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1.
J Orthop Case Rep ; 13(9): 52-56, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37753119

RESUMO

Introduction: Paralabral cyst is benign fluid-filled lesion that occurs adjacent to glenoid labrum. Origin of the cyst can be traumatic or atraumatic. This cystic lesion can compress nearby axillary nerve or suprascapular nerve, resulting in shoulder pain and numbness. In this case report, we will discuss about anteroinferior paralabral cyst with axillary neuropathy in atraumatic condition. Case Report: A 35-year-old male was admitted in our institute with complaining of numbness in the mid-part of the lateral arm and pain in the posterior aspect in the left shoulder for 2 weeks. The patient has on-and-off pain in the left shoulder on lifting weight. He had no history of trauma. X-ray was normal. On examination, tenderness presents over the dorsal aspect of shoulder and reduced sensations over deltoid muscle (regimen badge sign). Deltoid atrophy was noted. Range of motion was normal. On examination, cervical spine was normal, and reduced sensation over the lateral aspect of arm and deltoid atrophy was present. Magnetic resonance imaging (MRI) shows large multiloculated paralabral cyst caudal to inferior glenoid rim. The diagnosis was compressive axillary neuropathy which was confirmed by nerve condition study. Conclusion: According to this case report, accurate early clinical examination and MRI evaluation are crucial in patients with atraumatic shoulder pain associated with neurological symptoms. On identification, cyst can be successfully decompressed by shoulder arthroscopy which can prevent axillary nerve damage, muscle denervation, and also recurrence of cyst can be avoided.

2.
Indian J Nucl Med ; 38(4): 392-393, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38390546

RESUMO

Tertiary hyperparathyroidism (THPT) is characterized by over secretion of parathyroid hormone caused by long-standing secondary hyperparathyroidism. THPT can affect the bones as well as cause extraskeletal calcifications. The bony lesions often mimic multiple skeletal metastases or multiple myeloma. We report a case of a 48-year-old man with chronic kidney disease on dialysis, who presented with chief complaints of low back ache and swelling over the left clavicle. In view of clinical suspicion of malignancy with bony metastases, he underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography and was subsequently found to have parathyroid adenomas, which were confirmed on 99mTc-methoxy-isobutyl-isonitrile scintigraphy.

3.
Food Funct ; 13(15): 8283-8303, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35834215

RESUMO

Colon cancer is the most prevalent cause of death from cancer across the globe. Although chemotherapy drugs are predominantly used, their toxicity always remains a cause of concern. As an alternative to synthetic drugs, natural compounds or nutraceuticals are comparatively less toxic. Honey is widely used across different cultures as an alternative form of medicine. It represents a prominent source of plant-phenolic compounds and there is demonstrable evidence of its anti-oxidant and anti-microbial activities. The aim of the present work was to investigate the anti-proliferative effect of some Indian honeys and analyze their mechanism of action in colon cancer. In order to establish the composition-activity relationship, we evaluated the bioactive components present in selected honey samples by GC-MS and HPLC analysis. Indian honey samples showed a significant inhibitory impact on cell growth by restricting cell proliferation, causing apoptosis, and restricting the cell cycle in the G2/M phase specifically for colon cancer cells. The apoptotic activities, as imparted by the honey samples, were established by Annexin V/PI staining, real-time PCR, and immunoblot analyses. The treated cells showed increased expressions of p53 and caspases 3, 8, and 9, thus indicating the involvement of both extrinsic and intrinsic apoptotic pathways. The honey samples were also found to inhibit the ß-catenin/Wnt pathway. In the next phase of the study, the efficacy of these honey samples was evaluated in colon carcinoma induced SD-rats. Overall, these findings demonstrated that selected Indian honeys could be established as effective nutraceuticals for the prevention as well as cure of colon cancer.


Assuntos
Neoplasias do Colo , Mel , Animais , Apoptose , Proliferação de Células , Neoplasias do Colo/tratamento farmacológico , Mel/análise , Ratos , Via de Sinalização Wnt , beta Catenina
5.
J Nucl Med ; 60(8): 1087-1093, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30683766

RESUMO

Guidelines recommend true whole-body 18F-FDG PET/CT scans from vertex to toes in pediatric lymphoma patients, although this suggestion has not been validated in large clinical trials. The objective of the study was to evaluate the incidence and clinical impact of lesions outside the "eyes to thighs" regular field of view (R-FOV) in 18F-FDG PET/CT staging (sPET) and interim (iPET) scans in pediatric lymphoma patients. Methods: True whole-body sPET and iPET scans were prospectively obtained in pediatric lymphoma patients (11 worldwide centers). Expert panel central review of sPET and iPET scans were evaluated for lymphoma lesions outside the R-FOV and clinical relevance of these findings. Results: A total of 610 scans were obtained in 305 patients. The sPET scans did not show lesions outside the R-FOV in 91.8% of the patients, whereas in 8.2% patients the sPET scans demonstrated lesions also outside the R-FOV (soft tissue, bone, bone marrow, and skin); however, the presence of these lesions did not change the clinical stage of any patient and did not affect treatment decision. Among the 305 iPET scans, there were no new positive 18F-FDG-avid lesions outside the R-FOV, when compared with their paired sPET scans. A single lesion outside the R-FOV on iPET occurred in 1 patient (0.3%), with the primary lesion diagnosed in the femur on sPET that persisted on iPET. Conclusion: The identification of additional lesions outside the R-FOV (eyes to thighs) using 18F-FDG PET/CT has no impact in the definition of the clinical stage of disease and minimal impact in the treatment definition of patients with pediatric lymphoma. As so, R-FOV for both sPET and iPET scans could be performed.


Assuntos
Fluordesoxiglucose F18/farmacologia , Linfoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adolescente , Criança , Pré-Escolar , Feminino , Doença de Hodgkin/diagnóstico por imagem , Humanos , Lactente , Linfoma não Hodgkin/diagnóstico por imagem , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Imagem Corporal Total/métodos
6.
J Neurosurg Pediatr ; 23(2): 187-197, 2018 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-30497135

RESUMO

OBJECTIVEEndoscope-assisted hemispherotomy (EH) has emerged as a good alternative option for hemispheric pathologies with drug-resistant epilepsy.METHODSThis was a prospective observational study. Parameters measured included primary outcome measures (frequency, severity of seizures) and secondary outcomes (cognition, behavior, and quality of life). Blood loss, operating time, complications, and hospital stay were also taken into account. A comparison was made between the open hemispherotomy (OH) and endoscopic techniques performed by the senior author.RESULTSOf 59 cases (42 males), 27 underwent OH (8 periinsular, the rest vertical) and 32 received EH. The mean age was 8.65 ± 5.41 years (EH: 8.6 ± 5.3 years; OH: 8.6 ± 5.7 years). Seizure frequency per day was 7 ± 5.9 (EH: 7.3 ± 4.6; OH: 15.0 ± 6.2). Duration of disease (years since first episode) was 3.92 ± 1.24 years (EH: 5.2 ± 4.3; OH: 5.8 ± 4.5 years). Number of antiepileptic drugs per patient was 3.9 ± 1.2 (EH: 4.2 ± 1.2; OH: 3.8 ± 0.98). Values for the foregoing variables are expressed as the mean ± SD. Pathologies included the following: postinfarct encephalomalacia in 19 (EH: 11); Rasmussen's syndrome in 14 (EH: 7); hemimegalencephaly in 12 (EH: 7); hemispheric cortical dysplasia in 7 (EH: 4); postencephalitis sequelae in 6 (EH: 2); and Sturge-Weber syndrome in 1 (EH: 1). The mean follow-up was 40.16 ± 17.3 months. Thirty-nine of 49 (79.6%) had favorable outcomes (International League Against Epilepsy class I and II): in EH the total was 19/23 (82.6%) and in OH it was 20/26 (76.9%). There was no difference in the primary outcome between EH and OH (p = 0.15). Significant improvement was seen in the behavioral/quality of life performance, but not in IQ scores in both EH and OH (p < 0.01, no intergroup difference). Blood loss (p = 0.02) and hospital stay (p = 0.049) were less in EH.CONCLUSIONSEH was as effective as the open procedure in terms of primary and secondary outcomes. It also resulted in less blood loss and a shorter postoperative hospital stay.


Assuntos
Corpo Caloso/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , Hemisferectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Adolescente , Adulto , Perda Sanguínea Cirúrgica , Criança , Pré-Escolar , Cognição , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Feminino , Seguimentos , Hemisferectomia/efeitos adversos , Humanos , Lactente , Tempo de Internação , Imageamento por Ressonância Magnética , Masculino , Neuroendoscópios , Fotografação , Estudos Prospectivos , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
7.
Acta Cytol ; 62(5-6): 371-379, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30253413

RESUMO

OBJECTIVES: Solid variant of papillary thyroid carcinoma (SVPTC) is rare, differing from classical PTC (cPTC) in architecture and outcome. We evaluated the cytomorphology of SVPTC cases to assess the feasibility of a preoperative diagnosis. STUDY DESIGN: SVPTC cases were evaluated for architecture, nuclear features, and Bethesda category and were compared with noninvasive follicular thyroid neoplasm with papillary-like nuclear features/follicular variant of PTC (NIFTP/FVPTC), cPTC, and poorly differentiated thyroid carcinoma (PDTC). RESULTS: Nine SVPTCs, 29 NIFTP/FVPTCs, 12 cPTCs, and 4 PDTCs were included. The predominant architecture in most SVPTCs was solid fragment, which is helpful in differentiating them from NIFTP/FVPTC (p < 0.001) and cPTC (p = 0.006) but not from PDTC. The presence of microfollicles led to misinterpretation as NIFTP/FVPTC/follicular neoplasm in 4 patients. All but 1 SVPTC showed diffuse nuclear features. Intranuclear pseudoinclusions (INIs) were seen in 67% of SVPTCs as compared to 83% of cPTCs, 14% of NIFTP/FVPTCs (p = 0.005), and none of PDTCs. SVPTC cases were commonly (78%) categorized as intermediate/suspicious. CONCLUSIONS: The presence of solid fragments and lack of true papillae are helpful in differentiating SVPTC from cPTC. Solid fragments, trabeculae, the extent of nuclear features, and INIs should be looked for in cases with prominent microfollicles for distinguishing SVPTC from NIFTP/FVPTC. None of the features were helpful in differentiating SVPTC from PDTC.


Assuntos
Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Diferenciação Celular , Diagnóstico Diferencial , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos
8.
BMJ Case Rep ; 20152015 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-26174734

RESUMO

Topical latanoprost is a most effective and commonly used antiglaucoma medication. Use of prostaglandin analogues (PGA) in the early postoperative period is controversial due to its proinflammatory properties. We report a case of a 64-year-old man with primary open angle glaucoma, post-trabeculectomy 17 years prior, with good intraocular pressure (IOP) control on topical levobunolol 0.5% and latanoprost 0.005%. He underwent a clear corneal phacoemulsification surgery in his left eye and the PGA was stopped. He had an uneventful postoperative course and was prescribed eyeglasses at 4-week follow-up. Two weeks later, he presented to the emergency department with decreased vision in the left eye, flat anterior chamber, IOP of 00 mm Hg and 360° choroidal detachment. The continued use of topical latanoprost in the operated eye was implicated as the cause. This case illustrates the serious vision-threatening side effect of PGA when used in the early postoperative period.


Assuntos
Extração de Catarata/métodos , Doenças da Coroide/etiologia , Corioide/patologia , Glaucoma de Ângulo Aberto/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , Implante de Lente Intraocular , Prostaglandinas F Sintéticas/efeitos adversos , Administração Tópica , Câmara Anterior/patologia , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Catarata/complicações , Glaucoma de Ângulo Aberto/prevenção & controle , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Latanoprosta , Masculino , Erros de Medicação , Pessoa de Meia-Idade , Hipotensão Ocular/etiologia , Facoemulsificação , Cuidados Pós-Operatórios , Complicações Pós-Operatórias , Prostaglandinas F Sintéticas/administração & dosagem , Prostaglandinas F Sintéticas/uso terapêutico , Tonometria Ocular , Trabeculectomia , Acuidade Visual
9.
Clin Endocrinol (Oxf) ; 82(3): 445-52, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25040494

RESUMO

OBJECTIVE: Distant metastases, although rare, account for maximum disease-related mortality in differentiated thyroid cancer (DTC). Lungs and bones are the most frequent sites of metastases. We sought to identify the prognostic factors in adult DTC patients presenting with pulmonary metastases at initial diagnosis. DESIGN: Retrospective cohort study. PATIENTS: From the medical records of 4370 patients, 200 patients aged more than 21 years who were identified to have pulmonary metastases at the time of diagnosis were included in the analysis. RESULTS: The sites of metastases were lungs alone in 133 (67%) patients, and additional sites in remaining 67 (33%) patients were as follows: bones in 59, liver in 4, brain in 2 and both bone and liver in two patients. During the mean follow-up of 61 months (range, 12-312 months), 76 patients achieved remission, 121 (60·5%) patients had biochemically and/or structurally persistent disease and three patients showed disease progression. Multivariate analysis revealed presence of macro-nodular (chest X-ray positive) pulmonary metastases and concomitant skeletal metastases as independent factors decreasing the likelihood of remission. Of the 76 patients with remission, 16 (21%) developed subsequent recurrence. Patient age >45 years and follicular histopathology were independently associated with greater hazards of developing recurrence. CONCLUSION: This study suggests that the patients with macro-nodular lung metastases and/or concomitant skeletal metastases have reduced odds of achieving remission. Moreover, significant number of patients recur even after complete remission with RAI treatment, hence strict surveillance is recommended especially in patients with age >45 years and/or with follicular histology of DTC.


Assuntos
Neoplasias Pulmonares/patologia , Neoplasias da Glândula Tireoide/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
10.
Int J Obstet Anesth ; 23(4): 348-56, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25223644

RESUMO

BACKGROUND: Acute aortic dissection in pregnant women is a rare but potentially life-threatening event. Our aim was to evaluate maternal and fetal outcomes of acute aortic dissection during pregnancy. METHODS: We conducted a review of literature of the PubMed database to identify publications related to pregnant women with acute aortic dissections during the period 2003-2013: 59 articles were included in the study. RESULTS: A total of 75 patients were included in the analyses. Stanford type A dissections were the most common form, accounting for 77% of all cases. The majority (78%) occurred in the third trimester and immediate postpartum period. Inherited connective tissue disorders were causative in 49% of patients. Maternal mortality was not statistical different between type A and type B dissections (21% vs. 23%), but fetal outcomes were worse in type B dissections (35% vs. 10.3%; P<0.05). Fetal mortality in type A dissections was dependent on the timing of aortic repair, with antepartum aortic repair associated with a higher mortality (36%). CONCLUSION: Despite advances in diagnostic and surgical techniques, maternal and fetal mortalities in pregnant patients with aortic dissection remain high. Patients undergoing combined cesarean section with aortic repair had favorable fetal outcomes.


Assuntos
Aneurisma Aórtico/complicações , Dissecção Aórtica/complicações , Resultado da Gravidez/epidemiologia , Doença Aguda , Adulto , Dissecção Aórtica/mortalidade , Dissecção Aórtica/cirurgia , Aneurisma Aórtico/mortalidade , Aneurisma Aórtico/cirurgia , Doenças do Tecido Conjuntivo/complicações , Feminino , Humanos , Gravidez , Terceiro Trimestre da Gravidez , Procedimentos Cirúrgicos Vasculares
11.
Clin Nucl Med ; 39(7): 653-4, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24686213

RESUMO

Ga NOTA-bisphosphonate is a new bone-seeking PET radiotracer undergoing clinical evaluation. We report a case of a carcinoma breast who underwent Ga NOTA-bisphosphonate PET/CT for detection of skeletal metastasis. In addition to skeletal metastasis, a focal area of abnormal radiotracer uptake was noted in the brain, which was confirmed as brain metastasis on MRI.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Complexos de Coordenação , Difosfonatos , Compostos Heterocíclicos , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adulto , Feminino , Radioisótopos de Gálio , Compostos Heterocíclicos com 1 Anel , Humanos , Imageamento por Ressonância Magnética , Imagem Multimodal
12.
Clin Nucl Med ; 38(3): 188-94, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23412597

RESUMO

OBJECTIVES: The aim of this work was to calculate the radiation absorbed dose to kidneys, liver, spleen, pituitary gland, and neuroendocrine tumors (NETs) of patients treated with (177)Lu-DOTATATE. METHODS: We enrolled 61 patients (male/female patients, 40/21) with mean age of 48.1 ± 15.3 years affected by different types of NETs diagnosed with (68)Ga-DOTANOC PET-CT and biochemical markers. For radiation protection of kidneys, amino acid mixture (lysine and arginine) was coinfused; 3.7 to 7.4 GBq (100-200 mCi) of (177)Lu-DOTATATE was infused to each patient over 30 minutes. Each patient underwent a series of 9 whole-body scans at 30 minutes (prevoid) and 4, 8, 12, 24, 48, 96, 144, and 168 h. The organs included in dosimetric calculation were kidney, liver, spleen, pituitary gland, and NETs. All dosimetric calculations were done using the OLINDA/EXM 1.0 software. RESULTS: Physiological uptake of (177)Lu-DOTATATE was seen in all patients in kidneys, liver, spleen, and pituitary gland. Radiation absorbed doses were calculated: 0.57 ± 0.09 mGy/MBq for kidneys, 0.27 ± 0.05 mGy/MBq for liver, 1.17 ± 0.14 mGy/MBq for spleen, 0.058 ± 0.011 mGy/MBq for pituitary gland, and 3.41 ± 0.68 mGy/MBq for NETs. CONCLUSIONS: The maximum cumulative activity of (177)Lu-DOTATATE that can be safely administered to a patient within permissible renal threshold in our study was found to be 40 GBq (1100 mCi). However, there are considerable interpatient differences in absorbed doses of all organs requiring individualized dosimetry for optimizing tumor dose.


Assuntos
Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/efeitos adversos , Compostos Organometálicos/uso terapêutico , Órgãos em Risco/efeitos da radiação , Feminino , Humanos , Rim/efeitos da radiação , Fígado/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Octreotida/efeitos adversos , Octreotida/uso terapêutico , Hipófise/efeitos da radiação , Radiometria , Baço/efeitos da radiação
13.
J Laryngol Otol ; 125(6): 576-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21457592

RESUMO

OBJECTIVE: To review outcomes following implantation of an 8.5 mm bone-anchored hearing aid abutment, as regards post-operative management of scalp soft tissue overgrowth. STUDY DESIGN: Retrospective chart review of paediatric and adult patients implanted with bone-anchored hearing aids between 2003 and 2008 who subsequently underwent revision surgery for excessive soft tissue growth. SETTING: A tertiary referral centre and a private otology and neurotology clinic. SUBJECTS: A total of 80 patients underwent bone-anchored hearing aid placement between 2003 and 2008. Of these patients, 14 had significant scalp soft tissue overgrowth unresponsive to first-line, nonsurgical local wound care. RESULTS: Fourteen patients underwent an average of 2.1 surgical procedures each for soft tissue overgrowth around their bone-anchored hearing aid abutment. The mean time between initial implantation and revision surgery was 13.6 months. Of these 14 patients, 11 were eventually fitted with an 8.5 mm abutment. Following placement of the longer abutment, only one patient required additional surgical reduction of soft tissue overgrowth (mean follow-up time 11.8 months). All patients were able to use their bone-anchored hearing aid. CONCLUSION: The 8.5 mm bone-anchored hearing aid abutment is successful in preventing the need for additional surgical intervention in the small but significant number of patients with post-implantation soft tissue overgrowth. Early consideration should be given to this option when first-line soft tissue care is inadequate.


Assuntos
Auxiliares de Audição/efeitos adversos , Desenho de Prótese , Implantação de Prótese/métodos , Couro Cabeludo , Dermatopatias/etiologia , Âncoras de Sutura , Adolescente , Adulto , Criança , Cicatriz Hipertrófica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Reoperação , Estudos Retrospectivos , Fatores de Risco , Dermatopatias/cirurgia , Transplante de Pele/métodos , Fatores de Tempo , Resultado do Tratamento , Cicatrização/fisiologia , Adulto Jovem
14.
Food Chem Toxicol ; 48(4): 1013-8, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20079795

RESUMO

UNLABELLED: This study investigated the protective effect of the hydro-alcoholic extract of roots of Rubia cordifolia Linn. (HARC) against ethylene glycol induced urolithiasis and its possible underlying mechanisms using male Wistar albino rats. Ethylene glycol feeding resulted in hyperoxaluria, hypocalciuria as well as increased renal excretion of phosphate. Supplementation with HARC significantly prevented change in urinary calcium, oxalate and phosphate excretion dose-dependently. The increased calcium and oxalate levels and number of calcium oxalate crystals deposits in the kidney tissue of calculogenic rats were significantly reverted by HARC treatment. The HARC supplementation also prevents the impairment of renal functions. RESULTS: Indicate that the HARC can protect against ethylene glycol induced urolithiasis as it reduced and prevented the growth of urinary stones. Therefore, HARC is helpful to prevent the recurrence of the disease as it showed its effect on early stages of stone development. The mechanism underlying this effect is mediated possibly through an antioxidant, nephroprotection and its effect on the urinary concentration of stone-forming constituents and risk factors.


Assuntos
Antioxidantes/farmacologia , Etilenoglicol/toxicidade , Extratos Vegetais/farmacologia , Rubia/química , Urolitíase/prevenção & controle , Animais , Cálcio/urina , Modelos Animais de Doenças , Etanol/química , Hiperoxalúria/induzido quimicamente , Hiperoxalúria/prevenção & controle , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Oxalatos/metabolismo , Raízes de Plantas/química , Ratos , Ratos Wistar , Urinálise , Micção/efeitos dos fármacos , Urolitíase/induzido quimicamente , Urolitíase/patologia , Água/química
16.
Rapid Commun Mass Spectrom ; 23(18): 2965-74, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19681066

RESUMO

A new class of diastereomeric pairs of non-natural amino acid peptides derived from butyloxycarbonyl (Boc-)protected cis-(2S,3R)- and trans-(2S,3S)-beta-norbornene amino acids including a monomeric pair have been investigated by electrospray ionization (ESI) tandem mass spectrometry using quadrupole time-of-flight (Q-TOF) and ion-trap mass spectrometers. The protonated cis-BocN-beta-nbaa (2S,3R) (1) (betanbaa = beta-norbornene amino acid) eliminates the Boc group to form [M+H-Boc+H](+), whereas an additional ion [M+H-C(4)H(8)](+) is formed from trans-BocN-beta-nbaa (2S,3S) (2). Similarly, it is observed that the peptide diastereomers (di-, tri- and tetra-), with cis-BocN-beta-nbaa (2S,3R)- at the N-terminus, initially eliminate the Boc group to form [M+H-Boc+H](+) which undergo further fragmentation to give a set of product ions that are different for the peptides with trans-BocN-beta-nbaa (2S,3S)- at the N-terminus. Thus the Boc group fragments differently depending on the configuration of the amino acid present at the N-terminus. It is also observed that the peptide bond cleavage in these peptides is less favoured and most of the product ions are formed due to retro-Diels-Alder fragmentation. Interestingly, sodium-cationized peptide diastereomers mainly yield a series of retro-Diels-Alder fragment ions which are different for each diastereomer as they are formed starting from [M+Na-Boc+H](+) in peptides with cis-BocN-beta-nbaa (2S,3R)- at the N-terminus, and [M+Na-C(4)H(8)](+) in peptides with trans-BocN-beta-nbaa (2S,3S)- at the N-terminus. All these results clearly indicate that these diastereomeric pairs of peptides yield characteristic product ions which help distinguish the isomers.


Assuntos
Aminoácidos/química , Peptídeos/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Estereoisomerismo
17.
Bioorg Med Chem Lett ; 16(16): 4391-4, 2006 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-16793266

RESUMO

Nimbolide (1), a limonoid isolated from Azadirachta indica, is the chief cytotoxic principle in Neem leaves extract. Using nimbolide as a lead compound for anti-cancer analogue design, a series of nimbolide derivatives have been synthesized and evaluated for in vitro cytotoxic activity against a panel of human cancer cell lines. Out of 10 compounds screened 2g, 2h and 2i showed potent activity.


Assuntos
Amidas/química , Antineoplásicos/farmacologia , Limoninas/química , Azadirachta/metabolismo , Linhagem Celular Tumoral , Química Farmacêutica/métodos , Desenho de Fármacos , Humanos , Concentração Inibidora 50 , Modelos Químicos , Extratos Vegetais/metabolismo , Folhas de Planta , Plantas Medicinais/metabolismo
18.
Mol Carcinog ; 45(5): 320-32, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16526022

RESUMO

Curcumin (diferuloyl methane), the major yellow pigment from the rhizomes of turmeric (Curcuma longa Linn), has anticancer properties. Infection with high-risk human papillomaviruses (HPV) leads to development of cervical carcinoma, predominantly through the action of viral oncoproteins E6 and E7. The present study aims at analyzing the antitumor and antiviral properties of curcumin, on HPV associated cervical cancer cells. Our findings indicate curcumin to be cytotoxic to cervical cancer cells in a concentration-dependent and time-dependent manner. The cytotoxic activity was selectively more in HPV16 and HPV18 infected cells compared to non-HPV infected cells. Balance between tumor cell proliferation and spontaneous cell death via apoptosis had an important role in regulation of tumor cell growth. Curcumin-induced apoptosis in cervical cancer cells. Morphological hallmarks of apoptosis such as nuclear fragmentation and internucleosomal fragmentation of DNA were observed. Curcumin also selectively inhibited expression of viral oncogenes E6 and E7, evident from RT-PCR and Western blotting data. Electrophoretic mobility shift assay revealed that activation of NFkappaB-induced by TNFalpha is down regulated by curcumin. Curcumin blocked IkBalpha phosphorylation and degradation, leading to abrogation of NFkappaB activation. Curcumin also down regulated the expression of COX-2, a gene regulated by NFkappaB. Binding of AP-1, an indispensable component for efficient epithelial tissue-specific gene expression of HPV was also selectively down regulated by curcumin. These results provide attractive data for the possible use of curcumin in the management of HPV associated tumors.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Curcumina/farmacologia , NF-kappa B/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Infecções por Papillomavirus/tratamento farmacológico , Fator de Transcrição AP-1/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Western Blotting , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2 , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação para Baixo , Ensaio de Desvio de Mobilidade Eletroforética , Fator de Crescimento Epidérmico/farmacologia , Feminino , Humanos , NF-kappa B/genética , Proteínas Oncogênicas Virais/antagonistas & inibidores , Proteínas Oncogênicas Virais/genética , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/genética , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Transporte Proteico , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição AP-1/genética , Fator de Necrose Tumoral alfa/farmacologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia
19.
Bioorg Med Chem Lett ; 14(14): 3687-9, 2004 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-15203144

RESUMO

A straight forward entry into nine membered B ring of eleutherobin as oxy analog and its cyctotoxic properties on HBL cell lines is described. Molecular modeling studies were carried out to ascertain the binding of the model compound to the active site of beta-tubulin.


Assuntos
Antineoplásicos/síntese química , Diterpenos/síntese química , Desenho de Fármacos , Antineoplásicos/farmacologia , Sítios de Ligação , Diterpenos/farmacologia , Feminino , Humanos , Conformação Molecular , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Células Tumorais Cultivadas
20.
Helicobacter ; 9(2): 124-9, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15068413

RESUMO

BACKGROUND: Studies on eradication therapy in developing countries have shown a success rate of 70-85%, which is suboptimal. Duration of therapy may be an important factor dictating eradication success in such regions. AIMS: The study was undertaken to evaluate the effect of increasing the treatment period on eradication of Helicobacter pylori in duodenal ulcer disease. METHODS: A randomized trial was carried out in which 64 consecutive H. pylori-infected patients with duodenal ulcer disease were enrolled. The patients were randomized to one of the three trial arms. Therapy consisted of lansoprazole 30 mg twice a day (b.i.d.), amoxycillin 1 g b.i.d. and tinidazole 500 mg b.i.d. The treatment period was 1 week in group I, 2 weeks in group II and 3 weeks in group III. At inclusion, patients underwent endoscopy and the presence of H. pylori was documented by a positive urease test and C14 urea breath test. Four weeks after completion of eradication therapy, the patients were subjected to repeat endoscopy to assess ulcer healing and tests for H. pylori infection. RESULTS: Sixty-four patients (55 male and nine female; mean age 35.5 years) were enrolled in each group. The H. pylori eradication rate for group I (1 week of therapy) was 47.6%, that for group II (2 weeks of therapy) was 80%, and that for group III (3 weeks of therapy) was 91.3% (p =.003). The ulcer healing rates were 71.4, 80 and 95.6% in groups I, II and III, respectively (p =.09). CONCLUSIONS: The 3-week regimen significantly improved the eradication rate as compared with the 1-week regime. Increasing the duration of therapy significantly improved the chances of eradication of H. pylori in duodenal ulcer disease.


Assuntos
Antibacterianos/administração & dosagem , Úlcera Duodenal/tratamento farmacológico , Úlcera Duodenal/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Imidazóis/administração & dosagem , Omeprazol/análogos & derivados , 2-Piridinilmetilsulfinilbenzimidazóis , Adolescente , Adulto , Idoso , Amoxicilina/administração & dosagem , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Antiulcerosos/administração & dosagem , Antiulcerosos/uso terapêutico , Testes Respiratórios , Quimioterapia Combinada , Endoscopia Gastrointestinal , Feminino , Infecções por Helicobacter/microbiologia , Humanos , Imidazóis/efeitos adversos , Imidazóis/uso terapêutico , Lansoprazol , Masculino , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Omeprazol/efeitos adversos , Omeprazol/uso terapêutico , Projetos Piloto , Estudos Prospectivos , Fatores de Tempo , Tinidazol/administração & dosagem , Tinidazol/efeitos adversos , Tinidazol/uso terapêutico , Ureia/análise
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