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1.
Front Immunol ; 15: 1330796, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38665909

RESUMEN

Introduction: There is no useful method to discriminate between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB). This study aimed to investigate the potential of cytokine profiles to discriminate between LTBI and active PTB using whole-blood stimulation with Mycobacterium tuberculosis (MTB) antigens, including latency-associated antigens. Materials and methods: Patients with active PTB, household contacts of active PTB patients and community exposure subjects were recruited in Manila, the Philippines. Peripheral blood was collected from the participants and used for whole-blood stimulation (WBS) with either the early secretory antigenic target and the 10-kDa culture filtrate protein (ESAT-6/CFP-10), Rv3879c or latency-associated MTB antigens, including mycobacterial DNA-binding protein 1 (MDP-1), α-crystallin (Acr) and heparin-binding hemagglutinin (HBHA). Multiple cytokine concentrations were analyzed using the Bio-Plex™ multiplex cytokine assay. Results: A total of 78 participants consisting of 15 active PTB patients, 48 household contacts and 15 community exposure subjects were eligible. The MDP-1-specific IFN-γ level in the active PTB group was significantly lower than that in the household contact group (p < 0.001) and the community exposure group (p < 0.001). The Acr-specific TNF-α and IL-10 levels in the active PTB group were significantly higher than those in the household contact (TNF-α; p = 0.001, IL-10; p = 0.001) and community exposure (TNF-α; p < 0.001, IL-10; p = 0.01) groups. However, there was no significant difference in the ESAT-6/CFP-10-specific IFN-γ levels among the groups. Conclusion: The patterns of cytokine profiles induced by latency-associated MTB antigens using WBS have the potential to discriminate between LTBI and active PTB. In particular, combinations of IFN-γ and MDP-1, TNF-α and Acr, and IL-10 and Acr are promising. This study provides the first demonstration of the utility of MDP-1-specific cytokine responses in WBS.


Asunto(s)
Antígenos Bacterianos , Citocinas , Tuberculosis Latente , Mycobacterium tuberculosis , Tuberculosis Pulmonar , Humanos , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/sangre , Masculino , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/inmunología , Tuberculosis Latente/sangre , Tuberculosis Latente/microbiología , Femenino , Mycobacterium tuberculosis/inmunología , Filipinas , Adulto , Citocinas/sangre , Persona de Mediana Edad , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/microbiología , Adulto Joven , Proteínas Bacterianas/inmunología
2.
Dev Comp Immunol ; 156: 105178, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38599553

RESUMEN

In the present study, using transgenic frogs that express GFP specifically in myeloid cells under the myeloperoxidase enhancer sequence, we found that myeloperoxidase-positive cells are localized in the liver cortex at the late tadpole stages. Immunohistochemical analysis revealed that myelopoiesis in the liver cortex became evident after st. 50 and reached its peak by st. 56. Transplantation experiments indicated that cells with a high density at the liver cortex were derived from the dorso-lateral plate tissue in the neurula embryo. Analysis of smear samples of the cells isolated from collagenase-treated liver tissues of the transgenic tadpoles indicated that myeloid cells were the major population of blood cells in the larval liver and that, in addition to myeloid colonies, erythroid colonies expanded in entire liver after metamorphosis. Cells that were purified from the livers of transgenic tadpoles according to the GFP expression exhibited the multi-lobed nuclei. The results of present study provide evidence that the liver cortex of the Xenopus tadpole is a major site of granulopoiesis.


Asunto(s)
Animales Modificados Genéticamente , Larva , Hígado , Células Mieloides , Xenopus laevis , Animales , Hígado/citología , Mielopoyesis , Proteínas Fluorescentes Verdes/metabolismo , Proteínas Fluorescentes Verdes/genética , Peroxidasa/metabolismo , Metamorfosis Biológica
3.
Am Surg ; 90(4): 897-901, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37993112

RESUMEN

Among women with breast cancer, delays in diagnosis and earlier presentation have been documented among minority women. Consequently, initiation of breast cancer screening at a later age may disproportionately harm minority groups. This study seeks to determine whether minority women face a higher proportional risk of younger age breast cancer than their White peers. Using publicly available data from the Ohio Department of Public Health Data Warehouse, we constructed a database allowing for retrospective evaluation of all breast cancer patients in the state of Ohio from 1996 to 2020. White women represented the bulk of total breast cancer cases in each age group and overall; however, the proportion of cancers attributable to White women increased in each successively older cohort group: 80.7% of cases under age 40 up to 91.3% of the 80 or older group. By a significant margin, the opposite is true in minority groups with African American women accounting for 15% of cases under the age of 40, trending down to 7.8% of the 80 and older group. Comparison of the proportions of these groups demonstrates statistically significant proportional decreases among minority groups and statistically significant increases among White women. Our findings suggest that women of color in the Ohio population face a disproportionately high risk of being diagnosed with younger age breast cancer and support the findings of other authors who recommend tailoring breast cancer screening by racial cohort. Efforts should be made to promote younger-age screening for minority women to prevent disproportionate harm.


Asunto(s)
Neoplasias de la Mama , Detección Precoz del Cáncer , Humanos , Femenino , Adulto , Grupos Minoritarios , Neoplasias de la Mama/diagnóstico , Ohio/epidemiología , Estudios Retrospectivos
4.
Eur J Case Rep Intern Med ; 10(10): 003949, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37789979

RESUMEN

Introduction: Guillain-Barré syndrome is an immune-mediated inflammatory polyneuritis characterised by rapidly progressive flaccid paralysis. Guillain-Barré syndrome may present with posterior reversible encephalopathy syndrome or reversible cerebral vasoconstriction syndrome in rare cases. Case description: A woman in her 60s with a history of follicular lymphoma presented with a one-week history of difficulty walking and thunderclap headaches. The patient was diagnosed with Guillain-Barré syndrome based on neurological examination, cerebrospinal fluid analysis and nerve conduction findings. Further diagnosis of posterior reversible encephalopathy and reversible cerebral vasoconstriction syndromes was based on imaging findings and headache history. The patient was treated with intravenous immunoglobulin and amlodipine, and symptoms improved. Discussion: We reviewed the literature on Guillain-Barré syndrome associated with posterior reversible encephalopathy and/or reversible cerebral vasoconstriction syndrome. The underlying pathophysiology may involve dysautonomia resulting in unstable blood pressure, and hyponatraemia causing endothelial dysfunction. The SNOOP mnemonic highlights the 'red flags'. This SNOOP mnemonic suggests the possibility of secondary headaches that require imaging studies. In this case, the patient exhibited three SNOOP symptoms: S (history of malignancy: follicular lymphoma), O (sudden-onset headache) and O (over 50 years old). Conclusion: This case highlights the importance of considering coexisting central neurological disorders in patients with Guillain-Barré syndrome. LEARNING POINTS: Guillain-Barré syndrome (GBS) alone rarely causes headaches; therefore, when GBS patients complain of severe headaches, especially when the headache is associated with 'red flags', other complications and differential diagnosis should be considered.Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) can be triggered by GBS.Hyponatraemia, age over 50 years and female gender may be risk factors for developing PRES and RCVS in GBS patients.

6.
Sci Rep ; 13(1): 12685, 2023 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-37542102

RESUMEN

Accurate point-of-care testing (POCT) is critical for managing tuberculosis (TB). However, current antibody-based diagnosis shows low specificity and sensitivity. To find proper antigen candidates for TB diagnosis by antibodies, we assessed IgGs responsiveness to Mycobacterium tuberculosis proteins in pulmonary TB (PTB) patients. We employed major secreted proteins, such as Rv1860, Ag85C, PstS1, Rv2878c, Ag85B, and Rv1926c that were directly purified from M. tuberculosis. In the first screening, we found that IgG levels were significantly elevated in PTB patients only against Rv1860, PstS1, and Ag85B among tested antigens. However, recombinant PstS1 and Ag85B from Escherichia coli (E. coli) couldn't distinguish PTB patients and healthy controls (HC). Recombinant Rv1860 was not checked due to its little expression. Then, the 59 confirmed PTB patients from Soetomo General Academic Hospital, Surabaya, Indonesia, and 102 HC were tested to Rv1860 and Ag85B only due to the low yield of the PstS1 from M. tuberculosis. The ROC analysis using native Ag85B and Rv1860 showed an acceptable area under curve for diagnosis, which is 0.812 (95% CI 0.734-0.890, p < 0.0001) and 0.821 (95% CI 0.752-0.890, p < 0.0001). This study indicates that taking consideration of native protein structure is key in developing TB's POCT by antibody-based diagnosis.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Pulmonar , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Proteínas Bacterianas/química , Antígenos Bacterianos , Escherichia coli/metabolismo , Tuberculosis Pulmonar/diagnóstico , Tuberculosis/diagnóstico , Anticuerpos Antibacterianos
7.
Front Immunol ; 14: 1222428, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37520555

RESUMEN

Introduction: Controlling pulmonary Mycobacterium avium complex (MAC) disease is difficult because there is no way to know the clinical stage accurately. There have been few attempts to use cell-mediated immunity for diagnosing the stage. The objective of this study was to characterize cytokine profiles of CD4+T and CD19+B cells that recognize various Mycobacterium avium-associated antigens in different clinical stages of MAC. Methods: A total of 47 MAC patients at different stages based on clinical information (14 before-treatment, 16 on-treatment, and 17 after-treatment) and 17 healthy controls were recruited. Peripheral blood mononuclear cells were cultured with specific antigens (MAV0968, 1160, 1276, and 4925), and the cytokine profiles (IFN-γ, TNF-α, IL-2, IL-10, IL-13, and IL-17) of CD4+/CD3+ and CD19+ cells were analyzed by flow cytometry. Results: The response of Th1 cytokines such as IFN-γ and TNF-α against various antigens was significantly higher in both the on-treatment and after-treatment groups than in the before-treatment group and control (P < 0.01-0.0001 and P < 0.05-0.0001). An analysis of polyfunctional T cells suggested that the presence of IL-2 is closely related to the stage after the start of treatment (P = 0.0309-P < 0.0001) and is involved in memory function. Non-Th1 cytokines, such as IL-10 and IL-17, showed significantly higher responses in the before-treatment group (P < 0.0001 and P < 0.01-0.0001). These responses were not observed with purified protein derivative (PPD). CD19+B cells showed a response similar to that of CD4+T cells. Conclusion: There is a characteristic cytokine profile at each clinical stage of MAC.


Asunto(s)
Enfermedades Pulmonares , Infección por Mycobacterium avium-intracellulare , Humanos , Complejo Mycobacterium avium , Interleucina-10 , Interleucina-17 , Interleucina-2/uso terapéutico , Factor de Necrosis Tumoral alfa/uso terapéutico , Leucocitos Mononucleares , Citocinas
8.
J Pharm Biomed Anal ; 234: 115565, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37453146

RESUMEN

Nutmeg is an inexpensive, readily available spice used in a variety of recipes. However, the use of nutmeg powder as a recreational drug for its hallucinogenic effects is resulting in an increase in overdose rates. We encountered a male patient being hospitalized after ingesting 75 g of commercially available nutmeg powder with the intent of committing suicide. There are no available reports documenting the toxic or comatose-fatal blood concentrations or time-course of drug action in cases of nutmeg poisoning. Therefore, to improve patient management, we endeavored to determine the blood serum levels and time-course of the major psychoactive compounds (safrole, myristicin, and elemicin) present in nutmeg. We designed a simple and reliable method using the MonoSpin® extraction kit and gas chromatography-tandem mass spectrometry to detect the presence of these psychoactive compounds in human serum. The method had detection and quantitation limits of 0.14-0.16 and 0.5 ng/mL (lowest calibration points), respectively. The calibration curves displayed excellent linearity (0.996-0.997) for all three compounds at 0.5-300 ng/mL blood concentrations. The intra- and inter-day precision values for quality assurance were in the ranges of 2.4-11 % and 2.5-11 %, respectively; bias ranged from - 2.6 % to 2.1 %. Blood serum levels of safrole, myristicin, and elemicin were measured at admission (approximately 8 h post-ingestion) and approximately 94 h after a post-admission fluid therapy to evaluate their biological half-lives. We developed this method to obtain information on the psychoactive constituents of nutmeg and, thereby, determine the toxicokinetic parameters of nutmeg in a case of nutmeg poisoning.


Asunto(s)
Myristica , Safrol , Humanos , Masculino , Safrol/análisis , Safrol/química , Espectrometría de Masas en Tándem , Myristica/química , Cromatografía de Gases y Espectrometría de Masas/métodos , Polvos , Suero/química , Compuestos de Bencilo/análisis , Compuestos de Bencilo/química
9.
Surg Case Rep ; 9(1): 126, 2023 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-37428342

RESUMEN

BACKGROUND: A few cases of small omphalocele with umbilical evagination of the bladder have been reported. However, its embryology is yet to be elucidated. Only a few reports have indicated the existence of urachal anomalies and umbilical cysts related to bladder evagination. The incidence of urachal anomalies at birth is reported to be 1 in 5000-8000 live birth, and urachal aplasia is rare. Herein, we report a rare, novel case of urachal aplasia. CASE PRESENTATION: We encountered a small omphalocele with bladder evagination associated with urachal aplasia for which the neonate underwent surgery one day after birth. The patient was a one-day-old boy with a prenatally diagnosed omphalocele. A fetal magnetic resonance image (MRI) scan (25 weeks of gestation) revealed a 30 × 33 mm (approximately 1.3 in.) cystic lesion which was suspected to be an umbilical cyst. The baby was born vaginally at 38 weeks, weighing 2956 g. An omphalocele (hernial orifice diameter, 4 cm × 3 cm) with bladder prolapse was recognized. After sac excision, the prolapsed bladder was resected and closed with two-layer sutures. In order to secure sufficient bladder capacity, we estimated the minimum residual volume as 21 ml after bladder plasty. The remaining bladder capacity was confirmed to be 30 ml by injecting a contrast dye and saline into the bladder. The neonate had no associated cardiac urogenital or skeletal anomalies. Postoperative course was uneventful. The patient was regularly followed up for two years after surgery and underwent umbilicoplasty. He had no trouble with urinary function. CONCLUSION: In this case, we experienced extremely rare condition of a small omphalocele with bladder evagination associated with urachal aplasia and reviewed 7 case reports of anomalies similar to those in the present case. Umbilical cord cysts may be an informative indicator of these symptoms in utero. Therefore, ultrasonography scans should be conducted until delivery, despite the spontaneous disappearance of cord cysts.

10.
AIMS Public Health ; 10(1): 169-182, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37063358

RESUMEN

Objective: The primary goal was to evaluate the validity of food photographic estimation for nutritional assessment compared with weighed food record (WFR). Methods: We evaluated the validity and reproducibility of photographic estimation of foods provided in evacuation shelters. We analyzed 35 meals served at 12 shelters in Kumamoto Prefecture in Japan, affected by a heavy rain disaster in 2020. In this context, we compared 21 senior students' portion size estimation by food photographs to WFR. In addition, we assigned five meals for each of the 21 senior students, and the same meal photograph was estimated by three students to test reproducibility. Results: No statistically significant difference was detected between the two methods regarding energy, the total grams of meal, the protein, and vitamins B1, B2, and C, except for salt. In addition, the students who never self-cooked underestimated the total grams. Conclusion: Food photographic estimation could simplify the nutritional assessment in evacuation shelters. However, unclear photographs and food items served by weight could weaken the estimation accuracy. According to previous studies and the applied postestimation questionnaire, photographs taken from specified angles and reference food photobooks for portion size estimation may improve accuracy.

11.
Case Rep Neurol Med ; 2022: 4828549, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36340934

RESUMEN

Background. In the acute phase of stroke, it is well known that the incidence and severity of unilateral spatial neglect (USN) are more significant in the right hemisphere injuries. Still, the detection of USN in left hemisphere injuries has been increasing in recent years. This trend is because behavioral assessments have prevented the exclusion of patients who are difficult to assess for USN or apathy using conventional paper-and-pencil tests (e.g., aphasia). Right USN and post-stroke apathy share many common lesions. Therefore, clinical symptoms may overlap, but little validation considers this. Case Study. A man (62 years old) determined to have the right USN and apathy was treated for six weeks in 3 terms. In the first term (weeks 1 to 2), the patient was treated for the right USN by conventional therapy. In the second term (3-4 weeks), treatment for right USN and apathy by goal-directed therapy based on affinity behavior was implemented. In the third term (5-6 weeks), goal-directed therapy based on affinity behavior was discontinued, and treatment was returned to conventional therapy only. In the second term (goal-directed therapy based on affinity behavior), the improvement in patients' apathy (clinical assessment for spontaneity) was more significant than the effect size in the third term (conventional therapy). There were no significant differences in USN (catherine bergego scale) and intrinsic motivation (pittsburgh rehabilitation participation scale). However, the effect size in the second term tended to be larger than in the third term (conventional therapy). Clinical Rehabilitation Impact. This report aims to demonstrate the limitations of current treatment for cases determined to have both right USN and apathy. Second, to assess the extent to which this new intervention can complement the limitations of current treatment.

12.
Sci Rep ; 12(1): 4310, 2022 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-35279668

RESUMEN

Tuberculosis (TB) is fatal in elephants, hence protecting elephants from TB is key not only in the conservation of this endangered animal, but also to prevent TB transmission from elephants to humans. Most human TB cases arise from long-term asymptomatic infections. Significant diagnostic challenges remain in the detection of both infection and disease development from latency in elephants due to their huge bodies. In this study, we assessed cryopreserved sera collected for over 16 years, from the first Japanese treatment case of elephant TB. Semi-quantification of IgG levels to 11 proteins showed high detection levels of 3 proteins, namely ESAT6/CFP10, MPB83 and Ag85B. The level of IgG specific to these 3 antigens was measured longitudinally, revealing high and stable ESAT6/CFP10 IgG levels regardless of onset or treatment. Ag85B-specifc IgG levels were largely responsive to onset or treatment, while those of MPB83 showed intermediate responses. These results suggest that ESAT6/CFP10 is immunodominant in both asymptomatic and symptomatic phases, making it useful in the detection of infection. On the other hand, Ag85B has the potential to be a marker for the prediction of disease onset and in the evaluation of treatment effectiveness in elephants.


Asunto(s)
Elefantes , Mycobacterium tuberculosis , Tuberculosis , Animales , Antígenos Bacterianos , Proteínas Bacterianas , Elefantes/microbiología , Inmunoglobulina G , Tuberculosis/diagnóstico , Tuberculosis/veterinaria
13.
Biol Pharm Bull ; 45(5): 643-648, 2022 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-35236811

RESUMEN

Plasmalogens are a group of glycerophospholipids containing a vinyl-ether bond at the sn-1 position in the glycerol backbone. Cellular membrane plasmalogens are considered to have important roles in homeostasis as endogenous antioxidants, differentiation, and intracellular signal transduction pathways including neural transmission. Therefore, reduced levels of plasmalogens have been suggested to be associated with neurodegenerative diseases such as Alzheimer's disease. Interestingly, although arachidonic acid is considered to be involved in learning and memory, it could be liberated and excessively activate neuronal activity to the excitotoxic levels seen in Alzheimer's disease patients. Here, we examined the protective effects of several kinds of plasmalogens against cellular toxicity caused by arachidonic acid in human neuroblastoma SH-SY5Y cells. As a result, only phosphatidylcholine-plasmalogen-oleic acid (PC-PLS-18) showed protective effects against arachidonic acid-induced cytotoxicity based on the results of lactate dehydrogenase release and ATP depletion assays, as well as cellular morphological changes in SH-SY5Y cells. These results indicate that PC-PLS-18 protects against arachidonic acid-induced cytotoxicity, possibly via improving the stability of the cellular membrane in SH-SY5Y cells.


Asunto(s)
Enfermedad de Alzheimer , Plasmalógenos , Ácido Araquidónico , Humanos , Lecitinas , Ácido Oléico , Plasmalógenos/química , Plasmalógenos/metabolismo , Plasmalógenos/farmacología
15.
J Pharmacol Toxicol Methods ; 100: 106610, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31302166

RESUMEN

INTRODUCTION: Paraquat (PQ) is one of the most toxic herbicides to humans. However, it is still in use in many countries, including Japan, and many incidents, such as homicides, intentional ingestions, and occupational accidents, have been reported thus far. In PQ poisoning cases, it is possible to predict severity and prognosis using nomograms. Therefore, if the serum PQ level is determined immediately, a treatment plan can be rapidly established. However, most known analytical methods are time-consuming and therefore hardly ever contribute to patient treatment. METHODS: We developed a new method for PQ quantitation in serum by combining a probe electrospray ionization technique with mass spectrometry. This method requires virtually no serum pretreatment and can yield quantitation values in 18 s. RESULTS: We applied the proposed method to samples from real poisoning cases and compared the results with those obtained via liquid-chromatography-tandem mass spectrometry, revealing the absence of any significant differences at the 5% significance level (t(8) = 1.000, p > .05). The limits of detection and quantitation were 0.004 and 0.015 µg/L, respectively, and the calibration curve exhibited good linearity over the concentration range of 0.015-4.0 µg/mL (r2 = 0.998). DISCUSSION: As the proposed method is fast and easy to perform, it should be useful in emergency medical settings.


Asunto(s)
Herbicidas/sangre , Paraquat/sangre , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida , Herbicidas/envenenamiento , Humanos , Límite de Detección , Paraquat/envenenamiento , Factores de Tiempo
16.
J Food Drug Anal ; 27(3): 786-792, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31324294

RESUMEN

Poisoning incidents caused by drugs, accidental ingestion of poisons, attempted suicide, homicide, and exposure to toxic compounds occur frequently every year across the globe. This raises the need to rapidly identify toxic agents in poisoned patients in a clinical emergency setting. In addition, determining drug/poison concentration is undoubtedly necessary to arrive at a toxicological treatment plan. The purpose of this study was to develop an ultra-rapid drug screening method for the clinical treatment of poisoning. Probe electrospray ionization (PESI), one of the ambient ionization techniques, is able to detect compounds from various biological materials almost directly. We applied the PESI technique to the rapid detection of acetaminophen (APAP). Blood serum samples were diluted 100-fold with 10 mM ammonium formate/ethanol (1:1 v/v) solution including deuterium-labeled internal standards (IS; APAP-d4). Only 10 µL of the diluted sample was used for measurement. The tandem mass spectrometer (MS/MS) equipped with a PESI was used in selected reaction monitoring mode for the quantitation of APAP; the measurement time was only 18 s. Transitions were set at 152 > 110 for quantitation, 152 > 65 for qualifier, and 156 > 114 for IS (APAP-d4). All measurements were conducted in positive mode. The calibration curve (1/x2) was linear over the range of 1.56-200 µg/mL (r2 = 0.998), and the limit of detection and quantitation were 0.37 µg/mL and 1.56 µg/mL, respectively. The accuracy (bias) and precision (RSD%) of the method were within an acceptable range (-0.15-2.8% and 2.3-6.1%, respectively) and matrix effect at 3 concentrations (95.1-104%) indicated that PESI-MS/MS is only slightly affected by matrices. In real forensic cases, quantitative values of APAP determined by the PESI-MS/MS were almost identical to those determined by the liquid chromatography-MS/MS method. Since PESI-MS/MS is a simple, reliable, and rapid determination method for toxic agents with virtually no need for blood serum pre-treatment, it would be highly suitable for poisoning cases in clinical emergency settings. In the future, a method for simultaneous rapid determination of multiple toxic agents will be developed.


Asunto(s)
Acetaminofén/sangre , Analgésicos no Narcóticos/sangre , Acetaminofén/química , Analgésicos no Narcóticos/química , Evaluación Preclínica de Medicamentos , Humanos , Estructura Molecular , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en Tándem
17.
J Pharm Biomed Anal ; 174: 175-181, 2019 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-31170631

RESUMEN

Glufosinate and glyphosate, which are non-selective herbicides that include an amino acid moiety in their structures, are frequently used worldwide to control unwanted vegetation. Unfortunately, these readily available herbicides are also used by people to commit suicide, and thus represent important chemicals of interest in the fields of clinical medicine and forensics. Because of the high water solubility of these herbicides, most analytical methods for their detection require a derivatization step, which results in longer analysis times. Therefore, derivatization-based methods do not currently contribute to judgements on treatment decisions in emergency medicine. In this study, we addressed this limiting factor by developing an ultra-rapid and simple analytical technique using a combination of probe electrospray ionization (PESI) and tandem mass spectrometry (MS/MS), which gives quantitative results within 0.3 min. Herbicide standards were added to human serum that was then subjected to analysis (N = 5 per concentration). The analysis was repeated daily over eight consecutive days. The limit of detection (LOD) was 0.59 µg/mL for glufosinate and 0.20 µg/mL for glyphosate. The limit of quantitation (LOQ), i.e., the lowest point on the calibration curves, was 1.56 µg/mL for both the herbicides. The matrix effects were observed at three different concentrations (between 95.7%-104% for glufosinate, and between 90.7%-95.7% for glyphosate). When applied to samples taken from actual poisoning cases (six samples for each herbicide), the present method gave almost the same quantitative values as those obtained by conventional high-performance liquid chromatography with fluorescence detection. Thus, we believe that PESI-MS/MS could emerge as a rapid diagnosis method in the clinical emergency field.


Asunto(s)
Aminobutiratos/sangre , Glicina/análogos & derivados , Herbicidas/sangre , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodos , Aminobutiratos/envenenamiento , Calibración , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Glicina/sangre , Glicina/envenenamiento , Herbicidas/envenenamiento , Humanos , Límite de Detección , Estándares de Referencia , Reproducibilidad de los Resultados , Extracción en Fase Sólida , Glifosato
18.
PLoS One ; 13(10): e0204160, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30359374

RESUMEN

Tuberculosis causes the highest mortality among all single infections. Asymptomatic tuberculosis, afflicting one third of the global human population, is the major source as 5-10% of asymptomatic cases develop active tuberculosis during their lifetime. Thus it is one of important issues to develop diagnostic tools for accurately detecting asymptomatic infection. Mycobacterial DNA-binding protein 1 (MDP1) is a major protein in persistent Mycobacterium tuberculosis and has potential for diagnostic use in detecting asymptomatic infection. However, a previous ELISA-based study revealed a specificity problem; IgGs against MDP1 were detected in both M. tuberculosis-infected and uninfected individuals. Although the tertiary structures of an antigen are known to influence antibody recognition, the MDP1 structural details have not yet been investigated. The N-terminal half of MDP1, homologous to bacterial histone-like protein HU, is predicted to be responsible for DNA-binding, while the C-terminal half is assumed as totally intrinsically disordered regions. To clarify the relationship between the MDP1 tertiary structure and IgG recognition, we refined the purification method, which allow us to obtain a recombinant protein with the predicted structure. Furthermore, we showed that an IgG-ELISA using MDP1 purified by our refined method is indeed useful in the detection of asymptomatic tuberculosis.


Asunto(s)
Proteínas Bacterianas/química , Proteínas Bacterianas/inmunología , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/inmunología , Inmunoglobulina G/metabolismo , Tuberculosis/diagnóstico , Adulto , Anciano , Sitios de Unión , Estudios de Casos y Controles , Dicroismo Circular , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Moleculares , Unión Proteica , Multimerización de Proteína , Estructura Secundaria de Proteína , Adulto Joven
19.
JMIR Res Protoc ; 6(4): e63, 2017 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-28428168

RESUMEN

BACKGROUND: Diet and fluid restrictions that need continuous self-management are among the most difficult aspects of dialysis treatment. Smartphone applications may be useful for supporting self-management. OBJECTIVE: Our objective is to investigate the feasibility and usability of a novel smartphone-based self-management support system for dialysis patients. METHODS: We developed the Self-Management and Recording System for Dialysis (SMART-D), which supports self-monitoring of three mortality-related factors that can be modified by lifestyle: interdialytic weight gain and predialysis serum potassium and phosphorus concentrations. Data is displayed graphically, with all data evaluated automatically to determine whether they achieve the values suggested by the Japanese Society for Dialysis Therapy guidelines. In a pilot study, 9 dialysis patients used SMART-D system for 2 weeks. A total of 7 of them completed questionnaires rating their assessment of SMART-D's usability and their satisfaction with the system. In addition, the Kidney Disease Quality of Life scale was compared before and after the study period. RESULTS: All 9 participants were able to use SMART-D with no major problems. Completion rates for body weight, pre- and postdialysis weight, and serum potassium and phosphorus concentrations were, respectively, 89% (SD 23), 95% (SD 7), and 78% (SD 44). Of the 7 participants who completed the usability survey, all were motivated by the sense of security derived from using the system, and 6 of the 7 (86%) reported that using SMART-D helped improve their lifestyle and self-management. CONCLUSIONS: Using SMART-D was feasible, and the system was well regarded by patients. Further study with larger scale cohorts and longer study and follow-up periods is needed to evaluate the effects of SMART-D on clinical outcomes and quality of life.

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