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1.
J Inorg Biochem ; 212: 111210, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33010530

RESUMEN

Curcumin, a constituent of Curcuma longa L-Zingiberaceae is used in traditional Indian and worldwide medicine and shows anticancer and antioxidant properties. Curcumin has numerous biological and pharmacological activities but due to its hydrophobic nature, the major drawback is poor absorption and rapid elimination, rendering curcumin with the tag of a poor biomaterial. Hence, there is a need to develop functional metal containing curcumin model systems (FMCCMS) as a metallo-biomolecule to enhance the bioavailability of curcumin. We designed the interaction of silver metal ion with curcumin to form curcumin-silver nanocomposite (CURC-AgNCP) via ultrasonic synthetic route. Formations of FMCCMS were characterized by spectroscopic techniques. The crystalline face-centered cubic pattern and particle size of the nanocomposite was evaluated using X-ray diffraction and high-resolution transmission electron microscopy. The bonding of silver metal to curcumin was confirmed by X-ray photon spectroscopy. Interaction of the nanocomposite with bovine serum albumin (BSA) protein was performed using excitation, emission, and circular dichroism spectroscopy. In binding interaction of BSA, the negative value of ∆S° (-358.04 J mol-1 K-1) and ∆H° (-129.42 KJ mol-1) demonstrates the hydrophilic nature of the nanocomposite. The binding distance r evaluated according to the Forster resonance energy transfer theory and was 4.69 nm for CURC-AgNCP, which suggested non-radiative transfer of energy between CURC-AgNCP and BSA. The role of FMCCMS metallo-biomolecule CURC-AgNCP in medicine for cancer activity can have immense importance and hence we performed Sulphorhodamine B based in-vitro cytotoxicity assay on human breast cancer Michigan Cancer Foundation-7 cell line.


Asunto(s)
Curcumina/química , Nanocompuestos/química , Albúmina Sérica Bovina/química , Plata/química , Disponibilidad Biológica , Línea Celular Tumoral , Humanos , Microscopía Electrónica de Transmisión , Análisis Espectral/métodos
2.
Eur Arch Otorhinolaryngol ; 273(12): 4543-4547, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27338720

RESUMEN

Voice symptoms are frequently reported early after thyroidectomy, even in the absence of laryngeal nerves injury. We evaluated the short-term outcomes of these functional alterations. Thirty-nine patients were enrolled in a prospective observational trial, evaluating voice function before and 3 months after uncomplicated thyroidectomy, using VoiSS as assessed using a validated patient rated questionnaire; and perceptual voice analysis using GRBAS scale (Grade, Roughness, Breathiness, Asthenia, Strain). Impact of dysphonia on patient's life using VoiSS questionnaire revealed differences between pre- and postoperative assessment. There was statistically significant worsening in the impairment subgroup of VoiSS (p = 0.027). GRBAS evaluation was consistent between the three independent raters but showed differences between pre- and postoperative voice assessment. Age, TSH and a preoperative finding of laryngopharyngeal reflux significantly predicted quality of voice after thyroid surgery (all p < 0.004), as identified by the GRBAS assessment tool, but not type of surgery, gender or smoking status; although prediction of total variance in changes of voice was modest (r 2 = 0.07). Voice changes may occur after thyroidectomy without evident laryngeal nerve injury. Patients should be made aware of possible mild changes in voice even after uncomplicated thyroid surgery and this might be considered to be part of the informed consent.


Asunto(s)
Tiroidectomía/efectos adversos , Trastornos de la Voz/etiología , Calidad de la Voz , Factores de Edad , Humanos , Reflujo Laringofaríngeo/complicaciones , Complicaciones Posoperatorias , Estudios Prospectivos , Fumar/efectos adversos , Encuestas y Cuestionarios , Tirotropina/análisis
3.
Indian J Cancer ; 53(1): 29-33, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27146734

RESUMEN

BACKGROUND: Neo-adjuvant chemotherapy (NAC) in locally advanced breast cancer is the present trend. Following NAC, a considerable alteration of morphology occurs in the tumor. AIMS: To study effects of NAC on morphology of breast carcinoma and to evaluate the pathologic response (PR). MATERIALS AND METHODS: A total of 39 surgically resected mastectomy specimens of patients of invasive locally advanced breast carcinoma who received NAC were evaluated for macroscopic and microscopic (by routine stains and immunohistochemistry) alteration of morphology. RESULTS: Macroscopically well-defined tumor noted in 25 cases (64.1%) and in the rest (14 cases, 35.9%), only fibrotic areas identified. Microscopic examination identified malignant cells in 29 (74.4%), significant chronic inflammation in 24 (61.5%), hyalinized fibrosed stroma in 25 (64.1%) and necrosis in 11 (28.2%) cases. Immunohistochemistry assisted in differentiating malignant cells from histiocytes. In 15 cases (38.5%), axillary lymph nodes isolated where fibrosis seen in 12 (30.8%) and malignant cell in 8 (20.5%) cases. In 34 cases where the pre-treatment biopsy were available, complete pathologic response (pCR) and partial pathologic response (pPR) were achieved in 7 (20.6%) and 23 (67.4%) cases respectively. DISCUSSION: Protocol of systematic evaluation of morphological changes is different in cases of a patient treated by NAC. Nature of malignancy was difficult to categorize as morphology of typical breast carcinomas were altered. Sometimes, immunohistochemistry is advantageous as routine H and E stains are not sufficient to isolate malignant cells in fibrotic and necrotic areas. Appropriate morphological evaluation of the mastectomy specimen is absolutely crucial for assessment of PR and subsequent management.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Adulto , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante
4.
Oncogenesis ; 5: e225, 2016 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-27159678

RESUMEN

Tumor suppressor p53 is a critical player in the fight against cancer as it controls the cell cycle check point, apoptotic pathways and genomic stability. It is known to be the most frequently mutated gene in a wide variety of human cancers. Single-nucleotide polymorphism of p53 at codon72 leading to substitution of proline (Pro) in place of arginine (Arg) has been identified as a risk factor for development of many cancers, including nasopharyngeal carcinoma (NPC). However, the association of this polymorphism with NPC across the published literature has shown conflicting results. We aimed to conduct a case-control study for a possible relation of p53 codon72 Arg>Pro polymorphism with NPC risk in underdeveloped states of India, combine the result with previously available records from different databases and perform a meta-analysis to draw a more definitive conclusion. A total of 70 NPC patients and 70 healthy controls were enrolled from different hospitals of north-eastern India. The p53 codon72 Arg>Pro polymorphism was typed by polymerase chain reaction, which showed an association with NPC risk. In the meta-analysis consisting of 1842 cases and 2330 controls, it was found that individuals carrying the Pro allele and the ProPro genotype were at a significantly higher risk for NPC as compared with those with the Arg allele and the ArgArg genotype, respectively. Individuals with a ProPro genotype and a combined Pro genotype (ProPro+ArgPro) also showed a significantly higher risk for NPC over a wild homozygote ArgArg genotype. Additionally, the strength of each study was tested by power analysis and genotype distribution by Hardy-Weinberg equilibrium. The outcome of the study indicated that both allele frequency and genotype distribution of p53 codon72 Arg>Pro polymorphism were significantly associated with NPC risk. Stratified analyses based on ethnicity and source of samples supported the above result.

5.
Indian J Cancer ; 53(4): 538-541, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28485346

RESUMEN

BACKGROUND: Tobacco consumption is the major risk factor for developing head and neck squamous cell cancer (SCC). The site of development of HNSCC may depend on the way the tobacco is consumed. While laryngeal cancers are more common among smokers, oral cancers are more common among tobacco chewers. Since the use of smokeless tobacco is increasing, it is important to know whether this difference is restricted only to site wise distribution or it has other clinical and pathological implications. PATIENTS AND METHODS: We analyzed a prospectively collected dataset of HNSCC patients other than nasopharyngeal cancers attending our outpatient department at a single unit of the head and neck services at Tata Memorial Hospital, Mumbai, India, between January 2010 and September 2011. There were 747 eligible patients and were divided into three groups: Those with chewing as the only habit (chewers), those with smoking as the only habit (smokers), and those with no habits. Patients with regular use of alcohol were excluded from the study. The clinical and pathological parameters were analyzed. RESULTS: Of the 747 patients, the tobacco chewers formed 69.3% followed by smokers (19.5%) and patients with no habits (11.1%). Majority of smokers were men (98%). Site distribution revealed patients with chewing as the only habit had oral cancers (most commonly gingivobuccal complex cancers) as the most common site and those with smoking as the only habit had larynx as the most common site. In patients with no habits, oral tongue was found to be the most common site. No statistically significant pathological differences were observed in between these groups in patients who underwent surgery (n = 366) at the initial modality of treatment. CONCLUSIONS: There is a direct relationship between the form of tobacco use and site of appearance of HNSCC. However, there are no differences in clinical or pathological parameters between HNSCC caused by tobacco chewing or tobacco smoking.


Asunto(s)
Carcinoma de Células Escamosas/etiología , Neoplasias de Cabeza y Cuello/etiología , Neoplasias Laríngeas/etiología , Neoplasias de la Boca/etiología , Fumar Tabaco/efectos adversos , Uso de Tabaco/efectos adversos , Neoplasias de la Lengua/etiología , Adolescente , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Neoplasias Laríngeas/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Fumadores , Carcinoma de Células Escamosas de Cabeza y Cuello , Neoplasias de la Lengua/patología , Adulto Joven
6.
Cell Death Differ ; 23(4): 707-22, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26494468

RESUMEN

Mutation in the TP53 gene positively correlates with increased incidence of chemoresistance in different cancers. In this study, we investigated the mechanism of chemoresistance and epithelial-to-mesenchymal transition (EMT) in colorectal cancer involving the gain-of-function (GOF) mutant p53/ephrin-B2 signaling axis. Bioinformatic analysis of the NCI-60 data set and subsequent hub prediction identified EFNB2 as a possible GOF mutant p53 target gene, responsible for chemoresistance. We show that the mutant p53-NF-Y complex transcriptionally upregulates EFNB2 expression in response to DNA damage. Moreover, the acetylated form of mutant p53 protein is recruited on the EFNB2 promoter and positively regulates its expression in conjunction with coactivator p300. In vitro cell line and in vivo nude mice data show that EFNB2 silencing restores chemosensitivity in mutant p53-harboring tumors. In addition, we observed high expression of EFNB2 in patients having neoadjuvant non-responder colorectal carcinoma compared with those having responder version of the disease. In the course of deciphering the drug resistance mechanism, we also show that ephrin-B2 reverse signaling induces ABCG2 expression after drug treatment that involves JNK-c-Jun signaling in mutant p53 cells. Moreover, 5-fluorouracil-induced ephrin-B2 reverse signaling promotes tumorigenesis through the Src-ERK pathway, and drives EMT via the Src-FAK pathway. We thus conclude that targeting ephrin-B2 might enhance the therapeutic potential of DNA-damaging chemotherapeutic agents in mutant p53-bearing human tumors.


Asunto(s)
Neoplasias Colorrectales/metabolismo , Daño del ADN , Resistencia a Antineoplásicos , Efrina-B2/metabolismo , Transición Epitelial-Mesenquimal , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Efrina-B2/genética , Femenino , Xenoinjertos , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
8.
J Viral Hepat ; 22(10): 817-27, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25720442

RESUMEN

Effective recognition of viral infection and successive activation of antiviral innate immune responses are vital for host antiviral defence, which largely depends on multiple regulators, including Toll-like receptors (TLRs) and microRNAs. Several early reports suggest that specific TLR-mediated immune responses can control hepatitis B virus (HBV) replication and express differentially with disease outcome. Considering the versatile function of miR-155 in the TLR-mediated innate immune response, we aimed to study the association between miR-155 and TLRs and their subsequent impact on HBV replication using both a HBV-replicating stable cell line (HepG2.2.15) and HBV-infected liver biopsy and serum samples. Our results showed that miR-155 was suppressed during HBV infection and a subsequent positive correlation of miR-155 with TLR7 activation was noted. Further, ectopic expression of miR-155 in vitro reduced HBV load as evidenced from reduced viral DNA, mRNA and subsequently reduced level of secreted viral antigens (HBsAg and HBeAg). Our results further suggested that CCAAT/enhancer-binding protein-ß (C/EBP-ß), a positive regulator of HBV transcription, was inhibited by miR-155. Taken together, our study established a correlation between miR-155 and TLR7 during HBV infection and also demonstrated in vitro that increased miR-155 level could help to reduce HBV viral load by targeting C/EBP-ß.


Asunto(s)
Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Virus de la Hepatitis B/inmunología , Hepatocitos/inmunología , Hepatocitos/virología , Hígado/virología , MicroARNs/biosíntesis , Receptor Toll-Like 7/biosíntesis , Línea Celular , Virus de la Hepatitis B/fisiología , Humanos , Hígado/patología , Replicación Viral
9.
Cell Death Discov ; 1: 15016, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-27551450

RESUMEN

For rapid tumor growth, cancer cells often reprogram the cellular metabolic processes to obtain enhanced anabolic precursors and energy. The molecular changes of such metabolic rewiring are far from established. Here we explored the role of mTOR (mechanistic target of rapamycin), which serves as a key regulator of cell growth, proliferation and survival, in the metabolic reprograming of cancer cells. When we inhibited mTOR in human hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) cells, using pharmacologic inhibitors or by RNA interference, we noticed shuttle of the glycolytic flux to gluconeogenesis pathway along with reduction in cellular proliferation and survival. Augmentation of gluconeogenesis was mechanistically linked to upregulation of the key gluconeogenic enzymes PCK1 and G6PC expressions, enhanced lactate dehydrogenase activity and glucose-derived lipogenesis without causing any attenuation in mitochondrial function. Interestingly, concomitant knocking down of PCK1 and not G6PC along with mTOR pathway could overcome the inhibition of cancer cell proliferation and survival. These observations were validated by identifying distinctive diminution of PCK1 and G6PC expressions in human HCC and RCC transcriptome data. Significant correlation between mTOR-dependent upregulation of PCK1 and cell death in different cancer cell lines further emphasizes the physiological relevance of this pathway. We reveal for the first time that inhibition of mTORC2 and consequent redistribution of glycolytic flux can have a prosurvival role in HCC and RCC cancer cells only in the presence of downregulation of gluconeogenesis pathway genes, thus identifying novel pivots of cancer cell metabolic rewiring and targets for therapy.

10.
Diabet Med ; 31(12): 1594-9, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24975463

RESUMEN

AIM: To evaluate the role of fetuin-A levels in predicting glycaemic outcomes (progression to diabetes or reversion to normoglycaemia) in people with prediabetes. METHODS: A total of 2119 people were screened, of whom 144 people with prediabetes, 50 people with normoglycaemia and 66 people with newly diagnosed diabetes underwent estimation of fasting insulin, fetuin-A, interleukin-6, interleukin-1ß, tumour necrosis factor-α, lipid and 25-hydroxyvitamin-D levels and assessment of non-alcoholic fatty liver disease using ultrasonography and the fatty liver index. People with prediabetes were followed and analysed according to glycaemic outcome and quartile of fetuin-A level. RESULTS: Fetuin-A, interleukin-1ß, interleukin-6, tumour necrosis factor-α and triglyceride levels and presence of non-alcoholic fatty liver disease increased across the glycaemic spectrum and were highest in people with diabetes. A total of 32 people with prediabetes reverted to normoglycaemia, 23 progressed to diabetes and 65 remained with prediabetes over a mean ± sd follow-up of 32.12 ± 8.4 months. People progressing to diabetes had higher baseline glycaemia rates, fetuin-A levels, interleukin-1ß levels, fatty liver index scores and prevalence of non-alcoholic fatty liver disease and lower 25-hydroxyvitamin-D levels. People with prediabetes in the highest fetuin-A quartile had the highest risk of progression to diabetes (relative risk 2.68, 95% CI 0.95-7.55; P = 0.06) and the lowest rate of reversion to normoglycaemia (relative risk 0.27, 95% CI 0.08-0.85; P = 0.03). Fetuin-A levels correlated with interleukin-1ß levels (r = 0.420; P < 0.001), interleukin-6 levels (r = 0.231; P = 0.022) and fatty liver index scores (r = 0.319; P < 0.001). Cox regression showed that higher fetuin-A levels and higher BMI and lower 25-hydroxyvitamin-D levels were predictive of lower rates of reversion to normoglycaemia. Age, triglyceride levels, and interleukin-6 and interleukin-1ß levels were predictive of progression to diabetes. CONCLUSIONS: Increased fetuin-A level has an adverse impact on glycaemic outcomes in prediabetes. This study highlights the importance of fetuin-A as a predictor of glycaemic outcomes in prediabetes.


Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Resistencia a la Insulina , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Estado Prediabético/metabolismo , alfa-2-Glicoproteína-HS/metabolismo , Adulto , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Diabetes Mellitus Tipo 2/epidemiología , Progresión de la Enfermedad , Femenino , Humanos , India/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Estado Prediabético/epidemiología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Triglicéridos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Vitamina D/análogos & derivados , Vitamina D/metabolismo
11.
JNMA J Nepal Med Assoc ; 52(194): 831-3, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-26905714

RESUMEN

Hashimoto's thyroiditis (HT) has been found to be associated with lymphoma, papillary carcinoma and Hürthle cell neoplasms of thyroid. In contrast, there are only a few reports of co-existence of HT with medullary carcinoma of thyroid. An overall prevalence of medullary carcinoma of only 0.35% has been reported in HT patients. Such a rare combination is being presented here. A 33 year old female presented with history of goiter for one year. Fine needle aspiration cytology (FNAC) of the swelling revealed cytological features suggestive of medullary carcinoma of thyroid. Histopathological examination of total thyroidectomy specimen revealed Hashimoto's thyroiditis along with medullary carcinoma of thyroid. Although Hashimoto's thyroiditis can uncommonly co-exist with thyroid neoplasm, its association with medullary carcinoma is extremely rare and hence being presented.


Asunto(s)
Carcinoma Neuroendocrino/complicaciones , Enfermedad de Hashimoto/complicaciones , Neoplasias de la Tiroides/complicaciones , Adulto , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/cirugía , Femenino , Enfermedad de Hashimoto/patología , Enfermedad de Hashimoto/cirugía , Humanos , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Tiroidectomía
12.
J Nepal Health Res Counc ; 12(27): 144-6, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25575010

RESUMEN

Tuberculosis affects many organs, however isolated tubercular breast lesion is rare. Clinically as well as radiologically it may mimic both pyogenic abscess and malignancy. One such case is being reported where a middle aged woman presented with painful, gradually increasing breast lump and was diagnosed clinically, radiologically, cytologically and even histologically as pyogenic abscess. Poor response to antibiotics raised the suspicion of malignancy for which repeat fine needle aspiration cytology was done. Well formed granulomas, necrosis and finally demonstration of acid fast bacilli established the diagnosis of tubercular abscess. No other organs were involved by tuberculosis in this case. Patient responded well to antitubercular drugs. Thus diagnostic challenge lies in the demonstration of acid fast bacilli in cases of equivocal morphology in routine cytology as well as histology. High clinical suspicion, poor response to antibiotics, suggestive radiological findings, cytology, histology and demonstration of acid fast bacilli -all contributes to the diagnosis of breast tuberculosis.


Asunto(s)
Enfermedades de la Mama/diagnóstico , Enfermedades de la Mama/microbiología , Tuberculosis/diagnóstico , Adulto , Antituberculosos/uso terapéutico , Biopsia con Aguja Fina , Enfermedades de la Mama/tratamiento farmacológico , Femenino , Humanos , Tuberculosis/tratamiento farmacológico
13.
Kathmandu Univ Med J (KUMJ) ; 12(47): 219-21, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25855117

RESUMEN

Tumors of the broad ligament are uncommon. Leiomyoma, which is the commonest female genital neoplasm, is also the most common solid tumor of the broad ligament. Leiomyomas affect 30% of all women of reproductive age but the incidence of broad-ligament leiomyoma is <1%. These benign tumors are usually asymptomatic. A case is being described where a 52 year old presented with gradual abdominal swelling which was clinically and radiologically diagnosed as ovarian malignancy. On abdominal and bimanual palpation a soft cystic mass was noted in the right pelvic region. CA 125 was mildly raised. CEA, CA 19.9 levels were within normal limit. The radiological diagnosis was ovarian cyst with possibility of malignant changes. Staging laparotomy and histopathological examination of the resected specimen revealed a right sided broad ligament leiomyoma with cystic changes. The degenerative changes in the leiomyoma lead to the clinical and radiological diagnostic confusion. Thus, though uncommon, broad ligament leiomyoma should be considered during evaluation of adnexal masses for optimal patient management. The above description of leiomyoma in the broad ligament is a highly unique case and thus deserves appropriate attention.


Asunto(s)
Ligamento Ancho/patología , Leiomioma/diagnóstico , Neoplasias de los Músculos/diagnóstico , Neoplasias Ováricas/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Laparotomía , Persona de Mediana Edad
14.
J Nepal Health Res Counc ; 11(24): 215-7, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-24362615

RESUMEN

We report a case of retroperitoneal mass involving lumbar spine (L2 region) of eight months duration in a male aged 26 years. X ray of the lumbar spine was suggestive of tuberculosis. However, as there was no response to specific therapy, a CT scan was performed which was indicative of a soft tissue sarcoma. Subsequent biopsy of the tumor showed it to be a giant cell tumor of bone (GCT). The tumor was inoperable and the patient is presently undergoing radiotherapy. Giant cell tumors only rarely arise in the axial skeleton. GCT of the spine is uncommon, accounting for 1.3-6.5% of all cases in various series. The case is being presented because of its rarity, diagnostic dilemma encountered and to emphasize the role of surgical biopsy.


Asunto(s)
Tumor Óseo de Células Gigantes/diagnóstico , Vértebras Lumbares , Neoplasias de la Columna Vertebral/diagnóstico , Adulto , Diagnóstico Diferencial , Tumor Óseo de Células Gigantes/radioterapia , Humanos , Región Lumbosacra , Masculino , Neoplasias Retroperitoneales/diagnóstico , Neoplasias de la Columna Vertebral/radioterapia
15.
Aliment Pharmacol Ther ; 37(7): 720-9, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23441892

RESUMEN

BACKGROUND: Elevated iron indices are described in non-alcoholic fatty liver disease and iron reduction has been suggested as a potential therapy. AIM: To determine whether phlebotomy is an effective therapy for non-alcoholic fatty liver disease. METHODS: Patients with biopsy proven non-alcoholic fatty liver disease underwent baseline evaluation to determine severity of metabolic and liver disease. A Phase II trial of phlebotomy was carried out to achieve near-iron depletion (serum ferritin ≤50 µg/L or haemoglobin 100 g/L). Repeat liver biopsy, anthropometric and biochemical measurements were performed 6 months following the end of treatment. Primary outcome was improvement in liver histology, assessed using the non-alcoholic fatty liver disease activity score. RESULTS: Thirty-one patients completed follow-up. Iron reduction resulted in a significant improvement in the non-alcoholic fatty liver disease activity score (-0.74 ± 1.83, P = 0.019). Reductions in individual histological features of lobular inflammation (-0.29 ± 1.07, P = 0.182), steatosis (-0.26 ± 0.82, P = 0.134), hepatocyte ballooning (-0.19 ± 0.70, P = 0.213) did not achieve significance nor did the score for fibrosis (-0.32 ± 0.94, P = 0.099). CONCLUSIONS: This prospective Phase II study of phlebotomy with paired liver biopsies evaluating phlebotomy therapy in non-alcoholic fatty liver disease patients suggests that iron reduction may improve liver histology. However, the effect size of phlebotomy raises questions of whether treatment could have sufficient clinical significance to justify a definitive Phase III trial. This trial has been registered with the US National Institute of Health (clinicaltrials.gov, Identifier NCT 00641524).


Asunto(s)
Hígado Graso/terapia , Flebotomía/métodos , Adulto , Hígado Graso/sangre , Femenino , Ferritinas/sangre , Humanos , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico
16.
Ann Hepatol ; 11(6): 870-5, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23109450

RESUMEN

BACKGROUND: The prevalence of occult HBV, defined by the presence of HBV DNA in individuals with antibodies to HBV core antigen and with absence of HBV surface antigen, but its clinical significance and virological features in HIV-infected patients is still unclear. AIM: To investigate the prevalence, clinical significance and molecular characterization of occult hepatitis B virus infection in ART-Naive HIV-positive individuals. MATERIAL AND METHODS: Among the 1077 HIV-infected patients with different risk factors for HIV infection, 297 were HBsAg-ve ART-naive, of them 112 was randomly selected for the study. HBV DNA was tested by in-house PCR and quantified by qPCR. Molecular characterization was performed by sequencing the envelope and overlapping polymerase genes. RESULTS: We found the prevalence of occult HBV to be 10.7% among a randomly selected group of HBsAg-ve/antiHBc+ve HIV-infected patients. Overall 33.9% (38 of 112) of the patients were antiHBc positive indicating exposure to HBV infection. HBV DNA was detected in 12/38 (31.5%) antiHBc positive samples and 50% of them had CD4 T cell count < 200 cells/mm(3). HCV coinfection was low (2.7%). No surrogate marker for OBI could be identified. Presence of antiHBs antibodies did not rule out OBI. Liver biopsy in six cases showed varying stages of chronic hepatitis. Several mutations were detected but not the common immune escape mutant G145R. CONCLUSION: In conclusion the prevalence of OBI was significantly high among HIV coinfected patients, which highlights the importance of HBV DNA testing in these patients and indicates need for further prospective studies in larger cohorts to assess its clinical significance.


Asunto(s)
Coinfección , Infecciones por VIH/epidemiología , Antígenos del Núcleo de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B/epidemiología , Derivación y Consulta , Adolescente , Adulto , Biomarcadores/sangre , Biopsia , Recuento de Linfocito CD4 , Distribución de Chi-Cuadrado , ADN Viral/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por VIH/diagnóstico , Hepatitis B/diagnóstico , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Mutación , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Prevalencia , ARN Viral/sangre , Análisis de Secuencia de ADN , Adulto Joven
17.
AJNR Am J Neuroradiol ; 33(6): 1182-6, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22322607

RESUMEN

BACKGROUND AND PURPOSE: IAs are found in 2.3% of adults; the mean age at detection is 52 years. Prevalence is <0.5% in young adults. Early studies suggest that 10%-50% of patients with aortic coarctation have IAs. Screening recommendations are variable. We sought to examine the prevalence of IAs through screening with MRA. MATERIALS AND METHODS: Consecutive patients older than 16 years of age with coarctation undergoing brain MRA between May 1999 and October 2007 were included. MRA was performed by using a 1.5T scanner with a 3D time-of-flight protocol; simultaneous MR imaging was performed of the heart and aorta. Cerebral MRAs were double-reported by a neuroradiologist. Statistics are described as mean ± SD and median ± range. Continuous variables were compared by using Student t tests and Mann-Whitney U tests (categoric variables, by using the Fisher exact test). RESULTS: One hundred seventeen MRAs were double-reported. The median age was 29 ± 11 years (range, 16-59 years). IAs were found in 12 patients (10.3%). The mean diameter of IAs was 3.9 mm (range, 2.0-8.0 mm). Patients with aneurysms were older (median, 37 years; range, 16-50 years) than those without (median, 23 years; range, 16-59 years; Z = -2.01, P = .04). Hypertension was more common in those with IAs (IA 83% versus no IA 43%, P = .01). There was no association between ascending aortopathy, bicuspid aortic valves, and IAs. CONCLUSIONS: Patients with coarctation have a higher prevalence of IAs, occurring at an earlier age than in population studies. Whether routine screening is appropriate for this group of patients is unclear. Hypertension is likely to be an important pathophysiologic factor.


Asunto(s)
Coartación Aórtica/diagnóstico , Coartación Aórtica/epidemiología , Aneurisma Intracraneal/diagnóstico , Aneurisma Intracraneal/epidemiología , Angiografía por Resonancia Magnética/estadística & datos numéricos , Tamizaje Masivo/estadística & datos numéricos , Adolescente , Adulto , Anciano , Causalidad , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Reino Unido/epidemiología
18.
Placenta ; 33(3): 143-50, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22230251

RESUMEN

The placenta is a highly vascularized organ thus angiogenesis is a key process in placental development. The contribution that different cells in the villous stroma play in placental angiogenesis is largely unknown. In this study we identified a novel stromal cell type in sections of term placenta which is morphologically fibroblastic and expressing the fibroblast marker TE-7 but also positive for the monocytic markers CD115 and CD14 and designated these cells as fibrocyte-like cells. Populations of fibrocyte-like cells from the placenta were isolated by two methods: culture of adherence-selected placental cells and, for higher purity, by CD45 fluorescence activated cell sorting (FACS). Fibrocyte-like cell conditioned medium increased endothelial tubule-like structure formation 2-fold versus control medium. Both pro-angiogenic growth factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) and the anti-angiogenic factor soluble-Flt were found in the conditioned medium. Neutralizing antibodies against VEGF and b-FGF reduced endothelial cell tubule-like structures to control levels. These data suggests that fibrocyte-like cells, a previously unidentified cell of the villous stroma, may play an important role in the regulation of placental angiogenesis.


Asunto(s)
Fibroblastos/citología , Fibroblastos/fisiología , Placenta/citología , Separación Celular/métodos , Células Cultivadas , Vellosidades Coriónicas/metabolismo , Vellosidades Coriónicas/fisiología , Células Endoteliales/citología , Células Endoteliales/metabolismo , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Macrófagos/metabolismo , Macrófagos/fisiología , Monocitos/metabolismo , Monocitos/fisiología , Neovascularización Fisiológica/fisiología , Placenta/irrigación sanguínea , Placenta/fisiología , Embarazo , Cultivo Primario de Células
19.
Indian J Otolaryngol Head Neck Surg ; 64(3): 248-51, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23998029

RESUMEN

To estimate the prevalence of neonatal nasal septal deviation and to identify the precipitating factors. 250 neonates were examined on the 2nd day using Gray's struts for the presence of deviated nasal septum. Struts passing up to the 4 cm mark was taken to be normal, while struts getting stuck before the 4 cm mark was diagnosed to have deviated septum on that particular side. Out of 250 neonates, 49 had nasal septal deviation. There was significantly higher number of deviations in neonates of primiparas, emergency LSCS and in high birth weight babies. Neonatal septal deviation is quite common, being present in approximately 20% of all newborns. Greater amount of birth trauma increases its incidence further.

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