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1.
Bioorg Chem ; 145: 107242, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428285

RESUMO

Colostrum/Milk is a chief repertoire of antioxidant peptides. Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a viable target for Parkinson's Disease (PD), as this pathway deduced to be impaired in PD. Cullin-3 is one of the crucial E3 ligase responsible for its regulation. The present study screened peptide libraries of buffalo colostrum & milk peptides for Cullin-3 inhibition, thus ensuing activation of Nrf2 to alleviate the molecular etiopathology in PD using the C. elegans as a model. The structure was modelled, binding sites analyzed and peptide-interactions analyzed by docking. Among the 55 sequences (≤1 kDa), the peptide SFVSEVPEL having the highest dock score (-16.919) was synthesized and evaluated for its effects on oxidative stress markers, antioxidant enzymes, neurochemical marker and Nrf2/Skn-1 levels. The lead peptide alleviated the oxidative pathophysiology and behavioural deficits associated with PD in C. elegans.


Assuntos
Fármacos Neuroprotetores , Doença de Parkinson , Animais , Feminino , Gravidez , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Antioxidantes/farmacologia , Búfalos/metabolismo , Proteínas Culina/metabolismo , Caenorhabditis elegans/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Colostro/metabolismo , Estresse Oxidativo , Peptídeos/farmacologia , Peptídeos/metabolismo , Fármacos Neuroprotetores/farmacologia
2.
World J Surg ; 48(6): 1555-1561, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38588034

RESUMO

BACKGROUND: Early video-assisted thoracoscopic surgery (VATS) is the recommended treatment of choice for retained hemothorax (RH). A prospective single-center randomized control study was conducted to compare outcomes between VATS and thoracostomy tube (TT) reinsertion for patients with RH after penetrating trauma in a resource constrained unit. Our hypothesis was that patients with a RH receiving VATS instead of TT reinsertion would have a shorter hospital stay and lesser complications. MATERIALS AND METHODS: From January 2014 to November 2019, stable patients with thoracic penetrating trauma complicated with retained hemothoraces were randomized to either VATS or TT reinsertion. The outcomes were length of hospital stay (LOS) and complications. RESULTS: Out of the 77 patients assessed for eligibility, 65 patients were randomized and 62 analyzed: 30 in the VATS arm and 32 in the TT reinsertion arm. Demographics and mechanisms of injury were comparable between the two arms. Length of hospital stay was: preprocedure: VATS 6.8 (+/-2.8) days and TT 6.6 (+/- 2.4) days (p = 0.932) and postprocedure: VATS 5.1 (+/-2.3) days, TT 7.1 (+/-6.3) days (p = 0.459), total LOS VATS 12 (+/- 3.9) days, and TT 14.4 (+/-7) days (p = 0.224). The TT arm had 15 complications compared to the VATS arm of four (p = 0.004). There were two additional procedures in the VATS arm and 10 in the TT arm (p = 0.014). CONCLUSION: VATS proved to be the better treatment modality for RH with fewer complications and less need of additional procedures, while the LOS between the two groups was not statistically different.


Assuntos
Tubos Torácicos , Hemotórax , Tempo de Internação , Traumatismos Torácicos , Cirurgia Torácica Vídeoassistida , Toracostomia , Ferimentos Penetrantes , Humanos , Cirurgia Torácica Vídeoassistida/métodos , Hemotórax/etiologia , Hemotórax/cirurgia , Masculino , Feminino , Estudos Prospectivos , Adulto , Toracostomia/métodos , Traumatismos Torácicos/complicações , Traumatismos Torácicos/cirurgia , Tempo de Internação/estatística & dados numéricos , Ferimentos Penetrantes/cirurgia , Ferimentos Penetrantes/complicações , Resultado do Tratamento , Pessoa de Meia-Idade , Adulto Jovem , Fatores de Tempo , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
3.
J Food Sci Technol ; 56(10): 4526-4534, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31686684

RESUMO

C-phycocyanin (C-PC) a blue color phycobiliproteins used as a food colorant, therapeutics, medicines, health food and biomarkers. In the present study, morphological property of encapsulated C-PC and its stability under various conditions like temperature, pH conditions are discussed. Microencapsulated droplets formed by extrusion found to be spherical with average size 1.2 ± 0.1 mm. SEM micrographs of freeze dried encapsulate confirmed the spherical shape. The effect of droplet formation with varying alginate percentage (1.5%, 2.0% and 2.5% w/v) was studied. In the stability test at 70 °C and 80 °C relative concentration (CR  %) was found to be 86.89 and 88.19%, respectively. The encapsulated C-PC showed a slow degradation at higher temperature compared to without encapsulated C-PC which was confirmed by UV-visible absorbance. At 45 °C and 55 °C temperatures the stability was studied at various pH conditions (pH 4.5, 5.5, 6.5, and 7.0) and reported. Aggregation of C-PC protein will not change during encapsulation was confirmed by SDS-PAGE. FTIR analysis of encapsulate and the alginate depicted similar characteristics of the compound compared to that of native C-phycocyanin colorant. Microencapsulation improves the stability and increases the shelf life of colorant.

4.
World J Surg ; 42(8): 2412-2420, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29387958

RESUMO

BACKGROUND: The purpose of this study was to determine whether the outcomes of hemodynamically stable patients undergoing exploratory laparotomy for penetrating abdominal trauma differed as a result of their HIV status. METHODS: This was an observational, prospective study from February 2016 to May 2017. All hemodynamically stable patients with penetrating abdominal trauma requiring a laparotomy were included. The mechanism of injury, the HIV status, age, the penetrating abdominal trauma index (PATI), and the revised trauma score (RTS) were entered into a binary logistic regression model. Outcome parameters were in-hospital death, morbidity, admission to intensive care unit (ICU), relaparotomy within 30 days, and length of stay longer than 30 days. RESULTS: A total of 209 patients, 94% male, with a mean age of 29 ± 10 years were analysed. Twenty-eight patients (13%) were HIV positive. The two groups were comparable. Ten (4.8%) laparotomies were negative. There were two (0.96%) deaths, both in the HIV negative group. The complication rate was 34% (n = 72). Twenty-nine patients (14%) were admitted to the ICU. A higher PATI, older age, and a lower RTS were significant risk factors for ICU admission. After 30 days, 12 patients (5.7%) were still in hospital. Twenty-four patients (11%) underwent a second laparotomy. The PATI score was the single independent predictor for complications, relaparotomy, and hospital stay longer than 30 days. CONCLUSIONS: Preliminary results reveal that HIV status does not influence outcomes in patients with penetrating abdominal trauma.


Assuntos
Traumatismos Abdominais/cirurgia , Soronegatividade para HIV , Soropositividade para HIV/complicações , Ferimentos Penetrantes/cirurgia , Traumatismos Abdominais/complicações , Síndrome da Imunodeficiência Adquirida/complicações , Adulto , Contagem de Linfócito CD4 , Feminino , Humanos , Laparotomia/efeitos adversos , Tempo de Internação , Modelos Logísticos , Masculino , Complicações Pós-Operatórias , Estudos Prospectivos , Resultado do Tratamento , Ferimentos Penetrantes/complicações
6.
Pancreatology ; 17(4): 592-598, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28596059

RESUMO

BACKGROUND: This study sought to develop a pancreatic injury mortality score (PIMS) to identify patients at greatest risk of in-hospital mortality after a major pancreatic injury. METHODS: The study used data from a prospective database of 473 patients treated for pancreatic injuries between January 1990 and December 2015. Two thirds of the patients were assigned to the derivation cohort and one third to the validation cohort. Clinical correlates of in-hospital death were identified and considered in stepwise logistic regression analyses that identified the factors included in the risk index. RESULTS: Five variables, age >55, shock on admission, a vascular injury, number of associated injuries and American Association for the Study of Trauma (AAST) pancreatic injury scale correlated with in-hospital death and were used to calculate PIMS. The final score ROC in the derivation dataset was 0.84 (95% CI 0.79-0.89) and in the validation dataset was 0.91 (95% CI 0.84-0.97), which were comparable (p = 0.1). Finally, cut-off scores were used to generate three risk groups and the rate of mortality within the low (PIMS 0-4), medium (PIMS 5-9), and high risk (PIMS 10-20) groups were not significantly different. The scoring system was tested in a validation cohort and showed good calibration and discrimination for in-hospital mortality. CONCLUSIONS: We have derived and validated the PIMS, a novel organ-specific risk prediction score calculated from five variables for in-hospital mortality following major pancreatic trauma. PIMS is simple, quick and easily understandable, increases clinical risk prediction for patients with complex pancreatic and can be used as a benchmark for survival.

7.
Ann Surg ; 263(5): 1018-27, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26445471

RESUMO

OBJECTIVES: To characterize and evaluate indications for use of damage control (DC) surgery in civilian trauma patients. BACKGROUND: Although DC surgery may improve survival in select, severely injured patients, the procedure is associated with significant morbidity, suggesting that it should be used only when appropriately indicated. METHODS: Two investigators used an abbreviated grounded theory method to synthesize indications for DC surgery reported in peer-reviewed articles between 1983 and 2014 into a reduced number of named, content-characteristic codes representing unique indications. An international panel of trauma surgery experts (n = 9) then rated the appropriateness (expected benefit-to-harm ratio) of the coded indications for use in surgical practice. RESULTS: The 1107 indications identified in the literature were synthesized into 123 unique pre- (n = 36) and intraoperative (n = 87) indications. The panel assessed 101 (82.1%) of these indications to be appropriate. The indications most commonly reported and assessed to be appropriate included pre- and intraoperative hypothermia (median temperature <34°C), acidosis (median pH <7.2), and/or coagulopathy. Others included 5 different injury patterns, inability to control bleeding by conventional methods, administration of a large volume of packed red blood cells (median >10 units), inability to close the abdominal wall without tension, development of abdominal compartment syndrome during attempted abdominal wall closure, and need to reassess extent of bowel viability. CONCLUSIONS: This study identified a comprehensive list of candidate indications for use of DC surgery. These indications provide a practical foundation to guide surgical practice while studies are conducted to evaluate their impact on patient care and outcomes.


Assuntos
Cuidados Críticos/métodos , Procedimentos Cirúrgicos Operatórios/métodos , Ferimentos e Lesões/cirurgia , Consenso , Humanos , Planejamento de Assistência ao Paciente
8.
Ann Surg ; 261(3): 573-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25664535

RESUMO

OBJECTIVE: To determine the sensitivity of emergency department ultrasonography (US) in the diagnosis of occult cardiac injuries. BACKGROUND: Internationally, US has become the investigation of choice in screening patients for a possible cardiac injury after penetrating chest trauma by detecting blood in the pericardial sac. METHODS: Patients presenting with a penetrating chest wound and a possible cardiac injury to the Groote Schuur Hospital Trauma Centre between October 2001 and February 2009 were prospectively evaluated. All patients were hemodynamically stable, had no indication for emergency surgery, and had an US scan followed by subxiphoid pericardial window exploration. RESULTS: There were a total of 172 patients (median age = 26 years; range, 11-65 years). The mechanism of injury was stab wounds in 166 (96%) and gunshot wounds in 6. The sensitivity of US in detecting hemopericardium was 86.7%, with a positive predictive value of 77%. There were 18 false-negatives. Eleven of these false-negatives had an associated hemothorax and 6 had pneumopericardium. A single patient had 2 negative US examinations and returned with delayed cardiac tamponade. CONCLUSIONS: The sensitivity of US to detect hemopericardium in stable patients was only 86.7%. The 2 main factors that limit the screening are the presence of a hemothorax and air in the pericardial sac. A new regimen for screening of occult injuries to make allowance for this is proposed.


Assuntos
Traumatismos Cardíacos/diagnóstico por imagem , Derrame Pericárdico/diagnóstico por imagem , Ferimentos Penetrantes/diagnóstico por imagem , Adolescente , Adulto , Idoso , Criança , Diagnóstico Diferencial , Reações Falso-Negativas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , África do Sul , Centros de Traumatologia , Ultrassonografia
9.
Ann Surg ; 261(4): 760-4, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25185470

RESUMO

OBJECTIVE: The primary aim of this study was to delineate the role of computed tomography (CT) in patients undergoing NOM for AGSW. BACKGROUND: Nonoperative management (NOM) of abdominal gunshot wounds (AGSWs) remains controversial. METHODS: This prospective study included all patients with abdominal gunshot injuries admitted to our trauma center from April 1, 2004 to September 30, 2009. Exclusion criteria included patients with peritonitis, hemodynamic instability, unreliable physical examination, head and spinal cord injury with an AGSW underwent immediate laparotomy. The remaining patients were selected for NOM. Nonperitonitic stable patients with right-sided thoracoabdominal/right upper quadrant gunshots and/or hematuria underwent mandatory CT with intravenous contrast. CT to detect missile trajectory was optional. The primary outcome measure was failure of NOM. Secondary outcomes were unnecessary laparotomy rates and mortality. RESULTS: A total of 1106 patients with abdominal gunshot injuries were admitted. Of these, 834 (75.4%) underwent immediate laparotomy, whereas 272 (24.6%) were selected for NOM. In the former group, there were 56 (6.7%) deaths and 29 (3.5%) unnecessary laparotomies, whereas in the latter NOM group, 82 (30.1%) patients were managed by serial clinical examination alone, whereas 190 (69.9%) patients underwent abdominal CT scanning, in addition to serial clinical examination. The overall NOM success rate was 95.2%. Of the 13 patients undergoing delayed laparotomy, there were 10 therapeutic, 2 nontherapeutic, and 1 negative laparotomy. CONCLUSIONS: The NOM of appropriately selected patients with AGSW with selective use of CT scanning is feasible, safe, and effective, but largely based on findings from serial clinical examinations.


Assuntos
Traumatismos Abdominais/diagnóstico por imagem , Traumatismos Abdominais/terapia , Ferimentos por Arma de Fogo/diagnóstico por imagem , Ferimentos por Arma de Fogo/terapia , Traumatismos Abdominais/mortalidade , Adolescente , Adulto , Drenagem , Feminino , Seguimentos , Humanos , Escala de Gravidade do Ferimento , Rim/diagnóstico por imagem , Rim/lesões , Laparotomia/estatística & dados numéricos , Tempo de Internação , Fígado/diagnóstico por imagem , Fígado/lesões , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Baço/diagnóstico por imagem , Baço/lesões , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/lesões , Ferimentos por Arma de Fogo/mortalidade , Adulto Jovem
10.
Ann Surg ; 259(3): 438-42, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23604058

RESUMO

OBJECTIVE: To determine if stable patients with a hemopericardium detected after penetrating chest trauma can be safely managed with pericardial drainage alone. BACKGROUND: The current international practice is to perform a sternotomy and cardiac repair if a hemopericardium is detected after penetrating chest trauma. The experience in Cape Town, South Africa, on performing a mandatory sternotomy in hemodynamically stable patients was that a sternotomy was unnecessary and the cardiac injury, if present, had sealed. METHODS: A single-center parallel-group randomized controlled study was completed. All hemodynamically stable patients with a hemopericardium confirmed at subxiphoid pericardial window (SPW), and no active bleeding, were randomized. The primary outcome measure was survival to discharge from hospital. Secondary outcomes were complications and postoperative hospital stay. RESULTS: Fifty-five patients were randomized to sternotomy and 56 to pericardial drainage and wash-out only. Fifty-one of the 55 patients (93%) randomized to sternotomy had either no cardiac injury or a tangential injury. There were only 4 patients with penetrating wounds to the endocardium and all had sealed. There was 1 death postoperatively among the 111 patients (0.9%) and this was in the sternotomy group. The mean intensive care unit (ICU) stay for a sternotomy was 2.04 days (range, 0-25 days) compared with 0.25 days (range, 0-2) for the drainage (P < 0.001). The estimated mean difference highlighted a stay of 1.8 days shorter in the ICU for the drainage group (95% CI: 0.8-2.7). Total hospital stay was significantly shorter in the SPW group (P < 0.001; 95% CI: 1.4-3.3). CONCLUSIONS: SPW and drainage is effective and safe in the stable patient with a hemopericardium after penetrating chest trauma, with no increase in mortality and a shorter ICU and hospital stay. (ClinicalTrials.gov Identifier: NCT00823160).


Assuntos
Drenagem/métodos , Derrame Pericárdico/cirurgia , Esternotomia/métodos , Traumatismos Torácicos/cirurgia , Ferimentos Penetrantes/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Tempo de Internação/tendências , Masculino , Derrame Pericárdico/etiologia , Derrame Pericárdico/mortalidade , Técnicas de Janela Pericárdica , Estudos Retrospectivos , África do Sul/epidemiologia , Taxa de Sobrevida/tendências , Resultado do Tratamento
11.
HPB (Oxford) ; 16(11): 1043-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24841125

RESUMO

BACKGROUND: This single-centre study evaluated the outcome of a pancreatoduodenectomy for Grade 5 injuries of the pancreas and duodenum. METHODS: Prospectively recorded data of patients who underwent a pancreatoduodenectomy for trauma at a Level I Trauma Centre during a 22-year period were analysed. RESULTS: Nineteen (17 men and 2 women, median age 28 years, range 14-53 years) out of 426 patients with pancreatic injuries underwent a pancreatoduodenectomy (gunshot n = 12, blunt trauma n = 6 and stab wound n = 1). Nine patients had associated inferior vena cava (IVC) or portal vein (PV) injuries. Five patients had initial damage control procedures and underwent a definitive operation at a median of 15 h (range 11-92) later. Twelve had a pylorus-preserving pancreatoduodenectomy (PPPD) and 7 a standard Whipple. Three patients with APACHE II scores of 15, 18, 18 died post-operatively of multi-organ failure. All 16 survivors had Dindo-Clavien grade I (n = 1), grade II (n = 7), grade IIIa (n = 2), grade IVa (n = 6) post-operative complications. Factors complicating surgery were shock on admission, number of associated injuries, coagulopathy, hypothermia, gross bowel oedema and traumatic pancreatitis. CONCLUSIONS: A pancreatoduodenectomy is a life-saving procedure in a small cohort of stable patients with non-reconstructable pancreatic head injuries. Damage control before a pancreatoduodenectomy will salvage a proportion of the most severely injured patients who have multiple injuries.


Assuntos
Duodeno/cirurgia , Traumatismo Múltiplo/cirurgia , Pâncreas/cirurgia , Pancreaticoduodenectomia , APACHE , Adolescente , Adulto , Duodeno/lesões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Traumatismo Múltiplo/diagnóstico , Traumatismo Múltiplo/mortalidade , Pâncreas/lesões , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/mortalidade , Estudos Retrospectivos , África do Sul , Fatores de Tempo , Centros de Traumatologia , Resultado do Tratamento , Adulto Jovem
12.
Open Forum Infect Dis ; 11(7): ofae321, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38947737

RESUMO

Dolutegravir resistance is emerging in routine clinical contexts in southern Africa, primarily in patients with prior treatment experience failing dolutegravir-based antiretroviral therapy (ART). This potential issue was raised by The Nucleosides and Darunavir/Dolutegravir in Africa trial that compared dolutegravir and boosted protease inhibitor-based therapy as second-line ART, in which new dolutegravir resistance was observed at failure. However, recent data suggest that also at risk are patients who were transitioned to dolutegravir from non-nucleoside reverse transcriptase inhibitor-based ART while viremic. Identifying patients experiencing failure of dolutegravir with resistance will be difficult given current gaps in viral load monitoring and limited capacity for genotypic resistance testing. As a result, in the short term, most patients affected will go unrecognized, with particularly important implications for patients affected who have advanced HIV or who are pregnant/breastfeeding. Prospective research is needed to understand the scope of the problem, identify additional risk factors, and determine best management. In the short term, for most patients with dolutegravir resistance and prior non-nucleoside reverse transcriptase inhibitor exposure, the best option will be a timely switch to a regimen anchored by a boosted protease inhibitor, with a high genetic barrier to resistance.

13.
BMJ Open ; 13(2): e065706, 2023 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-36806134

RESUMO

OBJECTIVES: To assess the experiences and knowledge of nurses in the area of iron deficiency. DESIGN: A cross-sectional, exploratory study using online survey. SETTING: Data were collected from nurses working at various primary, secondary and tertiary Australian health practices and organisations. PARTICIPANTS: Australian nurses currently in practice. METHOD: Australian nurses currently in practice were invited to complete an online survey about their work background, personal experiences with iron deficiency and iron-deficiency identification and treatment. The survey included a nine-item questionnaire to assess knowledge of iron-deficiency risk factors and biochemistry. RESULTS: A total of 534 eligible nurses participated in the survey. Participants were more likely to be female, aged 55-64 years, and working in general practice. Just under half (45.1%) reported being diagnosed with iron deficiency themselves. Unusual fatigue or tiredness was the most frequent symptom that alerted nurses to potential iron deficiency in patients (reported by 91.9% of nurses). Nurses who had participated in formal training around iron deficiency in the last 5 years demonstrated a significantly higher knowledge score (4.2±2.1) compared with those who had not or were not sure about their formal training status (3.7±1.9, p=0.035). Knowledge around the understanding of functional iron deficiency was limited. CONCLUSIONS: Nurses report personal experiences of iron deficiency and show good knowledge of symptoms, demonstrating the potential for them to take a leading role in managing iron deficiency in patients. Educational programmes are required to address knowledge gaps and should be offered via various methods to accommodate a diverse nurse cohort. Our research highlights the potential for an expanded scope of practice for nurses in the primary care setting in the area of iron deficiency.


Assuntos
Deficiências de Ferro , Enfermeiras e Enfermeiros , Humanos , Feminino , Masculino , Austrália/epidemiologia , Estudos Transversais , Escolaridade , Fadiga
14.
Crit Care ; 16(3): 314, 2012 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-22731873

RESUMO

BACKGROUND: ß2-adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies of acute lung injury (ALI). METHODS: Objective: To determine whether an aerosolized ß2-agonist would improve clinical outcomes in patients with ALI. Design: Multi-center, phase III randomized, placebo-controlled clinical trial. Setting: 33 hospitals participating National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Subjects: Patients who were intubated and receiving mechanical ventilation, had bilateral infiltrates consistent with edema on frontal chest radiograph, had a ratio of PaO2 to FIO2 (fraction of inspired oxygen) of 300 or less, and not had clinical evidence of left atrial hypertension. A maximum enrolment of 1,000 patients was planned. Intervention: Patients were randomized to receive aerosolized albuterol (5 mg) or saline placebo every 4 hours for up to 10 days. Outcomes: The primary outcome variable was ventilator-free days (VFD). Secondary outcome measures included mortality before hospital discharge on day 60 and day 90, the number of intensive care unit (ICU)-free days and the number of organ failure-free days. RESULTS: There were 282 patients enrolled before the trial was stopped for futility after the second interim analysis. The VFDs difference with albuterol treatment was unfavourable by -2.2 days, well past the futility boundary of -0.4 VFDs. VFDs were not significantly different between the albuterol and placebo groups (means of 14.4 and 16.6 days, respectively; 95% confidence interval for the difference, -4.7 to 0.3 days; P = 0.087). Rates of death before hospital discharge and the number of organ failure-free days were also not significantly different between the two groups. The number of ICU-free days was lower in the albuterol group in comparison with the placebo group (means of 13.5 and 16.2 days respectively; 95% confidence intervals for the mean difference, -4.9 to -0.4 days; P = 0.023). Overall, heart rates were significantly higher in the albuterol group by approximately 5 beats/minute in the first 2 days after randomization (P < 0.05), but rates of new onset atrial fibrillation (10% in both groups) and other cardiac dysrhythmias were not significantly different. CONCLUSIONS: These results suggest that aerosolized albuterol does not improve clinical outcomes in ALI patients. Routine use of ß2 agonist therapy in mechanically ventilated ALI patients cannot be recommended.


Assuntos
Lesão Pulmonar Aguda/terapia , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Albuterol/administração & dosagem , Feminino , Humanos , Masculino
15.
Mol Divers ; 16(3): 553-62, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22918724

RESUMO

We propose a novel cheminformatics approach that combines structure and ligand-based design to identify target-specific pharmacophores with well-defined exclusion ability. Our strategy includes the prediction of selective interactions, developing structure, and knowledge-based selective pharmacophore models, followed by database screening and molecular docking. This unique strategy was employed in addressing the off-target toxicity of Gsk3ß and CDKs. The connections of Gsk3ß in eukaryotic cell apoptosis and the extensive potency of Gsk3ß inhibitors to block cell death have made it a potential drug-discovery target for many grievous human disorders. Gsk3ß is phylogenetically very closely related to the CDKs, such as CDK1 and CDK2, which are suggested to be the off-target proteins of Gsk3ß inhibitors. Here, we have employed novel computational approaches in designing the ligand candidates that are potentially inhibitory against Gsk3ß, with well-defined the exclusion ability to CDKs. A structure-ligand -based selective pharmacophore was modeled. This model was used to retrieve molecules from the zinc database. The hits retrieved were further screened by molecular docking and protein-ligand interaction fingerprints. Based on these results, four molecules were predicted as selective Gsk3ß antagonists. It is anticipated that this unique approach can be extended to investigate any protein-ligand specificity.


Assuntos
Desenho de Fármacos , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Quinase 3 da Glicogênio Sintase/metabolismo , Informática/métodos , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Avaliação Pré-Clínica de Medicamentos , Quinase 3 da Glicogênio Sintase/química , Glicogênio Sintase Quinase 3 beta , Ligantes , Modelos Moleculares , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica , Inibidores de Proteínas Quinases/química , Especificidade por Substrato
16.
Int J Biol Macromol ; 207: 1038-1047, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35364203

RESUMO

Lignocellulosic biomass from agricultural residues serves as the critical component to replace synthetic polymeric materials in the coming future. Agricultural residues can be used to obtain cellulose by delignification followed by bleaching. Further, cellulose is converted into nanocellulose by various methods. Nanocellulose is used in multiple pharmaceutical applications as a polymer in hydrogels, transdermal drug delivery systems, aerogels, wound healing dressing materials, as superdisintegrants in fast dissolving tablets, emulgel, microparticles, gels, foams, thickening agents, stabilizers, cosmetics, medical implants, tissue engineering, liposomes, food and composites, etc. This review provides detailed knowledge about the nature of nanocellulose regarding its high surface area, high polymerization, loading, and binding capacity of hydrophilic and hydrophobic active pharmaceutical ingredients and significance of various applications of nanocellulose. Biocompatible and non-toxic, it makes it an ideal material for applications in the biomedical field. A significant advantage is a biocompatibility, which is non-toxic for many biomedical applications.


Assuntos
Nanoestruturas , Celulose/química , Hidrogéis/química , Nanoestruturas/química , Polímeros , Engenharia Tecidual
17.
World J Surg ; 35(5): 962-6, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21360307

RESUMO

BACKGROUND: The surgical management and outcome of penetrating axillary artery (AA) injuries is presented. PATIENTS AND METHODS: Patients presenting to Groote Schuur Hospital with penetrating AA injuries from January 2003 to December 2009 were reviewed. Demographic data, mechanism of injury, associated injuries, angiographic findings, surgical treatment, complications, and mortality were noted. RESULTS: Sixty-eight patients with AA injuries were identified from an operating trauma database. Stab and gunshot wounds accounted for 54 (79.4%) and 14 injuries, respectively. The mean Revised Trauma Score was 7.5 (range: 3.8-7.8). Angiography was done in 49 patients; false aneurysms (32) and total occlusions (15) were the two commonest findings. Primary repair of the injured AA was possible in 41 (60.3%) patients. Five AA (7.4%) injuries were ligated. Morbidity was restricted to associated brachial plexus injuries. The limb salvage rate was 100%. CONCLUSIONS: Primary repair of AA injuries was possible in 60% of patients, and ligation was life-saving in critically ill patients. The associated brachial plexus injury was the cause of major long-term morbidity.


Assuntos
Artéria Axilar/lesões , Ferimentos por Arma de Fogo/epidemiologia , Ferimentos Perfurantes/epidemiologia , Adolescente , Adulto , Falso Aneurisma/cirurgia , Artéria Axilar/cirurgia , Plexo Braquial/lesões , Feminino , Humanos , Ligadura , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ferimentos por Arma de Fogo/cirurgia , Ferimentos Perfurantes/cirurgia , Adulto Jovem
18.
Protein J ; 40(3): 310-327, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33840006

RESUMO

The COVID-19, an acute respiratory syndrome caused by SARS-CoV2 is a major catastrophic event of the twenty first century. Relentless efforts for the development of effective pharmaco-therapeutics are in progress but the respite is the development of effective vaccines. However, monotherapy might not always exhibit complete efficacy and may culminate in the rapid evolution of drug-resistant viral strains. Hence, simultaneous modulation of multiple druggable targets not only enhances therapeutic efficacy but also quell the prospects of mutant viruses. Currently, milk peptides have bloomed beyond just being a quintessential part of nutrition to prominent therapeutic implications in human health and diseases. Hence, we have focused on colostrum/milk peptides as they have already been acknowledged for their high potency, target specificity with significantly low or no side effects and bio-toleration. The results presented provide a conceptual strategy for the rational designing of prospective multitargeted peptide inhibitors for SARS-CoV2.


Assuntos
Antivirais/química , Tratamento Farmacológico da COVID-19 , Simulação de Acoplamento Molecular , Peptídeos/química , SARS-CoV-2/química , Proteínas do Soro do Leite/química , Animais , Antivirais/uso terapêutico , Bovinos , Humanos , Peptídeos/uso terapêutico
19.
Colomb Med (Cali) ; 52(2): e4034519, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-34188321

RESUMO

Definitive management of hemodynamically stable patients with penetrating cardiac injuries remains controversial between those who propose aggressive invasive care versus those who opt for a less invasive or non-operative approach. This controversy even extends to cases of hemodynamically unstable patients in which damage control surgery is thought to be useful and effective. The aim of this article is to delineate our experience in the surgical management of penetrating cardiac injuries via the creation of a clear and practical algorithm that includes basic principles of damage control surgery. We recommend that all patients with precordial penetrating injuries undergo trans-thoracic ultrasound screening as an integral component of their initial evaluation. In those patients who arrive hemodynamically stable but have a positive ultrasound, a pericardial window with lavage and drainage should follow. We want to emphasize the importance of the pericardial lavage and drainage in the surgical management algorithm of these patients. Before this concept, all positive pericardial windows ended up in an open chest exploration. With the coming of the pericardial lavage and drainage procedure, the reported literature and our experience have shown that 25% of positive pericardial windows do not benefit and/or require further invasive procedures. However, in hemodynamically unstable patients, damage control surgery may still be required to control ongoing bleeding. For this purpose, we propose a surgical management algorithm that includes all of these essential clinical aspects in the care of these patients.


El manejo definitivo de los pacientes hemodinámicamente estables con heridas cardíacas penetrantes continúa siendo controversial con abordajes invasivos versus manejos conservadores. Estas posiciones contrarias se extienden hasta aquellos casos de pacientes hemodinámicamente inestables donde se ha descrito y considerado la cirugía de control de daños como un procedimiento útil y efectivo. El objetivo de este artículo es presentar la experiencia en el manejo quirúrgico de heridas cardíacas penetrantes con la creación de un algoritmo práctico que incluye los principios básicos del control de daños. Se recomienda que a todos los pacientes con heridas precordiales penetrantes se les debe realizar un ultrasonido torácico como componente integral de la evaluación inicial. Aquellos que presenten un ultrasonido torácico positivo y se encuentren hemodinámicamente estables se les debe realizar una ventana pericárdica con posterior lavado. Se ha demostrado que el 25% de las ventanas pericárdicas positivas no se benefician ni requieren de posteriores abordajes quirúrgicos invasivos. Antes de este concepto, todos los pacientes con ventana pericárdica positiva terminaban en una exploración abierta del tórax y del pericárdico.Los pacientes hemodinámicamente inestables requieren de una cirugía de control de daños para un adecuado y oportuno control del sangrado. Con este propósito, se propone un algoritmo de manejo quirúrgico que incluye todos estos aspectos esenciales en el abordaje de este grupo de pacientes.


Assuntos
Algoritmos , Traumatismos Cardíacos/cirurgia , Técnicas de Janela Pericárdica , Ferimentos Penetrantes/cirurgia , Colômbia/epidemiologia , Drenagem , Traumatismos Cardíacos/diagnóstico , Traumatismos Cardíacos/diagnóstico por imagem , Traumatismos Cardíacos/epidemiologia , Hemorragia/terapia , Técnicas Hemostáticas , Humanos , Ilustração Médica , Complicações Pós-Operatórias , Irrigação Terapêutica , Ultrassonografia/métodos , Ferimentos Penetrantes/diagnóstico , Ferimentos Penetrantes/diagnóstico por imagem , Ferimentos Penetrantes/epidemiologia
20.
World J Emerg Surg ; 16(1): 46, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507603

RESUMO

On January 2020, the WHO Director General declared that the outbreak constitutes a Public Health Emergency of International Concern. The world has faced a worldwide spread crisis and is still dealing with it. The present paper represents a white paper concerning the tough lessons we have learned from the COVID-19 pandemic. Thus, an international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making. With the present paper, international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making.


Assuntos
COVID-19/epidemiologia , Saúde Global , Pandemias , Pesquisa Biomédica , COVID-19/diagnóstico , COVID-19/terapia , Vacinas contra COVID-19 , Atenção à Saúde/organização & administração , Política de Saúde , Acessibilidade aos Serviços de Saúde , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Humanos , Cooperação Internacional , Vacinação em Massa/organização & administração , Pandemias/prevenção & controle , Política , Atenção Primária à Saúde/organização & administração , Telemedicina/organização & administração
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