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The increase in research funding for the development of antimalarials since 2000 has led to a surge of new chemotypes with potent antimalarial activity. High-throughput screens have delivered several thousand new active compounds in several hundred series, including the 4,7-diphenyl-1,4,5,6,7,8-hexahydroquinolines, hereafter termed dihydropyridines (DHPs). We optimized the DHPs for antimalarial activity. Structure-activity relationship studies focusing on the 2-, 3-, 4-, 6-, and 7-positions of the DHP core led to the identification of compounds potent (EC50 < 10 nM) against all strains of P. falciparum tested, including the drug-resistant parasite strains K1, W2, and TM90-C2B. Evaluation of efficacy of several compounds in vivo identified two compounds that reduced parasitemia by >75 % in mice 6 days post-exposure following a single 50 mg/kg oral dose. Resistance acquisition experiments with a selected dihydropyridine led to the identification of a single mutation conveying resistance in the gene encoding for Plasmodium falciparum multi-drug resistance protein 1 (PfMDR1). The same dihydropyridine possessed transmission blocking activity. The DHPs have the potential for the development of novel antimalarial drug candidates.
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Antimaláricos , Di-Hidropiridinas , Plasmodium falciparum , Antimaláricos/farmacologia , Antimaláricos/química , Antimaláricos/síntese química , Di-Hidropiridinas/farmacologia , Di-Hidropiridinas/química , Di-Hidropiridinas/síntese química , Relação Estrutura-Atividade , Plasmodium falciparum/efeitos dos fármacos , Animais , Camundongos , Estereoisomerismo , Testes de Sensibilidade Parasitária , Estrutura Molecular , Relação Dose-Resposta a Droga , HumanosRESUMO
BACKGROUND: Pulmonary vein stenosis (PVS) is an uncommon but known cause of morbidity and mortality in adults and children and can be managed with percutaneous re-vascularization strategies of pulmonary vein balloon angioplasty (PBA) or pulmonary vein stent implantation (PSI). AIM: To study the safety and efficacy outcomes of PBA vs PSI in all patient categories with PVS. METHODS: We performed a literature search of all studies comparing outcomes of patients evaluated by PBA vs PSI for PVS. We selected all published studies comparing PBA vs PSI for PVS with reported outcomes of restenosis and procedure-related complications in all patient categories. In adults, PVS following atrial fibrillation ablation and in children PVS related to congenital etiology or post-procedural PVS following total or partial anomalous pulmonary venous return repair were included. The patient-centered outcomes were risk of restenosis requiring re-intervention and procedural-related complications. The meta-analysis was performed by computing odds ratios (ORs) using the random effects model based on underlying statistical heterogeneity. RESULTS: Eight observational studies treating 768 severe PVS in 487 patients met our inclusion criteria. The age range of patients was 6 months to 70 years and 67% were males. The primary outcome of the re-stenosis requiring re-intervention occurred in 196 of 325 veins in the PBA group and 111 of 443 veins in the PSI group. Compared to PSI, PBA was associated with a significantly increased risk of re-stenosis (OR 2.91, 95%CI: 1.15-7.37, P = 0.025, I 2 = 79.2%). Secondary outcomes of the procedure-related complications occurred in 7 of 122 patients in the PBA group and 6 of 69 in the PSI group. There were no statistically significant differences in the safety outcomes between the two groups (OR: 0.94, 95%CI: 0.23-3.76, P = 0.929), I 2 = 0.0%). CONCLUSION: Across all patient categories with PVS, PSI is associated with reduced risk of re-intervention and is as safe as PBA and should be considered first-line therapy for PVS.
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With increasing drug resistance in tuberculosis (TB) patient populations, there is an urgent need for new drugs. Ideally, new agents should work through novel targets so that they are unencumbered by preexisting clinical resistance to current treatments. Benzofuran 1 was identified as a potential lead for TB inhibiting a novel target, the thioesterase domain of Pks13. Although, having promising activity against Mycobacterium tuberculosis, its main liability was inhibition of the hERG cardiac ion channel. This article describes the optimization of the series toward a preclinical candidate. Despite improvements in the hERG liability in vitro, when new compounds were assessed in ex vivo cardiotoxicity models, they still induced cardiac irregularities. Further series development was stopped because of concerns around an insufficient safety window. However, the demonstration of in vivo activity for multiple series members further validates Pks13 as an attractive novel target for antitubercular drugs and supports development of alternative chemotypes.
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Antituberculosos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Benzofuranos/farmacologia , Palmitoil-CoA Hidrolase/antagonistas & inibidores , Piperidinas/farmacologia , Policetídeo Sintases/antagonistas & inibidores , Benzofuranos/síntese química , Cardiotoxicidade , Descoberta de Drogas , Canal de Potássio ERG1 , Coração/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Mycobacterium tuberculosis/efeitos dos fármacos , Piperidinas/síntese química , Relação Estrutura-AtividadeRESUMO
PURPOSE: Cardiac power (CP) index is a product of mean arterial pressure (MAP) and cardiac output (CO). In aortic stenosis, however, MAP is not reflective of true left ventricular (LV) afterload. We evaluated the utility of a gradient-adjusted CP (GCP) index in predicting survival after transcatheter aortic valve replacement (TAVR), compared to CP alone. MATERIALS AND METHODS: We included 975 patients who underwent TAVR with 1 year of follow-up. CP was calculated as (CO×MAP)/[451×body surface area (BSA)] (W/m²). GCP was calculated using augmented MAP by adding aortic valve mean gradient (AVMG) to systolic blood pressure (CP1), adding aortic valve maximal instantaneous gradient to systolic blood pressure (CP2), and adding AVMG to MAP (CP3). A multivariate Cox regression analysis was performed adjusting for baseline covariates. Receiver operator curves (ROC) for CP and GCP were calculated to predict survival after TAVR. RESULTS: The mortality rate at 1 year was 16%. The mean age and AVMG of the survivors were 81±9 years and 43±4 mm Hg versus 80±9 years and 42±13 mm Hg in the deceased group. The proportions of female patients were similar in both groups (p=0.7). Both CP and GCP were independently associated with survival at 1 year. The area under ROCs for CP, CP1, CP2, and CP3 were 0.67 [95% confidence interval (CI), 0.62-0.72], 0.65 (95% CI, 0.60-0.70), 0.66 (95% CI, 0.61-0.71), and 0.63 (95% CI 0.58-0.68), respectively. CONCLUSION: GCP did not improve the accuracy of predicting survival post TAVR at 1 year, compared to CP alone.
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Pressão Arterial/fisiologia , Débito Cardíaco/fisiologia , Substituição da Valva Aórtica Transcateter , Idoso de 80 Anos ou mais , Área Sob a Curva , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Curva ROC , Fatores de Risco , Substituição da Valva Aórtica Transcateter/mortalidade , Resultado do TratamentoRESUMO
OBJECTIVE: Cardiac power to left ventricular mass (LVM) ratio, also termed cardiac efficiency (CE), reflects the rate of cardiac work delivered to the potential energy stored in LVM. We sought to assess the association between baseline resting CE and survival post transcatheter aortic valve replacement (TAVR). METHODS: We retrospectively extracted data of patients who received TAVR in the Mayo Clinic Foundation with follow up data available at 1 year. Cardiac output was measured using Doppler echocardiography at baseline. CE was calculated using the formula, (cardiac output × mean arterial blood pressure)/(451 × LVM × 100) W/100 g. Survival score analysis was performed to identify cut off value for CE to identify the maximum difference in mortality in the study cohort. Patients were subsequently divided into 2 groups CE < 0.38 W/100 g and CE ≥ 0.38 W/100 g. Survival was determined using Kaplan-Meier method. RESULTS: We included 954 patients in the final analysis. CE in group1 vs group 2 was 0.31 ± 0.05 W/100 g vs 0.59 ± 0.18 W/100 g. Patients in group1 were more likely to be male, had a higher prevalence of atrial fibrillation, prior myocardial infarction, mitral and tricuspid regurgitation. They also had a higher STS risk score, NYHA functional class, and lower aortic valve area. The remainder of the baseline characteristics was similar in both groups. A lower CE was associated with higher 1-year mortality following TAVR based on multivariate analysis. (Group1: 22.18% vs Group 2: 9.89%, p < .0001). CONCLUSION: In our cohort, a low baseline CE (<0.38 W/100 g) conferred higher mortality risk following TAVR.
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Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Atrial fibrillation (AF) and coronary artery disease (CAD) are commonly associated. Cotreatment with multiple antithrombotic agents can increase the risk of bleeding. We sought to evaluate patient-centered outcomes in patients with AF on double therapy with direct oral anticoagulants (DOACs) compared to patients with standard triple therapy, [a vitamin K antagonist (VKA) plus dual antiplatelet therapy]. METHODS: We performed a literature search of randomized controlled trials (RCTs) reporting outcomes of patients receiving double therapy with DOACs compared to triple therapy with VKAs in patients with AF undergoing percutaneous coronary intervention (PCI). Patient-centered outcomes were the International Society of Thrombosis and Hemostasis (ISTH) major or clinically relevant nonmajor bleeding (CRNB), all-cause mortality, major adverse cardiovascular events (MACE), stent thrombosis, myocardial infarction, and stroke. RESULTS: Four RCTs (9602 patients) met our inclusion criteria. Compared to VKAs, DOACs were associated with significantly lower ISTH major bleeding/ CRNB (RR: 0.75, 95% CI: 0.67-0.82, P < .00001, I 2 = 11%). There were no statistically significant differences in the efficacy outcomes, including myocardial infarction (RR: 0.99, 95% CI :0.79-1.25, P = .96), stent thrombosis (RR: 0.97, 95% CI: 0.6-1.55, P = .89), ischemic stroke (RR: 0.76, 95% CI: 0.5-1.15, P = .19), all-cause mortality (RR: 1.06, 95% CI: 0.85-1.31, P = .61), and MACE (RR: 1.06, 95% CI: 0.91-1.22, P = .97). CONCLUSION: Compared with triple therapy with VKAS, double therapy with DOACs is associated with a reduced risk of bleeding and is as effective in patients with AF undergoing PCI.
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OBJECTIVE: Cardiac power index (CPI) is an integrative hemodynamic measure of cardiac pumping capability and is the product of the simultaneously measured mean arterial pressure and the cardiac output. We assessed the association between baseline resting CPI and survival post transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: We retrospectively abstracted data of patients who underwent TAVR at the Mayo Clinic Foundation with follow-up data available at 1 year. Baseline demographic, clinical, and echocardiographic data were abstracted. CPI was calculated using the formula, (cardiac output x mean arterial blood pressure) / (451 x body surface area) W/m². Patients were divided into CPI <0.48 W/m² (group 1) and CPI ≥0.48 W/m² (group 2). Survival according to CPI was determined using Kaplan-Meier method. Multivariate Cox regression analysis was performed to adjust for covariates. Nine hundred and seventy-five patients were included in the final analysis. CPI in group 1 vs group 2 was 0.41 ± 0.05 W/m² vs 0.66 ± 0.14 W/m², respectively (P<.001, two-sided t-test). Patients in group 1 were more likely to be male and to have a prior history of myocardial infarction, coronary revascularization, peripheral arterial disease, diabetes mellitus, transient ischemic attack, carotid artery disease, atrial fibrillation, lower left ventricular ejection fraction, and moderate to severe mitral and tricuspid regurgitation. After adjusting for baseline covariates, a lower CPI was associated with higher 1-year mortality among patients undergoing TAVR (24.39% in group 1 vs 8.28% in group 2; P<.001). CONCLUSION: Low baseline CPI (<0.48 W/m²) confers higher mortality risk among patients undergoing TAVR and provides additional prognostic information, which can help risk-stratify patients.
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Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/cirurgia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Volume Sistólico , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
Renal denervation (RDN) is a catheter-based ablation procedure designed to treat resistant hypertension (RH). The objective of our study is to determine the effect of RDN on blood pressure and renal function in patients with RH in comparison to medical therapy alone. We performed an extensive literature search for randomized control trials (RCT) reporting office and 24 hr. blood pressure changes and estimated glomerular filtration rate (eGFR) at baseline and 6 months. We calculated a weighted standardized mean difference of blood pressure and renal outcomes between RDN and control groups using random effects models. Our search yielded 608 studies of which we included 15 studies for the final analysis. A total of 857 patients were treated with RDN and 616 patients treated with medical therapy ± sham procedure. Only 5 studies were double-blinded RCT with sham control. The adjusted standardized mean difference in the change in office based systolic and diastolic pressures (p = 0.18; p = 0.14); 24 hr. systolic and diastolic pressures (p = 0.20; p = 0.18); and eGFR (p = 0.20) from baseline to 6 months is statistically insignificant with significant heterogeneity. Subgroup analysis showed that among sham controlled trials, 24 hr. systolic blood pressure showed a modest but statistically significant benefit favoring renal denervation in patients with RH. Our meta-analysis of 15 RCTs showed no significant benefit of RDN on blood pressure control in patients with resistant hypertension. Subgroup analysis of sham control studies showed a modest benefit in 24 hr. systolic blood pressure at 6 months with RDN.
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Denervação/métodos , Hipertensão/cirurgia , Rim/inervação , Pressão Sanguínea , Taxa de Filtração Glomerular , Humanos , Rim/fisiologia , Rim/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Widespread resistance to first-line TB drugs is a major problem that will likely only be resolved through the development of new drugs with novel mechanisms of action. We have used structure-guided methods to develop a lead molecule that targets the thioesterase activity of polyketide synthase Pks13, an essential enzyme that forms mycolic acids, required for the cell wall of Mycobacterium tuberculosis. Our lead, TAM16, is a benzofuran class inhibitor of Pks13 with highly potent in vitro bactericidal activity against drug-susceptible and drug-resistant clinical isolates of M. tuberculosis. In multiple mouse models of TB infection, TAM16 showed in vivo efficacy equal to the first-line TB drug isoniazid, both as a monotherapy and in combination therapy with rifampicin. TAM16 has excellent pharmacological and safety profiles, and the frequency of resistance for TAM16 is â¼100-fold lower than INH, suggesting that it can be developed as a new antitubercular aimed at the acute infection. PAPERCLIP.
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Antituberculosos/farmacologia , Benzofuranos/farmacologia , Desenho de Fármacos , Farmacorresistência Bacteriana , Mycobacterium tuberculosis/efeitos dos fármacos , Piperidinas/farmacologia , Tuberculose/microbiologia , Animais , Antituberculosos/química , Benzofuranos/química , Benzofuranos/farmacocinética , Linhagem Celular , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Piperidinas/química , Piperidinas/farmacocinética , Organismos Livres de Patógenos EspecíficosRESUMO
Orphan drugs (ODs) are intended for the diagnosis, prevention, or treatment of rare diseases. Many cancer subtypes, including all childhood cancers, are defined as rare diseases, and over one-third of ODs are now intended to treat oncology indications. However, market access for oncology ODs is becoming increasingly challenging; ODs are prone to significant uncertainty around their cost-effectiveness, while payers must balance the need for these vital innovations with growing sensitivity to rising costs. The objective of this review was to evaluate different mechanisms that have been introduced to facilitate patient access to oncology ODs in five different countries (Australia, Canada, England, France, and Sweden), using eight oncology ODs and non-orphan oncology drugs as examples of their application. A targeted literature review of health technology assessment (HTA) agency websites was undertaken to identify country-specific guidance and HTA documentation for recently evaluated oncology ODs and non-orphan oncology drugs. None of these countries were found to have explicit HTA criteria for the assessment of ODs, and therefore, oncology ODs are assessed through the usual HTA process. However, distinct and additional processes are adopted to facilitate access to oncology ODs. Review of eight case-study drugs showed that these additional assessment processes were rarely used, and decisions were largely driven by proving cost-effectiveness using standard incremental cost-effectiveness ratio (ICER) thresholds. The predominant implication arising from this study is that application of standard HTA criteria to oncology ODs in many countries fails to take into account any uncertainties around their clinical- and cost-effectiveness, resulting in disparities in HTA reimbursement decisions based on differences in addressing or accepting uncertainty. In order to address this issue, HTA agencies should adopt a more flexible approach to cost-effectiveness, as typified by the Tandvårds-och Läkemedelsförmånsverket in Sweden, which takes into account the small patient numbers involved, limited budget impact, and high unmet medical needs.
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Phenotypic whole-cell screening in erythrocytic cocultures of Plasmodium falciparum identified a series of dihydroisoquinolones that possessed potent antimalarial activity against multiple resistant strains of P. falciparum in vitro and show no cytotoxicity to mammalian cells. Systematic structure-activity studies revealed relationships between potency and modifications at N-2, C-3, and C-4. Careful structure-property relationship studies, coupled with studies of metabolism, addressed the poor aqueous solubility and metabolic vulnerability, as well as potential toxicological effects, inherent in the more potent primary screening hits such as 10b. Analogues 13h and 13i, with structural modifications at each site, were shown to possess excellent antimalarial activity in vivo. The (+)-(3S,4S) enantiomer of 13i and similar analogues were identified as the more potent. On the basis of these studies, we have selected (+)-13i for further study as a preclinical candidate.
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Anilidas/química , Antimaláricos/química , Isoquinolinas/química , Plasmodium falciparum/efeitos dos fármacos , Anilidas/síntese química , Anilidas/farmacologia , Anilidas/toxicidade , Animais , Antimaláricos/síntese química , Antimaláricos/farmacologia , Antimaláricos/toxicidade , Técnicas de Cocultura , Eritrócitos/citologia , Eritrócitos/parasitologia , Humanos , Isoquinolinas/síntese química , Isoquinolinas/farmacologia , Isoquinolinas/toxicidade , Camundongos , Microssomos Hepáticos/metabolismo , Plasmodium falciparum/fisiologia , Solubilidade , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
We present an interesting method of shaping a vascularized medial femoral condyle (MFC) flap into a "neophalanx" for phalangeal reconstruction. Our patient presented with limited strength and function secondary to fracture nonunion of the proximal phalanx of the dominant thumb. Following excision of the pseudarthrosis, an MFC corticoperiosteal flap was harvested, sculpted into a prism shape and inset. The superomedial genicular pedicle was anastomosed to the princeps pollicis artery and a cephalic tributary. On follow-up, new bone growth was seen on radiographs and the patient had substantially improved function, with full metacarpophalangeal extension, a Kapandji score of 9, and a markedly reduced Disabilities of the Arm, Shoulder and Hand score of 2.68. The MFC flap is useful for reconstruction of bony defects, with minimal donor morbidity. This versatile vascularized flap can be crafted to requisite shapes and is useful for small defects in the hand, including phalangeal reconstruction.
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Homophthalic anhydride (HPA) dimerizes under the influence of base to provide, sequentially, the (3-4')-C-acyl dimer, a pair of chiral diastereomeric bis(lactones), 3-(2-carboxybenzyl)isocoumarin-4-carboxylic acid, and finally, 3-(2-carboxybenzyl)isocoumarin. The structures of the bis(lactones) were misassigned in 1970 based on the (presumed) cis thermal decarboxylative elimination reaction of the lower melting one. The preferred pathway should be trans-anti, however, and crystallographic analysis of one of the bis(lactones) reverses the earlier assignment. The formal cycloaddition reaction of HPA with imines occurs in preference to HPA dimerization; the mechanistic implications of this reactivity difference are discussed.
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BACKGROUND: Crohn's disease (CD) is associated with a substantial healthcare burden that affects the patient, healthcare systems and society in general. AIM: To provide a systematic evaluation of published data relating to the economic and health-related quality-of-life (HRQoL) burden of CD in selected European countries (Germany, France, UK, Italy, Spain) and the USA since 2000. METHODS: We undertook a systematic review of publications relating to CD, its economic burden and impact on HRQoL. Research questions focused on the disease costs from a societal perspective and HRQoL burden in adults and pediatric/adolescent patients according to disease stage/severity. Total, direct and indirect costs were identified, as well as the impact of CD on HRQoL measured using both generic and disease-specific instruments. RESULTS: Overall, 61 publications met the research criteria (38 on costs, 23 on HRQoL). CD in the USA and Europe together was associated with annual total costs of nearly
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Efeitos Psicossociais da Doença , Doença de Crohn/economia , Doença de Crohn/psicologia , Custos de Cuidados de Saúde , Qualidade de Vida , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Doença de Crohn/epidemiologia , Doença de Crohn/terapia , Progressão da Doença , Europa (Continente)/epidemiologia , Gastos em Saúde , Humanos , Lactente , Recém-Nascido , Modelos Econômicos , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Drug discovery for malaria has been transformed in the last 5 years by the discovery of many new lead compounds identified by phenotypic screening. The process of developing these compounds as drug leads and studying the cellular responses they induce is revealing new targets that regulate key processes in the Plasmodium parasites that cause malaria. We disclose herein that the clinical candidate (+)-SJ733 acts upon one of these targets, ATP4. ATP4 is thought to be a cation-transporting ATPase responsible for maintaining low intracellular Na(+) levels in the parasite. Treatment of parasitized erythrocytes with (+)-SJ733 in vitro caused a rapid perturbation of Na(+) homeostasis in the parasite. This perturbation was followed by profound physical changes in the infected cells, including increased membrane rigidity and externalization of phosphatidylserine, consistent with eryptosis (erythrocyte suicide) or senescence. These changes are proposed to underpin the rapid (+)-SJ733-induced clearance of parasites seen in vivo. Plasmodium falciparum ATPase 4 (pfatp4) mutations that confer resistance to (+)-SJ733 carry a high fitness cost. The speed with which (+)-SJ733 kills parasites and the high fitness cost associated with resistance-conferring mutations appear to slow and suppress the selection of highly drug-resistant mutants in vivo. Together, our data suggest that inhibitors of PfATP4 have highly attractive features for fast-acting antimalarials to be used in the global eradication campaign.
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Antimaláricos/farmacologia , ATPases Transportadoras de Cálcio/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Isoquinolinas/farmacologia , Malária/tratamento farmacológico , Modelos Moleculares , Plasmodium/efeitos dos fármacos , Antimaláricos/farmacocinética , ATPases Transportadoras de Cálcio/genética , Senescência Celular/efeitos dos fármacos , Descoberta de Drogas , Resistência a Medicamentos/genética , Eritrócitos/efeitos dos fármacos , Citometria de Fluxo , Compostos Heterocíclicos de 4 ou mais Anéis/farmacocinética , Ensaios de Triagem em Larga Escala , Isoquinolinas/farmacocinética , Estrutura MolecularRESUMO
The addition of N-methylimidazole (NMI) to the reaction of homophthalic anhydride with imines such as pyridine-3-carboxaldehyde-N-trifluoroethylimine (9) reduces the amount of elimination byproduct and improves the yield of the formal cycloadduct, tetrahydroisoquinolonic carboxylate 10. Carboxanilides of such compounds are of interest as potential antimalarial agents. A mechanism that rationalizes the role of NMI is proposed, and a gram-scale procedure for the synthesis and resolution of 10 is also described.
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Aldeídos/química , Ácidos Carboxílicos/química , Imidazóis/química , Iminas/química , Isoquinolinas/química , Isoquinolinas/síntese química , Anidridos Ftálicos/química , Piridinas/química , Estrutura MolecularRESUMO
Preoperative perforator marking for deep inferior epigastric artery perforator flaps is vital to the success of the procedure in breast reconstruction. Advances in imaging have facilitated accurate identification and preselection of potentially useful perforators. However, the reported imaging accuracy may be lost when preoperatively marking the patient, due to 'mapping errors', as this relies on the use of 2 reported vectors from a landmark such as the umbilicus. Observation errors have been encountered where inaccurate perforator vector measurements have been reported in relation to the umbilicus. Transcription errors have been noted where confusing and wordy reports have been typed or where incorrect units have been given (millimetres vs. centimetres). Interpretation errors have also occurred when using the report for preoperative marking. Furthermore, the marking process may be unnecessarily time-consuming. We describe a bespoke template, created using an individual computed tomography angiography image, that increases the efficiency and accuracy of preoperative marking. The template is created to scale, is individually tailored to the patient, and is particularly useful in cases where multiple potential suitable perforators exist.
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Lymph leaks after vascular groin dissections can be a challenging postoperative complication for both patient and surgeon. A multidisciplinary team at a district general hospital in the United Kingdom consisting of breast, plastic, and vascular surgeons performed intraoperative lymphatic mapping using patent blue V dye to locate the exact location of a groin lymph leak before sealing the leak with direct vision ligation and Floseal Hemostatic Matrix (Baxter Healthcare Corp., Hayward, CA).