of concomitant exposure to BaP may have implications for colon cancer risks arising from human dietary exposure to PAH mixtures through consumption of barbecued meat.
The FASEB Journal, Apr 1, 2012
Experimental and Toxicologic Pathology, Aug 1, 2008
The objective of this study was to evaluate the reproductive risk associated with exposure of adu... more The objective of this study was to evaluate the reproductive risk associated with exposure of adult male Fisher-344 rats to inhaled benzo(a)pyrene (BaP). Rats were assigned randomly to a treatment or control group. Treatment consisted of sub-chronic exposure of rats via inhalation to 75μg BaP/ m 3 , 4 hours daily for 60 days, while control animals were unexposed (UNC). Blood samples were collected immediately after the cessation of exposures (time 0) and subsequently at 24, 48, and 72 hrs, to assess the effect of bioavailable BaP on plasma testosterone and luteinizing hormone (LH) concentrations. Rats were sacrificed after the last blood collection. Testes were harvested, weighed and prepared for histology and morphometric analysis, and cauda epididymides were isolated for the determination of progressive motility and density of stored spermatozoa. BaP exposure reduced testis weight compared with UNC (Mean ± SE; 2.01 ± 0.11 vs. 3.04 ± 0.16 g; P< 0.025), and caused significant reductions in the components of the steroidogenic and spermatogenic compartments of the testis. Progressive motility and mean density of stored spermatozoa were reduced (P< 0.05). Plasma testosterone concentrations were decreased by two-thirds in BaPexposed rats throughout the time periods studied compared with those of their UNC counterparts (P< 0.05), concomitant with increased concentrations of LH in BaP-exposed rats (P< 0.05). These data suggest that sub-chronic exposure to inhaled BaP contribute to reduced testicular and epididymal function in exposed rats.
Hygiene and environmental health advances, Dec 1, 2022
![Research paper thumbnail of Benzo[a]pyrene Potentiates the Pathogenesis of Abdominal Aortic Aneurysms in Apolipoprotein E Knockout Mice](https://attachments.academia-assets.com/108931681/thumbnails/1.jpg)
Cellular Physiology and Biochemistry, 2012
The objective of this study was to determine the effect of benzo[a]pyrene (BaP), an abundant envi... more The objective of this study was to determine the effect of benzo[a]pyrene (BaP), an abundant environmental polycyclic aromatic hydrocarbon compound, on the pathogenesis of abdominal aortic aneurysms (AAA). Earlier studies have shown that BaP promotes vasculopathy, including atherosclerosis, a predisposing factor for AAA development. In two experimental arms, 203 apolipoprotein E knockout (ApoE-/-) mice were evaluated in 4 groups: BaP, angiotensin II (AngII), BaP+AngII and control. Mice in the first arm were exposed to 5mg/kg/week of BaP for 42 days, and in the second arm to 0.71mg/kg daily for 60 days. In arm one, AAA incidence was higher in the BaP+AngII (14/28) versus AngII (8/27) group (p < 0.05), rupture (n=3) was observed only in BaP+AngII treated mice (p < 0.05). In the second arm, AAA incidence did not differ between AngII (17/30) and BaP+AngII (16/29) groups. However, intact AAA diameter was larger in the BaP+AngII (2.3 ± 0.1mm) versus AngII (1.9 ± 0.1mm) group (p < 0.05), but AAA rupture did not differ (p=NS). In both experimental arms, BaP+AngII mice showed increased expression of tumor necrosis factor alpha (TNF-α), cyclophilin A (Cyp A), and matrix metalloproteinase-9 (MMP9) (p < 0.05). No AAA occurred in control or BaP groups. These findings suggest the role of BaP exposure in potentiating AAA pathogenesis, which may have potential public health significance.
![Research paper thumbnail of Sex Differences in Embryonic Gonad Transcriptomes and Benzo[a]pyrene Metabolite Levels After Transplacental Exposure](https://a.academia-assets.com/images/blank-paper.jpg)
Endocrinology, Nov 3, 2021
Polycyclic aromatic hydrocarbons like benzo[a]pyrene (BaP) are generated during incomplete combus... more Polycyclic aromatic hydrocarbons like benzo[a]pyrene (BaP) are generated during incomplete combustion of organic materials. Prior research has demonstrated that BaP is a prenatal ovarian toxicant and carcinogen. However, the metabolic pathways active in the embryo and its developing gonads and the mechanisms by which prenatal exposure to BaP predisposes to ovarian tumors later in life remain to be fully elucidated. To address these data gaps, we orally dosed pregnant female mice with BaP from embryonic day (E) 6.5 to E11.5 (0, 0.2, or 2 mg/kg/day) for metabolite measurement or E9.5 to E11.5 (0 or 3.33 mg/kg/day) for embryonic gonad RNA sequencing. Embryos were harvested at E13.5 for both experiments. The sum of BaP metabolite concentrations increased significantly with dose in the embryos and placentas, and concentrations were significantly higher in female than male embryos and in embryos than placentas. RNA sequencing revealed that enzymes involved in metabolic activation of BaP are expressed at moderate to high levels in embryonic gonads and that greater transcriptomic changes occurred in the ovaries in response to BaP than in the testes. We identified 490 differentially expressed genes (DEGs) with false discovery rate P-values &lt; 0.05 when comparing BaP-exposed to control ovaries but no statistically significant DEGs between BaP-exposed and control testes. Genes related to monocyte/macrophage recruitment and activity, prolactin family genes, and several keratin genes were among the most upregulated genes in the BaP-exposed ovaries. Results show that developing ovaries are more sensitive than testes to prenatal BaP exposure, which may be related to higher concentrations of BaP metabolites in female embryos.
Elsevier eBooks, 2017
Abstract Infertility cases among men and women of reproductive age have registered a global incre... more Abstract Infertility cases among men and women of reproductive age have registered a global increase in the last decade. Some infertility cases are idiopathic in nature and may originate from exposures to chemical contaminants in domestic and occupational environmental settings. One group of chemical contaminants that have generated a lot of interest in view of their ubiquitous environmental distribution is polycyclic aromatic hydrocarbons (PAHs), a family of semivolatile and lipophilic compounds that are products of combustion. This chapter focuses on how PAHs impact reproduction and development in animal models and humans using benzo(a)pyrene [B(a)P] as a prototypical PAH toxicant. Topics covered in this chapter include the effect of B(a)P on female reproduction, follicular growth, fetal survival, puberty, reproductive tract function and menopause, male reproduction, and PAH-induced DNA damage in reproductive tissues. The mechanisms that underlie these toxic effects are explained in the context of B(a)P biotransformation and kinetics of B(a)P-reactive metabolite disposition in reproductive tissues. The information presented in this chapter is expected to provoke debate among toxicologists and also raise awareness among caregivers about damage to reproductive health when occupationally exposed individuals dominate the patient populations that frequent infertility clinics.
PLOS ONE, Sep 8, 2016
We previously reported that overexpression of catalase upregulated xenobiotic-metabolizing enzyme... more We previously reported that overexpression of catalase upregulated xenobiotic-metabolizing enzyme (XME) expression and diminished benzo(a)pyrene (BaP) intermediate accumulation in mouse aortic endothelial cells (MAECs). Endoplasmic reticulum (ER) is the most active organelle involved in BaP metabolism. To examine the involvement of ER in catalase-induced BaP detoxification, we compared the level and distribution of XMEs, and the profile of BaP intermediates in the microsomes of wild-type and catalase transgenic endothelial cells. Our data showed that endothelial microsomes were enriched in cytochrome P450 (CYP) 1A1, CYP1B1 and epoxide hydrolase 1 (EH1), and contained considerable levels of NAD(P)H: quinone oxidoreductase-1 (NQO1) and glutathione S-transferase-pi (GSTP). Treatment of wildtype MAECs with 1μM BaP for 2 h increased the expression of microsomal CYP1A1, 1B1 and NQO1 by~300, 64 and 116%, respectively. However, the same treatment did not significantly alter the expression of EH1 and GSTP. Overexpression of catalase did not significantly increase EH1, but upregulated BaP-induced expression of microsomal CYP1A1, 1B1, NQO1 and GSTP in the following order: 1A1>NQO1>GSTP>1B1. Overexpression of catalase did not alter the distribution of each of these enzymes in the microsomes. In contrast to our previous report showing lower level of BaP phenols versus BaP diols/diones in the whole-cell, this report demonstrated that the sum of microsomal BaP phenolic metabolites were~60% greater than that of the BaP diols/diones after exposure of microsomes to BaP. Overexpression of catalase reduced the concentrations of microsomal BaP phenols and diols/diones bỹ 45 and 95%, respectively. This process enhanced the ratio of BaP phenol versus diol/dione metabolites in a potent manner. Taken together, upregulation of phase II XMEs and CYP1 proteins, but not EH1 in the ER might be the mechanism by which overexpression of catalase reduces the levels of all the BaP metabolites, and enhances the ratio of BaP phenolic metabolites versus diol/diones in endothelial microsomes.
Patient Experience Journal
Assess the effect of patient-centered communication (PCC) scale on the patient satisfaction of he... more Assess the effect of patient-centered communication (PCC) scale on the patient satisfaction of healthcare providers (HCPs). The 2020 Health Information National Trends Survey (HINTS) was used to analyze the patient's satisfaction of HCPs. This survey includes 2466 patients' responses and were analyzed using the multivariable binary Hyperbolastic regression model of type II. The study examines the effects of PCC scale on patients' satisfaction of HCPs while controlling for pandemic status, employment, education, marital status, race, political views, waiting time status, sex, income, and age. PCC scale was the most significant predictor of patients' satisfaction of their HCPs (P-value < 0.001) followed by waiting time status (P-value < 0.001), and age (P-value = 0.016). The odds of patient satisfaction with the healthcare provider services were approximately 20% higher prior to the pandemic than during the pandemic (P-value = 0.415). The odds of satisfaction for patients earning $100k+ was approximately three times more than those making less than $35,000 (P-value = 0.003). PCC scale is a powerful measure that may be used as a metric for patients' satisfaction of HCPs. Taking steps to improve communication between HCPs and patients is a key factor in patient satisfaction. Concentrating on the seven domains of PCC will result in higher patient satisfaction of HCPs. The improvement in PCC will encourage each patient to disclose vital information about his or her health. This may increase the accuracy of diagnosis, quality of care, and health outcomes.
Journal of Primary Care & Community Health
Background: The objective of the study was to measure the risk of death due to COVID-19 in relati... more Background: The objective of the study was to measure the risk of death due to COVID-19 in relation to individuals’ characteristics, and severity of their disease during the dominant periods of Alpha, Delta, and Omicron variants have influenced mortality rates. Methods: This study was conducted using COVID-19 Centers for Disease Control and Prevention (CDC) Case Surveillance Public Data Taskforce for 57 states, and United States territories between January 1, 2020 and March 20, 2022. Multivariable binary Hyperbolastic regression of type I was used to analyzes the data. Results: Seniors and ICU-admitted patients had the highest risk of death. For each additional percent increase in fully vaccinated individuals, the odds of death deceased by 1%. The odds of death prior to vaccine availability, compared to post vaccine availability, was 1.27. When comparing the time periods each variant was dominant, the odds of death was 3.45-fold higher during Delta compared to Alpha. All predictor v...
PLOS ONE
Background Literature presents limited information on histological subtypes and their association... more Background Literature presents limited information on histological subtypes and their association with other factors influencing the survival of melanoma patients. To explore the risk of death due to melanoma associated with histological subtypes, this retrospective study used the Surveillance, Epidemiology, and End Results program (SEER) data from 1998 to 2019. Methods A total of 27,532 patients consisting of 15,527 males and 12,005 females. The Hypertabastic Accelerated Failure Time model was used to analyze the impact of histology on the survival of patients with cutaneous or mucosal melanoma. Results The median survival time (MST) for cutaneous patients was 149 months, whereas those diagnosed with mucosal melanoma was 34 months. Nodular melanoma had a hazard ratio of 3.40 [95% CI: (2.94, 3.94)] compared to lentigo maligna melanoma. Across all histological subtypes, females had a longer MST, when compared to males. The hazard ratio (HR) of distant to localized melanoma was 9.56 [...
The Annals of Family Medicine
This article explains the importance of a communities of practice (CoP) model for continually ali... more This article explains the importance of a communities of practice (CoP) model for continually aligning medical education and clinical transformation with contemporary health issues. It describes the evolution and advantages of using CoP as a model for transforming medical education and clinical practice and applies the CoP methodology to addressing the changing needs of socially vulnerable populations (LGBTQ [lesbian, gay, bisexual, transgender, and queer/questioning], persons experiencing homelessness, and migrant farm workers). In conclusion, this article describes CoP-led activities, achievements, and value creation in medical education by the National Center for Medical Education Development and Research established at the Meharry Medical College.
Journal of Primary Care & Community Health, 2022
Cancer Research, 2018
Colorectal cancer (CRC) is the third most common diagnosed cancer and the third leading cause of ... more Colorectal cancer (CRC) is the third most common diagnosed cancer and the third leading cause of cancer-related deaths in the United States. Epidemiological evidence show estrogen might influence the incidence of CRC in women by acting in a protective role via estrogen receptor beta (ERβ) but the mechanism of action is not known. Benzo(a)pyrene [B(a)P], a member of the polycyclic aromatic hydrocarbon (PAH) family of compounds is a well-characterized environmental toxicant that has been proven to be a major contributor to the development of sporadic colon cancer. Literature provides evidence of crosstalk between Aryl Hydrocarbon Receptor (AhR), a receptor for B(a)P, and estrogen receptors (ERs) which negatively affect ER-mediated transcription. This study aims to elucidate the effect of AhR/ERB crosstalk on B(a)P-induced expression of AHR target genes in adult Polyposis In the Rat Colon (PIRC) model. We hypothesize that estrogen inhibits B(a)P-induced expression of AHR target genes a...
Cancer Research, 2017
Colorectal cancer (CRC) is the third most common diagnosed cancer and the third leading cause of ... more Colorectal cancer (CRC) is the third most common diagnosed cancer and the third leading cause of cancer-related deaths in the United States. It has also been reported that colon cancer incidence and mortality rates are higher in men than woman, but there is yet a determined mechanistic link to show the factors that underlie the sex-specific differences in CRC initiation and progression. Benzo(a)pyrene [B(a)P], a member of the polycyclic aromatic hydrocarbon (PAH) family of compounds is a well-characterized environmental toxicant that has been proven to be a major contributor to the development of sporadic colon cancer. Published studies indicate that Aryl Hydrocarbon Receptor (AhR), a receptor for [B(a)P], bind to estrogen receptor (ER) and negatively affect AhR-target gene transcription. This study aims to elucidate the sex-specific differences in B(a)P-induced colon cancer in adult Polyposis In the Rat Colon (PIRC) model. We hypothesize that sex-specific differences in B(a)P biotr...
Toxicology, 2012
In utero exposure of the fetus to benzo(a)pyrene [B(a)P], a polycyclic aromatic hydrocarbon, is t... more In utero exposure of the fetus to benzo(a)pyrene [B(a)P], a polycyclic aromatic hydrocarbon, is thought to dysregulate cardiovascular development. To investigate the effects of in utero B(a)P exposure on cardiovascular development, timed-pregnant Long Evans Hooded (LEH) rats were exposed to diluent or B(a)P (150, 300, 600 and 1200 μg/kg/BW) by oral gavage on embryonic (E) days E14 (the metamorphosing embryo stage) through E17 (the 1st fetal stage). There were no significant effects of in utero exposure to B(a)P on the number of pups born per litter or in preweaning growth curves. Pre-weaning profiles for B(a)P metabolite generation from cardiovascular tissue were shown to be dose-dependent and elimination of these metabolites was shown to be time-dependent in exposed offspring. Systolic blood pressure on postnatal day P53 in the middle and high exposure groups of offspring were significantly elevated as compared to controls. Microarray and quantitative real-time PCR results were directly relevant to a biological process pathway in animal models for "regulation of blood pressure". Microarray and quantitative realtime PCR analysis revealed upregulation of mRNA expression for angiotensin (AngII), angiotensinogen (AGT) and endothelial nitric oxide synthase (eNOS) in exposed offspring. Biological network analysis and gene set enrichment analysis subsequently identified potential signaling mechanisms and molecular pathways that might explain the elevated systolic blood pressures observed in B(a)P-exposed offspring. Our findings suggest that in utero exposure to B(a)P predispose offspring to functional deficits in cardiovascular development that may contribute to cardiovascular dysfunction in later life.
![Research paper thumbnail of MODULATION IN THE DEVELOPMENTAL EXPRESSION PROFILE OF Sp1 SUBSEQUENT TO TRANSPLACENTAL EXPOSURE OF FETAL RATS TO DESORBED BENZO[a]PYRENE FOLLOWING MATERNAL INHALATION](https://attachments.academia-assets.com/108931674/thumbnails/1.jpg)
Inhalation Toxicology, 2000
Any alteration of the critical sequence of genes that are required to coordinate the differentiat... more Any alteration of the critical sequence of genes that are required to coordinate the differentiation of cells, the promotion of migration, dendritic arborization, synapse formation, and myelination in the developing nervous system would be expected to have deleterious consequences. The focus of this article is a molecular evaluation of the neurotoxicological effects that result subsequent to the transplacental exposure of fetal rats to desorbed benzo(a) pyrene (BaP) following maternal inhalation. A state-of-the-art, newly designed, fabricated, and tested model aerosol generation system was utilized in these studies. Timed-pregnant Sprague Dawley rats were exposed for 4 h on gestation day 15 of a 21day gestation period to an acute dose of BaP:carbon black aerosol (100 µg/ m 3). Controls received carbon black only. Nominal and chamber concentrations of the particulate aerosol were determined gravimetrically with a seven-stage cascade impactor. The aerosol exhibited a trimodal distribution with 95% cumulative mass less than 15.85 µm, 90% cumulative mass less than 10 µm, 67.5% cumulative mass less than 2.5 µm and 66.2% cumulative mass less than 1.0 µm. Time-course bioavailability results indicated that greater than 95% of the parent compound is cleared from blood 240 min postexposure. An Sp1 transcription factor consensus sequence was examined by electrophoretic mobility shift analysis of nuclear extracts from various brain regions of resulting pups on postnatal days 3, 5, 7, 10, and 15. It revealed perturbations in the developmental expression profile of Sp1 abundance as a result of nose-only particulate aerosol exposure to the timed-pregnant dam. The data obtained on the temporal and spatial regulation of gene expression in the brain indicate that (1) Sp1 DNA-binding is developmentally regulated and expressed very highly in actively developing brain regions, and (2) a consequence of the transplacental deposition of desorbed BaP to the fetus is in utero neurotoxicity.
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Papers by Aramandla Ramesh