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1.
J Neurointerv Surg ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38782568

RESUMEN

BACKGROUND: Early identification of intracranial atherosclerotic disease (ICAD) may impact the management of patients undergoing mechanical thrombectomy (MT). We sought to develop and validate a scoring system for pre-thrombectomy diagnosis of ICAD in anterior circulation large vessel/distal medium vessel occlusion strokes (LVOs/DMVOs). METHODS: Retrospective analysis of two prospectively maintained comprehensive stroke center databases including patients with anterior circulation occlusions spanning 2010-22 (development cohort) and 2018-22 (validation cohort). ICAD cases were matched for age and sex (1:1) to non-ICAD controls. RESULTS: Of 2870 MTs within the study period, 348 patients were included in the development cohort: 174 anterior circulation ICAD (6% of 2870 MTs) and 174 controls. Multivariable analysis ß coefficients led to a 20 point scale: absence of atrial fibrillation (5); vascular risk factor burden (1) for each of hypertension, diabetes, smoking, and hyperlipidemia; multifocal single artery stenoses on CT angiography (3); absence of territorial cortical infarct (3); presence of borderzone infarct (3); or ipsilateral carotid siphon calcification (2). The validation cohort comprised 56 ICAD patients (4.1% of 1359 MTs): 56 controls. Area under the receiver operating characteristic curve was 0.88 (0.84-0.91) and 0.82 (0.73-0.89) in the development and validation cohorts, respectively. Calibration slope and intercept showed a good fit for the development cohort although with overestimated risk for the validation cohort. After intercept adjustment, the overestimation was corrected (intercept 0, 95% CI -0.5 to -0.5; slope 0.8, 95% CI 0.5 to 1.1). In the full cohort (n=414), ≥11 points showed the best performance for distinguishing ICAD from non-ICAD, with 0.71 (95% CI 0.65 to 0.78) sensitivity and 0.82 (95% CI 0.77 to 0.87) specificity, and 3.92 (95% CI 2.92 to 5.28) positive and 0.35 (95% CI 0.28 to 0.44) negative likelihood ratio. Scores ≥12 showed 90% specificity and 63% sensitivity. CONCLUSION: The proposed scoring system for preprocedural diagnosis of ICAD LVOs and DMVOs presented satisfactory discrimination and calibration based on clinical and non-invasive radiological data.

2.
BMC Res Notes ; 17(1): 30, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38243331

RESUMEN

OBJECTIVES: The data was collected for a cohort study to assess the capability of thermal videos in the detection of SARS-CoV-2. Using this data, a published study applied machine learning to analyze thermal image features for Covid-19 detection. DATA DESCRIPTION: The study recorded a set of measurements from 252 participants over 18 years of age requesting a SARS-CoV-2 PCR (polymerase chain reaction) test at the Hospital Zambrano-Hellion in Nuevo León, México. Data for PCR results, demographics, vital signs, food intake, activities and lifestyle factors, recently taken medications, respiratory and general symptoms, and a thermal video session where the volunteers performed a simple breath-hold in four different positions were collected. Vital signs recorded include axillary temperature, blood pressure, heart rate, and oxygen saturation. Each thermal video is split into 4 scenes, corresponding to front, back, left and right sides, and is available in MPEG-4 format to facilitate inclusion into pipelines for image processing. Raw JPEG images of the background between subjects are included to register variations in room temperatures.


Asunto(s)
COVID-19 , Humanos , Adolescente , Adulto , COVID-19/diagnóstico , SARS-CoV-2 , Estudios de Cohortes , Proyectos Piloto , Hospitales
3.
Pathogens ; 12(6)2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37375474

RESUMEN

Ticks and tick-borne diseases affect livestock productivity and cause significant economic losses. Therefore, surveillance of these pathogens and vectors is paramount to reducing these effects in livestock. This study aimed to identify Anaplasma marginale and Borrelia burgdorferi sensu lato in ticks collected from cattle. Molecular biology techniques were utilized to identify A. marginale for both types of samples, i.e., ticks and bovine blood. Serology of cattle using indirect immunofluorescence assay (IFA) was conducted to determine antibodies to B. burgdorferi s.l. from seven locations in Nuevo Leon, Mexico, between 2015 and 2017. From 404 bovines, 2880 ticks were collected: Rhipicephalus microplus (2391 females and 395 males), Amblyomma spp. (51 females and 42 males) and Dermacentor variabilis (1 female). Rhipicephalus microplus represented the largest specimens captured, with 96.7% within the seven study sites. PCR processed only 15% (442) of tick samples to identify A. marginale. Field genera proportions were followed to select testing tick numbers. Results showed that 9.9% (44/442) of A. maginale infected the pooled tick species, whereas the highest percent corresponded to 9.4% (38/404) in R. microplus. Regarding the molecular analysis of blood samples, 214 of 337 (63.5%) were positive for A. maginale. In each of the seven locations, at least one bovine sample tested positive for A. maginale. Borrelia burgdorferi s.l. was not found either in the ticks or serum samples. Two A.marginale DNA nucleotide sequences obtained in this study were deposited in the GenBank with the following accession numbers OR050501 cattle, and OR050500 R.microplus tick. Results of this work point to current distribution of bovine anaplasmosis in northern Mexico.

4.
Comput Ind Eng ; 168: 108101, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36569989

RESUMEN

One of the critical actions that emerged during the onset of the New Normalcy after COVID-19 lockdowns, is the safe return to schools and workplaces. Therefore, dedicated transportation services need to adapt to meet new requirements such as arrival reliability for multiple bell times, the consequent staggering of arrivals and departures, and the decrease in bus capacity due to the physical distancing required by regulators. In this work, we address these issues plus additional labor conditions concerning drivers for a university context; with the goal of optimizing social interests such as covering demand and travel time under limited resources. We propose a bi-level approach, where firstly a bus routing generation sub-problem is solved before a bus scheduling sub-problem. This (strategic) solution is then considered as the baseline for subsequent dynamic (operational) routing. The latter is based on real-time demand provided by the students via a mobile app and considers stop-skipping to further minimize travel time. This integrated transport solution was tested in a university case, showing that with the same resources, it can meet these new requirements. In addition, numerical experimentation was also carried out with benchmark instances to identify, among available and literature-recommended solution algorithms and an effective tailored Tabu Search implementation, those that perform best for this type of problems.

5.
AAPS PharmSciTech ; 23(7): 271, 2022 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-36175743

RESUMEN

Rituximab is a monoclonal antibody used in the treatment of lymphoma non-Hodgkin. This mAb is photosensitive as it is administrated to the patient by infusion/perfusion; therefore, photostability is a decisive factor in the efficacy of this biologic. To better understand the photodegradation mechanisms of Rituximab, this biologic was exposed to different irradiance conditions. We show in this study that this mAb photodegrade proportionally to irradiance intensities. The main modifications of Rituximab by irradiance correlate to the increase in aggregates, decrease in its Tm, acidic charge variants, oxidation of the Trp (36) in the heavy chain, and decrease in complement-dependent cytotoxicity (CDC) potency. To understand the relationship between real-life photo-exposition conditions and ICH standardized light tests, a full characterization was set up. Worst photo-stress cases were evaluated, 1 and 2 h under direct sunlight through a window, mimicking the ID65 electromagnetic radiation profile. Our results show that only exposition to direct sun irradiance during 2 h, (≈ 150 kluxes•h), increases critically soluble and insoluble aggregates, diminishing Tm, increasing acidic charge variants, and the photooxidation of the Trp (36) in the heavy chain measured by peptide mapping-RP-UPLC-MS. A decrease in CDC below 80% resulted under this condition, which correlates with physicochemical analyses. While inside light-room exposition (similar to ICH test) and ICH conditions do not have any contribution to the degradation of Rituximab measured by these physicochemical and biological analytical methods. These results indicate that exposition of Rituximab to below ≈ 75 kluxes•h of sun light cannot photodegrade critically this biologic inside of its primary container.


Asunto(s)
Productos Biológicos , Espectrometría de Masas en Tándem , Anticuerpos Monoclonales , Cromatografía Liquida , Radiación Electromagnética , Humanos , Fotólisis , Rituximab
6.
Infect Dis (Lond) ; 54(11): 810-818, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35854671

RESUMEN

BACKGROUND: COVID-19 may trigger an acute hyperinflammatory syndrome characterised by heightened levels of acute phase reactants and is associated with adverse outcomes among hospitalised individuals. The relationship between 48-hour changes in acute phase reactants and adverse outcomes is unclear. This study evaluated the relationship between change in four acute phase reactants (interleukin-6, procalcitonin, ferritin, and C-reactive protein), and the risk for in-hospital death and invasive mechanical ventilation. METHODS: A retrospective cohort among 2,523 adult patients hospitalised with COVID-19 pneumonia was conducted. Changes in IL-6, procalcitonin, ferritin, and CRP from admission to 48 h after admission were recorded. Delta was calculated using the difference in each acute phase reactant at admission and at 48-hours. Delta in acute phase reactants and the risk for in-hospital death and invasive mechanical ventilation was assessed using logistic regression models adjusting for demographics and comorbidities. RESULTS: Patients with both admission and 48-hour measurement for interleukin-6 (IL-6) (n = 541), procalcitonin (n = 828), ferritin (n = 1022), and C-reactive protein (CRP) (n = 1919) were included. Baseline characteristics were similar across all four populations. Increases in ferritin associated with a heightened risk of in-hospital death (OR 1.00032; 95%CI 1.00007- 1.00056; p < .001) and invasive mechanical ventilation (OR 1.00035; 95%CI 1.00014- 1.00055; p = .001). Therefore, for every 100 ng/mL increase in ferritin, the odds for in-hospital death and invasive mechanical ventilation increase by 3.2% and 3.5%, respectively. CONCLUSIONS: Delta in ferritin is associated with in-hospital death and invasive mechanical ventilation. Other acute phase reactants were not associated with these outcomes among COVID-19 inpatients.


Asunto(s)
COVID-19 , Adulto , Proteína C-Reactiva , COVID-19/terapia , Ferritinas , Mortalidad Hospitalaria , Humanos , Interleucina-6 , Polipéptido alfa Relacionado con Calcitonina , Respiración Artificial , Estudios Retrospectivos , SARS-CoV-2
7.
Med Hypotheses ; 160: 110774, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35095174

RESUMEN

Diethylcarbamazine, the antiparasitic drug, also possesses anti-inflammatory and immunomodulatory activities. The anti-fibrotic activity of diethylcarbamazine makes it a potential candidate to treat coronavirus disease 2019 (COVID-19)-related pulmonary fibrosis. Experimental and clinical studies should assess this possible effect.

8.
J Neurol Sci ; 430: 119988, 2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34547616

RESUMEN

AIM: Systemic inflammatory response syndrome (SIRS) has been associated with poor outcomes after acute ischemic stroke (AIS). The primary goal of this study was to determine whether SIRS status on admission correlated with functional outcomes in AIS treated with mechanical thrombectomy (MT). METHODS: Consecutive patients from September 2015 to April 2019 were retrospectively reviewed for SIRS on admission. SIRS was defined as the presence of ≥2 of the following: temperature < 36 °C or > 38 °C, heart rate > 90, respiratory rate > 20, and white blood cell count <4000/mm or > 12,000 mm. RESULTS: Of 202 patients, 188 met inclusion criteria. 49 patients (26%) had evidence of SIRS. Neither basic patient demographics nor standard stroke risk factors predicted the development of SIRS. However, presentation with SIRS was correlated with higher rates of death (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.2-5.5) as well as lower rates of favorable functional outcomes at discharge (OR, 0.09; 95% CI, 0.02-0.40) and 3-month follow up (OR 0.12; 95% CI 0.03-0.43). These results remained significant even after adjustment for age, sex, baseline NIHSS, recanalization status, and prior co-morbidities. CONCLUSION: In our sample population, SIRS was associated with worse outcomes and higher rates of mortality in AIS patients treated with MT. Recognition of key risk factors can provide better prognostication and possible future therapeutic targets.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/complicaciones , Isquemia Encefálica/terapia , Humanos , Estudios Retrospectivos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Trombectomía , Resultado del Tratamiento
9.
Insects ; 12(8)2021 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-34442229

RESUMEN

Aedes aegypti control programs require more sensitive tools in order to survey domestic and peridomestic larval habitats for dengue and other arbovirus prevention areas. As a consequence of the COVID-19 pandemic, field technicians have faced a new occupational hazard during their work activities in dengue surveillance and control. Safer strategies to monitor larval populations, in addition to minimum householder contact, are undoubtedly urgently needed. Drones can be part of the solution in urban and rural areas that are dengue-endemic. Throughout this study, the proportion of larvae breeding sites found in the roofs and backyards of houses were assessed using drone images. Concurrently, the traditional ground field technician's surveillance was utilized to sample the same house groups. The results were analyzed in order to compare the effectiveness of both field surveillance approaches. Aerial images of 216 houses from El Vergel village in Tapachula, Chiapas, Mexico, at a height of 30 m, were obtained using a drone. Each household was sampled indoors and outdoors by vector control personnel targeting all the containers that potentially served as Aedes aegypti breeding sites. The main results were that the drone could find 1 container per 2.8 found by ground surveillance; however, containers that were inaccessible by technicians in roofs and backyards, such as plastic buckets and tubs, disposable plastic containers and flowerpots were more often detected by drones than traditional ground surveillance. This new technological approach would undoubtedly improve the surveillance of Aedes aegypti in household environments, and better vector control activities would therefore be achieved in dengue-endemic countries.

10.
IDCases ; 25: e01168, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34094866

RESUMEN

Some HIV-infection diagnostic guidelines and health care providers still rely on the ELISA-Western blot diagnostic algorithm. We present a near misdiagnosis case with discordant test results and a lack of proper counseling. We point out the need for an assertive update of health care providers on diagnostic HIV-tests.

11.
Nutrients ; 13(5)2021 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-33922959

RESUMEN

Diabetic kidney disease (DKD) remains the number one cause of end-stage renal disease in the western world. In experimental diabetes, mitochondrial dysfunction in the kidney precedes the development of DKD. Reactive 1,2-dicarbonyl compounds, such as methylglyoxal, are generated from sugars both endogenously during diabetes and exogenously during food processing. Methylglyoxal is thought to impair the mitochondrial function and may contribute to the pathogenesis of DKD. Here, we sought to target methylglyoxal within the mitochondria using MitoGamide, a mitochondria-targeted dicarbonyl scavenger, in an experimental model of diabetes. Male 6-week-old heterozygous Akita mice (C57BL/6-Ins2-Akita/J) or wildtype littermates were randomized to receive MitoGamide (10 mg/kg/day) or a vehicle by oral gavage for 16 weeks. MitoGamide did not alter the blood glucose control or body composition. Akita mice exhibited hallmarks of DKD including albuminuria, hyperfiltration, glomerulosclerosis, and renal fibrosis, however, after 16 weeks of treatment, MitoGamide did not substantially improve the renal phenotype. Complex-I-linked mitochondrial respiration was increased in the kidney of Akita mice which was unaffected by MitoGamide. Exploratory studies using transcriptomics identified that MitoGamide induced changes to olfactory signaling, immune system, respiratory electron transport, and post-translational protein modification pathways. These findings indicate that targeting methylglyoxal within the mitochondria using MitoGamide is not a valid therapeutic approach for DKD and that other mitochondrial targets or processes upstream should be the focus of therapy.


Asunto(s)
Benzamidas/uso terapéutico , Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus Experimental/complicaciones , Enfermedades Renales/prevención & control , Mitocondrias/efectos de los fármacos , Piruvaldehído/metabolismo , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL
12.
Eur J Orthop Surg Traumatol ; 31(4): 705-710, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33128631

RESUMEN

BACKGROUND: Distal phalanx fractures are frequently encountered in our daily practice. They are often caused by crush injuries and are the most frequent work-related hand fractures. Different types of fixation have been proposed for displaced fractures. METHODS: A retrospective study was performed on two fixation types. Twenty-four distal phalanx fractures were treated with k-wire fixation with fluoroscopic control in a main operating room setting. Twenty-five distal phalanx fractures were treated with hypodermic needle fixation without fluoroscopic control in an emergency treatment room setting. Clinical and radiological data were collected on fracture type, fracture healing and complications. The cost of both types of surgery was assessed. RESULTS: No significant difference in healing time, union, delayed union and non-union was found between the two groups. Loosening was significantly more frequent in the hypodermic needle group, without affecting clinical or radiographic outcome. No infections were encountered in both groups. Surgery performed in the emergency treatment room reduced the cost with 9000 dollars when compared to surgery performed the main operating room. CONCLUSION: Treatment of displaced distal phalanx fractures with hypodermic needle fixation yields good results. Performing this procedure in a treatment room is safe and might reduce operative time, institutional costs and radiation exposure for both surgeon and patients.


Asunto(s)
Fijación Interna de Fracturas , Agujas , Hilos Ortopédicos , Fluoroscopía , Humanos , Estudios Retrospectivos , Resultado del Tratamiento
13.
J Neurointerv Surg ; 13(3): 247-250, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32620576

RESUMEN

BACKGROUND: Patients with cerebral aneurysms treated with the Pipeline embolization device (PED) are maintained on dual antiplatelet therapy (DAPT) to prevent thromboembolic complications. Rates of minor, "nuisance" bleeding in these patients remain unknown. We sought to evaluate the frequency and factors associated with this bleeding and its effect on DAPT compliance. METHODS: We performed a multicenter retrospective cohort study on consecutive cases of intracranial aneurysms treated with PED. Patient characteristics, aneurysm characteristics, and bleeding complications were analyzed. Severity of bleeding was defined according to a previously published classification defining nuisance bleeding as easy bruising, bleeding from small cuts, petechia, and ecchymosis. RESULTS: 245 PED aneurysm procedures on 243 patients were retrospectively collected from three academic centers over a 4.25-year period. Sixty-seven patients (27%) had nuisance bleeds. Patients with a higher risk of nuisance bleeding were older (59.1±3.4 vs . 54.7±2.2, P=0.032). Patients with nuisance bleeds were more likely to have their DAPT regimen changed or dose lowered (29% vs 8.3%, P<0.001), were on DAPT for less time (10.0 months±2.60 vs. 14.6 months±1.95, P=0.005) and were more likely to have aneurysm occlusion at 6 months (P<0.001). Stepwise logistic regression found age predictive of a nuisance bleed (OR=1.033) CONCLUSIONS: Nuisance bleeding was a common complaint of PED-treated aneurysm patients maintained on DAPT. Increasing age and aneurysmal occlusion at 6 months were the only factors predictive of nuisance bleeds. Clinicians were more likely to adjust antiplatelet regimens or stop DAPT early given a nuisance bleed.


Asunto(s)
Terapia Antiplaquetaria Doble/efectos adversos , Embolización Terapéutica/efectos adversos , Aneurisma Intracraneal/epidemiología , Aneurisma Intracraneal/terapia , Hemorragias Intracraneales/epidemiología , Stents Metálicos Autoexpandibles/efectos adversos , Adulto , Anciano , Prótesis Vascular/efectos adversos , Prótesis Vascular/tendencias , Estudios de Cohortes , Terapia Antiplaquetaria Doble/tendencias , Embolización Terapéutica/tendencias , Femenino , Estudios de Seguimiento , Humanos , Aneurisma Intracraneal/diagnóstico , Hemorragias Intracraneales/diagnóstico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Stents Metálicos Autoexpandibles/tendencias , Resultado del Tratamiento , Adulto Joven
14.
Cardiovasc Drugs Ther ; 34(6): 823-834, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32979176

RESUMEN

PURPOSE: HFpEF (heart failure with preserved ejection fraction) is a major consequence of diabetic cardiomyopathy with no effective treatments. Here, we have characterized Akita mice as a preclinical model of HFpEF and used it to confirm the therapeutic efficacy of the mitochondria-targeted dicarbonyl scavenger, MitoGamide. METHODS AND RESULTS: A longitudinal echocardiographic analysis confirmed that Akita mice develop diastolic dysfunction with reduced E peak velocity, E/A ratio and extended isovolumetric relaxation time (IVRT), while the systolic function remains comparable with wild-type mice. The myocardium of Akita mice had a decreased ATP/ADP ratio, elevated mitochondrial oxidative stress and increased organelle density, compared with that of wild-type mice. MitoGamide, a mitochondria-targeted 1,2-dicarbonyl scavenger, exhibited good stability in vivo, uptake into cells and mitochondria and reactivity with dicarbonyls. Treatment of Akita mice with MitoGamide for 12 weeks significantly improved the E/A ratio compared with the vehicle-treated group. CONCLUSION: Our work confirms that the Akita mouse model of diabetes replicates key clinical features of diabetic HFpEF, including cardiac and mitochondrial dysfunction. Furthermore, in this independent study, MitoGamide treatment improved diastolic function in Akita mice.


Asunto(s)
Benzamidas/farmacología , Fármacos Cardiovasculares/farmacología , Cardiomiopatías Diabéticas/prevención & control , Insuficiencia Cardíaca/prevención & control , Volumen Sistólico/efectos de los fármacos , Disfunción Ventricular Izquierda/prevención & control , Función Ventricular Izquierda/efectos de los fármacos , Animales , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/fisiopatología , Modelos Animales de Enfermedad , Productos Finales de Glicación Avanzada/metabolismo , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Masculino , Ratones Endogámicos C57BL , Ratones Mutantes , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Disfunción Ventricular Izquierda/metabolismo , Disfunción Ventricular Izquierda/fisiopatología
15.
Eur J Pharm Sci ; 153: 105467, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-32682933

RESUMEN

Etanercept is a biotechnological product that has a complex glycosylation profile. To elucidate Etanercept glycosylation effect over biological activity and stability, we deglycosylated sequentially this molecule. Sequential deglycosylation was performed to understand which glycans are critical for Etanercept folding and activity. Extended study showed that gross glycosylation differences, affect thermal stability, hydrodynamic radius, pI, CDC, ADCC, protection against oxidation and charge surface exposition with any effect (within biological assay dispersion) over TNFα neutralization, indicating which glycoforms have a critical effect over Etanercept ADCC, CDC and stability. In this regard, complete remotion of sialic acids have a predominant importance over pI, ADCC, CDC and surface charge while N and O glycosylation over thermal stability, hydrophobicity, aggregation and protection against oxidation. Our research suggest that gross differences in the glycosylation profile are relevant for the stability and biological main activities of Etanercept, and that significant differences that affect the activities related to this fusion protein could be detected with proper analytical methods and stability studies.


Asunto(s)
Polisacáridos , Etanercept , Glicosilación , Interacciones Hidrofóbicas e Hidrofílicas
16.
BMC Nephrol ; 21(1): 87, 2020 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-32143585

RESUMEN

BACKGROUND: Interstitial fibrosis (IF) on kidney biopsy is one of the most potent risk factors for kidney disease progression. The furosemide stress test (FST) is a validated tool that predicts the severity of acute kidney injury (especially at 2 h) in critically ill patients. Since furosemide is secreted through the kidney tubules, the response to FST represents the tubular secretory capacity. To our knowledge there is no data on the correlation between functional tubular capacity assessed by the FST with IF on kidney biopsies from patients with chronic kidney disease (CKD). The aim of this study was to determine the association between urine output (UO), Furosemide Excreted Mass (FEM) and IF on kidney biopsies after a FST. METHODS: This study included 84 patients who underwent kidney biopsy for clinical indications and a FST. The percentage of fibrosis was determined by morphometry technique and reviewed by a nephropathologist. All patients underwent a FST prior to the biopsy. Urine volume and urinary sodium were measured in addition to urine concentrations of furosemide at different times (2, 4 and 6 h). We used an established equation to determine the FEM. Values were expressed as mean, standard deviation or percentage and Pearson Correlation. RESULTS: The mean age of the participants was 38 years and 44% were male. The prevalence of diabetes mellitus, hypertension and diuretic use was significantly higher with more advanced degree of fibrosis. Nephrotic syndrome and acute kidney graft dysfunction were the most frequent indications for biopsy. eGFR was inversely related to the degree of fibrosis. Subjects with the highest degree of fibrosis (grade 3) showed a significant lower UO at first hour of the FST when compared to lower degrees of fibrosis (p = 0.015). Likewise, the total UO and the FEM was progressively lower with higher degrees of fibrosis. An inversely linear correlation between FEM and the degree of fibrosis (r = - 0.245, p = 0.02) was observed. CONCLUSIONS: Our findings indicate that interstitial fibrosis correlates with total urine output and FEM. Further studies are needed to determine if UO and FST could be a non-invasive tool to evaluate interstitial fibrosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT02417883.


Asunto(s)
Furosemida/orina , Túbulos Renales Proximales/fisiopatología , Riñón/patología , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/fisiopatología , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/orina , Adulto , Biopsia/métodos , Progresión de la Enfermedad , Femenino , Fibrosis , Furosemida/administración & dosificación , Humanos , Masculino , Pronóstico , Insuficiencia Renal Crónica/orina , Factores de Riesgo , Sodio/orina , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/administración & dosificación
18.
J Clin Neurosci ; 73: 159-161, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31973917

RESUMEN

Alzheimer's Disease (AD) is the main cause of dementia worldwide. Inflammatory cytokines and chemokines are related to different stages of AD and may be related to the progression of the disease. A Case-control study of AD patients healthy, age and sex-matched controls was carried out at the University Hospital "Dr. José E. Gonzalez", UANL. Cytokines and chemokines were measured from blood samples taken from the cubital vein after 8 h of fast. We included 78 subjects from which 29 had AD and 49 were healthy controls. CTACK (p = 0.003), MIG (p = 0.043) and SDF-1α (p = 0.001) were increased in subjects with AD, whereas no change was observed in other cytokines and chemokines. CTACK, MIG and SDF-1α are present in the Central Nervous System and are related to inflammation and endothelial dysfunction. Longitudinal studies evaluating the change of these chemokines in AD are needed to understand their role in AD progression and possibly lead to new diagnostic and therapeutic targets.


Asunto(s)
Enfermedad de Alzheimer/sangre , Biomarcadores/sangre , Quimiocinas/sangre , Anciano , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Estudios Longitudinales , Masculino
19.
Anal Bioanal Chem ; 412(8): 1795-1806, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31982923

RESUMEN

Biopharmaceuticals are in direct contact with different plastic materials, which can contribute to process-related impurities. Polyethylene terephthalate glycol (PETG) is used for storage and transportation of biopharmaceuticals and it is synthetized from the poly-condensation reaction between ethylene glycol, 1,4-cyclodimethanol and dimethyl terephthalate. PETG bottles are analyzed for such impurities prior to release; however, the nature of the pharmaceutical matrix can extract impurities, so it is important to measure these contaminants in biopharmaceuticals. This study shows a liquid chromatography method for the quantification of ethylene glycol in PETG materials as an alternative to the standard USP colorimetric method. The method is based on the derivatization of ethylene glycol with benzoyl chloride in a Schotten-Baumann reaction. We present a comprehensive method development and validation. The method allows the detection and quantification of leached and extracted ethylene glycol directly in biopharmaceuticals after years of storage in contact with PETG bottles. Results showed residual ethylene glycol in drug substances to a level of ≈  0.1-0.5 µg/mL exposed during 2-6 years of storage in PETG bottles and ≈ 0.2-0.9 µg/mL in biopharmaceuticals. Graphical abstract Biopharmaceuticals must be free or low concentration for leachables, FR-UHPLC-UV analysis is a precise and accurate analytical method for ethylene glycol measurement. This leachable is commonly present in products in direct contact with PETG plastic.


Asunto(s)
Productos Biológicos/química , Cromatografía Líquida de Alta Presión/métodos , Cromatografía de Fase Inversa/métodos , Glicol de Etileno/análisis , Límite de Detección , Plásticos/química , Polímeros/química , Reproducibilidad de los Resultados
20.
Cardiovasc Drugs Ther ; 33(6): 669-674, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31654171

RESUMEN

PURPOSE: Methylglyoxal, a by-product of glycolysis and a precursor in the formation of advanced glycation end-products, is significantly elevated in the diabetic myocardium. Therefore, we sought to investigate the mitochondria-targeted methylglyoxal scavenger, MitoGamide, in an experimental model of spontaneous diabetic cardiomyopathy. METHODS: Male 6-week-old Akita or wild type mice received daily oral gavage of MitoGamide or vehicle for 10 weeks. Several morphological and systemic parameters were assessed, as well as cardiac function by echocardiography. RESULTS: Akita mice were smaller in size than wild type counterparts in terms of body weight and tibial length. Akita mice exhibited elevated blood glucose and glycated haemoglobin. Total heart and individual ventricles were all smaller in Akita mice. None of the aforementioned parameters was impacted by MitoGamide treatment. Echocardiographic analysis confirmed that cardiac dimensions were smaller in Akita hearts. Diastolic dysfunction was evident in Akita mice, and notably, MitoGamide treatment preferentially improved several of these markers, including e'/a' ratio and E/e' ratio. CONCLUSIONS: Our findings suggest that MitoGamide, a novel mitochondria-targeted approach, offers cardioprotection in experimental diabetes and therefore may offer therapeutic potential for the treatment of cardiomyopathy in patients with diabetes.


Asunto(s)
Amidas/farmacología , Benzamidas/farmacología , Cardiotónicos/farmacología , Cardiomiopatías Diabéticas/tratamiento farmacológico , Difenilamina/farmacología , Mitocondrias Cardíacas/efectos de los fármacos , Piruvaldehído/metabolismo , Función Ventricular Izquierda/efectos de los fármacos , Animales , Benzamidas/uso terapéutico , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/fisiopatología , Modelos Animales de Enfermedad , Insulina/genética , Masculino , Ratones Endogámicos C57BL , Mitocondrias Cardíacas/metabolismo , Mutación
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