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Browsing by Author "Darabad, Raheleh Rahimi"
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Item Case Series: Cancer-Related Facial Pain Treated with Stellate Ganglion Block(Mary Ann Liebert, Inc., 2020-12-02) Darabad, Raheleh Rahimi; Kalangara, Jerry P.; Woodbury, Anna; Anesthesia, School of MedicineStellate ganglion block (SGB) is believed to modify the pathologic sympathetic pain response and has been commonly used to treat complex regional pain syndrome. We report successful treatment of cancer-related facial pain with SGB in three patients, suggesting a possible sympathetic pain-related mechanism. All patients exhibited clinically significant improvement of pain 12 weeks following the procedure. SGB should be considered a palliative pain treatment option in cancer-related facial pain.Item Dihydrotestosterone suppression of proinflammatory gene expression in human meibomian gland epithelial cells(Elsevier, 2020-04) Sahin, Afsun; Liu, Yang; Kam, Wendy R.; Darabad, Raheleh Rahimi; Sullivan, David A.; Medicine, School of MedicinePurpose: We discovered that dihydrotestosterone (DHT) decreases the ability of lipopolysaccharide, a bacterial toxin, to stimulate the secretion of leukotriene B4, a potent proinflammatory mediator, by immortalized human meibomian gland epithelial cells (IHMGECs). We hypothesize that this hormone action reflects an androgen suppression of proinflammatory gene activity in these cells. Our goal was to test this hypothesis. For comparison, we also examined whether DHT treatment elicits the same effect in immortalized human corneal (IHC) and conjunctival (IHConj) ECs. Methods: Differentiated cells were cultured in media containing vehicle or 10 nM DHT. Cells (n = 3 wells/treatment group) were then processed for RNA isolation and the analysis of gene expression by using Illumina BeadChips, background subtraction, cubic spline normalization and Geospiza software. Results: Our results demonstrate that DHT significantly suppressed the expression of numerous immune-related genes in HMGECs, such as those associated with antigen processing and presentation, innate and adaptive immune responses, chemotaxis, and cytokine production. DHT also enhanced the expression of genes for defensin β1, IL-1 receptor antagonist, and the anti-inflammatory serine peptidase inhibitor, Kazal type 5. In contrast, DHT had no effect on proinflammatory gene expression in HCECs, and significantly increased 33 gene ontologies linked to the immune system in HConjECs. Conclusions: Our findings support our hypothesis that androgens suppress proinflammatory gene expression in IHMGECs. This hormone effect may contribute to the typical absence of inflammation within the human meibomian gland.Item Influence of lipopolysaccharide on proinflammatory gene expression in human corneal, conjunctival and meibomian gland epithelial cells(Elsevier, 2018-07) Chen, Di; Sahin, Afsun; Kam, Wendy R.; Liu, Yang; Darabad, Raheleh Rahimi; Sullivan, David A.; Anesthesia, School of MedicinePURPOSE: Lipopolysaccharide (LPS), a bacterial endotoxin, is known to stimulate leuokotriene B4 (LTB4) secretion by human corneal (HCECs), conjunctival (HConjECs) and meibomian gland (HMGECs) epithelial cells. We hypothesize that this LTB4 effect represents an overall induction of proinflammatory gene expression in these cells. Our objective was to test this hypothesis. METHODS: Immortalized HCECs, HConjECs and HMGECs were cultured in the presence or absence of LPS (15 μg/ml) and ligand binding protein (LBP; 150 ng/ml). Cells were then processed for RNA isolation and the analysis of gene expression by using Illumina BeadChips, background subtraction, cubic spline normalization and GeneSifter software. RESULTS: Our findings show that LPS induces a striking increase in proinflammatory gene expression in HCECs and HConjECs. These cellular reactions are associated with a significant up-regulation of genes associated with inflammatory and immune responses (e.g. IL-1β, IL-8, and tumor necrosis factor), including those related to chemokine and Toll-like receptor signaling pathways, cytokine-cytokine receptor interactions, and chemotaxis. In contrast, with the exception of Toll-like signaling and associated innate immunity pathways, almost no proinflammatory ontologies were upregulated by LPS in HMGECs. CONCLUSIONS: Our results support our hypothesis that LPS stimulates proinflammatory gene expression in HCECs and HConjECs. However, our findings also show that LPS does not elicit such proinflammatory responses in HMGECs.Item Sex Effects on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome(ARVO, 2018-11-01) Tellefsen, Sara; Morthen, Mathias Kaurstad; Richards, Stephen M.; Lieberman, Scott M.; Darabad, Raheleh Rahimi; Kam, Wendy R.; Sullivan, David A.; Anesthesia, School of MedicinePurpose: Sjögren syndrome is an autoimmune disease that occurs primarily in women, and is associated with lacrimal gland inflammation and aqueous-deficient dry eye. We hypothesize that sex-associated differences in lacrimal gland gene expression are very important in promoting lymphocyte accumulation in this tissue and contribute to the onset, progression, and/or severity of the inflammatory disease process. To test our hypothesis, we explored the nature and extent of sex-related differences in gene expression in autoimmune lacrimal glands. Methods: Lacrimal glands were collected from age-matched, adult, male and female MRL/MpJ-Tnfrsf6lpr (MRL/lpr) and nonobese diabetic/LtJ (NOD) mice. Glands were processed for the analysis of differentially expressed mRNAs by using CodeLink Bioarrays and Affymetrix GeneChips. Data were evaluated with bioinformatics and statistical software. Results: Our results show that sex significantly influences the expression of thousands of genes in lacrimal glands of MRL/lpr and NOD mice. The immune nature of this glandular response is very dependent on the Sjögren syndrome model. Lacrimal glands of female, as compared with male, MRL/lpr mice contain a significant increase in the expression of genes related to inflammatory responses, antigen processing, and chemokine pathways. In contrast, it is the lacrimal tissue of NOD males, and not females, that presents with a significantly greater expression of immune-related genes. Conclusions: These data support our hypothesis that sex-related differences in gene expression contribute to lacrimal gland disease in Sjögren syndrome. Our findings also suggest that factors in the lacrimal gland microenvironment are critically important in mediating these sex-associated immune effects.Item Targeted Drug Delivery for the Treatment of Abdominal Pain in Chronic Pancreatitis: A Retrospective Case Series(Springer Nature, 2024-03-30) Cooper, Guy P., Jr.; Progar, Victor; Grott, Kelly; Patel, Feenalie; Mon, Jackie; Bick, Benjamin; Kelly, Timothy D.; Darabad, Raheleh Rahimi; Anesthesia, School of MedicineSummary: Abdominal pain secondary to chronic pancreatitis (CP) is difficult to manage and often requires chronic oral opioid therapy (OOT). Targeted drug delivery (TDD) allows for a diminished dose of opioid intake and improved pain levels. TDD has been used in different pain syndromes with only limited reports in CP. Objective: The objective of this article is to perform a retrospective review of CP patients treated with TDD versus OOT to compare chronic pain control and consumed morphine-equivalent doses. Methods: Patients receiving TDD between September 2011 and August 2018 were included. All patients were weaned off oral opioids one week before intrathecal trial and pump implantation. Patients with intrathecal trials providing at least 50% pain relief underwent pump implantation. Data were collected while on OOT and at two weeks, three months, and nine months post-implant. Data were analyzed with Microsoft Excel 365 MSO using means and standard deviations. P-values were calculated using a two-tailed student’s t-test with paired two-sample means. Results: Twenty-three patients were analyzed. Pre-trial average pain score was 6.5/10 with a mean improvement with trials greater than 71%. The mean chronic baseline oral morphine milligram equivalents (MME) was 188. The mean MME on TDD at two weeks (0.36), three months (1.39), and nine months (2.47) were significantly lower than OOT. Mean pain scores were 6, 4.9, and 5.6 at two weeks, three months, and nine months, respectively, compared to 6.5 on OOT. Discussion: The results of this study indicate that TDD provides improved pain control with significantly lower opioid doses.