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1.
J Org Chem ; 89(14): 9783-9788, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38989836

RESUMO

A one-pot, sequential phosphate tether-mediated method for the synthesis of simplified 2-desmethyl sanctolide A analogs is reported. Western side-chain diversification was achieved using a pot-efficient, sequential cross metathesis (CM)/ring-closing metathesis (RCM)/H2/dephosphorylation procedure. Further diversification was achieved by Me3Al-mediated amide formation, Yamaguchi esterification, and RCM macrocyclization to access five C11/C12 Z-configured, 2-des-methyl sanctolide A analogs with improved stability.

2.
J Surg Res ; 260: 155-162, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33340869

RESUMO

BACKGROUND: Burn progression is a phenomenon that remains poorly characterized. The mechanisms of burn conversion are not completely understood, and consequently, both predictive diagnostic tools and interventions are limited. The rat comb burn model is a commonly used approach to study horizontal burn conversion. However, there is significant variability in how the model is performed. Skin contact duration, comb device heating method, comb heating duration, amount of pressure applied, the weight of the comb, and associated depth of burn are all variables that are heterogeneous in studies utilizing the model. MATERIALS AND METHODS: Here, contact duration was examined to determine the impact the duration of burn delivery has on the conversion of interspaces in this model. Data from multiple experiments consisting of 10, 15, 20, 30, 40, and 45 s comb burns were compiled and assessed. Burns were made using combs heated in a 100°C dry bath and then monitored for 2 d. Interspace viability was assessed by digital and laser doppler imaging and biopsy procurement. RESULTS: Laser Doppler Imaging and viable interspace measurements showed that as burn duration increased, the percentage of the viable interspace and interspace perfusion decreased. Additionally, a contact time of 30 s or greater was required to result in 100% interspace conversion. CONCLUSIONS: These results demonstrate a need to better characterize and potentially standardize the rat comb burn model to reduce variation and maintain it as a valuable tool for controlled studies of the pathophysiology of burn wound progression.


Assuntos
Queimaduras/patologia , Modelos Animais , Ratos Sprague-Dawley/lesões , Pele/patologia , Animais , Queimaduras/diagnóstico por imagem , Queimaduras/etiologia , Queimaduras/fisiopatologia , Fluxometria por Laser-Doppler , Masculino , Ratos , Pele/diagnóstico por imagem , Pele/fisiopatologia , Fatores de Tempo , Cicatrização/fisiologia
3.
Lasers Med Sci ; 36(3): 521-528, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32494979

RESUMO

Transurethral endoscopic incision is an established treatment option for management of obstructing ureterocele. It can be performed using monopolar electrocautery or holmium laser as an energy source. The present study was carried out to evaluate outcomes of transurethral ureterocele incision (TUI) by two different energy sources, i.e., monopolar electrocautery versus holmium laser. A retrospective review of the data of all patients who underwent endoscopic TUI from 2007-2017 was performed. Preoperative clinical, biochemical, and radiological characteristics and operative parameters were reviewed and compared between the two groups. Associated stone in the ureterocele was fragmented using pneumatic lithotripter or Mauermeyer stone punch forceps in the electrocautery group and holmium laser in the laser group. Statistical analysis was performed using IBM SPSS version 21.0. Chi-squared test was used for categorical/dichotomous variables. Unpaired t test was used for continuous variables. Out of total 44 patients, 28 patients had duplex system ureterocele and 16 patients had single system ureterocele. Mean age was 18.5 + 7.4 years (range 14-26 years). Six patients had associated stones in the ureterocele. Most common presentation was flank pain followed by urinary infections and bladder outlet obstruction. Preoperative vesico-ureteric reflux was seen in 18% patients. Monopolar TUI was performed in 20 patients and laser-TUI in 24 patients. Three patients had associated stone in ureterocele in each group. Fragmentation of stone was successfully done with holmium laser without changing the instrument and with less associated surgical morbidity in the laser group. Postoperative successful decompression was evident in 38 (90%) patients. Renal parenchyma thickness was improved on ultrasound scan and renal scan showed non-obstructed system in all patients at follow-up. Both laser and monopolar incision have similar efficacy in decompressing the ureterocele in long-term follow-up. However, laser has added advantage of stone lithotripsy with the same instruments with lesser morbidity and lower incidence of persistent reflux.


Assuntos
Eletrocoagulação , Lasers de Estado Sólido/uso terapêutico , Atenção Terciária à Saúde , Ureterocele/cirurgia , Uretra/cirurgia , Adolescente , Adulto , Eletrocoagulação/efeitos adversos , Feminino , Humanos , Injeções Intravenosas , Rim/diagnóstico por imagem , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia/efeitos adversos , Ureter/diagnóstico por imagem , Ureterocele/complicações , Ureterocele/diagnóstico por imagem , Bexiga Urinária/diagnóstico por imagem , Urografia , Adulto Jovem
4.
Int Braz J Urol ; 46(3): 363-373, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32167698

RESUMO

INTRODUCTION: Use of androgen deprivation therapy (ADT) in carcinoma prostate (CaP) has deleterious effect on bone mineral density (BMD) leading to increase incidence of osteoporosis and skeletal-related events. We evaluated bone health status and impact of bone-directed therapy (BDT) and ADT on BMD in these patients from Jan 2015-Dec 2018. MATERIALS AND METHOD: Baseline bone health was assessed using Tc-99 MDP Bone scan/DEXA scan for patients on ADT. Monthly zoledronic acid (ZA) was given to high-risk candidates (T-score ≤2.5 or previous hip/vertebral fracture) or Skel et al. metastatic patients who were receiving ADT. Baseline and follow-up (at 12-months) BMD using DEXA scan at various sites (spine, femur total, femur neck and radius) and subjective improvement in bony pain using Numeric Pain Rating Score after administration of ZA were compared. RESULTS: A total of 96-patients of locally advanced and metastatic prostate cancer receiving ADT with or without BDT were included in the study cohort. Mean age of presentation was 68.4±15.61 years. Median serum PSA was 32.2±13.1ng/mL. There was significant improvement in mean BMD (T-score) in 64-patients post ZA therapy at 12-months (at femoral total, femoral neck and spine; 0.95, 0.79 and 0.68, respectively) (p < 0.05) while there was significant deterioration in mean BMD at 12-months (at spine, femoral neck and femoral total; -0.77, -0.55 and -0.66, respectively) in 32 patients who did not receive ZA and were on ADT (p < 0.05). Pain scores significantly decreased in patients after 12-months of ZA use (-2.92±2.16, p < 0.01). CONCLUSION: Bone-directed therapy (Zoledronic acid) leads to both subjective and objective improvement in bone health of prostate cancer patients on ADT.


Assuntos
Antagonistas de Androgênios , Densidade Óssea , Neoplasias da Próstata , Idoso , Idoso de 80 Anos ou mais , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada por Raios X
5.
J Contemp Dent Pract ; 20(2): 152-157, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31058628

RESUMO

AIM: Aim of the present study was to evaluate the apical leakage in gutta-percha/AH plus and resilon/epiphany filled root canals using two dye penetration techniques. MATERIALS AND METHODS: Sixty freshly extracted human single-rooted teeth were collected. The crown portion of each tooth was sectioned from the cementoenamel junction using a diamond disk. The canals were instrumented using Step back technique up to a caliber of 40. The roots were randomly divided into four experimental groups of 15 sample units each. All the groups are obturated using lateral compaction technique. Samples were placed in India ink and stored in an incubator for 7 days after which they were thoroughly washed under tap water and dried. The roots were divided into longitudinal splitting technique with diamond disks and using clearing technique was checked for linear dye penetration using stereomicroscope. The surfaces were scanned and surfaces with greatest dye penetration were measured by using De winter Biowizard software system. RESULTS: The mean leakage for groups I, II, III, and IV are 2.31980, 2.68140, 4.11567, and 4.21047 respectively. One-way ANOVA was applied to the mean leakage scores of different groups, found a significant difference between mean leakage scores. F value of 3.266 and it was found to be significant with a p value of 0.028. Significant differences were obtained for mean comparisons of groups I and III, groups I and IV and groups III and IV. Further, between groups I and II, groups II and III, and groups III and IV no significant differences were observed. CONCLUSION: In conclusion, gutta-percha/AH Plus sealed root canals showed lesser leakage than the Resilon Epiphany groups and there was no significant difference in the two different methodologies used for dye penetration. CLINICAL SIGNIFICANCE: Tightly adapted endodontic filling material is one of the goals in successful clinical endodontics and Improvements in the adhesive technology have fostered attempts to reduce apical and coronal leakage by bonding to the root canal walls to obtain a solid monoblock.


Assuntos
Infiltração Dentária , Materiais Restauradores do Canal Radicular , Cavidade Pulpar , Resinas Epóxi , Guta-Percha , Humanos , Obturação do Canal Radicular
6.
J Pharm Technol ; 35(4): 155-163, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34861032

RESUMO

Background: Critical appraisal of published literature for hospital clinicians has never been taken as an initiative in developing countries. Objective: This study was aimed at evaluating the nature of pharmacotherapy consultations from the drug information center (DIC) of the Postgraduate Institute of Medical Education and Research, Chandigarh, India. Methods: The DIC received pharmacotherapy consultation requests from January 2016 to December 2017. Various aspects such as clinical queries, patient-related factors, and disease-related information in these requests were recorded and analyzed. Descriptive statistics and χ2 test were used for the analysis of the data and feedback evaluation, respectively. Results: During the study, a total of 179 consultation requests were documented. On 19 (10.61%) encounters, pharmacotherapy consultations occurred for emergency patient care. Of the 179 queries, 31 (17.3%) were answered immediately while 148 (82.68%) were answered within an average time of 1.6 hours. The most common type of query was the pharmacotherapy of disease, followed by dose calculation and dose modification. Communications with DIC staff took place for timely critical appraisal of the medical literature, followed by a judicious selection of higher antimicrobials and other drugs. The time taken for answering a query was found to be a statistically significant determinant of user satisfaction (P < .05). Conclusion: The evidence level-specific drug information service was established and catered to hospital clinicians through critical evaluation of offline and online resources. DIC services have the potential to revolutionize the pharmacy and pharmacology curriculum in developing countries.

7.
Indian J Urol ; 35(3): 237-239, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367079

RESUMO

Prostatic extra-gastrointestinal stromal tumors (E-GIST) are rare mesenchymal tumors with only 9-cases reported in the English literature so far. We herein describe a case of E-GIST causing massive enlargement of the prostate gland. A 55-year-old male was diagnosed with localized prostatic E-GIST causing massive prostatomegaly (1230 cc) during workup for lower urinary tract symptoms (LUTS). The patient was managed with Imatinib mesylate therapy as high anesthetic risks precluded surgery. Given the rarity, E-GISTs should be included in the differential diagnosis of patients presenting with LUTS as it may influence the treatment decisions.

8.
Indian J Palliat Care ; 25(1): 53-56, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30820102

RESUMO

OBJECTIVE: To evaluate the role of percutaneous nephrostomy (PCN) in patients of carcinoma bladder presenting with obstructive uropathy. MATERIAL AND METHODS: We evaluated medical records of 33 patients of bladder cancer with obstructive uropathy that presented to a tertiary care hospital in north India from January 2015 to December 2016. Outcome measures included technical success rates, change in blood urea and serum creatinine (measured on Day 1, 7, and 14); and complications of PCN according to Society of Interventional Radiology Guidelines for Percutaneous Nephrostomy. RESULTS: PCN was done in 30 patients. The mean age of patients was 51 years (range 42-67). 24 patients were male and 6 patients were female. The technical success rates for PCN placement were 93.33%. In 12 patients there was no improvement after PCN insertion. Improvement in clinical condition/kidney function occurred in 18 patients. Out of these 6 patients underwent radical cystectomy with ileal conduit formation and palliative radiotherapy/chemotherapy was given to 5 cases. In the remaining 7 patients, after an initial improvement that lasted for 2 weeks after PCN progressive renal dysfunction developed due to malignancy. Minor complications of PCN were seen in 16.6% of patients and major complications were seen in 10 % of cases. CONCLUSION: In selected patients with bladder carcinoma with obstructive uropathy, PCN insertion may improve kidney function tests to normal levels and enable them to receive tumor-specific curative/palliative treatment.

9.
Biochim Biophys Acta Proteins Proteom ; 1866(8): 913-923, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29807137

RESUMO

Leishmaniasis, a parasitic protozoan disease, is still a worldwide concern due to persistent issues with chemotherapy, rapid emerging drug resistance; and non- availability of approved vaccine for the control of disease. Therefore, the search of parasite specific proteins to identify new anti-leishmanial drug targets and vaccine candidates is an urgent priority. In this context, proteins that are secreted, in vitro during parasite growth under defined conditions, can be explored as potential tool for studying their roles in parasite survival inside host and disease pathogenesis. From the last few years, various approaches have been exploited to identify the proteins secreted out by the parasites under defined conditions at particular stage or time. Due to availability of genomic information on various Leishmania species, proteomics have been emerged as most promising approach for analyzing the complexity of exoproteome of different Leishmania species. Herein, we have summarized various secretion mechanisms used by Leishmania parasites to export the proteins into the extracellular space; followed by the role of proteomics in exoproteome analysis along with special emphasis on various applications to study the exoproteome, which might provide potential targets for drug design or novel antigens for vaccine development.


Assuntos
Leishmania/metabolismo , Proteoma/metabolismo , Proteínas de Protozoários/metabolismo , Animais , Antígenos de Protozoários/metabolismo , Antiprotozoários/farmacologia , Resistência a Medicamentos , Interações Hospedeiro-Parasita , Humanos , Leishmaniose/tratamento farmacológico , Proteômica
10.
J Clin Psychopharmacol ; 38(1): 47-50, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29200012

RESUMO

BACKGROUND: Although many studies have evaluated prescription patterns, there is lack of information on the choice of antidepressants among patients who do not respond antidepressants. Similarly, information on switching strategies is also limited. This naturalistic study aimed to evaluate the switching strategies and preferred antidepressants by the psychiatrists among patients who do not respond to or who are not able to tolerate an antidepressant. METHODS: A cross-sectional observational study design was followed. Patients diagnosed with affective and anxiety disorders, who were recommended a change in antidepressant, were recruited. Details of antidepressant before switching, antidepressants considered at the time of switching, coprescription advised at the time of switching, reasons considered for switching, and strategy advised at the time of switching were noted down. RESULTS: A total of 102 patients were recruited. The most common change strategy was selective serotonin reuptake inhibitor (SSRI) to a serotonin norepinephrine reuptake inhibitor (SNRI) (N = 42; 41.17%), and this was followed by SSRI to SSRI (N = 18; 17.64%) and SNRI to SSRI (N = 10; 9.8%). In majority of the patients (N = 79; 77.45%) cross-taper of older antidepressant with gradual increase in dose of newer antidepressants was followed. About 44.1% of the patients were on adjuvant medications at the time of considering change in antidepressants, and 37.25% of the patients were additionally started on some adjuvant medications during the change of antidepressants. CONCLUSIONS: The present study suggests that the most common strategy followed during change of antidepressant is from SSRI to SNRI and this is followed by SSRI to SSRI and SNRI to SSRI. Cross-taper switching strategy along with the use of adjuvant medications like benzodiazepines during the process of switching is most commonly followed.


Assuntos
Antidepressivos/administração & dosagem , Transtornos de Ansiedade/tratamento farmacológico , Benzodiazepinas/administração & dosagem , Transtornos do Humor/tratamento farmacológico , Adulto , Idoso , Estudos Transversais , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores da Recaptação de Serotonina e Norepinefrina/administração & dosagem , Centros de Atenção Terciária , Adulto Jovem
11.
Cardiol Young ; 28(3): 494-497, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29233212

RESUMO

Percutaneous closure of patent ductus arteriosus is well established in infants weighing >5 kg, but data regarding outcome of preterm especially very low birth weight infants is minimal. Although surgical ligation of patent ductus arteriosus is the preferred and well-accepted modality of treatment after failure of drug therapy in preterm infants, it has also got its own demerits in such a small and fragile subset. Device closure in infants weighing <1.5 kg is rarely attempted because of high chances of complications, especially acute arterial injury due to the arterial sheath. We received a 1.4-kg ventilator-dependent infant for closure of large patent ductus arteriosus. Percutaneous closure of patent ductus arteriosus was done successfully and the infant was discharged on room air with a weight of 1.8 kg. We present here an innovative technique in which successful patent ductus arteriosus device closure was done in a 1.4-kg infant without using arterial sheath.


Assuntos
Cateterismo Cardíaco/métodos , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/terapia , Dispositivo para Oclusão Septal , Cateterismo Cardíaco/instrumentação , Ecocardiografia Doppler em Cores , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Masculino , Resultado do Tratamento
12.
J Contemp Dent Pract ; 19(12): 1463-1468, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30713174

RESUMO

AIM: This study aimed to evaluate the efficacy of Intracanal calcium hydroxide removal with different techniques. MATERIALS AND METHODS: Seventy-five freshly extracted, non-carious, single canalled lower first premolars, having anatomic characteristics similar to each other, extracted for the orthodontic purpose were collected. After the root canal preparation, Calcium hydroxide was placed into the working length using lentulo spiral instrument till the medicament was visible at the apex. The specimens were segregated into three groups; Group 1: Rotary Files, Group 2: EndoVac system and Group 3: Ultrasonics. The evaluation was done with SEM in the coronal and apical third of the roots with a magnification of 1000x. The statistical analysis was done using statistical packages for social sciences (SPSS) software, version 20.0 for Windows (SPSS Inc., Chicago, IL). A p-value of less than 0.05 was considered significant statistically. RESULTS: Maximum removal of Ca(OH)2 was analyzed in the EndoVac system (2.90 ± 0.12) followed by the rotary files (1.76 ± 0.26) and least was seen with Ultrasonics (1.32 ± 0.14). The p-value of 0.001 was seen between the coronal and apical third with the EndoVac system which is statistically significant. The significant difference statistically was observed between Rotary Files vs. Ultrasonics at apical third and with the EndoVac system vs. Ultrasonics at coronal third as well as at the apical third with p-value 0.001. CONCLUSION: It can be concluded that the EndoVac technique was effective in removing Ca(OH)2 medicament from the coronal and apical third of the root canal significantly. CLINICAL SIGNIFICANCE: Calcium hydroxide removal before the obturation was of priority as the Ca(OH)2 remnants have a negative impact of the ability for sealing the obturation material. Therefore, having a complete knowledge regarding the effective technique is much important.


Assuntos
Hidróxido de Cálcio , Cavidade Pulpar/ultraestrutura , Microscopia Eletroquímica de Varredura , Irrigantes do Canal Radicular , Preparo de Canal Radicular/métodos , Humanos , Preparo de Canal Radicular/instrumentação , Irrigação Terapêutica/métodos , Ultrassom/instrumentação , Ultrassom/métodos
13.
J Infect Dis ; 216(suppl_1): S24-S32, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28838189

RESUMO

The requirements under objective 2 of the Polio Eradication and Endgame Strategic Plan 2013-2018-to introduce at least 1 dose of inactivated poliomyelitis vaccine (IPV); withdraw oral poliomyelitis vaccine (OPV), starting with the type 2 component; and strengthen routine immunization programs-set an ambitious series of targets for countries. Effective implementation of IPV introduction and the switch from trivalent OPV (containing types 1, 2, and 3 poliovirus) to bivalent OPV (containing types 1 and 3 poliovirus) called for intense global communications and coordination on an unprecedented scale from 2014 to 2016, involving global public health technical agencies and donors, vaccine manufacturers, World Health Organization and United Nations Children's Fund regional offices, and national governments. At the outset, the new program requirements were perceived as challenging to communicate, difficult to understand, unrealistic in terms of timelines, and potentially infeasible for logistical implementation. In this context, a number of core areas of work for communications were established: (1) generating awareness and political commitment via global communications and advocacy; (2) informing national decision-making, planning, and implementation; and (3) in-country program communications and capacity building, to ensure acceptance of IPV and continued uptake of OPV. Central to the communications function in driving progress for objective 2 was its ability to generate a meaningful policy dialogue about polio vaccines and routine immunization at multiple levels. This included efforts to facilitate stakeholder engagement and ownership, strengthen coordination at all levels, and ensure an iterative process of feedback and learning. This article provides an overview of the global efforts and challenges in successfully implementing the communications activities to support objective 2. Lessons from the achievements by countries and partners will likely be drawn upon when all OPVs are completely withdrawn after polio eradication, but also may offer a useful model for other global health initiatives.


Assuntos
Erradicação de Doenças , Programas de Imunização , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio Oral/administração & dosagem , Planejamento em Saúde Comunitária , Tomada de Decisões Gerenciais , Erradicação de Doenças/métodos , Erradicação de Doenças/organização & administração , Saúde Global , Humanos , Programas de Imunização/métodos , Programas de Imunização/organização & administração , Vacina Antipólio de Vírus Inativado/provisão & distribuição , Vacina Antipólio Oral/provisão & distribuição
14.
Chemistry ; 23(65): 16574-16585, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-28940589

RESUMO

Inhibition of the heat shock protein 90 (Hsp90) C-terminus represents a promising therapeutic strategy for the treatment of cancer. Novobiocin, a coumarin antibiotic, was the first Hsp90 C-terminal inhibitor identified, however, it manifested poor anti-proliferative activity (SKBr3, IC50 ≈700 µm). Subsequent structure-activity relationship (SAR) studies on novobiocin led to development of several analogues that exhibited improved anti-proliferative activity against several cancer cell lines. Recent studies demonstrate that the biphenyl core could be used in lieu of the coumarin ring system, which resulted in more efficacious analogues. In continuation of previous efforts, the work described herein has identified the phenyl cyclohexyl core as a novel scaffold for Hsp90 C-terminal inhibition. Structure-activity relationship (SAR) studies on this scaffold led to the development of compounds that manifest mid-nanomolar activity against SKBr3 and MCF-7 breast cancer cell lines through Hsp90 inhibition.


Assuntos
Amidinas/química , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Amidinas/síntese química , Amidinas/toxicidade , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Células MCF-7 , Novobiocina/química , Novobiocina/toxicidade , Domínios Proteicos , Relação Estrutura-Atividade
15.
Bioorg Med Chem ; 25(2): 451-457, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-27914946

RESUMO

Hsp90 is a promising therapeutic target for the development of anti-cancer agents due to its integral role in the stability and function of proteins associated with all ten hallmarks of cancer. Novobiocin, a coumarin antibiotic, was the first natural product identified that targeted the Hsp90 C-terminal domain and manifested anti-proliferative activity (SKBr3 IC50∼700µM). Subsequent structural investigations on novobiocin led to analogues with significantly improved anti-proliferative activity against multiple cancer cell lines. In an effort to develop more efficacious and diverse analogues, it was recently found that the coumarin ring of novobiocin could be replaced with the biphenyl core without compromising activity. Based on these prior studies, a series of alkylamino biphenylamides was designed, synthesized and evaluated for anti-proliferative activity against two breast cancer cell lines. SAR studies demonstrated that the incorporation of an alkylamino side chain onto the biphenyl core improved anti-proliferative activity and resulted in compounds that exhibit sub-micromolar to mid-nanomolar activity through Hsp90 inhibition. Importantly, these studies indicate the presence of a hydrophilic region about the central core that can be exploited for the design of new inhibitors.


Assuntos
Amidas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Desenho de Fármacos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Amidas/síntese química , Amidas/química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
16.
Biomarkers ; 21(5): 436-40, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26999557

RESUMO

Coronary artery disease (CAD) has been increasing alarmingly in India. We had earlier shown that vitamin B12 deficiency is associated with CAD in Indian population. However, only about a quarter of the total vitamin B12 is internalised in the cells by the proteins transcobalamin II. Vitamin B12-bound transcobalamin II (holotranscobalamin, holoTC) is thus referred to as biologically active B12. In this study, we ascertained the levels of holoTC in 501 CAD cases and 1253 healthy controls and for the first time show that holoTC levels are significantly lower (p = 2.57E-4) in CAD (26.81 pmol/l) cases as compared to controls (29.97 pmol/l).


Assuntos
Doença da Artéria Coronariana/etiologia , Transcobalaminas/análise , Vegetarianos , Vitamina B 12/sangue , Povo Asiático , Estudos de Casos e Controles , Doença da Artéria Coronariana/epidemiologia , Humanos , Índia , Prevalência , Vitamina B 12/fisiologia
17.
Bioorg Med Chem ; 24(8): 1771-7, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26988804

RESUMO

In vitro anti-mycobacterial activities of novel 4-amino-5-alkynylpyrimidine-2(1H)-ones were investigated. 4-Amino-5-heptynylpyrimidine-2(1H)-one (3) and 4-amino-5-(2-phenylethynyl)pyrimidine-2(1H)-one (7) displayed potent in vitro activity against Mycobacterium bovis and Mycobacterium tuberculosis. Compounds 3 and 7 were also assessed for their in vivo activity in BALB/c mice infected with M. tuberculosis (H37Ra). Both compounds showed promising in vivo efficacy at a dose of 25 mg/kg for 2 weeks. Importantly, compounds 3 and 7 interacted synergistically with the front-line anti-tuberculosis drug isoniazid in vitro and in vivo. These results suggest that this class of compounds has strong anti-mycobacterial potential.


Assuntos
Antibacterianos/farmacologia , Mycobacterium bovis/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Pirimidinonas/farmacologia , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Administração Oral , Animais , Antibacterianos/administração & dosagem , Antibacterianos/química , Antibacterianos/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pirimidinonas/administração & dosagem , Pirimidinonas/química , Pirimidinonas/uso terapêutico , Relação Estrutura-Atividade
18.
J Orthop Traumatol ; 17(3): 239-47, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26879890

RESUMO

BACKGROUND: Thorough curettage and cement augmentation is the procedure of choice for treating giant cell tumor lesions, particularly those associated with large defects. Its association with pathological fractures has not been studied to a great extent, although a pathological fracture following a giant cell tumor is not a contraindication to treatment by curettage and cementation. We present our experience of bone cementation following intralesional curettage for treatment of giant cell tumors of the long bones of lower limbs with associated pathological fractures. MATERIALS AND METHODS: A total of 38 patients who had undergone a procedure in the weight-bearing long bones of lower limbs were included in the study. The age of the patients ranged from 18-79 years with a mean age of 38.57 years. The average follow-up was 102.42 months (8.5 years) ranging from 60-186 months (5-15.5 years). Results were based on serial radiographs showing consolidation of the lesion along with a subjective clinical examination and Enneking functional evaluation noted in the patient's records. RESULTS: Approximately 76 % of the lesions occurred around the knee. The results were graded as excellent (72 %), good (12.82 %) fair (10.25 %) and poor (5.12 %). Four cases developed a recurrence. Apart from a few documented complications, the lesions showed good consolidation and healed well. CONCLUSION: Giant cell tumors of the long bones of lower limbs with an associated pathological fracture at diagnosis can be managed with thorough curettage and cement augmentation of the bone defect with a satisfactory outcome. LEVEL OF EVIDENCE: Level IV.


Assuntos
Cimentos Ósseos/uso terapêutico , Curetagem , Neoplasias Femorais/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas Espontâneas/cirurgia , Tumor de Células Gigantes do Osso/cirurgia , Tíbia/cirurgia , Adolescente , Adulto , Idoso , Feminino , Neoplasias Femorais/patologia , Seguimentos , Fraturas Espontâneas/patologia , Tumor de Células Gigantes do Osso/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Tíbia/patologia , Resultado do Tratamento
19.
Catheter Cardiovasc Interv ; 84(3): 473-7, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-24753393

RESUMO

Sinus venosus atrial septal defect (SVASD) is located high in the atrial septum where the right superior vena cava (RSVC) enters the right atrium, and is commonly associated with partial anomalous pulmonary venous return of right upper pulmonary vein (RUPV) into RSVC. Transcatheter closure of such defects has not been described in the literature. We have developed an innovative technique to close this defect by transcatheter means. We present here a 35-year old patient with SVASD and anomalous drainage of RUPV in RSVC in whom we closed the defect along with rerouting of RUPV to left atrium (LA) using a 12 mm × 61 mm adventa V12 covered stent in the RSVC with good outcome.


Assuntos
Anormalidades Múltiplas , Cateterismo Cardíaco/métodos , Procedimentos Cirúrgicos Cardíacos/métodos , Comunicação Interatrial/cirurgia , Veias Pulmonares/anormalidades , Malformações Vasculares/diagnóstico , Veia Cava Superior/anormalidades , Adulto , Ecocardiografia Transesofagiana , Feminino , Comunicação Interatrial/diagnóstico , Humanos , Tomografia Computadorizada por Raios X
20.
Catheter Cardiovasc Interv ; 83(7): 1131-4, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24478204

RESUMO

Stenting of patent ductus arteriosus (PDA) is a palliative technique that is evolving as an alternative to shunt surgery. Patients with duct-dependant pulmonary circulation and branch pulmonary artery stenosis are often palliated by shunt surgery with repair of branch pulmonary arteries under cardiopulmonary bypass. We present here an 8-month-old male child with duct-dependant pulmonary circulation with bifurcation stenosis who was palliated successfully by transcatheter means. He had stenosed PDA with tight pulmonary artery bifurcation stenosis and underwent successful "Y" stenting of PDA with simultaneous deployment of two stents. He successfully underwent bidirectional Glenn surgery 8 months after the procedure. Simultaneous stenting of bifurcation stenosis of branch pulmonary arteries with two stents has not been described in the literature.


Assuntos
Arteriopatias Oclusivas/cirurgia , Cateterismo Cardíaco/métodos , Procedimentos Cirúrgicos Cardíacos/métodos , Permeabilidade do Canal Arterial/cirurgia , Artéria Pulmonar/anormalidades , Stents , Anormalidades Múltiplas , Arteriopatias Oclusivas/congênito , Arteriopatias Oclusivas/diagnóstico , Permeabilidade do Canal Arterial/diagnóstico , Ecocardiografia , Humanos , Lactente , Masculino , Artéria Pulmonar/cirurgia
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