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1.
Environ Monit Assess ; 196(4): 352, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38466376

RESUMEN

With characterized for complex and maximum substance (suspended solids, broke up oil, a mixture of inorganic and chromium sulfides), tannery wastewater was subjected to a treatment process on removal of chemical oxygen demand (COD) via upstream anaerobic sludge blanket reactor where we found reduced departure efficiencies and that process limits were affected by the assortments in regular stacking rates, closeness of chromium, and sulfides. Hence, a combination of the aerobic-anaerobic hybrid reactor was set up for sequential treatment to determine possible COD reduction. This study investigated the biological degradation of tannery wastewater in a laboratory-scale sequential up-flow aerobic-anaerobic reactor. The aerobic zone at the top was packed with spherical ball-shaped polyhedral polypropylene, and the anaerobic zone at the bottom was packed medium with granular media. The aeration flow rate varied by 2 L/min, 4 L/min, and 6 L/min in the aerobic zone, and the reactor maintained an organic loading rate (OLR) of 5 kg COD/m3/d. Parameters like COD and gas yield assess the performance of the reactor. The maximum COD of 86% is removed in the anaerobic zone with an aeration rate of 6 L/min, and the 1800-mL methane gas yield is measured by the 29th day.


Asunto(s)
Reactores Biológicos , Aguas Residuales , Anaerobiosis , Análisis de la Demanda Biológica de Oxígeno , Monitoreo del Ambiente , Cromo , Sulfuros , Eliminación de Residuos Líquidos , Oxígeno
2.
Lett Appl Microbiol ; 75(2): 243-248, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35426154

RESUMEN

Four dissimilar bacterial colonies were isolated from the intestine of ornamental fish Swordtail Xiphophorus helleri through serial dilution. The isolated colonies were identified as Enterobacter sp., Bacillus sp., Streptococcus sp. and Pseudomonas sp. using biochemical tests. Enzyme productivity and antibacterial activity of intestinal bacteria of Swordtail were carried out against pathogens such as Enterococcus faecalis, Shigella flexneri, Streptococcus pyogenes and Klebshilla pneumoniae along with commercial antibiotic Tetracycline. Based on biochemical tests, enzyme productivity and antibacterial activity mass multiplication of Enterobacter sp., Bacillus sp. and Streptococcus sp. were done in nutrient broth. Four different feeds such as feed I (Control) (without bacteria), Feed II (1ml Bacillus sp.), Feed III (1 ml of each of Bacillus sp. and Streptococcus sp.) and Feed IV (1 ml each of Bacillus sp., Streptococcus sp. and Enterobacter sp.) were prepared. A total of 60 fishes were used for the study. Feed utilization parameters of the Swordtail were estimated after 21 days. Based on the antibacterial test, the Bacillus sp. and Enterobacter sp. have higher inhibition. Most of the feed utilization parameters were higher in feed IV. From the results, it was concluded that the combination of three dissimilar bacteria in the feed enhanced the growth of the Swordtail.


Asunto(s)
Bacillus , Ciprinodontiformes , Animales , Antibacterianos/farmacología , Enterobacter , Streptococcus
3.
Niger J Clin Pract ; 25(10): 1635-1640, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36308232

RESUMEN

Background: Congenital diaphragmatic hernia (CDH) is an anomaly with significant morbidity in neonates. It has been traditionally managed by an open approach with a recent trend toward a minimally invasive approach. Aim: This is a retrospective study of our institutional experience with neonatal thoracoscopic management of CDH, with the impact of few technical nuances. Patients and Methods: The data was collected on neonatal thoracoscopic CDH repair between January 2015 and December 2018, in terms of the demographics, intra-operative parameters, post-operative status, recurrence, and mortality. While analyzing data, we found few technical modifications adopted by the surgeon such as trimming the margin of the defect, use of prosthetic mesh overlay reinforcement for repairs under tension, and to prefer extra-corporeal knotting along with higher placement of trocar, temporary increase in CO2, maximal use of muscle relaxant, extra-corporeal corner hitch stitch at some point, and continuation for further cases. An internal comparison was made to analyze the technical modifications influencing the outcomes, by dividing them into two groups, those with (group A) and without modifications (group B). The data was analyzed using SPSS software (IBM, Version 23). A P value of <0.05 was considered statistically significant. Results: Out of 45 newborns 64.4% were males with an average birth weight of 2.6 kg. Baseline variables were comparable between the groups. The operating time significantly reduced after a higher-level camera port was used (P-value: 0.0001). The mean follow-up was 30.8 months. There were totally seven recurrences (6 in group A and 1 in group B), all within 12 months. Seven parents gave the overall post-treatment feedback as "unsatisfied". The operating time, recurrence rate, and parental satisfaction feedback were significantly less in group B (P-value: 0.001). Conclusion: We recommend trimming the margin of the defect, use of prosthetic mesh overlay reinforcement for repairs under tension, and to prefer extra-corporeal knotting along with higher placement of trocar, temporary increase in CO2, maximal use of muscle relaxant, extra-corporeal corner hitch stitch to reduce the operating time, and recurrence after thoracoscopic CDH repair.


Asunto(s)
Hernias Diafragmáticas Congénitas , Masculino , Recién Nacido , Humanos , Femenino , Hernias Diafragmáticas Congénitas/cirugía , Estudios Retrospectivos , Toracoscopía , Dióxido de Carbono , Resultado del Tratamiento
4.
Dermatol Ther ; 34(1): e14555, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33210434

RESUMEN

Although intralesional triamcinolone acetonide (TA) is the most commonly prescribed treatment for localized alopecia areata (AA), the literature regarding the optimal concentration for attaining better efficacy with the most acceptable side effects is scarce. To compare hair regrowth and local side effects of various concentrations of intralesional TA in scalp AA using clinical and dermoscopic parameters. A double-blind randomized control trial with four treatment groups (10, 5, 2.5 mg/ml TA and normal saline [NS]) was conducted between March 2018 and August 2019. After recruitment, each AA patch was divided into quadrants and randomized before first injection. Injections were given and outcome parameters were analyzed every 4-weekly till 12-weeks. Statistical analysis was done by the R software employing generalized estimation equation. P-value <.05 was considered significant. Out of 105-patients (168-AA patches), 75-patients (121-patches) completed the study. Hair regrowth scale of all TA concentrations was better than NS group (P < .001). Other parameters such as quadrants with poor clinical response and dermoscopic disease activity signs were also favorable in TA groups in comparison to NS. However the evidence of atrophy and telangiectasia was maximum in 10 mg/mL group. 10 mg/mL TA showed a comparatively better response at the cost of increased adverse effects. Based on the clinical benefit and adverse risk assessment from our study, it may be better to start with 2.5 mg/mL intralesional TA in limited scalp AA patients. It can be implied that the concentration of TA can be increased as a step-up regimen based on the serial clinical and dermoscopic response.


Asunto(s)
Alopecia Areata , Triamcinolona Acetonida , Alopecia Areata/tratamiento farmacológico , Humanos , Inyecciones Intralesiones , Cuero Cabelludo , Resultado del Tratamiento , Triamcinolona Acetonida/efectos adversos
5.
Public Health ; 198: 273-279, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34492508

RESUMEN

OBJECTIVES: The role of overcrowded and multigenerational households as a risk factor for COVID-19 remains unmeasured. The objective of this study is to examine and quantify the association between overcrowded and multigenerational households and COVID-19 in New York City (NYC). STUDY DESIGN: Cohort study. METHODS: We conducted a Bayesian ecological time series analysis at the ZIP Code Tabulation Area (ZCTA) level in NYC to assess whether ZCTAs with higher proportions of overcrowded (defined as the proportion of the estimated number of housing units with more than one occupant per room) and multigenerational households (defined as the estimated percentage of residences occupied by a grandparent and a grandchild less than 18 years of age) were independently associated with higher suspected COVID-19 case rates (from NYC Department of Health Syndromic Surveillance data for March 1 to 30, 2020). Our main measure was an adjusted incidence rate ratio (IRR) of suspected COVID-19 cases per 10,000 population. Our final model controlled for ZCTA-level sociodemographic factors (median income, poverty status, White race, essential workers), the prevalence of clinical conditions related to COVID-19 severity (obesity, hypertension, coronary heart disease, diabetes, asthma, smoking status, and chronic obstructive pulmonary disease), and spatial clustering. RESULTS: 39,923 suspected COVID-19 cases were presented to emergency departments across 173 ZCTAs in NYC. Adjusted COVID-19 case rates increased by 67% (IRR 1.67, 95% CI = 1.12, 2.52) in ZCTAs in quartile four (versus one) for percent overcrowdedness and increased by 77% (IRR 1.77, 95% CI = 1.11, 2.79) in quartile four (versus one) for percent living in multigenerational housing. Interaction between both exposures was not significant (ßinteraction = 0.99, 95% CI: 0.99-1.00). CONCLUSIONS: Overcrowdedness and multigenerational housing are independent risk factors for suspected COVID-19. In the early phase of the surge in COVID cases, social distancing measures that increase house-bound populations may inadvertently but temporarily increase SARS-CoV-2 transmission risk and COVID-19 disease in these populations.


Asunto(s)
COVID-19 , Teorema de Bayes , Estudios de Cohortes , Humanos , SARS-CoV-2 , Factores Socioeconómicos
6.
Dermatol Ther ; 32(3): e12887, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30942949

RESUMEN

Platelet rich fibrin (PRF) gel is a new second generation platelet concentrate, which has been widely used in various dermatological conditions such as nonhealing diabetic foot ulcers, venous ulcers, and trophic ulcers in leprosy. In this case report, we present a patient with nonhealing ulcer secondary to ecthyma gangrenosum, who showed dramatic response with PRF gel. This case suggests a role of PRF gel in nonhealing ulcers of infectious etiology which has not been described in English language literature. Considering previous literature and our case, it may be concluded that PRF gel may be utilized as an effective alternative for nonhealing ulcers of nonneoplastic etiology.


Asunto(s)
Ectima/complicaciones , Fibrina Rica en Plaquetas , Úlcera Cutánea/terapia , Femenino , Geles , Humanos , Persona de Mediana Edad
7.
Br J Neurosurg ; 33(2): 176-183, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28532172

RESUMEN

Rosai-Dorfman disease (RDD) is a rare condition similar to lymphomas, presenting with cervical lymphadenopathy in young adults. Extra-nodal involvement is relatively common but involvement of the central nervous system (CNS) is rare. Cranial RDD presents with symptoms of raised intracranial pressure, focal or generalised seizures, while spinal RDD presents with pain, peripheral neurological deficits and radiculopathy. In contrast to other similar neoplastic or degenerative conditions affecting the CNS, RDD is a benign, non-infective, granulomatous disorder. Radiologically cranio-spinal RDD often mimics commoner dural-based lesions like meningioma, with only subtle radiological differentiating findings on Magnetic Resonance Imaging (MRI). The histopathology of RDD is diagnostic. Surgical excision is preferred modality of treatment. However, adjuvant therapies like steroids and radiation may help controlling residual or recurrent disease. There are multiple sporadic reports and short case publications in the literature, often focusing on a particular aspect of RDD. In this study, authors aim to present five cases of craniospinal RDD, and comprehensive review of literature and highlight neurological complications of systemic RDD.


Asunto(s)
Encefalopatías/patología , Histiocitosis Sinusal/patología , Enfermedades de la Columna Vertebral/patología , Adulto , Encefalopatías/cirugía , Diagnóstico Diferencial , Duramadre , Femenino , Histiocitosis Sinusal/cirugía , Humanos , Hipertensión Intracraneal/etiología , Imagen por Resonancia Magnética , Masculino , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , Dolor/etiología , Radiculopatía/patología , Proyectos de Investigación , Enfermedades de la Columna Vertebral/cirugía , Tomografía Computarizada por Rayos X
8.
Indian J Clin Biochem ; 34(4): 465-471, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31686734

RESUMEN

Thyroglobulin (Tg) is a proven tumor marker in the follow-up and post-operative management of patients with differentiated thyroid cancer (DTC). All assays for serum thyroglobulin (s-Tg) are based on immunoassays, however, the assay technique has a bearing on the variations seen in the estimations. We studied this using four in-house developed radioimmunoassays (RIA) and immunoradiometric assays (IRMA). Limit of detection, working range, recovery, dilution test, precision profiles and method comparison were evaluated. All four methods were used for the estimation of s-Tg in DTC patients and also compared for their performance using commercially available Tg IRMA kits from DiaSorin and Izotop. The s-Tg values measured by six different immunoassays showed very significant inter-method correlation (0.84-0.99, p < 0.001). However, among the in-house developed assays; the coated tube IRMA showed a better sensitivity and precision at the lower concentration range and hence, is preferable for the routine measurement of s-Tg in patients negative for Tg autoantibodies (TgAb). Although the second generation IRMAs offer practical benefits of having higher sensitivity, shorter turn-around time and convenience of automation, they, unfortunately, also have higher tendency for interference from both TgAb and heterophilic antibodies, if present in the sample. On the contrary, RIA is less prone to such interference and, hence, can be used in patients with TgAb. In order to effectively use this test, it is important that nuclear medicine physicians and endocrinologists understand these intrinsic technical limitations encountered during s-Tg measurement.

10.
Indian J Clin Biochem ; 33(1): 81-85, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29371774

RESUMEN

The prevalence of non-communicable diseases like diabetes mellitus (DM) and hypertension (HTN) is growing worldwide. Both lead to nephropathy if not controlled effectively. Microalbuminuria (MAU) is recognized as an early predictor for nephropathy. Additionally, the timely detection of advanced glycation end products (AGEs) is also considered to be an important prognostic factor for diabetic nephropathies. Hence, screening for the early detection of MAU and AGEs would be an useful and relatively inexpensive laboratory test for early clinical diagnosis for the incidence of nephropathy in these diseases. This study was conducted in DM, HTN and pregnancy induced hypertensive (PIH) subjects. MAU and Nε-Carboxymethyllysine (CML) levels were estimated by in-house RIA kits in the patient groups and controls, while the total AGEs level in serum was determined by ELISA. The levels of MAU, CML and AGE-BSA were observed to be significantly higher in DM, HTN and PIH subjects compared to controls (p < 0.001). Increased serum CML and AGEs levels in DM, HTN and PIH subjects indicated ongoing glycemic damage and their susceptibility to develop renal complications.

11.
Dig Dis Sci ; 62(9): 2318-2326, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28766243

RESUMEN

BACKGROUND: Frequent relapses sometimes necessitating hospitalization and the absence of pharmacological cure contribute to substantial healthcare costs in inflammatory bowel diseases (IBDs). The costs of health care in Indian patients with IBD are unknown. AIM: To evaluate the annual costs for treating Crohn's disease and ulcerative colitis. METHODS: A prevalence-based, micro-costing method was used to assess the components of annual costs in a prospective, observational study conducted in a tertiary healthcare center enrolled over a 24-month period beginning of July 2014. RESULTS: At enrollment, 43/59 (72.88%) patients with UC and 18/25 (72%) with CD were in remission. The annual median (IQR) cost per UC and CD patient in remission was INR 43,140 (34,357-51,031) [USD $707 (563-836)] and INR 43,763.5 (32,202-57,372) [USD $717 (527-940)], respectively, and in active disease was INR 52,436.5 (49,229-67,567.75) [$859 (807-1107)] and INR 72,145 (49,447-92,212) [USD $1182 (811-1512)], respectively. Compared with remission, active disease had a 1.4-fold higher cost for CD as compared to UC. In both groups, the greatest component of direct costs was drugs. Thirteen (22%) and 7 (28%) patients with UC and CD needed hospitalization accounting for 23.1 and 20.4% of the total costs, respectively. At one year, direct costs surmounted indirect costs in UC and CD (p < 0.001). Productivity losses contributed to 18.5 and 16% of the overall costs for UC and CD, respectively. CONCLUSION: This first, panoptic, health economic study for IBD from India shows that the costs are driven by medication, productivity losses, and not merely hospitalization alone.


Asunto(s)
Costo de Enfermedad , Enfermedades Inflamatorias del Intestino/economía , Enfermedades Inflamatorias del Intestino/epidemiología , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , India/epidemiología , Enfermedades Inflamatorias del Intestino/terapia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven
12.
J Immunoassay Immunochem ; 38(3): 271-284, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27801618

RESUMEN

We describe the development and validation of multianalyte immunoassays (MAIA) for three analytes, viz., thyroxine (T4), thyroid stimulating hormone (TSH), and thyroglobulin (Tg) essential for assessment of thyroid function but having widely varying molecular weights. Using polycarbonate (PC) track-etched membranes (TEM) as an immobilization support and 125I as the tracer, both competitive assay for T4 and non-competitive assay for TSH and Tg were performed on the same TEM. MAIA was found to be highly sensitive and precise with clinically useful working range and correlated very well with individual analyte immunoassays. While we have demonstrated this assay format with radiotracer, it can be used with non-isotopic tracers equally well.


Asunto(s)
Inmunoensayo/métodos , Tiroglobulina/análisis , Tirotropina/análisis , Tiroxina/análisis , Humanos , Radioisótopos de Yodo , Glándula Tiroides/química , Glándula Tiroides/metabolismo
13.
Indian J Clin Biochem ; 32(1): 39-44, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28149011

RESUMEN

Thyroglobulin autoantibodies (TgAb) are estimated to detect potential interferences in thyroglobulin (Tg) immunoassays and also for the diagnosis of autoimmune thyroid disease. A user friendly and robust in-house solid-phase radioassay was standardized and parameters like sensitivity, reproducibility and stability were assessed. Further, it was validated and evaluated for the detection of autoantibodies in differentiated thyroid cancer (DTC) patients. Totally 301 samples received in our laboratory for routine serum Tg estimation were studied. The samples were analyzed for TgAb by the solid-phase radioassay developed in-house and compared with commercial anti-hTg IRMA kit (Immunotech, France). The control group comprised of 37 euthyroid males from our Centre. The intra- and inter-assay CVs for the two quality control samples (Control A = 104 ± 12.6 IU/mL and Control B = 1029 ± 114 IU/mL) were found less than or equal to 6.05 and 13.85 % respectively. Solid-phase radioassay showed a good agreement on comparison with Immunotech IRMA (r = 0.99). Using the proposed cut-off thresholds (in-house solid-phase radioassay 52 IU/mL and Immunotech IRMA 30 IU/mL), 5.4 % of the control subjects were positive for TgAb by both the methods. Prevalence of TgAb in DTC patients was 17.3 and 16.6 % using the Immunotech kit and in-house solid-phase radioassay respectively. The in-house solid-phase radioassay has the requisite sensitivity for the evaluation of TgAb comparable to commercial kit and also suitable for routine use as it is rapid, user friendly and economical.

14.
Indian J Clin Biochem ; 32(2): 193-199, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28428694

RESUMEN

Serum thyroglobulin (Tg) and thyroid stimulating hormone (TSH) measurements have evolved as important analytes for monitoring the prognosis of patients with differentiated thyroid cancer, post-thyroidectomy. Individual analyte immunoassay is the current practice in clinical pathology, but the simultaneous assay for all relevant analytes for a given disease, can reduce assay costs, improve patient compliance and give the clinician more information for an unequivocal diagnosis. Microarray immunoassay (MI) can achieve this goal and, hence, we have developed and validated a immuno-radiometric MI for quantitation of serum TSH and Tg by using highly micro-porous polycarbonate (PC) track-etched membranes (TEM) to immobilize the monoclonal anti-TSH and polyclonal anti-Tg antibodies in ~1 mm diameter spots. Non-competitive immunoassays were performed using mixture of 125I labeled monoclonal anti-TSH and anti-Tg antibodies. Phosphorimager was used to quantify the bound radioactivity. TSH and Tg were detected with detection limit of 0.07 µIU/ml and 0.13 ng/ml respectively, which is lower than the clinically required cut-off level. The assay showed: acceptable intra-assay precision within 20 % and recovery in the range of 76-111.2 %. MI compared well with the established immunoradiometric assay (IRMA) with r = 0.98, p < 0.01 (n = 41). No cross-reactivity was seen between the immobilized antibodies. Although two hormones are addressed in this report, MI using PC TEM and isotopic/non-isotopic tracers has the potential for highly automated multiplexed analysis.

15.
Cell Immunol ; 300: 33-40, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26677761

RESUMEN

Chronic infections of Mycobacterium tuberculosis (MTB) cause oxidative stress, TLR activation and production of inflammatory cytokines and thus can create an environment reinforcing tumorigenesis, progression and metastasis. Epidemiological studies have established a relation between lung cancer and tuberculosis but cellular mechanism is still poorly understood. In present study, we have shown for the first time that MTB infection in human monocytic cell line (THP-1) enhances invasion and induces EMT characteristics in lung adenocarcinoma cell line (A549) during co-culture. After co-culture with MTB infected THP-1 cells A549 cells exhibited morphological and molecular signatures of EMT. During co-culture, expression of inflammatory cytokines like TNF-α, IL-1ß and IL-6 was enhanced in the microenvironment of A549 cells in comparison to single culture of A549 cells. Using pharmacological inhibitors of JNK (SP-600125) and p38 MAPK (SB-203580), we demonstrated the involvement of JNK and p38 MAPK in MTB induced EMT induction in A549 cells. To the best of our knowledge this is the first report demonstrating the role of MTB infection in induction of metastasis associated EMT in lung cancer.


Asunto(s)
Adenocarcinoma/microbiología , Adenocarcinoma/patología , Transición Epitelial-Mesenquimal/inmunología , Neoplasias Pulmonares/microbiología , Neoplasias Pulmonares/patología , Tuberculosis Pulmonar/complicaciones , Adenocarcinoma/inmunología , Adenocarcinoma del Pulmón , Western Blotting , Línea Celular Tumoral , Movimiento Celular , Técnicas de Cocultivo , Humanos , Neoplasias Pulmonares/inmunología , Mycobacterium tuberculosis , Tuberculosis Pulmonar/inmunología , Microambiente Tumoral/inmunología
16.
EMBO Rep ; 15(9): 991-9, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25074018

RESUMEN

Regulatory T cells (Tregs) control autoreactive T cells by inhibiting activation-induced proliferation and cytokine expression. The molecular mechanisms responsible for the inactivation of effector T cells by Tregs remain yet to be fully characterized. We report that T-helper cells stimulated in the presence of Tregs quickly activate NFAT1 and have increased NFAT1-dependent expression of the transcription repressor Ikaros. NFAT1 deficiency or dominant-negative Ikaros compromises Treg-mediated inhibition of T-helper cells in vitro and in vivo. Thus, our results place NFAT-dependent mechanisms as general regulators of T-cell tolerance and show that Treg-mediated suppression of T-helper cells results from the activation of NFAT-regulated gene expression.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Factor de Transcripción Ikaros/biosíntesis , Factores de Transcripción NFATC/inmunología , Linfocitos T Reguladores/inmunología , Animales , Linfocitos T CD4-Positivos/metabolismo , Proliferación Celular , Citocinas/biosíntesis , Regulación de la Expresión Génica , Factor de Transcripción Ikaros/genética , Activación de Linfocitos/inmunología , Ratones , Factores de Transcripción NFATC/biosíntesis , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Reguladores/metabolismo
17.
Bioorg Med Chem Lett ; 26(2): 645-649, 2016 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-26675440

RESUMEN

A series of novel quinoline-oxadiazole hybrid compounds was designed based on stepwise rational modification of the lead molecules reported previously, in order to enhance bioactivity and improve druglikeness. The hybrid compounds synthesized were screened for biological activity against Mycobacterium tuberculosis H37Rv and for cytotoxicity in HepG2 cell line. Several of the hits exhibited good to excellent anti-tuberculosis activity and selectivity, especially compounds 12m, 12o and 12p, showed minimum inhibitory concentration values<0.5µM and selectivity index>500. The results of this study open up a promising avenue that may lead to the discovery of a new class of anti-tuberculosis agents.


Asunto(s)
Antituberculosos/química , Antituberculosos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Oxadiazoles/química , Oxadiazoles/farmacología , Quinolinas/química , Quinolinas/farmacología , Animales , Antituberculosos/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Hep G2 , Humanos , Pruebas de Sensibilidad Microbiana , Microsomas Hepáticos/metabolismo , Oxadiazoles/metabolismo , Quinolinas/metabolismo , Ratas , Relación Estructura-Actividad , Tuberculosis/tratamiento farmacológico
19.
J Immunol ; 192(11): 5118-29, 2014 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-24778448

RESUMEN

Naive CD4(+) T cells require signals from the TCR and CD28 to produce IL-2, expand, and differentiate. However, these same signals are not sufficient to induce autocrine IL-2 production by naive CD8(+) T cells, which require cytokines provided by other cell types to drive their differentiation. The basis for failed autocrine IL-2 production by activated CD8(+) cells is unclear. We find that Ikaros, a transcriptional repressor that silences IL-2 in anergic CD4(+) T cells, also restricts autocrine IL-2 production by CD8(+) T cells. We find that CD8(+) T cell activation in vitro in the absence of exogenous cytokines and CD4 help leads to marked induction of Ikaros, a known repressor of the Il2 gene. Naive murine CD8 T cells haplo-insufficient for Ikzf1 failed to upregulate Ikaros, produced autocrine IL-2, and differentiated in an IL-2-dependent manner into IFN-γ-producing CTLs in response to TCR/CD28 stimulation alone. Furthermore, Ikzf1 haplo-insufficient CD8(+) T cells were more effective at controlling Listeria infection and B16 melanoma growth in vivo, and they could provide help to neighboring, non-IL-2-producing cells to differentiate into IFN-γ-producing effectors. Therefore, by repressing autocrine IL-2 production, Ikaros ensures that naive CD8(+) T cells remain dependent on licensing by APCs and CD4(+) T cells, and it may therefore act as a cell-intrinsic safeguard against inappropriate CTL differentiation and immunopathology.


Asunto(s)
Comunicación Autocrina/inmunología , Linfocitos T CD8-positivos/inmunología , Diferenciación Celular/inmunología , Factor de Transcripción Ikaros/inmunología , Interleucina-2/inmunología , Animales , Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/patología , Comunicación Autocrina/genética , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/patología , Diferenciación Celular/genética , Línea Celular Tumoral , Anergia Clonal/genética , Anergia Clonal/inmunología , Factor de Transcripción Ikaros/genética , Interleucina-2/genética , Listeriosis/genética , Listeriosis/inmunología , Listeriosis/patología , Melanoma Experimental/genética , Melanoma Experimental/inmunología , Melanoma Experimental/patología , Ratones , Ratones Noqueados , Regulación hacia Arriba/genética , Regulación hacia Arriba/inmunología
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