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In the present study, the antimicrobial, rheological, mechanical, barrier and optical properties of Carrageenan and Manihot esculenta (composite) starch biobased edible film incorporated with caraway (Carum carvi L.) essential oil (EO) were investigated. The Minimum Inhibitory Concentration (MIC) of caraway oil against B. cereus, E. coli, P. aeruginosa and S. aureus were found to be 0.6, 1.4, 1.4 and 0.8% respectively. The Gas Chromatography- Mass Spectroscopy (GC-MS) of caraway EO expressed a distinct chromatogram peak for phenolic compounds. Rheological results of Film-Forming Solution (FFS) revealed solid-like viscoelastic behavior. Incorporation of caraway EO in the film caused significant (P < 0.05) increase in moisture, moisture absorption, bio-degradability in terms of film solubility, L value, total color difference (ΔE), haziness and transparency value, however, significantly (P < 0.05) decreased tensile strength and whiteness index were observed. The zone of inhibition of caraway EO incorporated films against all test bacteria were highly significant (P < 0.01) than control whereas antibacterial activity was found more towards gram-positive bacteria than gram-negative bacteria. No significant (P>0.05) changes in thickness, density, water activity, swelling, elongation at break, water vapor transmission rate, a and b value were observed with increasing caraway EO concentration. These results with some good rheological, physic-mechanical, antimicrobial and optical characteristics suggest the application of such active film into a variety of foods with improved food safety and quality. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05028-1.
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Near-infrared optical excitation enables wideband frequency tuning of terahertz quantum-cascade lasers. In this work, we demonstrate the feasibility of the approach for molecular laser absorption spectroscopy. We present a physical model which explains the observed frequency tuning characteristics by the optical excitation of an electron-hole plasma. Due to an improved excitation configuration as compared to previous work, we observe a single-mode continuous-wave frequency coverage of as much as 40 GHz for a laser at 3.1 THz. This represents, for the same device, a ten-fold improvement over the usually employed tuning by current. The method can be readily applied to a large class of devices.
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We demonstrate a technique to simultaneously stabilize the frequency and output power of a terahertz quantum-cascade laser (QCL). This technique exploits frequency and power variations upon near-infrared illumination of the QCL with a diode laser. It does not require an external terahertz optical modulator. By locking the frequency to a molecular absorption line, we obtain a long-term (one-hour) linewidth of 260 kHz (full width at half maximum) and a root-mean-square power stability below 0.03%. With respect to the free-running case, this stabilization scheme improves the frequency stability by nearly two orders of magnitude and the power stability by a factor of three.
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AIMS: To assess the impact of social deprivation, demographics and centre on HbA1c outcomes with continuous subcutaneous insulin infusion (CSII) in adults with Type 1 diabetes. METHODS: Demographic data, postcode-derived English Index of Multiple Deprivation data and 12-month average HbA1c (mmol/mol) pre- and post-CSII were collated from three diabetes centres in the north west of England, University Hospital of South Manchester (UHSM), Salford Royal Foundation Hospital (SRFT) and Manchester Royal Infirmary (MRI). Univariable and multivariable regression models explored relationships between demographics, Index of Multiple Deprivation, centre and HbA1c outcomes. RESULTS: Data were available for 693 (78%) individuals (UHSM, n = 90; SRFT, n = 112; and MRI, n = 491) of whom 59% were women. Median age at CSII start was 39 (IQR 29.5-49.0) years and median diabetes duration was 20 (11-29) years. Median Index of Multiple Deprivation was 15 193 (6313-25 727). Overall median HbA1c improved from 69 to 64 mmol/mol (8.5% to 8.0%) within the first year of CSII. In multivariable analysis, higher pre-CSII HbA1c was significantly associated with higher deprivation (P = 0.036), being female (P < 0.001), and centre (MRI; P = 0.005). Following pre-CSII HbA1c adjustment, post-CSII HbA1c or HbA1c change were not related to demographic factors and deprivation, but remained significantly related to the centre; UHSM and SRFT had larger reductions in HbA1c with CSII compared with MRI [median -7.0 (-0.6%) vs. -6.0 (-0.55%) vs. -4.5 (-0.45%) mmol/mol; P = 0.005]. CONCLUSIONS: Higher pre-CSII HbA1c levels were associated with higher deprivation and being female. CSII improves HbA1c irrespective of social deprivation and demographics. Significant differences in HbA1c improvements were observed between centres. Further work is warranted to explain these differences and minimize variation in clinical outcomes with CSII.
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Carencia Cultural , Diabetes Mellitus Tipo 1 , Hemoglobina Glucada/metabolismo , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Sistemas de Infusión de Insulina , Insulina/administración & dosificación , Adulto , Glucemia/metabolismo , Demografía , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/epidemiología , Inglaterra/epidemiología , Femenino , Geografía , Hemoglobina Glucada/análisis , Humanos , Infusiones Subcutáneas , Masculino , Persona de Mediana Edad , Distancia Psicológica , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We report on the Doppler-free saturation spectroscopy of a molecular transition at 3.3 THz based on a quantum-cascade laser and an absorption cell in a collinear pump-probe configuration. A Lamb dip with a sub-Doppler linewidth of 170 kHz is observed for a rotational transition of HDO. We found that a certain level of external optical feedback is tolerable as long as the free spectral range of the external cavity is large compared to the width of the absorption line.
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Chemotherapy remains the mainstay of treatment for advanced pancreatic ductal adenocarcinoma (pda). Two randomized trials have demonstrated superiority of the combination regimens folfirinox (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) and gemcitabine plus nab-paclitaxel over gemcitabine monotherapy as a first-line treatment in adequately fit subjects. Selected pda patients progressing to first-line therapy can receive secondline treatment with moderate clinical benefit. Nevertheless, the optimal algorithm and the role of combination therapy in second-line are still unclear. Published second-line pda clinical trials enrolled patients progressing to gemcitabine-based therapies in use before the approval of nab-paclitaxel and folfirinox. The evolving scenario in second-line may affect the choice of the first-line treatment. For example, nanoliposomal irinotecan plus 5-fluouracil and leucovorin is a novel second-line option which will be suitable only for patients progressing to gemcitabine-based therapy. Therefore, clinical judgement and appropriate patient selection remain key elements in treatment decision. In this review, we aim to illustrate currently available options and define a possible algorithm to guide treatment choice. Future clinical trials taking into account sequential treatment as a new paradigm in pda will help define a standard algorithm.
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AIMS: To compare long-term HbA1c changes associated with different insulin pumps during routine care in a large cohort of adults with Type 1 diabetes representative of other clinic populations. METHODS: Observational, retrospective study of 508 individuals starting pump therapy between 1999 and 2014 (mean age, 40 years; 55% women; diabetes duration, 20 years; 94% Type 1 diabetes; median follow-up, 3.7 years). Mixed linear models compared covariate-adjusted HbA1c changes associated with different pump makes. RESULTS: The pumps compared were: 50% Medtronic, 24% Omnipod, 14% Roche and 12% Animas. Overall HbA1c levels improved and improvements were maintained during a follow-up extending to 10 years (HbA1c : pre-continuous subcutaneous insulin infusion (pre-CSII) vs. 12 months post CSII, 71 (61, 82) vs. 66 (56, 74) mmol/mol; 8.7 (7.7, 9.6) vs. 8.2 (7.3, 8.9)%; P < 0.0001). The percentage of individuals with HbA1c ≥ 64 mmol/mol (8.0%) reduced from a pre-CSII level of 68% to 55%. After adjusting for baseline confounders, there were no between-pump differences in HbA1c lowering (P = 0.44), including a comparison of patch pumps with traditional catheter pumps (P = 0.63). There were no significant (P < 0.05) between-pump differences in HbA1c lowering in pre-specified subgroups stratified by pre-pump HbA1c , age or diabetes duration. HbA1c lowering was positively related to baseline HbA1c (P < 0.001) and diabetes duration (P = 0.017), and negatively related to the number of years of CSII use (P = 0.024). CONCLUSIONS: Under routine care conditions, there were no covariate-adjusted differences in HbA1c lowering when comparing different pump makes, including a comparison of patch pumps vs. traditional catheter pumps. Therefore, the choice of CSII make should not be influenced by the desired degree of HbA1c lowering.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Sistemas de Infusión de Insulina , Insulina/administración & dosificación , Adulto , Instituciones de Atención Ambulatoria , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud , Estudios RetrospectivosRESUMEN
Elevated irritability during adolescence predicts mental health issues in adulthood. Social interactions commonly elicit symptoms of irritability. Prior research has traditionally examined neural activity during the anticipation of, and immediate reaction to, social feedback separately in irritable adolescents. However, studies suggest that irritable adolescents demonstrate altered brain activation when anticipating feedback, and these alterations may have downstream effects on the neural activity when actually presented with feedback. Thus, the goal of this study was to characterize the influence of irritability on the relationship between brain function during anticipation and receipt of social feedback. We leveraged the Virtual School task to mimic social interactions using dynamic stimuli. Parallel region of interest (ROI) analyses tested effects of anticipatory bilateral amygdala (or dorsal anterior cingulate cortex; dACC) activation on the dACC (or bilateral amygdala) activation during receipt of peer feedback. Parallel exploratory whole-brain analyses were conducted to identify the effects of anticipatory bilateral amygdala or dACC activation on other regions during receipt of peer feedback. In ROI analyses, more vs. less irritable adolescents showed distinct relationships between anticipatory bilateral amygdala activation and dACC activation when receiving predictably mean feedback. Across both whole-brain analyses, anticipatory bilateral amygdala and dACC activation were separately associated with activation in socioemotional regions of the brain during subsequent feedback. These relationships were modulated by irritability, and the valence and predictability of the feedback. This suggests that irritable adolescents may engage in altered emotion processing and regulation strategies, depending on the valence and predictability of social feedback.
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Encéfalo , Genio Irritable , Humanos , Adolescente , Retroalimentación , Genio Irritable/fisiología , Giro del Cíngulo/fisiología , Grupo Paritario , Imagen por Resonancia MagnéticaRESUMEN
LASER Haemorrhoidoplasty (LH) is a novel procedure in modern medical science. It is a no cut, painless and bloodless clinical procedure with comparatively fewer complications in comparison to Stapler Haemorrhoidopexy (SH) for the treatment of grade III-IV haemorrhoids. It is very applicable surgical procedure at shrinking the terminal branches of haemorrhiodal arteries with fewer complications than Stapler Haemorrhoidopexy (SH). The aim of the study was to compare LASER Haemorrhoidoplasty (LH) with Stapler Haemorrhoidopexy (SH). The comparative study was performed in Bangabandhu Sheikh Mujib Medical University (BSMMU), Anower Khan Modern Medical College and Hospital and Care Medical College and Hospital, Dhaka, Bangladesh from August 2019 to July 2020. A total of 84 patients with grade III-IV haemorrhoids were allocated into two groups: LASER Haemorrhoidoplasty (LH) and Stapler Haemorrhoidopexy (SH) with 42 patients in each group prospectively. Comparative results and post-operative follow up periods were 4 months. The mean operative time was 28.6min (LH) and 36.2min (SH) (p=0.0006). The average blood loss was 6.42ml (LH) and 12.6ml (SH) (p<0.05). The mean hospital stay 18.36 hours (LH) and 28.40 hours (SH) (p<0.05). Mean postoperative pain score (VAS) at 12 hours was 3.8 (LH) and 6.81 (SH) (p<0.05), at 24 hours was 2.6 (LH) and 4.6 (SH) (p<0.05), at 1 week was 0.46 (LH) and 0.88 (SH) (p=0.05) and at 3 months 0.04 (LH) and 0.10 (SH) (p=0.401). Complications were found in (2.4%) patients ≤1 week in the (LH) group 7(16.7%) in the (SH) group which was statistically significant (p<0.05) between the two groups. Patients with haemorrhoids treated with LASER Haemorrhoidoplasty had a better outcome than stapler haemorrhoidopexy in terms of early postoperative pain as well as complications and was associated with a shorter hospital stay and early return to work. LASER Haemorrhoidoplasty was most effective and alternative to the popular stapler Haemorrhoidopexy for grade III-IV haemorrhoids.
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Hemorroides , Bangladesh , Hemorroides/cirugía , Humanos , Rayos Láser , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Complicaciones Posoperatorias , Estudios Prospectivos , Grapado Quirúrgico , Resultado del TratamientoRESUMEN
Hepatotoxicity is a major dose-limiting side effect of CP chemotherapy besides nephrotoxicity and gastrointestinal dysfunction. TQ, a principal Nigella sativa seed oil constituent, has been shown to improve hepatic functions in various in vivo models of acute hepatic injury. In view of this, the present study aimed to evaluate the effect of TQ against CP-induced hepatotoxicity. Rats were divided into four experimental groups; control, CP, CP+TQ and TQ. Animals in CP+TQ and TQ groups were administered TQ (1.5 mg/kg bwt, orally), with or without a single hepatotoxic dose of CP (6 mg/kg bwt, i.p.) respectively, for 14 days before and four days following the CP treatment. CP induced an upsurge in serum ALT and AST activities, indicating liver injury, as also confirmed by the histopathological findings. CP caused significant alterations in the activities of membrane marker enzymes, carbohydrate metabolic enzymes, and the enzymatic and nonenzymatic components of the antioxidant defense system. TQ supplementation ameliorated all these adverse biochemical and histological changes in CP-treated rats. Thus, TQ may have excellent scope for clinical applications in combating CP-induced hepatic pathophysiology.
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Antineoplásicos/toxicidad , Benzoquinonas/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Cisplatino/toxicidad , Suplementos Dietéticos , Animales , Humanos , Masculino , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
The aim of the present study was to compare the sensitivity between Alvarado and RIPASA score for the diagnosis of acute appendicitis patients. A comparative study was conducted in the Dhaka National Medical College Hospital, Bangladesh from July 2015 to December 2015. The study was approved by the institutional ethical committee. Most of the appendicitis patients belonged to the between 21-30 years which was 64(32%). Male appendicitis patients (52%) are more than the female patients (48%). Majority of the patients (69%) complains pain occurs in the Right iliac fossa. Sensitivity of Alvarado scores was 81.60%, specificity 74.58%, accuracy 79.35%, positive and negative predictive values were 87.18% and 65.67% respectively. RIPASA score's sensitivity was 85.6%, specificity 69.49%, accuracy 80.40%, positive and negative predictive values were 85.60% and 85.60% respectively. This study reported that RIPASA score is significantly shown higher diagnostic accuracy then that Alvarado score.
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Apendicitis , Enfermedad Aguda , Apendicectomía , Apendicitis/diagnóstico , Bangladesh/epidemiología , Femenino , Humanos , Masculino , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
The role of defective glucose transport in the pathogenesis of noninsulin-dependent diabetes (NIDDM) was examined in Zucker diabetic fatty rats, a model of NIDDM. As in human NIDDM, insulin secretion was unresponsive to 20 mM glucose. Uptake of 3-O-methylglucose by islet cells was less than 19% of controls. The beta cell glucose transporter (GLUT-2) immunoreactivity and amount of GLUT-2 messenger RNA were profoundly reduced. Whenever fewer than 60% of beta cells were GLUT-2-positive, the response to glucose was absent and hyperglycemia exceeded 11 mM plasma glucose. We conclude that in NIDDM underexpression of GLUT-2 messenger RNA lowers high Km glucose transport in beta cells, and thereby impairs glucose-stimulated insulin secretion and prevents correction of hyperglycemia.
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Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Expresión Génica , Islotes Pancreáticos/metabolismo , Proteínas de Transporte de Monosacáridos/genética , 3-O-Metilglucosa , Animales , Transporte Biológico , Diabetes Mellitus/metabolismo , Femenino , Glucosa/farmacología , Immunoblotting , Insulina/metabolismo , Secreción de Insulina , Islotes Pancreáticos/efectos de los fármacos , Cinética , Masculino , Metilglucósidos/metabolismo , Proteínas de Transporte de Monosacáridos/metabolismo , Obesidad , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas , Ratas ZuckerRESUMEN
Hierarchical twinning, at multiple length scales, was noted in a metastable body-centered cubic (bcc) ß-titanium alloy on tensile deformation. Site-specific characterization within the deformation bands, carried out using EBSD and TEM, revealed {332} <113> type primary bcc twins, containing different variants of secondary and tertiary twins, as well as the formation of stress-induced martensite (α"). Within the primary {332} <113> type twin, "destruction" of the prior quenched-in athermal ω phase was observed, while a stress-induced ω phase reforms within the tertiary twins, revealing the intricate nature of coupling between deformation twinning and displacive ω transformation.
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In situ hybridization of proinsulin and proglucagon mRNA was performed in rat pancreas to assess prohormone gene expression during various glucopenic conditions. During a 4-d fast mean blood glucose declined by 48 mg/dl; proinsulin mRNA signal density remained normal while proglucagon mRNA signal density more than doubled. At the end of a continuous 12-d insulin infusion blood glucose averaged 53 +/- 12 mg/dl; proinsulin mRNA signal density declined to 30% of controls while proglucagon mRNA signal density more than doubled. In insulinoma-bearing NEDH rats blood glucose averaged 34 +/- 3.5 mg/dl; the proinsulin mRNA signal was virtually undetectable and proglucagon mRNA signal density was more than twice the controls. There was no detectable change in either beta-cell area or islet number in rats subjected to fasting or insulin infusion, but in insulinoma-bearing rats beta cell area was markedly reduced. Thus compensation during 4 d of starvation involves an increase in glucagon gene expression without change in insulin gene expression or beta cell mass. In moderate insulin-induced hypoglycemia glucagon gene expression is increased and insulin gene expression decreased. In more profound insulinoma-induced hypoglycemia, in addition to the foregoing changes in hormone gene expression, there is a profound reduction in the number of insulin-expressing cells.
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Ayuno , Glucagón/genética , Hipoglucemia/metabolismo , Proinsulina/genética , Precursores de Proteínas/genética , ARN Mensajero/análisis , Animales , Hibridación de Ácido Nucleico , Proglucagón , Ratas , Ratas EndogámicasRESUMEN
The roles of insulin resistance and beta-cell dysfunction in glucocorticoid-induced diabetes were determined in Wistar and Zucker (fa/fa) rats. All Wistar rats treated with 5 mg/kg per d of dexamethasone for 24 d exhibited increased beta-cell mass and basal and arginine-stimulated insulin secretion, indicating insulin resistance, but only 16% became diabetic. The insulin response to 20 mM glucose was normal in the perfused pancreas of all normoglycemic dexamethasone-treated rats but absent in every diabetic rat. Immunostainable high Km beta-cell transporter, GLUT-2, was present in approximately 100% of beta-cells of normoglycemic rats, but in only 25% of beta cells of diabetic rats. GLUT-2 mRNA was not reduced. All Zucker (fa/fa) rats treated with 0.2-0.4 mg/kg per d of dexamethasone for 24 d became diabetic and glucose-stimulated insulin secretion was absent in all. High Km glucose transport in islets was 50% below nondiabetic controls. Only 25% of beta cells of diabetic rats were GLUT-2-positive compared with approximately 100% in controls. Total pancreatic GLUT-2 mRNA was increased twofold suggesting a posttranscriptional abnormality. We conclude that dexamethasone induces insulin resistance, whether or not it induces hyperglycemia. Whenever hyperglycemia is present, GLUT-2-positive beta cells are reduced, high Km glucose transport into beta cells is attenuated and the insulin response to glucose is absent.
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Dexametasona/farmacología , Diabetes Mellitus Experimental/inducido químicamente , Resistencia a la Insulina , Islotes Pancreáticos/fisiopatología , Animales , Transporte Biológico/efectos de los fármacos , Diabetes Mellitus Experimental/fisiopatología , Técnica del Anticuerpo Fluorescente , Expresión Génica/efectos de los fármacos , Glucosa/metabolismo , Insulina/genética , Insulina/metabolismo , Proteínas de Transporte de Monosacáridos/genética , Proteínas de Transporte de Monosacáridos/metabolismo , ARN Mensajero/genética , Ratas , Tasa de Secreción/efectos de los fármacosRESUMEN
Saccharomyces cerevisiae contains two genes, CIT1 and CIT2, encoding functional citrate synthase (K.-S. Kim, M. S. Rosenkrantz, and L. Guarente, Mol. Cell. Biol. 6:1936-1942, 1986). We show here that CIT2 encodes a nonmitochondrial form of citrate synthase. The DNA sequence of CIT2 presented provides a possible explanation for why the CIT2 product, unlike the CIT1 product, fails to be imported into mitochondria. While the products of these two genes are highly homologous, they diverge strikingly at their amino termini. The amino terminus of the CIT1 primary translation product extends 39 residues beyond the amino termini of Escherichia coli and porcine citrate synthases. This extension consists of a typical mitochondrial targeting motif. The amino terminus of the CIT2 primary translation product extends 20 residues beyond the amino termini of the E. coli and porcine enzymes. The CIT2-encoded extension is not homologous to that of CIT1, resulting in a nonmitochondrial localization of the product. The CIT2-encoded extension, however, does bear certain similarities to mitochondrial targeting sequences. The possible role of this sequence in targeting this CIT2 product to a nonmitochondrial organelle is discussed.
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Citrato (si)-Sintasa/genética , ADN Mitocondrial/genética , Genes Fúngicos , Genes , Mitocondrias/enzimología , Oxo-Ácido-Liasas/genética , Saccharomyces cerevisiae/genética , Secuencia de Aminoácidos , Secuencia de Bases , Saccharomyces cerevisiae/enzimología , Homología de Secuencia de Ácido Nucleico , Fracciones Subcelulares/enzimologíaRESUMEN
Two-dimensional (1)H-(13)C INEPT MAS NMR experiments utilizing a (1)H-(1)H magnetization exchange mixing period are presented for characterization of lipid systems. The introduction of the exchange period allows for structural information to be obtained via (1)H-(1)H dipolar couplings but with (13)C chemical shift resolution. It is shown that utilizing a RFDR recoupling sequence with short mixing times in place of the more standard NOE cross-relaxation for magnetization exchange during the mixing period allowed for the identification and separation of close (1)H-(1)H dipolar contacts versus longer-range inter-molecular (1)H-(1)H dipolar cross-relaxation. These 2D INEPT experiments were used to address both intra- and inter-molecular contacts in lipid and lipid/cholesterol mixtures.
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Membrana Dobles de Lípidos/química , Resonancia Magnética Nuclear Biomolecular/métodos , Isótopos de Carbono , Colesterol/química , Lípidos/química , Modelos TeóricosRESUMEN
Cloned lines of Adriamycin (ADR)-sensitive and -resistant P388 leukemia have been established, including P388/ADR/3 and P388/ADR/7 that are 5- and 10-fold more resistant than the cloned sensitive cell line P388/4 (Cancer Res., 46: 2978, 1986). A time course of ADR-induced DNA double-strand breaks revealed that in sensitive P388/4 cells, evidence of DNA repair was noted 4 h after removal of drug, whereas in resistant clone 3 and 7 cells repair was observed 1 h after drug removal. The earlier onset of DNA repair was statistically significant (p = 0.0154 for clone 3 cells, and p = 0.0009 for clone 7 cells). By contrast, once the repair process was initiated, the rate of repair was similar for all three cell lines. The level of glutathione transferase activity was determined in whole cell extracts. Enzyme activity (mean +/- SE) in sensitive cells was 9.49 +/- 1.00 nmol/min/mg protein, that in resistant clone 3 cells was 13.36 +/- 1.03 nmol/min/mg, and that in clone 7 cells was 13.96 +/- 1.44 nmol/min/mg; the 1.44-fold increase in enzyme activity in resistant cells was statistically significant (p = 0.01). Further evidence of induction of glutathione transferase was provided by Northern blot analysis using a 32P-labeled cDNA for an anionic glutathione transferase, which demonstrated approximately a twofold increase in mRNA in resistant clone 7 cells. Western blot analysis with a polyvalent antibody against anionic glutathione transferase also revealed a proportionate increase in gene product in resistant cells. Dose-survival studies showed that ADR-resistant cells were cross-resistant to actinomycin D, daunorubicin, mitoxantrone, colchicine, and etoposide, but not to the alkylating agent melphalan; this finding provided evidence that these cells are multidrug resistant. Using a cDNA probe for P-glycoprotein, a phenotypic marker for multidrug resistance, Northern blot analysis showed an increase in the steady state level of mRNA of approximately twofold in resistant clone 3 and 7 cells. Southern analysis with the same cDNA probe showed no evidence of gene amplification or rearrangement. Western blot analysis with monoclonal C219 antibody demonstrated a distinct increase in P-glycoprotein in resistant cells. Efflux of Adriamycin as measured by the efflux rate constant was identical in all three cell lines. Furthermore, the metabolic inhibitors azide and dinitrophenol did not augment drug uptake in either sensitive or resistant cells. These findings suggest that despite the increase in P-glycoprotein, an active extrusion pump was not operational in these cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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Reparación del ADN , Resistencia a Medicamentos , Glutatión Transferasa/metabolismo , Leucemia Experimental/genética , Glicoproteínas de Membrana/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Animales , Transporte Biológico , Supervivencia Celular/efectos de los fármacos , ADN de Neoplasias/genética , Doxorrubicina/farmacología , Amplificación de Genes , Regulación de la Expresión Génica , Leucemia Experimental/enzimología , Ratones , Células Tumorales CultivadasRESUMEN
Prenatal exposure to lipopolysaccharide (LPS) has been exploited to simulate brain disorder in animal model. Prenatal LPS-exposure has shown elevated levels of pro-inflammatory cytokines in the early stages of the postnatal period. This study determines the effect of prenatal LPS-exposure on oxidative stress (OS) in the distinct brain regions in the early postnatal stages. LPS (50 µg/kg, i.p.) and water for injection (100 µl, i.p.) were given to the experimental (n=5) and control (n=5) group of pregnant Swiss albino mice respectively on gestational day (GD)-16 and 17. Animals were decapitated on postnatal day (PnD) - 1, 7, 14 and 21 to assay levels of oxidative markers from 6 distinct brain regions. When compared with the control, prenatal LPS-exposure alters levels of OS markers: (i) on PnD-1, glutathione (GSH) level is raised and superoxide dismutase (SOD) activity is dropped, (ii) on PnD-7, advanced oxidation of protein product (AOPP) level is elevated, (iii) on PnD-14, lipid peroxidation (MDA) and activity of catalase (CAT) are enhanced, (iv) on PnD-21, increased MDA continued. The hippocampus (HC) and cerebellum (CB) were mostly susceptible to OS in the early postnatal development. Levels of MDA and activity of CAT enzyme were increased on PnD-14 in the cortex, HC and CB. Except MDA, all OS markers recovered and returned to the level of control animals on PnD-21. Taken together, these results suggest that prenatal LPS-exposure induces age- and region-specific OS in the early postnatal stage.