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Tamoxifen and Src kinase inhibitors as neuroprotective/neuroregenerative drugs after spinal cord injury

Neural Regeneration Research 2015年第3期10卷 385-390页

作者： Iris K.Salgado Aranza I.Torrado Jose m.Santiago Jorge D.miranda Department of Physiology School of MedicineUniversity of Puerto Rico Medical Sciences Campus University of Puerto rico Carolina Campus Department of Natural Sciences

Spinal cord injury （SCI） is a devastating condition that produces significant changes in the life- style of patients. many molecular and cellular events are triggered after the initial physical impact to the cord. Two major phases have been described in the field of SCI： an acute phase and late phase. most of the therapeutic strategies are focused on the late phase because this provides an opportunity to target cellular events like apoptosis, demyelination, scar formation and axonal outgrowth. In this mini-review, we will focus on two agents （tamoxifen and a Src kinase family inhibitor known as PP2） that have been shown in our laboratory to produce neuroprotective （increase cell survival） and/or regenerative （axonal outgrowth） actions. The animal model used in our laboratory is adult female rat （N250 g） with a moderate contusion （12.5 mm） to the spinal cord at the T10 level, using the mASCIS impactor device. Tamoxifen or PP2 was administered by implantation of a 15 mg pellet （Innovative Research of America, Sarasota, FL, USA） or by intraperitoneal injections （1.5 mg/kg, every 3 days）, respectively, to produce a long-term effect （28 days）. Tamoxifen and the Src kinase inhibitor, PP2, are drugs that in rats with a moderate spinal cord injury promote functional locomotor recovery, increase spared white matter tissue, and stimulate axonal outgrowth. moreover, tamoxifen reduces the formation of reactive oxygen species. Therefore, these drugs are possible therapeutic agents that have a neuroprotective/regen- erative activity in vertebrates with SCI.

关键词： tamoxifen Src kinase PP2 trauma regeneration neuroprotection

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Key genes and drug delivery systems to improve the efficiency of chemotherapy

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Cancer Drug Resistance 2021年第1期4卷 163-191页

作者： Zally Torres-martinez Yamixa Delgado Yancy Ferrer-Acosta Ivette J Suarez-Arroyo Freisa m.Joaquin-Ovalle Louis J.Delinois Kai Griebenow Chemistry Department University of Puerto Rico-Rio Piedras campusSan JuanPR 00936USA Biochemistry&Pharmacology Department San Juan Bautista School of MedicineCaguasPR 00726USA Neuroscience Department Universidad Central del CaribeBayamonPR 00956USA Biochemistry Department Universidad Central del CaribeBayamonPR 00956USA

Cancer cells can develop resistance to anticancer drugs,thereby becoming tolerant to treatment through different *** biological mechanisms leading to the generation of anticancer treatment resistance include alterations in transmembrane proteins,DNA damage and repair mechanisms,alterations in target molecules,and genetic responses,among *** most common anti-cancer drugs reported to develop resistance to cancer cells include cisplatin,doxorubicin,paclitaxel,and *** anticancer drugs have different mechanisms of action,and specific cancer types can be affected by different *** development of drug resistance is a cellular response which uses differential gene expression,to enable adaptation and survival of the cell to diverse threatening environmental *** this review,we briefly look at the key regulatory genes,their expression,as well as the responses and regulation of cancer cells when exposed to anticancer drugs,along with the incorporation of alternative nanocarriers as treatments to overcome anticancer drug resistance.

关键词： Cancer resistance drug delivery systems resistance genes

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Outcomes of critically ill cancer patients with Acinetobacter baumannii infection

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World Journal of Critical Care medicine 2015年第3期4卷 258-264页

作者： Silvio A ?amendys-Silva Paulina Correa-García Francisco J García-Guillén maría O González-Herrera Américo Pérez-Alonso Julia Texcocano-Becerra Angel Herrera-Gómez Patricia Cornejo-Juárez Abelardo meneses-García Department of Critical Care medicine Instituto Nacional de Cancerología Department of Critical Care medicine Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Division of Education and Research Hospital de la Mujer Department of Infectious Diseases Instituto Nacional de Cancerología

AIm: To describe the intensive care unit(ICU) outcomes of critically ill cancer patients with Acinetobacter baumannii(AB) ***: This was an observational study that included 23 consecutive cancer patients who acquired AB infections during their stay at ICU of the National Cancer Institute of mexico(INCan), located in mexico City. Data collection took place between January 2011, and December 2012. Patients who had AB infections before ICU admission, and infections that occurred during the first 2 d of ICU stay were excluded. Data were obtained by reviewing the electronic health record of each patient. This investigation was approved by the Scientific and Ethics Committees at INCan. Because of its observational nature, informed consent of the patients was not ***: Throughout the study period, a total of 494 critically ill patients with cancer were admitted to the ICU of the INCan, 23(4.6%) of whom developed AB infections. Sixteen(60.9%) of these patients had hematologic malignancies. most frequent reasons for ICU admission were severe sepsis or septic shock(56.2%) and postoperative care(21.7%). The respiratory tract was the most frequent site of AB infection(91.3%). The most common organ dysfunction observed in our group of patients were the respiratory(100%), cardiovascular(100%), hepatic(73.9%) and renal dysfunction(65.2%). The ICU mortality of patients with 3 or less organ system dysfunctions was 11.7%(2/17) compared with 66.6%(4/6) for the group of patients with 4 or more organ system dysfunctions(P = 0.021). multivariate analysis identified blood lactate levels(BLL) as the only variable independently associated with inICU death(OR = 2.59, 95%CI: 1.04-6.43, P = 0.040). ICU and hospital mortality rates were 26.1% and 43.5%, ***: The mortality rate in critically ill patients with both Hm, and AB infections who are admitted to the ICU is high. The variable most associated with increased mortality was a BLL ≥ 2.6 mmol/L in

关键词： Outcomes Cancer patients Acinetobacter baumannii Intensive care Critical care

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Impact of rainfed and irrigated agriculture systems on soil carbon stock under different climate scenarios in the semi-arid region of Brazil

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Journal of Arid Land 2022年第4期14卷 359-373页

作者： André L CARVALHO Renato A ARAúJO-NETO Guilherme B LYRA Carlos E P CERRI Stoécio m F mAIA Center for Agrarian Sciences Federal University of AlagoasRio Largo 57072-900Brazil Luiz de Queiroz College of Agriculture The University of Sao PauloPiracicaba 13418-900Brazil Federal Institute of Alagoas Marechal Deodoro 57160-000Brazil

Understanding the dynamics of soil organic carbon(SOC) is of fundamental importance in land use and management, whether in the current researches or in future scenarios of agriculture systems considering climate change. In order to evaluate SOC stock of the three districts(Delmiro Gouveia, Pariconha, and Inhapi districts) in the semi-arid region of Brazil in rainfed and irrigated agriculture systems under different climate scenarios using the Century model, we obtained RCP4.5 and RCP8.5 climate scenarios derived from the Eta Regional Climate model(Eta-Had GEm2-ES and Eta-mIROC5) from the National Institute for Space Research, and then input the data of bulk density, p H, soil texture, maximum temperature, minimum temperature, and rainfall into the soil and climate files of the Century model. The results of this study showed that the Eta-Had GEm2-ES model was effective in estimating air temperature in the future period. In rainfed agriculture system, SOC stock under the baseline scenario was lower than that under RCP4.5 and RCP8.5 climate scenarios, while in irrigated agriculture system, SOC stock in the almost all climate scenarios(RCP4.5 and RCP8.5) and models(Eta-Had GEm2-ES and Eta-mIROC5) will increase by 2100. The results of this study will help producers in the semi-arid region of Brazil adopt specific agriculture systems aimed at mitigating greenhouse gas emissions.

关键词： soil carbon stock agriculture systems climate scenarios Century model semi-arid region

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Environmental and Economic Impact of Forest Fires in Puerto rico 2013-2014

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Open Journal of Forestry 2015年第4期5卷 353-363页

作者： méndez-Tejeda Rafael Santos-Corrada maría Ortiz-morales Sergio Claudio-Vargas Oscar Natural Science Department Atmospherical Science Laboratory University of Puerto Rico—Carolina Campus Carolina Puerto Rico School of Business and Entrepreneurship University of Turabo Gurabo Puerto Rico

This study presents an analysis of the impact of forest fires in Puerto rico for the period from 2013-2014. The climatological factors analyzed included precipitation, temperature, relative humidity, and wind. Several factors have combined to the increase of these forest fires, among others, a decrease in precipitation during this period, as well as an increase in the human involvement in these fires from approximately 40% occurs in the night period (5:00 pm to 8:00 am), where the weather conditions do not favor the appearance of these phenomena. An increase in fires of 44% occurred in 2013 compared to 2014, causing an economic loss of $13.8 million. Fire also adversely affected the flora and fauna of the island, but this was not evaluated in this paper.

关键词： Fires Forest Wildfire Economic Impact of Forest fires Precipitation and Weather Conditions

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Single Step microwave Assisted Synthesis and Antimicrobial Activity of Silver, Copper and Silver-Copper Nanoparticles

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Journal of materials Science and Chemical Engineering 2020年第8期8卷 13-29页

作者： myrna Reyes-Blas Nadja m. maldonado-Luna Carla m. Rivera-Quiñones Ana L. Vega-Avila Felix R. Roman-Velázquez Oscar J. Perales-Perez Department of Chemistry University of Puerto Rico at Mayagüez Mayaguez USA Department of mechanical Engineering University of Puerto Rico at Mayagüez Mayaguez USA Department of Chemical Engineering University of Puerto Rico at Mayagüez Mayaguez USA Department of Engineering Science & materials University of Puerto Rico at Mayagüez Mayaguez USA

Copper and silver nanoparticles were synthesized and characterized in two minutes at 175°C in a one-step synthesis using a modified polyol (ethylene glycol) method and a microwave heating process. We successfully synthesized spherical Silver (Ag) and Copper nanoparticles (CuNP) with a crystallite size of less than 10 nm, as well as irregular silver-copper nanoparticles (AgCuNP) with a crystallite size of less than 15 nm, as confirmed by X-Ray Diffraction (XRD) and High-Resolution Transmission Electron microscopy (HRTEm). The successful synthesis of AgCuNP with 1:1 molar ratio and constituted by 51.74% of copper and 48.26% of silver was corroborated using the Energy Dispersive X-ray (EDX) mapping technique. The AgNP and AgCuNP exhibited more stability in suspension, in comparison to CuNP, as observed by continuously monitoring the absorbance with UV-Vis spectroscopy for 12 days. Furthermore, the minimum inhibitory concentration (mIC) and minimum bactericidal concentration (mBC) of AgNP, CuNP, and AgCuNP were determined, against Gram-negative and Gram-positive bacteria, and yeast. The obtained mIC and mBC values indicate that AgCu nanoparticles exhibited bactericidal properties greater than its constituents. On the contrary, antifungal activity of AgCuNP against yeast was not observed.

关键词： Ag Nanoparticles Cu Nanoparticles microwave Synthesis modified Polyol method Antimicrobial Properties AgCu Nanoparticles

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Novel EPS/TiO2 Nanocomposite Prepared from Recycled Polystyrene

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materials Sciences and Applications 2013年第3期4卷 179-185页

作者： G. m. Herrera-Sandoval D. B. Baez-Angarita S. N. Correa-Torres O. m. Primera-Pedrozo S. P. Hernández-Rivera Department of Chemistry University of Puerto Rico-Mayaguez Mayagüez USA School of Science and Technology Universidad Metropolitana San Juan PR.

The synthesis and characterization of a new nanocomposite material that was prepared from recycled expanded polystyrene (EPS) and titanium dioxide (TiO2) is reported here. The EPS was obtained from chemical reagent box insulation. To obtain the nanocomposite, these materials were dispersed in a solvent, mixed with TiCl4 and heated. The resulting new material was characterized with SEm, TEm, TGA, BET, Raman and IR techniques. The Raman and IR spectra provided complementary information regarding the structure of the nanocomposite. The Raman spectra were used to identify the crystalline structure of TiO2 in the nanocomposite. In contrast, the IR spectra were used to identify the organic portion of the nanocomposite. The TEm images indicated that the nanocomposites had an average particle size of 6 - 12 nm. In addition, the adsorption and photocatalytic properties of the new material were evaluated. The EPS/TiO2 nanocomposite was efficient at degrading methylene blue (mB) dye solutions under UV irradiation. Furthermore, according to thermal analysis, this material had greater polymer stability due to the incorporation of TiO2.

关键词： Nanocomposite Expanded Polystyrene TiO2 Photodegradation methylene Blue

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Levamisole-Adultered Cocaine: Vasoconstrictive and Vasculitis Effects Occurring Simultaneously

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Case Reports in Clinical medicine 2022年第5期11卷 167-174页

作者： maría A. Rodríguez-Santiago Hillarie Ríos-Torres Giulianni Oliveras-maldonado Valeria martinez-Lebrón Suheiry márquez-márquez Adianez Santiago-Santiago Salvador Vilá-Pérez marcel mesa-Pabón Department of Internal medicine School of Medicine University of Puerto Rico San Juan Puerto Rico

This case presents a rarely seen combination of two Cocaine-induced syndromes occurring simultaneously. Levamisole-adultered cocaine leads to Levamisole-induced Vasculitis (LIV), while cocaine’s vasoconstrictive effect causes destruction of the osteo-cartilaginous structures of nose called Cocaine-induced midline destructive lesions (CImDL). This case raises awareness of a new pattern of recognition in order to avoid misdiagnosis. We present a case of a 51-year-old male cocaine user who developed severe left-sided ear pain and yellowish secretions with circular necrotic lesions in the nose, right earlobe, and dorsum of feet bilaterally. An extensive workup to assess purpuric lesions’ etiology, including vasculitis, collagen vasculitides, anti-phospholipid syndrome, hypercoagulable state and infectious process, was performed and found negative. He developed bilateral tympanic membrane perforation and purpuric necrotic skin lesions, at the same time, due to CImDL and LIV, respectively. These two syndromes rarely present simultaneously in a patient. This case report exhibits a new Cocaine-induced clinical presentation that will help hospitalists recognize the disease and avoid misdiagnosis leading to unnecessary tests, prolonged hospitalization, and higher healthcare costs. Diagnosis is challenging, as it consists of establishing a temporal relationship between cocaine ingestion and symptoms’ onset. This disease usually has a benign progression because symptoms frequently resolve without intervention.

关键词： Levamisole-Induced Vasculitis Cocaine-Induced midline Destructive Lesions Cocaine’s Side Effect Spectrum

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Diabetes mellitus and Colorectal Neoplasia

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Journal of Cancer Therapy 2012年第6期3卷 859-865页

作者： Alejandro Acevedo Yaritza Diaz Cynthia m. Perez maria Garau John Baron marcia Cruz-Correa Department of Biostatistics and Epidemiology Graduate School of Public Health Medical Sciences Campus University of Puerto Rico San Juan Puerto Rico Department of medicine Community and Family Medicine Dartmouth Medical School Dartmouth US Department of medicine Community and Family Medicine Dartmouth Medical School Hanover USA Department of medicine School of Medicine University of Puerto Rico San Juan Puerto Rico University of Puerto rico Comprehensive Cancer Center San Juan Puerto Rico

Background: many studies have provided evidence for an association between obesity, physical inactivity, and western diet as risk factors for colorectal cancer (CRC). Few studies directly address the association between type 2 Diabetes mellitus (Dm) and the risk of colorectal lesions at specific anatomic locations. methods: 2663 subjects with a previous history of adenoma (s) and removal of all current adenomas at study entry were followed for a mean time of three years across three different chemoprevention clinical trials. The primary endpoint was colorectal adenoma recurrence and number of lesions during the treatment phase;the secondary endpoints were presence of advanced colorectal neoplasia (CRN) and location of CRN. Using log linear regression, the effect of Dm status on the relative risk (RR) of CRN recurrence, advanced CRN, and location of CRN was assessed. Results: Dm status was not significantly associated with incidence of colorectal adenomas, incidence of advanced colorectal lesions, or left-sided colorectal neoplastic lesions. Subjects with Dm had a marginally increased risk of right-sided (p = 0.06) colorectal adenomas and a significant increased risk of multiple right-sided adenomas (p = 0.03) in the unadjusted model;this association was not significant after adjusting for age and other potential confounders (RR = 1.22, 95% CI: 0.85 - 1.76). Conclusion: We did not observe a statistically significant increased risk in CRN recurrence for overall neoplasia, advanced neoplasia or location of neoplasia in individuals with Dm compared to non-Dm individuals. However, given the patterns observed in this investigation, future studies with longer follow-up time and longer Dm exposure, incorporating objective measurements of type 2 Dm might help elucidate the risk of CRN among individuals with Dm.

关键词： Diabetes mellitus Colorectal Neoplasia Colorectal Adenomas Chemoprevention

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Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue

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Neural Regeneration Research 2014年第24期9卷 2164-2173页

作者： Odrick R.Rosas Aranza I.Torrado Jose m.Santiago Ana E.Rodriguez Iris K.Salgado Jorge D.miranda Department of Physiology School of Medicine University of Puerto Rico Medical Sciences Campus Department of Natural Sciences University of Puerto Rico Carolina Campus

The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase （SFK） activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a decrease in SFK activation by a long-term treatment with 4-amino-5-（4- chlorophenyl）-7-（t-butyl）pyrazolo[3,4-d]pyramidine （PP2）, a selective SFK inhibitor, after spinal cord contusion with the New York University （NYU） impactor device would generate a permissive environment that improves axonal sprouting and/or behavioral activity. Results demonstrated that long-term blockade of SFK activation with PP2 increases locomotor activity at 7, 14, 21 and 28 days post-iniury in the Basso, Beattie, and Bresnahan open field test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and serotonin fiber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or infiltration of cells from the immune system at 28 days post-injury. moreover, a reduced SFK activity with PP2 diminished Ephexin （a guanine nudeotide exchange factor） phosphorylation in the acute phase （4 days post-injury） after trauma. Together, these findings suggest a potential role of SFK in the regulation of spared tissue and/or axonal outgrowth that may result in functional locomotor recovery during the pathophysiology generated after spinal cord injury. Our study also points out that ephexinl phosphorylation （activation） by SFK action may be involved in the repulsive microenvironment generated after spinal cord injury.

关键词： nerve regeneration trauma regeneration Src family kinase Eph receptors ephexin spared tissue locomotor recovery GFAP ED1 serotonin fibers neural regeneration

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