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3. The dynamics of the lipopolysaccharide-binding protein (LBP) level in assessing the risk of adverse outcomes in operated colorectal cancer patients

Author

Yermek Turgunov, Alina Ogizbayeva, Kayrat Shakeyev, Miras Mugazov, Lyudmila Akhmaltdinova, Shynggys Nuraly, and Viktor Rudolf

Subjects
LBP, Colorectal neoplasms, Intestinal obstruction, Complications, Outcomes, Surgery, RD1-811
Abstract

Background: The main aim of this study is to analyze changes in the lipopolysaccharide-binding protein (LBP) level in blood serum over time and assess it as a potential risk factor for the development of SIRS, infectious and inflammatory complications, organ dysfunction and mortality in patients operated on colorectal cancer (CRC). Methods: 90 CRC patients were divided into 2 groups: Group 1–50 patients operated on for CRC without acute bowel obstruction (ABO); Group 2–40 patients operated on for CRC with ABO. To determine LBP by ELISA method venous blood was taken 1 h before surgery and 72 h after it (3rd day). Results: LBP level on the 3rd day after surgery was lower in CRC patients with SIRS, postoperative complications, organ dysfunction and in dead patients. With an LBP value on the 3rd day after surgery being at ≤821.95 ng/mL, the risk of SIRS occurrence is 3.5 times higher, that of the postoperative complications is 5.2 times higher and death is 12.9 times higher than with its higher level (OR 3.5, CI 1.46–8.4; OR 5.2, CI 1.80–15.12; OR 12.9, CI 1.54–108.21, respectively). If the LBP value on the 3rd day after surgery is ≤ 700.15 ng/mL, the risk of organ dysfunctions is 13.5 times higher than with its higher level (OR 13.5, CI 3.536–51.54). Conclusions: This study demonstrated that in the patients with CRC, the LBP can be used as a predictive criterion for the development of SIRS, postoperative infectious and inflammatory complications, organ dysfunction, and mortality.

Published
2024
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22. Clinical experience of TB in patients treated with anti-TNF-α

Author

H Knobel-Freud, N Carballo, Inmaculada López-Montesinos, J P Horcajada, Arenas-Miras M, Jové-Caballé N, F Sánchez-Martínez, J Villar-García, and S Grau

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, MEDLINE, Adalimumab, Gastroenterology, Infliximab, Infectious Diseases, Anti tnf α, Internal medicine, Medicine, Humans, Tuberculosis, In patient, Tumor Necrosis Factor Inhibitors, business
Published
2021

28. Kratom Alkaloids: A Blood–Brain Barrier Specific Membrane Permeability Assay-Guided Isolation and Cyclodextrin Complexation Study

Author

András Dohárszky, Erika Mária Vági, Árpád Könczöl, Alexandra Simon, Erzsébet Várnagy, Miras Muratov, Kristóf István Steiger, Bianka Várnai, Szabolcs Béni, Eszter Riethmüller, and Ida Fejős

Subjects
indole alkaloids, extraction, parallel artificial permeability assay, blood–brain barrier permeability, inclusion complexes, complex stability, Organic chemistry, QD241-441
Abstract

Mitragynine is an “atypic opioid” analgesic with an alternative mechanism of action and a favorable side-effect profile. Our aim was to optimize the alkaloid extraction procedure from kratom leaves and to determine and isolate the most relevant compounds capable of penetrating the central nervous system. The PAMPA-BBB study revealed that mitragynine and its coalkaloids, speciociliatine, speciogynine, and paynantheine, possess excellent in vitro BBB permeability. An optimized sequence of CPC, flash chromatography, and preparative HPLC methods was used to isolate the four identified BBB+ alkaloids. To improve the bioavailability of the isolated alkaloids, their cyclodextrin (CD) complexation behavior was investigated via affinity capillary electrophoresis using almost 40 CD derivatives. The apparent alkaloid–CD complex stability constants were determined and compared, and the most relevant CDs phase-solubility studies were also performed. Both the neutral and negatively charged derivatives were able to form complexes with all four kratom alkaloids. It was found that cavity size, substituent type, and degree of substitution also influenced complex formation. The negatively charged Sugammadex, Subetadex, and the sufoalkylated-beta-CD analogs were able to form the most stable complexes, exceeding 1000 M−1. These results serve as a good basis for further solubility and stability enhancement studies of kratom alkaloids.

Published
2024
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30. Unique and distinct identities and functions of leaf phloem cells revealed by single cell transcriptomics

Author

Martin J. Lercher, Efthymia Symeonidi, Miras M, Li Qing Chen, Tin Yau Pang, Ji-Yun Kim, Tom Denyer, Marja C.P. Timmermans, Diana Weidauer, Margaret Bezrutczyk, Nora R. Zöllner, Wolf B. Frommer, and Michael M. Wudick

Subjects
chemistry.chemical_classification, Cell type, biology, Chemistry, Cell, biology.organism_classification, Cell biology, Hydathode, Amino acid, Transcriptome, medicine.anatomical_structure, Arabidopsis, Guard cell, medicine, Phloem
Abstract

The leaf vasculature plays a key role in solute translocation. Veins consist of at least seven distinct cell types, with specific roles in transport, metabolism, and signaling. Little is known about the vascular cells in leaves, in particular the phloem parenchyma (PP). PP effluxes sucrose into the apoplasm as a basis for phloem loading; yet PP has only been characterized microscopically. Here, we enriched vascular cells from Arabidopsis leaves to generate a single-cell transcriptome atlas of leaf vasculature. We identified ≥19 cell clusters, encompassing epidermis, guard cells, hydathodes, mesophyll, and all vascular cell types, and used metabolic pathway analysis to define their roles. Clusters comprising PP cells were enriched for transporters, including SWEET11 and SWEET12 sucrose and UmamiT amino acid efflux carriers. PP development occurs independently from APL, a transcription factor required for phloem differentiation. PP cells have a unique pattern of amino acid metabolism activity distinct from companion cells (CC), explaining differential distribution/metabolism of amino acids in veins. The kinship relation of the vascular clusters is strikingly similar to the vein morphology, except for a clear separation of CC from the other vascular cells including PP. In summary, our scRNA-seq analysis provides a wide range of information into the leaf vasculature and the role and relationship of the leaf cell types.

Published
2020
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34. HeterozygousSTAT5bGene Mutations: Impact on Clinical Phenotype.

Author

Fofanova-Gambetti, OV, primary, Hwa, V, additional, Jorge, AAL, additional, Tonelli, CA, additional, Wit, JM, additional, Walenkamp, MJE, additional, Domene, H, additional, Jasper, HG, additional, Martinez, A, additional, Berberoglu, M, additional, Ocal, G, additional, Belgorosky, A, additional, Marino, R, additional, Miras, M, additional, and Rosenfeld, RG, additional

Published
2010
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37. Clinical and economic burden of community-onset multidrug-resistant infections requiring hospitalization

Author

L. Sorli Redó, A. Domínguez-Guasch, Juan Pablo Horcajada, Silvia Gómez-Zorrilla, Santiago Grau, Milagro Montero, A. Siverio-Parès, X. Duran-Jordà, Inmaculada López-Montesinos, and Arenas-Miras M

Subjects
Adult, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Multivariate analysis, 030106 microbiology, Burden, Community-onset infections, Multidrug resistance, 03 medical and health sciences, 0302 clinical medicine, Cost of Illness, Risk Factors, Drug Resistance, Multiple, Bacterial, Internal medicine, medicine, Humans, 030212 general & internal medicine, Resource consumption, Mortality, Clinical failure, Cross Infection, business.industry, Hazard ratio, Odds ratio, medicine.disease, Comorbidity, Confidence interval, Anti-Bacterial Agents, Hospitalization, Multiple drug resistance, Infectious Diseases, Case-Control Studies, SOFA score, business, Hospital costs, Community-onset healthcare-associated infections
Abstract

Objectives: To analyze the clinical and economic burden of community-acquired (CA) or community-onset healthcare-associated (COHCA) multidrug-resistant (MDR) infections requiring hospitalization. Methods: Case-control study. Adults admitted with CA or COHCA MDR infections were considered cases, while those admitted in the same period with non-MDR infections were controls. The matching criteria were source of infection and/or microorganism. Primary outcome was 30-day clinical failure. Secondary outcomes were 90-day and 1-year mortality, hospitalization costs and resource consumption. Results: 194 patients (97 cases and 97 controls) were included. Multivariate analysis identified age (odds ratio [OR], 1.07, 95% confidence interval [CI], 1.01-1.14) and SOFA score (OR, 1.45, CI95%, 1.15-1.84) as independent predictors of 30-day clinical failure. Age (hazard ratio [HR] 1.09, 95%CI, 1.03-1.16) was the only factor associated with 90-day mortality, whereas age (HR 1.06, 95%CI, 1.03-1.09) and Charlson Index (HR 1.2, 95%CI, 1.07-1.34) were associated with 1-year mortality. MDR group showed longer hospitalization (p

Published
2020

41. Etiology and evolution of newborns with congenital hypothyroidism and eutopic thyroid gland

Author

Testa, G., Signorino, M., Sobrero, G., Boyanovsky, A., Collet, I., Muñoz, L., Rivolta, C.M., Targovnik, H.M., and Miras, M.

Subjects
Pesquisa neonatal, Etiología, Congenital hypothyroidism, Hipotiroidismo congénito, Etiology, Eutopía tiroidea, Dishormonogénesis, Eutopic thyroid, Neonatal screening, Dyshormonogenesis
Abstract

RESUMEN Objetivos Analizar las características clínicas, bioquímicas, estudios complementarios, hallazgos moleculares y la prevalencia de glándula eutópica en neonatos con HC pertenecientes al Programa Provincial de Pesquisa Neonatal de Córdoba, Argentina, entre 1996 y 2015. Analizar la evolución de los pacientes que reunieron criterios para una reevaluación. Pacientes y métodos Se analizaron retrospectivamente las historias clínicas de 237 pacientes detectados por pesquisa neonatal en la provincia de Córdoba, Argentina, entre 1996-2015 con una incidencia promedio de 1/2146 pesquisados. Presentaron glándula eutópica 81 pacientes (34%) F35/M46; se excluyeron 10 con síndromes genéticos asociados. Se analizaron los niveles de: TSH, T4T, T4L, T3, TPOAb / TGAb y Tiroglobulina (ECLIA -ROCHE) (VR: >15 días: 6-83 ng/ ml; 40 uUI/ml (40-1186). TGAb and TPOAb fueron positivos en un niño. La determinación de TG fue normal en el 29% (21/71) de los casos, elevada en el 56% (39/71) y baja en el 14% (10/71). Los estudios de biología molecular resultaron diagnósticos en 26 pacientes de 18 familias, demostrándose mutaciones en los genes de: TPO: 9 pacientes, TG: 12 pacientes, NIS: 2 pacientes, DUOX2: 2 pacientes y TRβ: 1 paciente. Se encontraron 11 nuevas mutaciones: tres en TPO, cinco en TG, dos en NIS y una en DUOX2. Se informaron anomalías congénitas en el 11% (8/71) de los pacientes. Se reevaluó el 11% (8/71) de los niños, resultando: HC transitorio n: 5, permanente n: 2 y una niña con Síndrome de Resistencia a las Hormonas Tiroideas. La prevalencia de lactantes con HC y glándula eutópica se mantuvo constante a lo largo de 19 años del Programa. Conclusiones Nuestros estudios demuestran que la prevalencia de Hipotiroidismo Congénito con glándula eutópica se mantuvo estable en los períodos analizados. Este grupo de pacientes se caracterizó predominantemente por presentar HC de carácter permanente acompañado por fenotipos de moderada a severa intensidad. En el futuro deberá profundizarse el conocimiento respecto a la influencia de factores medioambientales, como posibles agentes de riesgo asociados a la génesis de Hipotiroidismo Congénito. abstract Objectives To describe clinical, biochemical characteristics and complementary studies to diagnosis, molecular findings and the prevalence of eutopic gland in newborn with CH detected through our neonatal screening program in Córdoba, Argentina, between 1996 and 2015. To analyze the evolution of the patients who met criteria for re-evaluation. Patients and methods We retrospectively analysed medical records of 237 patients with CH detected by neonatal screening in Córdoba, Argentina, from 1996 to 2015 with an average incidence of 1/2146 researched. 81 patients (34%) F35/M46 had eutopic thyroid gland; 10 patients with associated genetic syndromes were excluded. TT4, FT4, T3, TSH, TPOAb, TGAb and Thyroglobulin (VR: >15 days: 6-83 ng/ml; 40 uUI/ml (40-1186). TGAb and TPOAb were positive only in one baby. TG levels were: normal in 29% (21/71) of the cases, elevated in 56% (39/71) and low in 14% (10/71). Gene mutations were found in 26 patients from 18 families: TPO: 9 patients, TG: 12 patients, NIS: 2 patients, DUOX2: 2 patients y TRβ: 1 patient. Eleven new mutations were found: three in TPO, five in TG, two in NIS and one in DUOX2. Congenital anomalies were reported in 11% (8/71) patients. The 11% (8/71) of children were re-evaluated resulting in: 5 Transient CH, 2 Permanent CH and 1 with Resistance to Thyroid Hormones. The prevalence of infants with CH and eutopic gland remained constant along 19 years of the Program. Conclusions Our studies show that the prevalence of congenital hypothyroidism with eutopic gland remained stable in the periods analyzed. This group of patients was predominantly characterized by permanent CH accompanied by moderate to severe phenotypes. In the future, knowledge about the influence of environmental factors, as possible risk agents associated with the genesis of Congenital Hypothyroidism, should be deepened.

Published
2018

48. Biomarkers of Bacterial Translocation and Intestinal Wall Damage in Patients With Multiple Organ Dysfunction Syndrome

Author

Yermek Turgunov, Alina Ogizbayeva, Sofiko Asamidanova, Olga Avdiyenko, Dana Amanova, Nurlan Aukenov, and Miras Mugazov

Subjects
Medicine
Abstract

Conclusion: In patients with MODS, an increase in sCD14-ST, I-FABP, and REG3α in blood serum can indicate the violation of intestinal barrier function and increased bacterial translocation, which ultimately may aggravate the severity of MODS and increase the risk of death. It is required to further study the factors leading to intestinal wall permeability disorders in order to screen for timely intensive care measures that can help reduce the stay of patients in the intensive care unit (ICU) as well as mortality.

Published
2024
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49. Presepsin (soluble CD14 subtype) as a risk factor for the development of infectious and inflammatory complications in operated colorectal cancer patients

Author

Kayrat Shakeyev, Yermek Turgunov, Alina Ogizbayeva, Olga Avdiyenko, Miras Mugazov, Sofiko Grigolashvili, and Ilya Azizov

Subjects
scd14-st, colorectal neoplasms, intestinal obstruction, systemic inflammatory response syndrome, complications, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Purpose In this pilot study the dynamic of presepsin (soluble CD14 subtype, sCD14-ST) in blood serum was assessed as a possible risk factor for the development of systemic inflammatory response syndrome (SIRS) and infectious and inflammatory complications in operated colorectal cancer patients. Methods To determine sCD14-ST by enzyme-linked immunosorbent assay method venous blood was taken 1 hour before surgery and 72 hours after it (3rd day). The presence of SIRS and organ dysfunctions (ODs) according to the Sequential Organ Failure Assessment scale were assessed. Results Thiry-six patients with colorectal cancer were enrolled in the study. sCD14-ST level before surgery was 269.8±103.1 pg/mL (interquartile range [IQR], 196.7–327.1 pg/mL). Despite the presepsin level on the 3rd day being higher (291.1±136.5 pg/mL; IQR, 181.2–395.5 pg/mL), there was no statistical significance in its dynamics (P=0.437). sCD14-ST value both before surgery and on the 3rd day after it was significantly higher in patients with bowel obstruction (P=0.038 and P=0.007). sCD14-ST level before surgery above 330 pg/mL showed an increase in the probability of complications, SIRS, and OD (odds ratio [OR], 5.5; 95% confidence interval [CI], 1.1–28.2; OR, 7.0; 95% CI, 1.3–36.7; and OR, 13.0; 95% CI, 1.1–147.8; respectively). Patients with OD had higher levels on the 3rd day after surgery (P=0.049). Conclusion sCD14-ST level in operated colorectal cancer patients was much higher if they were admitted with complication like bowel obstruction. Higher preoperative levels of sCD14-ST increase the probability of postoperative complications, SIRS, and OD. Therefore, further studies with large sample size are needed.

Published
2022
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