THE HDAC INHIBITOR SODIUM PHENYLBUTYRATE ENHANCES THE CYTOTOXICITY INDUCED BY 5-FLUOROURACIL, OXALIPLATIN, AND IRINOTECAN IN COLORECTAL CANCER CELL LINES

Objective: The main objective of this study was to evaluate the ability of sodium phenylbutyrate (NaPB) to enhance the cytotoxicity of 5-fluorouracil, oxaliplatin, and irinotecan against colorectal cancer cell lines expressing wild-type and mutant p53.Methods: The antiproliferative effect of NaPB alone or in combination with 5-fluorouracil, oxaliplatin, or irinotecan in HCT-116 and HT-29 colorectal cancer cell lines was investigated using the MTT cell proliferation assay. IC50 values were calculated using Compusyn Software 1.0 (Combosyn Inc.). Synergy values (R) were calculated using the ratio of IC50 of each primary drug alone divided by combination IC50s. For each two pairs of experiments, student's t-test was used for analysis. In combination studies, one-way ANOVA test; Tukey post-hoc testing was performed using R 3.3.2 software. P-value<0.05 was considered significant.Results: NaPB inhibited the growth of HCT-116 and HT-29 cell lines in a dose-dependent manner (IC50s 4.7 mmol, and 10.1 mmol, respectively). HT-29 cell lines (mutant p53) were more sensitive to NaPB at low concentrations (<4 mmol). Moreover, the addition of NaPB to HCT-116 and HT-29 with 5-fluorouracil, oxaliplatin, or irinotecan synergistically induced the antiproliferative effect (R>1.6, p-value<0.05).Conclusion: NaPB enhanced the cytotoxicity of conventional chemotherapy against colorectal cancer cell lines harboring wild-type or mutant p53. Thus NaPB is a promising potential adjuvant chemotherapy in colorectal cancer

Quantifying engineered nanomaterial toxicity: comparison of common cytotoxicity and gene expression measurements

BACKGROUND: When evaluating the toxicity of engineered nanomaterials (ENMS) it is important to use multiple bioassays based on different mechanisms of action. In this regard we evaluated the use of gene expression and common cytotoxicity measurements using as test materials, two selected nanoparticles with known differences in toxicity, 5 nm mercaptoundecanoic acid (MUA)-capped InP and CdSe quantum dots (QDs). We tested the effects of these QDs at concentrations ranging from 0.5 to 160 µg/mL on cultured normal human bronchial epithelial (NHBE) cells using four common cytotoxicity assays: the dichlorofluorescein assay for reactive oxygen species (ROS), the lactate dehydrogenase assay for membrane viability (LDH), the mitochondrial dehydrogenase assay for mitochondrial function, and the Comet assay for DNA strand breaks. RESULTS: The cytotoxicity assays showed similar trends when exposed to nanoparticles for 24 h at 80 µg/mL with a threefold increase in ROS with exposure to CdSe QDs compared to an insignificant change in ROS levels after exposure to InP QDs, a twofold increase in the LDH necrosis assay in NHBE cells with exposure to CdSe QDs compared to a 50% decrease for InP QDs, a 60% decrease in the mitochondrial function assay upon exposure to CdSe QDs compared to a minimal increase in the case of InP and significant DNA strand breaks after exposure to CdSe QDs compared to no significant DNA strand breaks with InP. High-throughput quantitative real-time polymerase chain reaction (qRT-PCR) data for cells exposed for 6 h at a concentration of 80 µg/mL were consistent with the cytotoxicity assays showing major differences in DNA damage, DNA repair and mitochondrial function gene regulatory responses to the CdSe and InP QDs. The BRCA2, CYP1A1, CYP1B1, CDK1, SFN and VEGFA genes were observed to be upregulated specifically from increased CdSe exposure and suggests their possible utility as biomarkers for toxicity. CONCLUSIONS: This study can serve as a model for comparing traditional cytotoxicity assays and gene expression measurements and to determine candidate biomarkers for assessing the biocompatibility of ENMs.1R01GM84702-01 - National Institute of General Medical Science

Smoothening Transition of a Two-Dimensional Pressurized Polymer Ring

We revisit the problem of a two-dimensional polymer ring subject to an inflating pressure differential. The ring is modeled as a freely jointed closed chain of N monomers. Using a Flory argument, mean-field calculation and Monte Carlo simulations, we show that at a critical pressure, $p_c \sim N^{-1}$, the ring undergoes a second-order phase transition from a crumpled, random-walk state, where its mean area scales as $\sim N$, to a smooth state with $\sim N^2$. The transition belongs to the mean-field universality class. At the critical point a new state of polymer statistics is found, in which $\sim N^{3/2}$. For $p>>p_c$ we use a transfer-matrix calculation to derive exact expressions for the properties of the smooth state.Comment: 9 pages, 8 figure

Complex Regional Pain Syndrome Type 1 Treated with Vitamin C

Complex regional pain syndrome, formerly reflex sympathetic dystrophy or causalgia, is a chronic progressive disease characterized by severe pain, swelling, and changes in the skin. It often affects an arm or a leg and may spread to another part of the body and is associated with dysregulation of the autonomic nervous system resulting in multiple functional loss, impairment, and disability. It occurs mostly in of adolescence. Though treatment is often unsatisfactory, we report a young girl treated satisfactorily with vitamin C

Neuromodulation for Pelvic and Urogenital Pain

Chronic pain affecting the pelvic and urogenital area is a major clinical problem with heterogeneous etiology, affecting both male and female patients and severely compromising quality of life. In cases where pharmacotherapy is ineffective, neuromodulation is proving to be a potential avenue to enhance analgesic outcomes. However, clinicians who frequently see patients with pelvic pain are not traditionally trained in a range of neuromodulation techniques. The aim of this overview is to describe major types of pelvic and urogenital pain syndromes and the neuromodulation approaches that have been trialed, including peripheral nerve stimulation, dorsal root ganglion stimulation, spinal cord stimulation, and brain stimulation techniques. Our conclusion is that neuromodulation, particularly of the peripheral nerves, may provide benefits for patients with pelvic pain. However, larger prospective randomized studies with carefully selected patient groups are required to establish efficacy and determine which patients are likely to achieve the best outcomes.</jats:p

Graduate Medical Education on the Frontlines during the COVID-19 Pandemic in New York City- A Response to Promote Well-being

Introduction: The COVID-19 pandemic has driven many health care institutions in the United States beyond their capacity. Physicians-in-training in graduate medical education programs have suffered the strain of providing patient care during this unprecedented time of crisis. The significant prevalence of pre-existing resident and fellow burnout and depression makes the need for action by institutions to support the well-being of residents and fellows even more urgent. We aim to describe innovative adaptations our Office of Graduate Medical Education implemented with the support of institutional leadership as responses to promote the well-being of residents and fellows on the frontlines during the COVID-19 pandemic. Methods: The Office of Graduate Medical Education (GME), in collaboration with the Office of Well-being and Resilience, developed a set of resources and interventions to support trainees during the pandemic based on four major categories: workplace culture, personal factors and health, mental health support, and workplace efficiency and function. Examination of the capacity of existing services and gaps that needed to be filled in the rapidly evolving early days of the COVID pandemic led to a robust growth in resources. For example, the already established Student and Trainee Mental Health program was able to expand and adapt its role to serve trainee needs more effectively. Results: We expanded resources to target trainee well-being across a broad array of domains within a short time frame. With investment in access to the Student and Trainee Mental Health program, utilization increased by 25.7%, with 1,231 more visits in 2020 compared to the number of visits in 2019, prior to the COVID-19 pandemic. The creation of Recharge Rooms had a positive impact on the well-being of health care workers. After a single fifteen-minute experience in the Recharge Room, an average 59.6% reduction in self-reported stress levels was noted by users. Other interventions were noted to be helpful in regular town hall meetings with trainees. Conclusion: Addressing trainee well-being is an essential aspect of a crisis response. The Mount Sinai Health System was able to care for the physical, mental, psychosocial, and safety needs of our trainees thanks to the collaborative effort of a pre-existing institutional well-being program and the GME Office. The ability to implement such a response was enabled by our well-being foundation, which allowed leadership at the highest institutional level and the Office of GME to provide support in response to this unprecedented crisis

Nanocomposites in Controlled & Targeted Drug Delivery Systems

In recent years, development of different types of nanocomposites have increased their utilization in the biomedical and pharmaceutical sciences. The nanometer size range and unique composition make nanocomposites a beneficial alternative to any single conventional material. The present chapter provides a general overview of nanocomposites, discusses different types of nanocomposites such as metal, ceramic and polymer nanocomposites. The discussion is further focused on different nanocomposite based controlled and targeted systems developed for delivery of various drugs including anti-cancer, anti-microbial, anti-inflammatory, anti-diabetic and cardiovascular drugs