RESUMO
Tuberculosis (TB), the world's deadliest bacterial infection, afflicts more human males than females, with a male/female (M/F) ratio of 1.7. Sex disparities in TB prevalence, pathophysiology, and clinical manifestations are widely reported, but the underlying biological mechanisms remain largely undefined. This review assesses epidemiological data on sex disparity in TB, as well as possible underlying hormonal and genetic mechanisms that might differentially modulate innate and adaptive immune responses in males and females, leading to sex differences in disease susceptibility. We consider whether this sex disparity can be extended to the efficacy of vaccines and discuss novel animal models which may offer mechanistic insights. A better understanding of the biological factors underpinning sex-related immune responses in TB may enable sex-specific personalized therapies for TB.
Assuntos
Mycobacterium tuberculosis , Tuberculose , Animais , Suscetibilidade a Doenças , Feminino , Humanos , Imunidade , Masculino , Tuberculose/genéticaRESUMO
Benzoisoquinolones are aryl ring extended isoquinolinone derivatives, which are constituents of alkaloid natural products. This report describes the synthesis of novel benzoisoquinolone amino acid/peptide derivatives from the respective N-aryl amino esters/peptides through Ru-catalyzed C(sp2)-H annulation at room temperature. The N-terminal amide acts as an intrinsic directing group and coordinates with the active Ru(II) catalyst for the C-H bond activation and annulation of the aryl ring to produce benzoisoqunolone derivatives. Importantly, these benzoisoquinolinones exhibit fluorescence (QY â¼35%) in protic polar solvents, possibly due to charge transfer, and exhibit cell internalization to the cell nucleus without any significant cytotoxicity to human cell lines (HEK293T). Hence, our results are exceptional to transform standard amino acids/peptides into fluorescent peptides at room temperature in the late stage, which could be applicable for tracking specific target peptides by fluorescence microscopy.
RESUMO
BACKGROUND: Gestational age significantly influences children's growth and development. Yet, the effect of postterm birth (gestation beyond 42 weeks) on children's growth outcomes remains underexplored. OBJECTIVES: This study aimed to assess the impact of postterm birth on adverse growth outcomes in children using a nationally representative sample from China. METHODS: A retrospective cohort study was conducted in China from 1 April 2018, to 31 December 2019. The final analysis included 141,002 children aged 3-6 years from 551 cities. Postterm birth was defined as children with postterm birth at a gestational age of 42 weeks or more. Obesity, overweight and thinness were assessed using body mass index-for-age (BMI-for-age) z-scores, based on the World Health Organization (WHO) Child Growth Standards. Generalised additive models were employed to investigate the non-linear relationship between maternal gestational age and BMI-for-age z scores. Poisson regression models and subgroup analyses with forest plots were performed to examine the associations between postterm birth and the risks of obesity, overweight and thinness in children. RESULTS: We included 141,002 mother-child pairs, of whom 7314 (5.2%) children were classified as postterm births. There exists a non-linear relationship between gestational age and BMI-for-age z scores. Children born postterm exhibited a 46% increased risk of obesity, a 27% increased risk of combined overweight/obesity and a 13% increased risk of thinness. Similar associations were observed in most cases when further sensitivity and subgroup analysis were conducted. CONCLUSIONS: Postterm birth was associated with elevated risks of obesity, overweight and thinness in children aged 3-6 years, independent of sex. These findings underscore the importance of further research across diverse populations to understand the implications of postterm births on child health outcomes.
RESUMO
The study explores co-gasification of palm oil decanter cake and alum sludge, investigating the correlation between input variables and syngas production. Operating variables, including temperature (700-900 °C), air flow rate (10-30 mL/min), and particle size (0.25-2 mm), were optimized to maximize syngas production using air as the gasification agent in a fixed bed horizontal tube furnace reactor. Response Surface Methodology with the Box-Behnken design was used employed for optimization. Fourier Transformed Infra-Red (FTIR) and Field Emission Scanning Electron Microscopic (FESEM) analyses were used to analyze the char residue. The results showed that temperature and particle size have positive effects, while air flow rate has a negative effect on the syngas yield. The optimal CO + H2 composition of 39.48 vol% was achieved at 900 °C, 10 mL/min air flow rate, and 2 mm particle size. FTIR analysis confirmed the absence of CâCl bonds and the emergence of SiâO bonds in the optimized char residue, distinguishing it from the raw sample. FESEM analysis revealed a rich porous structure in the optimized char residue, with the presence of calcium carbonate (CaCO3) and aluminosilicates. These findings provide valuable insights for sustainable energy production from biomass wastes.
Assuntos
Compostos de Alúmen , Gases , Esgotos , Gases/química , Óleo de Palmeira , Temperatura , BiomassaRESUMO
BACKGROUND: Robotic technique of surgery allows surgeons to perform complex procedures in difficult-to-access areas of the abdominal/pelvic cavity (eg, radical prostatectomy and radical hysterectomy) with improved access and precision approach. At the same time, automated techniques efficiently deliver propofol total intravenous anesthesia (TIVA) with lower anesthetic consumption. As both above are likely to bring benefit to the patients, it is imperative to explore their effect on postanesthesia recovery. Quality of Recovery-15 (QoR-15) is a comprehensive patient-reported measure of the quality of postanesthesia recovery and assesses compendious patients' experiences (physical and mental well-being). This randomized study assessed the effect of automated propofol TIVA versus inhaled desflurane anesthesia on postoperative quality of recovery using the QoR-15 questionnaire in patients undergoing elective robotic surgery. METHODS: One hundred twenty patients undergoing robotic abdominal surgery under general anesthesia (GA) were randomly allocated to receive propofol TIVA administered by closed-loop anesthesia delivery system (CLADS) (CLADS group) or desflurane GA (desflurane group). Postoperative QoR-15 score on postoperative day 1 (POD-1) and postoperative day 2 (POD-2) (primary outcome variables), individual QoR-15 item scores (15 nos.), intraoperative hemodynamics (heart rate, mean blood pressure), anesthesia depth consistency, anesthesia delivery system performance, early recovery from anesthesia (time-to-eye-opening, and time to tracheal extubation), and postoperative adverse events (sedation, postoperative nausea and vomiting [PONV], pain, intraoperative awareness recall) (secondary outcome variables) were analyzed. RESULTS: On POD-1, the CLADS group scored significantly higher than the desflurane group in terms of "overall" QoR-15 score (QoR-15 score: 114.5 ± 13 vs 102.1 ± 20.4; P = .001) and 3 individual QoR-15 "items" scores ("feeling rested" 7.5 ± 1.9 vs 6.4 ± 2.2, P = .007; "good sleep" 7.8 ± 1.9 vs 6.6 ± 2.7, P = .027; and "feeling comfortable and in control" 8.1 ± 1.7 vs 6.9 ± 2.4, P = .006). On the POD-2, the CLADS group significantly outscored the desflurane group with respect to the "overall" QoR-15 score (126.0 ± 13.6 vs 116.3 ± 20.3; P = .011) and on "5" individual QoR-15 items ("feeling rested" 8.1 ± 1.4 vs 7.0 ± 2.0, P = .003; "able to return to work or usual home activities" 6.0 ± 2.2 vs 4.6 ± 2.6, P = .008; "feeling comfortable and in control" 8.6 ± 1.2 vs 7.7 ± 1.9, P = .004; "feeling of general well-being" 7.8 ± 1.6 vs 6.9 ± 2.0, P = .042; and "severe pain" 9.0 ± 1.9 vs 8.1 ± 2.5, P = .042). CONCLUSIONS: Automated propofol TIVA administered by CLADS is superior to desflurane inhalation GA with respect to early postoperative recovery as comprehensively assessed on the QoR-15 scoring system. The effect of combined automated precision anesthesia and surgery (robotics) techniques on postoperative recovery may be explored further.
Assuntos
Anestésicos Inalatórios , Propofol , Procedimentos Cirúrgicos Robóticos , Feminino , Humanos , Masculino , Período de Recuperação da Anestesia , Anestesia Geral/efeitos adversos , Anestesia Geral/métodos , Anestésicos Inalatórios/efeitos adversos , Desflurano/efeitos adversos , Dor/etiologia , Propofol/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversosRESUMO
STUDY DESIGN: Retrospective Observational Study. INTRODUCTION: Lumbar radicular pain has a prevalence of 3-5%. Level 1 evidence has demonstrated equivalence between surgical and injection treatment. We assess the outcomes from a transforaminal epidural steroid injection clinic in a tertiary neuroscience referral centre. METHODS: We performed an analysis of data from consecutive patients entered into a new internal referral database between August 2018 to May 2021. Radicular pain was classified as one of "first presentation" or "recurrence". Outcomes were obtained from follow up clinic letters and recorded in a binary manner of "positive result" or "negative result". Spinal pathology was documented from radiology reports and MRI images. RESULTS: We analysed 208 patients referred to the clinic. Excluding those who improved to a point of not requiring treatment, and those who underwent surgical intervention, 119 patients undergoing injection were included, of which 14 were lost to follow-up. 68 % of patients had a positive result from injection. Subgroup analysis demonstrated good outcomes for both hyperacute (<6 weeks) and chronic (>12 months). Contained disk pathologies had better outcomes than uncontained. There was no difference in outcomes across grades of compression, but previous same level surgery was associated with poorer response rates. CONCLUSIONS: There is a high rate of natural resolution of symptoms in patients with LSRP. In those where pain persists, TFESI is a valuable first line treatment modality. This study suggests the efficacy of TFESI is potentially independent of grade of stenosis and chronicity of symptoms. Contained disc pathologies respond better than uncontained.
Assuntos
Deslocamento do Disco Intervertebral , Ciática , Humanos , Injeções Epidurais/métodos , Dor , Raízes Nervosas Espinhais , Reino Unido , Resultado do Tratamento , Vértebras LombaresRESUMO
Background and Aims: Empirically adjusted, standard drug doses fail to address interindividual pharmacokinetic and pharmacodynamics variability. Target-controlled infusion (TCI) delivers drugs in calibrated boluses to achieve and maintain a selected target plateau drug level (plasma or effect site). Interactive total intravenous anesthesia (iTIVA™) smartphone software simulates TCI and employs 31 established pharmacokinetic models for 11 different intravenous agents and is coupled with standard volumetric infusion pumps for administering TCI. Material and Methods: This prospective, observational, study investigates the degree of agreement between iTIVA and a conventional TCI pump (CTP) for the volume of propofol infused using the Schnider pharmacokinetic model in adult patients of either sex undergoing oncosurgery lasting 1-3 h under total intravenous anesthesia. Bland-Altman analysis of 124 data pairs from 30 patients provided bias, precision, and limits of agreement between the volumes infused by CTP and iTIVA (V-CTP and V-iTIVA) during specific identical time periods. Spearman's rho and Kendall's tau rank correlation coefficients provided the degree of association between V-CTP and V-iTIVA. Results: Spearman's rho and Kendall's tau were 0.996 and 0.964, respectively. Bias or the mean of differences was -0.02, while the limits of agreement were 0.58 and -0.63, respectively (Bland-Altman plot). The maximum allowed difference of 2 ml was much larger than the 95% confidence intervals for the limits of agreement. The Mountain plot was short tailed (-1.28 to 1.55) and centred over zero (0.01). Conclusion: The volume of propofol infused using TCI pump was similar to that calculated by iTIVA in identical time periods, confirming the clinical applicability of iTIVA.
RESUMO
Isoindolinone is a constituent of several natural products that show a wide range of bioactivity, such as anticancer, antimicrobial, antiviral and anti-inflammatory properties. It would be interesting to explore the carbonyl group (H-bond acceptor) of isoindolinone and its structural and conformational changes. However, the synthesis of isoindolinone-comprising peptides in short steps is challenging. Herein, we have developed a synthetic methodology for introducing the isoindolinone residue to peptides via Pd-catalyzed C(sp2)-H activation/olefination, and demonstrated the conformational changes owing to the isoindolinone scaffold. Hence, isoindolinonyl peptides provide an avenue for the synthesis of novel foldamers and therapeutic agents.
Assuntos
Paládio , Peptídeos , Paládio/química , Catálise , Conformação Molecular , Peptídeos/químicaRESUMO
During the late stages of the HIV-1 lifecycle, immature virions are produced by the concerted activity of Gag polyproteins, primarily mediated by the capsid (CA) and spacer peptide 1 (SP1) domains, which assemble into a spherical lattice, package viral genomic RNA, and deform the plasma membrane. Recently, inositol hexakisphosphate (IP6) has been identified as an essential assembly cofactor that efficiently produces both immature virions in vivo and immature virus-like particles in vitro. To date, however, several distinct mechanistic roles for IP6 have been proposed on the basis of independent functional, structural, and kinetic studies. In this work, we investigate the molecular influence of IP6 on the structural outcomes and dynamics of CA/SP1 assembly using coarse-grained (CG) molecular dynamics (MD) simulations and free energy calculations. Here, we derive a bottom-up, low-resolution, and implicit-solvent CG model of CA/SP1 and IP6, and simulate their assembly under conditions that emulate both in vitro and in vivo systems. Our analysis identifies IP6 as an assembly accelerant that promotes curvature generation and fissure-like defects throughout the lattice. Our findings suggest that IP6 induces kinetically trapped immature morphologies, which may be physiologically important for later stages of viral morphogenesis and potentially useful for virus-like particle technologies.
Assuntos
HIV-1 , Proteínas do Capsídeo/metabolismo , Produtos do Gene gag/química , Produtos do Gene gag/genética , Produtos do Gene gag/metabolismo , HIV-1/metabolismo , Cinética , Ácido Fítico/metabolismo , RNA Viral/metabolismo , Vírion , Montagem de Vírus/fisiologiaRESUMO
AIM: Cabotegravir long-acting (LA) intramuscular (IM) injection is being investigated for HIV preexposure prophylaxis due to its potent antiretroviral activity and infrequent dosing requirement. A subset of healthy adult volunteers participating in a Phase I study assessing cabotegravir tissue pharmacokinetics underwent serial magnetic resonance imaging (MRI) to assess drug depot localization and kinetics following a single cabotegravir LA IM targeted injection. METHODS: Eight participants (four men, four women) were administered cabotegravir LA 600 mg under ultrasonographic-guided injection targeting the gluteal muscles. MRI was performed to determine injection-site location in gluteal muscle (IM), subcutaneous (SC) adipose tissue and combined IM/SC compartments, and to quantify drug depot characteristics, including volume and surface area, on Days 1 (≤2 hours postinjection), 3 and 8. Linear regression analysis examined correlations between MRI-derived parameters and plasma cabotegravir exposure metrics, including maximum observed concentration (Cmax ) and partial area under the concentration-time curve (AUC) through Weeks 4 and 8. RESULTS: Cabotegravir LA depot locations varied by participant and were identified in the IM compartment (n = 2), combined IM/SC compartments (n = 4), SC compartment (n = 1) and retroperitoneal cavity (n = 1). Although several MRI parameter and exposure metric correlations were determined, total depot surface area on Day 1 strongly correlated with plasma cabotegravir concentration at Days 3 and 8, Cmax and partial AUC through Weeks 4 and 8. CONCLUSION: MRI clearly delineated cabotegravir LA injection-site location and depot kinetics in healthy adults. Although injection-site variability was observed, drug depot surface area correlated with both plasma Cmax and partial AUC independently of anatomical distribution.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Imageamento por Ressonância Magnética Multiparamétrica , Adulto , Dicetopiperazinas , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Injeções Intramusculares , Cinética , Masculino , Piridonas , VoluntáriosRESUMO
Natural aromatic α-amino acid residues play critical roles in the structural and functional organization of proteins owing to π-interactions. Their aromatic residues are derived from benzenoid scaffolds. Non-benzenoid aromatic scaffolds such as tropone and tropolone are also constituents of troponoid natural products. Tropolone has also the ability to exhibit π-interactions along with additional hydrogen bonding. Thus, amino acids comprising troponyl could be potential building blocks of novel peptidomimetics. This report describes the synthesis of the L-aminotroponylalanine amino acid (ATA) and its unusual activity with the peptide coupling agent EDC. Importantly, its di-peptides form ß-sheet/-turn type secondary structures in organic solvents owing to the troponyl residue. This amino acid is an excellent scaffold for the synthesis of fluorescent amino acids such as BODIPY amino acid analogs. Nevertheless, this amino acid and its BODIPY derivatives can enter HeLa cells without exhibiting significant cytotoxicity at low concentrations (â¼50 µM). Hence, ATA and its BODIPY derivatives are promising aromatic amino acids for the construction of potential peptidomimetics and fluorescent labelling of target peptides.
Assuntos
Alanina , Aminoácidos , Humanos , Células HeLa , Peptídeos/farmacologiaRESUMO
This study reports the synthesis and characterization of zinc derivatized 3,5-dihydroxy 4', 7- dimethoxyflavone (DHDM-Zn) compound for the development of new antileishmanial agents. The interaction studies of DHDM with zinc were carried out by UV spectra and fluorescence spectra analysis. Characterization of the complex was further accomplished by multi-spectroscopic techniques such as FTIR, Raman, HRMS, NMR, FESEM-EDX. The morphological and topographical studies of synthesized DHDM-Zn were carried out using FESEM with EDX. Further, it was demonstrated that DHDM-Zn exhibited an excellent in vitro antagonistic effect against the promastigote form of L. donovani. In addition, the possible mechanisms of promastigote L. donovani cell death, by involvement of derivatized compound in arrest of the cell cycle in the G1 phase and residual cell count reduction were investigated. Promastigote growth kinetics performed in the presence of the derivatized compound revealed a slow growth rate. The combination of growth kinetics and cell cycle analysis, made it possible to interpret and classify the cause of leishmanial cell death accurately. These results support that zinc derivatized complex (DHDM-Zn) might work as a lead compound for designing and developing a new antileishmanial drug.
Assuntos
Antiprotozoários , Leishmania donovani , Leishmaniose , Antiprotozoários/farmacologia , Humanos , Zinco/farmacologiaRESUMO
The present research work describes development of dual drug-loaded lipid-polymer hybrid nanoparticles (LPHNPs) of anticancer therapeutics for the management of colon cancer. The epidermal growth factor (EGF)-functionalized LPHNPs coloaded with 5-fluorouracil (FU) and sulforaphane (SFN) were prepared by one-step nanoprecipitation method. Box-Behnken design was applied for optimizing the material attributes and process parameters. The optimized LPHNPs revealed particle size 198 nm, polydispersity index 0.3, zeta potential -25.3 mV, and drug loading efficiency 19-20.3% for 5-FU and SFN, respectively. EGF functionalization on LPHNPs was confirmed from positive magnitude of zeta potential to 21.3 mV as compared with the plain LPHNPs. In vitro drug release performance indicated sustained and non-Fickian mechanism release nature of the drugs from LPHNPs. Anticancer activity evaluation in HCT-15 colon cancer cells showed significant reduction (p < 0.001) in the cell growth and cytotoxicity of the investigated drugs from various treatments in the order: EGF-functionalized LPHNPs > plain LPHNPs > free drug suspensions. Overall, the research work corroborated improved treatment efficacy of EGF-functionalized LPHNPs for delivering chemotherapeutic agents for the management of colon carcinoma.
Assuntos
Carcinoma , Neoplasias do Colo , Nanopartículas , Humanos , Polímeros , Disponibilidade Biológica , Fluoruracila/farmacologia , Fator de Crescimento Epidérmico , Lipídeos , Sobrevivência Celular , Tamanho da Partícula , Neoplasias do Colo/tratamento farmacológico , Portadores de Fármacos , Sistemas de Liberação de Medicamentos/métodosRESUMO
Plant-derived phytoconstituents are well known for their therapeutic potential. It has been experimentally demonstrated that whole-plant extract or isolated phytoconstituents reveal various therapeutic potentials like hepatoprotective, antimicrobial, neuroprotective, antitumor, antioxidant, skin protectives, etc. Although these phytoconstituents have potential therapeutic benefits, their use is limited due to their poor bioavailability, stability in biological fluids, and authentication issues. These continue to be an open problem that affects the application of these valuable ancient herbal herbs in the effective treatment and management of various disease conditions. A potential solution to these difficult problems could be the loading of phytoactives in phospholipid-based vesicular systems. Phospholipid-based vesicles like liposomes, phytosomes, ethosomes as well as transfersomes were effectively utilized recently to solve drawbacks and for effective delivery of phytoactives. Several landmark studies observed better therapeutic efficacy of phytoactive loaded vesicles compared to conventional drug delivery. Thus phospholipid-based vesicles mediated phytoactive delivery is a recently developed promising and attractive strategy for better therapeutic control on disease conditions. The present short review highlights recent advances in herbal bioactive loaded phospholipid-based vesicles.
Assuntos
Lipossomos , Fosfolipídeos , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos , Lipossomos/farmacologia , Fosfolipídeos/metabolismo , Extratos Vegetais/metabolismo , Pele/metabolismoRESUMO
The disjoining pressure of water was estimated from wicking experiments in 1D silicon dioxide nanochannels of heights of 59, 87, 124, and 1015 nm. The disjoining pressure was found to be as high as â¼1.5 MPa while exponentially decreasing with increasing channel height. Such a relation resulting from the curve fitting of experimentally derived data was implemented and validated in computational fluid dynamics. The implementation was then used to simulate bubble nucleation in a water-filled 59 nm nanochannel to determine the nucleation temperature. Simultaneously, experiments were conducted by nucleating a bubble in a similar 58 nm nanochannel by laser heating. The measured nucleation temperature was found to be in excellent agreement with the simulation, thus independently validating the disjoining pressure relation developed in this work. The methodology implemented here integrates experimental nanoscale physics into continuum simulations thus enabling numerical study of various phenomena where disjoining pressure plays an important role.
Assuntos
Dióxido de Silício , Água , TemperaturaRESUMO
Sarcoidosis is an idiopathic granulomatous disease and can virtually affect any organ system. Multiple factors, including tubercular antigens organic and environmental exposures, have been implicated in its pathogenesis. In addition to drugs, sarcoid-like reactions have been reported following varicella and influenza vaccination. Few reports of erythema nodosum and Lofgren syndrome have been reported after the COVID19 vaccination, though no histologic diagnosis was pursued in these cases. We herein report a case of sarcoidosis presenting with bilateral acute onset vision loss with a temporal association with COVID19 vaccination (ChadOx-1 n-COV, COVISHIELDTM). Symptoms started within two weeks of receiving the vaccine. Alternate causes for optic neuritis were excluded. Transbronchial lung biopsy showed the presence of non-caseating epithelioid cell granulomas. The patient received high-dose corticosteroids immediately after diagnosis, albeit with incomplete clinical improvement in vision on a three-month follow-up. In conclusion, we report a novel case of sarcoidosis-related optic neuritis following COVID19 vaccination.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Neurite Óptica , Sarcoidose , Humanos , ChAdOx1 nCoV-19 , COVID-19/complicações , Vacinas contra COVID-19/efeitos adversos , Granuloma , Neurite Óptica/etiologia , Neurite Óptica/complicações , Sarcoidose/etiologia , Sarcoidose/complicações , Vacinação/efeitos adversosRESUMO
Introduction: Endoscopic retrograde cholangiopancreaticography (ERCP) is an essential therapeutic procedure with a significant risk of complications. Data regarding the complications and predictors of adverse outcomes such as mortality are scarce, especially from India and Asia. We aimed to look at the incidence and outcome of complications in ERCP patients. Materials and Methods: This study is a retrospective analysis of prospectively collected data of all the patients who underwent ERCP and had a complication from January 2012 to December 2018. Data were recorded in predesigned pro forma. The data analysis was done by appropriate statistical tests. Results: : A total of 17,163 ERCP were done. A total of 570 patients (3.3%) had complications; perforation (n = 275, 1.6%) was most common followed by pancreatitis (n = 177, 1.03%) and bleeding (n = 60, 0.35%). The majorities of perforations were managed conservatively (n = 205, 74.5%), and 53 (19%) required surgery. Overall, 69 (0.4%) patients died. Of these, 30 (10.9%) patients died with perforation. Age (odds ratio [OR]: 1.04, 95% confidence interval [CI]: 1.005-1.07) and need of surgery (OR: 5.11, 95% CI: 1.66-15.77) were the predictors of mortality in patients with perforation. The majority pancreatitis were mild (n = 125, 70.6%) and overall mortality was 5.6% (n = 10). Conclusion: ERCP complications have been remained static over the years, with perforation and pancreatitis contributing the most. Most perforations can be managed conservatively with good clinical outcomes.
RESUMO
Background and Aims: The LMA® ProSeal™, LMA® Supreme™ and Ambu® AuraGain™ are second-generation supraglottic airway devices (SADs) with integrated gastric access. In this study, we compared the clinical performance of these three devices in adults for controlled ventilation in anesthetized paralysed patients. Material and Methods: Two hundred and seventy adults, American Society of Anesthesiologists (ASA) Physical Status I-III, undergoing elective surgical procedures, were randomized into three groups with 90 patients in each: Group 1: LMA® ProSeal™, Group 2: LMA® Supreme™ and Group 3: Ambu® AuraGain™. All the three devices were evaluated for oropharyngeal seal pressure (OSP) and other parameters: ease and the number of attempts at device placement, fibreoptic laryngeal view and intraoperative and postoperative complications. Results: In the present study, the mean OSP was 38.9 ± 3.050 cm H2O in the LMA ProSeal™ group, 37.41 ± 4.097 cm H2O in LMA® Supreme™ group and 37.32 ± 3.740 cm H2O in Ambu® AuraGain™ group. The difference was found to be statistically significant (P = 0.006). The three groups were comparable for the ease of device insertion, number of attempts at device placement, fibreoptic laryngeal view, intraoperative and postoperative complications. Conclusion: In this study, we found that the LMA® ProSeal™ provided the highest OSP in comparison to the other two devices, even though this difference is not clinically relevant. The use of Ambu® AuraGain™ was associated with difficult and lowest first-time insertion success rate (P < 0.001) along with an increased incidence of airway trauma as compared to the other two SADs.
RESUMO
The synthetic unnatural amino acids and their peptides as peptidomimetics have shown remarkable structural and functional properties. In the repertoire of synthetic peptides, pseudopeptides have emerged as attractive small peptidomimetics that are capable of forming the characteristic secondary structures in the solid/solution phase, as in natural peptides. This report describes the synthesis and structural analyses of novel pseudopeptides as ethylenediprolyl (etpro) tetra/hexapeptides, comprising a chiral diaminedicarboxylate scaffold. Their NMR and CD spectral analyses strongly support the formation of the ß-turn-type structures in organic solvents (ACN/MeOH). Further, the single-crystal X-ray studies of tetrapseudopeptide confirm the formation of a unique self-assembly structure as ß-strand type in the solid state through hydrogen bonding. Importantly, their diamine moiety influences the formation of Cu-complexes with Cu(II) ions. A tetrapseudopeptide monocarboxylate-Cu(II) complex forms the single crystal that is studied by the single-crystal X-ray diffractometer. The crystal structure of the tetrapseudopeptide-Cu(II) complex confirms the formation of the distorted square planar geometry structure, almost like the amyloid ß(Aß)-peptide-Cu(II) complex structural geometry. Hence, these etpro-pseudopeptides are emerging peptidomimatics that form ß-turn types of structures and metal complexes mainly with Cu(II) ions. These molecules could be considered for the development of peptide-based catalysts and peptide-based therapeutic drug candidates.
Assuntos
Complexos de Coordenação , Peptídeos beta-Amiloides , Cobre , Cristalografia por Raios X , Ligação de Hidrogênio , ÍonsRESUMO
Isoindolinone is a constituent of various natural products and synthetic biologically active compounds. The classical multi-step synthetic methods used to prepare various indolinone derivatives are tedious and challenging. One-pot synthetic methods are attractive and economical. Transition-metal-catalyzed C-H activation is an emerging tool for synthesizing natural products and small organic molecules via reducing the number of synthetic steps necessary. This paper describes the synthesis of N-alkyl-3-methenyl chiral isoindolinone derivatives from aryl amides of L-amino acids and non-activated alkene via Pd-catalyzed C(sp2)-H olefination. Herein, the amino acid residue acts as a directing group for olefination at the aryl ring, and then cyclization occurs at the amide NH. Hence, this methodology could be helpful to transform standard amino acids into respective chiral isoindolinone derivatives.