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1.
J Drugs Dermatol ; 23(5): 311-315, 2024 May 01.
Article En | MEDLINE | ID: mdl-38709695

PURPOSE: In this review article, we sought to elucidate how the social determinants of health, including socioeconomic status, education, neighborhood or physical environment, access to healthcare, and race/ethnicity, affect the likelihood of receiving immunotherapy, a novel and expensive treatment for melanoma.  Methods: The PubMed database was queried up to May 2023, for studies pertaining to health disparities in melanoma, including studies examining the utilization of immunotherapy agents for the treatment of melanoma across various social determinants of health. RESULTS: Disparities in the utilization of immunotherapy exist across various social determinants. A total of 10 studies were found to report on disparities in receipt of immunotherapy. These studies reported an association between insurance status, education level, socioeconomic status, as well as proximity to a cancer research center, and a lower likelihood of receiving immunotherapy. CONCLUSION: As the number of novel immunotherapy drugs grows, it is important to understand the various disparities affecting the delivery of immunotherapy across social determinants. The findings from this study can help to drive public health policy aimed at addressing inequities in the treatment of melanoma as well as other cancers.    J Drugs Dermatol. 2024;23(5):311-315. doi:10.36849/JDD.7803.


Health Services Accessibility , Healthcare Disparities , Immunotherapy , Melanoma , Skin Neoplasms , Social Determinants of Health , Humans , Melanoma/therapy , Immunotherapy/methods , Healthcare Disparities/statistics & numerical data , Skin Neoplasms/therapy , Health Services Accessibility/statistics & numerical data , Social Class
2.
Methods Mol Biol ; 2759: 9-24, 2024.
Article En | MEDLINE | ID: mdl-38285135

Technological innovation in the design and manufacture of temporary immersion systems (TIS) has increased in the past decade. Innovations have involved the size, fitting, and replacement of components, as well as manufacturing materials. Air replacement by compressor has also been substituted by air replacement by preset tilting/rotation of culture bottles. This design modification aims to increase the biological yield (number of shoots) produced in these bottles and reduce manufacturing costs. However, the operative principle has remained unchanged through time: promote an environment where explant immersions in the culture medium are programmable. The changes in the TIS design involve advantages and disadvantages, generating the efficiency of one type over another. However, validation to identify the most effective type of TIS should be carried out for each plant species. This chapter lists the different types of temporary immersion available on the market, emphasizing the advantages and disadvantages of each when used for plant micropropagation.


Commerce , Immersion , Culture Media , Rotation
3.
J Immigr Minor Health ; 26(1): 23-33, 2024 Feb.
Article En | MEDLINE | ID: mdl-37615821

As the deadliest form of skin cancer, advanced-stage melanoma is a devastating disease. Encouragingly, with the introduction of immunotherapy, the overall survival of metastatic melanoma has improved drastically. However, access to novel immunotherapeutic drugs is not universal for all patients. Herein, we examined the association between various sociodemographic factors and the likelihood of using immunotherapy for melanoma treatment. This is a retrospective cohort study using the Texas Cancer Registry data for the years 2011-2018. Multivariable regression analysis was done to evaluate the association between patient characteristics and likelihood of receipt of immunotherapy. The association between sociodemographic factors and likelihood of presentation with metastasis at diagnosis was also examined. Having metastasis at diagnosis was strongly associated with higher odds of receiving immunotherapy (penalized adjusted OR 28.690, 95% CI 23.470-34.350, p < .0001). Compared to having private insurance, patients were less likely to receive immunotherapy if they were uninsured, had Medicare, or had missing/unknown insurance status (penalized adjusted OR's 0.700, 0.790, 0.130, p = .026, 0.027, and p < .0001 respectively). Results from our multivariate model highlighted several factors associated with a higher likelihood of presenting with metastatic disease which included Hispanic ethnicity and black race. Dermatologic disparities affecting the Hispanic population underscore the importance of targeted interventions to overcome community level barriers to melanoma treatment and diagnosis. This study highlights the need to further evaluate different insurance types and their effect on receipt of immunotherapy.


Melanoma , Skin Neoplasms , Humans , Aged , United States , Melanoma/therapy , Texas/epidemiology , Retrospective Studies , Skin Neoplasms/therapy , Medicare , Immunotherapy , Registries , Healthcare Disparities
5.
Cancer Causes Control ; 35(2): 265-275, 2024 Feb.
Article En | MEDLINE | ID: mdl-37702966

PURPOSE: The incidence of cutaneous melanoma is rising, and Melanoma related deaths are highest among people aged 65-74. Herein, we aim to understand the impact of novel and established melanoma treatment methods on CM related mortality and all-cause mortality. We further compared these effects among Hispanic and non-Hispanic Whites (NHW). METHODS: The data was extracted from the Texas Cancer Registry from 2007 to 2017. A Cox Proportional Hazard regression analysis was performed to assess treatment effect on melanoma mortality and all-cause mortality, with race-ethnicity as an effect modifier. RESULTS: A higher percentage of Hispanic patients presented with CM-related mortality (22.11%) compared to NHW patients (14.39%). In both the Hispanic and NHW, post-diagnosis radiation (HR = 1.610, 95% CI 0.984-2.634, HR = 2.348, 95% CI 2.082-2.648, respectively), post-diagnosis chemotherapy (HR = 1.899, 95% CI 1.085-3.322, HR = 2.035, 95% CI 1.664-2.489, respectively), and post-diagnosis immunotherapy (HR = 2.100, 95% CI 1.338-3.296, HR = 2.402, 95% CI 2.100-2.748) are each associated with an increased risk in CM-related mortality. Similar results were seen with post-diagnosis radiation (Hispanic HR = 1.640, 95% CI 1.121-2.400, NHW HR = 1.800, 95% CI 1.644-1.971), post-diagnostic chemotherapy (Hispanic HR = 1.457, 95% CI 0.898-2.364, NHW HR = 1.592, 95% CI 1.356-1.869), and post-diagnosis immunotherapy (Hispanic HR = 2.140, 95% CI 1.494-3.065, NHW HR = 2.190, 95% CI 1.969-2.435) with respect to all-cause mortality. Post-diagnosis surgery (HR = 0.581, 95% CI 0.395-0.856, HR = 0.622, 95% CI 0.571-0.678) had the opposite effect in CM-related mortality for Hispanics and NHWs respectively. CONCLUSION: Our results propose differences in all-cause and CM-only related mortality with separate treatment modalities, particularly with chemotherapy, radiation therapy and immunotherapy. In addition, this retrospective cohort study showed that health disparities exist in the Hispanic Medicare population of Texas with CM.


Melanoma , Skin Neoplasms , Humans , Aged , United States/epidemiology , Melanoma/therapy , Skin Neoplasms/therapy , Texas/epidemiology , Medicare , Retrospective Studies , Receptors, Antigen, T-Cell
6.
Vaccines (Basel) ; 11(9)2023 Sep 07.
Article En | MEDLINE | ID: mdl-37766141

While cancer immunotherapies have become central to treatment, challenges associated with the ability of tumors to evade the immune system remain significant obstacles. At the heart of this issue is the tumor immune microenvironment, the complex interplay of the tumor microenvironment and the immune response. Recent advances in mRNA cancer vaccines represent major progress towards overcoming some of the challenges posed by deleterious components of the tumor immune microenvironment. Indeed, major breakthroughs in mRNA vaccine technology, such as the use of replacement nucleotides and lipid nanoparticle delivery, led to the vital success of mRNA vaccine technology in fighting COVID-19. This has in turn generated massive additional interest and investment in the platform. In this review, we detail recent research in the nature of the tumor immune microenvironment and in mRNA cancer vaccines and discuss applications by which mRNA cancer vaccines, often in combination with various adjuvants, represent major areas of potential in overcoming tumor immune microenvironment-imposed obstacles. To this end, we also review current mRNA cancer vaccine clinical trials.

7.
Int J Mol Sci ; 24(1)2023 Jan 03.
Article En | MEDLINE | ID: mdl-36614268

Drug conjugates have become a significant focus of research in the field of targeted medicine for cancer treatments. Peptide-drug conjugates (PDCs), a subset of drug conjugates, are composed of carrier peptides ranging from 5 to 30 amino acid residues, toxic payloads, and linkers that connect the payload to the peptide. PDCs are further broken down into cell-penetrating peptides (CPPs) and cell-targeting peptides (CTPs), each having their own differences in the delivery of cytotoxic payloads. Generally, PDCs as compared to other drug conjugates-like antibody-drug conjugates (ADCs)-have advantages in tumor penetration, ease of synthesis and cost, and reduced off-target effects. Further, as compared to traditional cancer treatments (e.g., chemotherapy and radiation), PDCs have higher specificity for the target cancer with generally less toxic side effects in smaller doses. However, PDCs can have disadvantages such as poor stability and rapid renal clearance due to their smaller size and limited oral bioavailability due to digestion of its peptide structure. Some of these challenges can be overcome with modifications, and despite drawbacks, the intrinsic small size of PDCs with high target specificity still makes them an attractive area of research for cancer treatments.


Antineoplastic Agents , Cell-Penetrating Peptides , Immunoconjugates , Neoplasms , Humans , Pharmaceutical Preparations/metabolism , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Neoplasms/metabolism , Immunoconjugates/therapeutic use , Cell-Penetrating Peptides/therapeutic use , Antigens/therapeutic use
8.
Cancers (Basel) ; 14(17)2022 Aug 31.
Article En | MEDLINE | ID: mdl-36077792

The era of personalized cancer therapy is here. Advances in the field of immunotherapy have paved the way for the development of individualized neoantigen-based therapies that can translate into favorable treatment outcomes and fewer side effects for patients. Addressing challenges related to the identification, access, and clinical application of neoantigens is critical to accelerating the development of individualized immunotherapy for cancer patients.

9.
Plants (Basel) ; 11(13)2022 Jun 21.
Article En | MEDLINE | ID: mdl-35807581

Vanilla planifolia Jacks. ex Andrews is the vanilla species with the most commercial and greatest economic importance. It has been used as a case study in different cryopreservation studies that involve three vitrification-based approaches: droplet-vitrification (D-V), V-cryoplate (V-Cp) and D-cryoplate (D-Cp). The aim of this study was to compare the impact of these cryogenic techniques on vegetative growth (survival, stem length and leaf number) between cryo-derived plants and in vitro-derived controls during 12 months of greenhouse growth. Genetic stability was also assessed using the inter-simple sequence repeat (ISSR) markers. There were no significant differences found in the survival and stem lengths of the in vitro-derived regenerants and cryo-derived plants. A significant increase in the number of leaves was only detected in cryo-derived plants when using the V-Cp method. The electrophoretic profiles, based on seven ISSR primers, detected low variability: 81 total bands and 27% polymorphism. This is the first report on the assessment of vegetative growth and genetic integrity in cryo-derived V. planifolia plants recovered under greenhouse conditions. Of the three cryogenic approaches, D-Cp appears to yield V. planifolia regenerants plants with more vigorous vegetative growth and a lower level of polymorphism. Future research should focus on the reproductive growth of vanilla regenerants.

10.
Rev. Fac. Med. Hum ; 22(3): 572-583, julio-Septiembre 2022.
Article En, Es | LILACS-Express | LILACS | ID: biblio-1381871

El objetivo fue describir la prevalencia, las manifestaciones clínicas y los factores asociados de COVID-19 de larga duración. Se realizó una búsqueda bibliográfica de revisiones sistemáticas y metaanálisis sobre COVID-19 de larga duración en MEDLINE (vía PubMed) hasta el 7 de abril de 2022. Se encontraron 37 artículos y se incluyeron 3. La calidad de la evidencia fue evaluada a través de los criterios de AMSTAR 2. La prevalencia reportada de COVID-19 de larga duración fue 43% (IC95%: 39% ­ 46%). Las principales manifestaciones clínicas fueron debilidad (41% [IC95%: 25% ­ 59%]), malestar general (33% [IC95%: 15% ­ 57%]), fatiga (31% [IC95%: 24% ­ 39%]), alteración en la concentración (26% [IC95%: 21% ­ 32%]) y sensación de falta de aire (25% [IC95%: 18% ­ 34%]). Los factores asociados a COVID de larga duración incluyeron sexo femenino, severidad de cuadro inicial, edad y presencia de comorbilidades.


The aim was to describe the prevalence, clinical manifestations, and associated factors of long-COVID. Bibliographic research of systematic reviews and meta-analyses was carried out in MEDLINE (through PubMed) until April 7th, 2022. 37 articles were found and 3 were included. Evidence quality was assessed via AMSTAR 2 criteria. Long-COVID prevalence is 43% (IC95%: 39% ­ 46%). Main clinical manifestations were weakness (41% [IC95%: 25% ­ 59%]), malaise (33% [IC95%: 15% ­ 57%]), fatigue (31% [IC95%: 24% ­ 39%]), concentration impairment (26% [IC95%: 21% ­ 32%]), and breathlessness (25% [IC95%: 18% ­ 34%]). Factors associated with long COVID were female sex, initial disease severity, age, and presence of comorbidities.

11.
Rev. mex. anestesiol ; 44(1): 34-42, ene.-mar. 2021. tab
Article Es | LILACS-Express | LILACS | ID: biblio-1347713

Resumen: Introducción: La alteración en el metabolismo de los lípidos se ha involucrado en la patogénesis de complicaciones postoperatorias, primordialmente por inducir procesos inflamatorios que pueden afectar la morbilidad, además se ha observado un aumento en la vulnerabilidad/sensibilidad por isquemia reperfusión implicada por apoptosis por estrés mediado por el retículo endoplásmico. Durante el procedimiento anestésico los niveles séricos de lípidos pueden afectar la farmacocinética de varios agentes anestésicos. Objetivo: Determinar si existe evidencia científica que compruebe o refute el desarrollo de complicaciones en pacientes postoperados que cursan con descontrol lipídico en el período preoperatorio. Metodología: Se realizó una revisión en la literatura mediante los buscadores PUBMED, ScienceDirect y BioMed Central. Resultados: Con los criterios de búsqueda se revisaron 17 estudios (ensayos clínicos controlados, estudios de casos y controles, cohortes y estudios experimentales básicos). Conclusiones: Aunque es necesario mejorar la metodología de varios artículos revisados y aumentar la cantidad de los mismos, en la mayor parte de ellos se encontró relación entre dislipidemia con alteraciones postoperatorias que inciden en un aumento de morbilidad o mortalidad.


Abstract: Introduction: The alteration in lipid metabolism has been involved in the pathogenesis of postoperative complications primarily by inducing inflammatory processes that may affect morbidity, in addition an increase in vulnerability/sensitivity for ischemia reperfusion has been observed involved apoptosis by stress mediated by the endoplasmic reticulum. During the anesthetic procedure, serum lipid levels can affect the pharmacokinetics of various anesthetic agents. Objective: To determine if there is scientific evidence to prove or refute the development of complications in post-operated patients who present with lipid decontrol in the preoperative period. Methodology: A review was made in the literature through the search engines PubMed, ScienceDirect, and BiomedCentral. Results: With the search criteria, 17 studies were reviewed (controlled clinical trials, case and control studies, cohorts and basic experimental studies). Conclusions: Although it is necessary to improve the methodology of several articles reviewed and increase the number of them, in most of them a relationship was found between dyslipidemia with postoperative alterations that affect an increase in morbidity or mortality.

12.
Plant J ; 103(6): 2178-2192, 2020 09.
Article En | MEDLINE | ID: mdl-32578269

Members of the fungal genus Trichoderma stimulate growth and reinforce plant immunity. Nevertheless, how fungal signaling elements mediate the establishment of a successful Trichoderma-plant interaction is largely unknown. In this work, we analyzed growth, root architecture and defense in an Arabidopsis-Trichoderma co-cultivation system, including the wild-type (WT) strain of the fungus and mutants affected in NADPH oxidase. Global gene expression profiles were assessed in both the plant and the fungus during the establishment of the interaction. Trichoderma atroviride WT improved root branching and growth of seedling as previously reported. This effect diminished in co-cultivation with the ∆nox1, ∆nox2 and ∆noxR null mutants. The data gathered of the Arabidopsis interaction with the ∆noxR strain showed that the seedlings had a heightened immune response linked to jasmonic acid in roots and shoots. In the fungus, we observed repression of genes involved in complex carbohydrate degradation in the presence of the plant before contact. However, in the absence of NoxR, such repression was lost, apparently due to a poor ability to adequately utilize simple carbon sources such as sucrose, a typical plant exudate. Our results unveiled the critical role played by the Trichoderma NoxR in the establishment of a fine-tuned communication between the plant and the fungus even before physical contact. In this dialog, the fungus appears to respond to the plant by adjusting its metabolism, while in the plant, fungal perception determines a delicate growth-defense balance.


Arabidopsis/microbiology , Fungal Proteins/metabolism , Hypocreales/enzymology , NADPH Oxidases/metabolism , Symbiosis , Arabidopsis/metabolism , Fungal Proteins/physiology , Gene Expression Regulation, Plant , Hypocreales/metabolism , NADPH Oxidases/physiology , Plant Roots/growth & development , Plant Roots/microbiology , Plant Shoots/growth & development
13.
Curr Top Med Chem ; 20(9): 738-745, 2020.
Article En | MEDLINE | ID: mdl-32101124

AIMS: The present study aims to determine the phototoxic and haemolytic activity of organophosphorus. The use of alternative in vitro assays with human erythrocytes is suggested to predict the polluting effect of these products on health. METHODOLOGY: Human erythrocytes from Toluca Blood Bank were used. Sodium dodecyl sulfate was employed as a positive control. Additionally, the haemolysis percentage of three organophosphate (Acetate, Chlorpyrifos, Malathion, Methamidophos, Methyl Parathion) induced photo haemolysis formulated with surfactants on a concentration of 2 x 109 erythrocytes were evaluated. Finally, the products were classified as irritant or phototoxic. RESULTS: Results showed that the HC50 red blood cells were similar for each organophosphate (Malathion and Methamidophos) indicating very irritant action with ratio classification (L/D) of 0.041 and 0.053, respectively. On the other hand, Chlorpyrifos was classified as an irritant with L/D= 0.14. On the other hand, the HC50 obtained photo hemolysis assays irradiated red blood cells was similar for each organophosphate (Acetate, Chlorpyrifos, Malathion, Methamidophos, Methyl Parathion) indicating no phototoxic action. CONCLUSION: As a conclusion, it can be said that the parameters of haemolysis and denaturation of proteins are good indicators to classify organophosphorus formulated with surfactants as irritating or phototoxic.


Erythrocytes/metabolism , Hemolysis/drug effects , Hemolysis/radiation effects , Organophosphorus Compounds/chemistry , Photochemotherapy/methods , Surface-Active Agents/chemistry , Chlorpyrifos/chemistry , Humans , In Vitro Techniques , Malathion/chemistry , Organophosphate Poisoning , Organothiophosphorus Compounds/chemistry , Protein Denaturation/drug effects
14.
Rev. mex. anestesiol ; 42(3): 173-174, jul.-sep. 2019. tab
Article Es | LILACS-Express | LILACS | ID: biblio-1347641

Resumen En la actualidad, la mayor parte del tratamiento para los pacientes intervenidos quirúrgicamente se centra en el manejo nociceptivo transanestésico y en la modulación del dolor en el postanestésico; pero existe una problemática existente llamada dolor crónico postoperatorio, que presenta aún una necesidad de mejora en la terapéutica médica.


Abstract At present, most of the treatment for surgically treated patients is focused on transanesthetic nociceptive management and modulation of pain in the postanesthetic; but there is an existing problem called postoperative chronic pain that still presents a need for improvement in medical therapy.

15.
Curr Top Med Chem ; 19(11): 931-943, 2019.
Article En | MEDLINE | ID: mdl-31109276

BACKGROUND: In the last decade, the harmful use of dioxin has been demonstrated in human health and in the whole environment. It is well known among scientists that 2, 3, 7, 8-tetrachloro dibenzo-p-dioxin (TCDD) is an environmental pollutant that causes endocrine disruption, which causes male reproductive toxicity. OBJECTIVE: The objective of the present study was to evaluate the toxicity effect of low doses of TCDD in male CD1 mice. MATERIALS AND METHODS: Three concentrations of TCDD (0.375, 0.75, 1.5 mg / kg) were analyzed and the effects on spermatozoa were evaluated 10 days after oral administration of the product. As bioindicators of TCDD toxicity, an exhaustive analysis of several spermatic parameters including motility, vitality, count, morphology and viability, flow cytometry was used to determine the affected sperm population by cytotoxicity and apoptosis. In addition, a morphometric analysis of testicles was performed. RESULTS: The results show that the body weight of the treated animals was reduced in medium and high doses (0.75, 1.5 mg / kg) with respect to the control groups. In the groups treated with TCDD, the abnormal head of the sperm increased by 52.5% more than the control group. Significant differences in apoptosis were observed between the negative control and vehicle control, including the median dose (0.75 mg / kg). CONCLUSION: It is concluded that at these low doses there was an impact on the quality of the mouse sperm, adding an effect on apoptosis and cytotoxicity of sperm exposed to these doses of TCDD.


Polychlorinated Dibenzodioxins/toxicity , Spermatozoa/drug effects , Administration, Oral , Animals , Apoptosis/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Male , Mice , Polychlorinated Dibenzodioxins/administration & dosage , Spermatozoa/pathology , Structure-Activity Relationship
16.
Microb Pathog ; 114: 286-290, 2018 Jan.
Article En | MEDLINE | ID: mdl-29208542

Drug-resistant Salmonella is frequently detected in most parts of the world, and its rate of resistance has increased significantly in recent years. However, this study aimed to evaluate the minimum inhibitory concentration (MIC, determined with the Kirby-Bauer method) of quinolones in 86 Salmonella spp. strains isolated from pigs. Both the inside and outside of the QRDR region of strains were sequenced. The DNA sequence of the QRDR region of Salmonella spp. revealed the mutations S83F, D87N and S83Y. The region outside the QRDR showed a mutation in L582G. Forty-five isolates of Salmonella ssp. were categorized as quinolone-resistant; out of these, 16 corresponded to Salmonella enterica and isolates showed intermediate resistance (6.25%) to nalidixic acid. Three isolats (18.6%) were resistant to ampicillin; two (12.5%) were resistant to carbenicillin. Moreover, three (18.7%) isolates were resistant to gentamicin, nitrofurantoin and pefloxacin, and 8 (50%) were resistant to trimethoprim/sulfamethoxazole. Six percent of Salmonella spp. strains showed less resistance to antimicrobial agents compared to S. Thyphimurium (18%). The resistance to individual quinolones varied by serotypes. For S. anatum and S. Reading, it was 12.25%, and for S. choreaeaesuis, S. typhimurium monofasica, 6.25%. In contrast, S. agona, S. bredeney and S. london were sensitive to these antibiotics. In conclusion, quinolones have become the drugs of choice for the treatment of severe Salmonella infections. The study of mutations outside the QRDR region opens up new insights about the resistance of Salmonella to fluoroquinolones.


DNA Gyrase/genetics , Drug Resistance, Bacterial/genetics , Quinolones/pharmacology , Salmonella/drug effects , Salmonella/genetics , Animals , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Base Sequence , DNA, Bacterial/genetics , Disk Diffusion Antimicrobial Tests , Fluoroquinolones/pharmacology , Genes, Bacterial/genetics , Mutation , Nalidixic Acid/pharmacology , Salmonella/isolation & purification , Salmonella Infections/drug therapy , Salmonella enterica/genetics , Salmonella enterica/isolation & purification , Swine
17.
Curr Pharm Des ; 22(33): 5079-5084, 2016.
Article En | MEDLINE | ID: mdl-27494067

BACKGROUND: The emergence of reduced susceptibility to fluoroquinolones among Salmonella enterica serotype Typhimurium isolates leading to clinical failure of treatment poses a great therapeutic challenge. METHODS: The current study is focused on the evaluation of the minimum inhibitory concentration (MIC) of quinolones in 29 Salmonella typhimurium of 86 Salmonella spp. strains, obtained from pigs from the State of Mexico. The MIC was performed with the Kirby-Bauer method. On the other hand, the GyrA gene was sequenced. The present study was undertaken to describe the resistance profiles and fluoroquinolone resistance mechanism of Salmonella Typhimurium. RESULTS: The DNA sequence of the gyrA genes from Salmonella enterica serovar typhimurium revealed strong similarity between gyrA and its counterpart in Escherichia coli. The sequencing of quinolone resistance-determining region (QRDR) of the gyrA gene showed the presence of mutation at either S83 or at D87 in almost all the Salmonella typhimurium isolates. CONCLUSION: This mutation, although phenotypically expressed as decreased susceptibility to fluoroquinolones goes undetected by the disk diffusion method using the present method of Kirby-Bauer. Hence, it can increase morbidity and mortality due to delay in appropriate antibiotic treatment.


Anti-Bacterial Agents/pharmacology , DNA Gyrase/genetics , Drug Resistance, Bacterial/drug effects , Mutation , Quinolones/pharmacology , Salmonella typhimurium/drug effects , Animals , Anti-Bacterial Agents/chemistry , Microbial Sensitivity Tests , Polymerase Chain Reaction , Quinolones/chemistry , Sequence Analysis, DNA , Swine
18.
Curr Pharm Des ; 22(33): 5114-5119, 2016.
Article En | MEDLINE | ID: mdl-27494066

We can combine experimental techniques like Flow Cytometry Analysis (FCA) with Chemoinformatics methods to predict the complex networks of interactions between organic compounds and targets in the immune system. In this work, we determined experimentally the values of EC50 = 17.82 µg/mL and Cytotoxicity = 20.6 % for the anti-microbial / anti-parasite drug Dermofural over Balb/C CD9 lymphocytes using flow cytometry. After that, we developed a new Perturbation-theory model for Drug-Cell Target Interactome in Lymphocytes based on dispersion-polarization moments of drug structure. The models correctly classifies 34591 out of 42715 (Accuracy = 80.9%) cases of perturbations in assay endpoints of 11492 drugs (including both train and validation series). Each endpoint correspond to one out of 2616 assays, 38 molecular and cellular targets, 77 standard type measures, in four possible (human and rodents).


Flow Cytometry , Lymphocytes/chemistry , Pharmaceutical Preparations/chemistry , Thermodynamics , Animals , Humans , Lymphocytes/drug effects
19.
Curr Drug Metab ; 15(4): 414-28, 2014.
Article En | MEDLINE | ID: mdl-25204826

The immune system helps to halt the infections caused by pathogenic microbial and parasitic agents. The ChEMBL database lists very large datasets of cytotoxicity of organic compounds but notably, a large number of compounds have unknown effects over molecular and cellular targets in the immune system. Flow Cytometry Analysis (FCA) is a very important technique to determine the effect of organic compounds over these molecular and cellular targets in the immune system. In addition, multi-target Quantitative Structure- Property Relationship (mt-QSPR) models can predict drug-target interactions, networks. The objectives of this paper are the following. Firstly, we carried out a review of general aspects and some examples of applications of FCA to study the effect of drugs over different cellular targets. However, we focused more on methods, materials, and experimental results obtained in previous works reported by our group in the study of the drug Dermofural. We also reviewed different mt-QSPR models useful to predict the immunotoxicity and/or the effects of drugs over immune system targets including immune cell lineages or proteins. Secondly, we included new results not published before. Initially, we used ChEMBL data to train and validate a new model but with emphasis in the effect of drugs over lymphocytes. Lastly, we report unpublished results of the computational and FCA study of a new nitro-vinyl-furan compound over thymic lymphocytes T helpers (CD4+) and T cytotoxic (CD8+) population.


Drug-Related Side Effects and Adverse Reactions , Flow Cytometry , Immune System/drug effects , Models, Biological , Quantitative Structure-Activity Relationship , Animals , Databases, Factual , Furans/toxicity , Humans
20.
J Biomed Biotechnol ; 2011: 968984, 2011.
Article En | MEDLINE | ID: mdl-22174560

Obesity, type II diabetes, and hyperlipidaemia, which frequently coexist and are strongly associated with oxidative stress, increase the risk of cardiovascular disease. An increase in carbohydrate intake, especially of fructose, and a high-fat diet are both factors that contribute to the development of these metabolic disorders. In recent studies carried out in diabetic rats, authors reported that Ibervillea sonorae had hypoglycaemic activity; saponins and monoglycerides present in the plant could be responsible for the effects observed. In the present study, we determined the effects of an aqueous I. sonorae extract on a murine model of obesity and hyperglycaemia, induced by a high-calorie diet, and the relationship of these effects with hepatic oxidation. A high-fat diet over a period of 8 weeks induced weight gain in the mice and increased triglycerides and blood glucose levels. Simultaneous treatment with I. sonorae aqueous extracts, at doses of 100, 200, and 400 mg/kg, decreased triglycerides and glycaemia levels, prevented an increase in body weight in a dose-dependent manner, and decreased hepatic lipid oxidation at a dose of 200 mg/kg. These data suggest that the aqueous extract from I. sonorae root prevents obesity, dyslipidaemia, and hyperglycaemia induced by a hypercaloric diet; however, high doses may induce toxicity.


Anti-Obesity Agents/pharmacology , Fructose/chemistry , Hyperglycemia/drug therapy , Obesity/drug therapy , Plant Extracts/pharmacology , Animal Feed , Animals , Body Weight , CD8-Positive T-Lymphocytes/immunology , Dose-Response Relationship, Drug , Hyperglycemia/metabolism , Liver/metabolism , Male , Mice , Mice, Inbred ICR , Oxygen/chemistry , Plant Roots , Triglycerides/chemistry , Water/chemistry
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