52 research outputs found

    Actividad antibacteriana y antioxidante de los extractos de Piper cubeba (Piperaceae)

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    Piper cubeba L. (Piperaceae), commonly known as ‘cubeb’, is native to Indonesia, and also found in many other countriesof the South-East Asia, and in some African countries. This plant has been used as a popular food additive, andin folklore medicine to treat various ailments, particularly bacterial infections. The n-hexane, dichloromethane (DCM)and methanol (MeOH) extracts of the dried berries (fruit) of this plant were assessed for their antioxidant (free radicalscavenging) and antibacterial activities using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and the micro titre basedantimicrobial assay incorporating resazurin as an indicator of cell growth, respectively. While all extracts showed antioxidantactivity in the qualitative assay, the most prominent antioxidant activity was observed with the MeOH extract inthe quantitative assay with a RC50 value of 2.71 x 10-1 mg/mL. The antioxidant potency of the DCM extract was about3 fold less (RC50 = 6.50 x 10-1 mg/mL) than that of the MeOH extract. None of the extracts showed any antibacterialproperty against Bacillus subtilis, Escherichia coli, and ampicillin resistant Escherichia coli. While both the n-hexaneand the DCM extracts inhibited the growth of Bacillus cereus, Pseudomonas aeruginosa and Staphylococcus aureus, theMeOH extract was active only against B. cereus and P. aeruginosa. The most potent antibacterial activity was displayedby the n-hexane extract against B. cereus with an MIC value of 1.56 mg/mL. All antibacterial activities of the extractswere found to be bacteriostatic rather than bactericidal.Piper cubeba L. (Piperaceae), conocida comúnmente como ‘cubeb’, es autóctona de Indonesia y también se encuentraen muchos otros países del sureste de Asia, así como en algunos países africanos.Esta planta se ha utilizado como un popular aditivo alimentario y, en la medicina tradicional, para tratar diversasdolencias, especialmente infecciones bacterianas. Para evaluar la actividad antioxidante (barrido de radicales libres)y la actividad antibacteriana de los extractos de n-hexano, diclorometano (DCM) y metanol (MeOH) de las bayassecas (fruto) de esta planta, se llevó a cabo un ensayo 2,2-difenil-1-picrilhidracil (DPPH) y un ensayo antimicrobianobasado en microtitulación que incorporaba resazurina como indicador del crecimiento celular, respectivamente. Aunquetodos los extractos mostraron actividad antioxidante en el ensayo cualitativo, la actividad antioxidante más destacadase observó con el extracto de MeOH en el ensayo cuantitativo con un valor de RC50 de 2,71 x 10-1 mg/mL.La potencia antioxidante del extracto de DCM fue aproximadamente 3 veces menor (RC50 = 6,50 x 10-1 mg/mL)que la del extracto de MeOH.Ninguno de los extractos mostró propiedades antibacterianas frente a Bacillus subtilis, Escherichia coli y Escherichiacoli resistente a la ampicilina. Aunque ambos extractos, el n-hexano y el DCM, inhibieron el crecimiento de Bacilluscereus, Pseudomonas aeruginosa y Staphylococcus aureus, el extracto de MeOH sólo mostró actividad frente a B.cereus y P. aeruginosa. El extracto de n-hexano fue el que mostró mayor potencia antibacteriana frente a B. cereus,con un valor de concentración inhibitoria mínima (CIM) de 1,56 mg/mL. Se observó que todas las actividades antibacterianasde los extractos resultaron más bacteriostáticas que bactericidas

    Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion

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    Toxoplasma (toxoplasmosis) and Plasmodium (malaria) use unique secretory organelles for migration, cell invasion, manipulation of host cell functions, and cell egress. In particular, the apical secretory micronemes and rhoptries of apicomplexan parasites are essential for successful host infection. New findings reveal that the contents of these organelles, which are transported through the endoplasmic reticulum (ER) and Golgi, also require the parasite endosome-like system to access their respective organelles. In this review, we discuss recent findings that demonstrate that these parasites reduced their endosomal system and modified classical regulators of this pathway for the biogenesis of apical organelles

    Acquisition of naturally occurring antibody responses to recombinant protein domains of Plasmodium falciparum erythrocyte membrane protein 1

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    Background: Antibodies targeting variant antigens expressed on the surface of Plasmodium falciparum infected erythrocytes have been associated with protection from clinical malaria. The precise target for these antibodies is unknown. The best characterized and most likely target is the erythrocyte surface-expressed variant protein family Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). Methods: Using recombinant proteins corresponding to five domains of the expressed A4 var gene, A4 PfEMP1, the naturally occurring antibody response was assessed, by ELISA, to each domain in serum samples obtained from individuals resident in two communities of differing malaria transmission intensity on the Kenyan coast. Using flow cytometry, the correlation in individual responses to each domain with responses to intact A4-infected erythrocytes expressing A4 PfEMP1 on their surface as well as responses to two alternative parasite clones and one clinical isolate was assessed. Results: Marked variability in the prevalence of responses between each domain and between each transmission area was observed, as wasa strong correlation between age and reactivity with some but not all domains. Individual responses to each domain varied strikingly, with some individuals showing reactivity to all domains and others with no reactivity to any, this was apparent at all age groups. Evidence for possible cross-reactivity in responses to the domain DBL4γ was found. Conclusion: Individuals acquire antibodies to surface expressed domains of a highly variant protein. The finding of potential cross-reactivity in responses to one of these domains is an important initial finding in the consideration of potential vaccine targets

    Ross, Macdonald, and a Theory for the Dynamics and Control of Mosquito-Transmitted Pathogens

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    Ronald Ross and George Macdonald are credited with developing a mathematical model of mosquito-borne pathogen transmission. A systematic historical review suggests that several mathematicians and scientists contributed to development of the Ross-Macdonald model over a period of 70 years. Ross developed two different mathematical models, Macdonald a third, and various “Ross-Macdonald” mathematical models exist. Ross-Macdonald models are best defined by a consensus set of assumptions. The mathematical model is just one part of a theory for the dynamics and control of mosquito-transmitted pathogens that also includes epidemiological and entomological concepts and metrics for measuring transmission. All the basic elements of the theory had fallen into place by the end of the Global Malaria Eradication Programme (GMEP, 1955–1969) with the concept of vectorial capacity, methods for measuring key components of transmission by mosquitoes, and a quantitative theory of vector control. The Ross-Macdonald theory has since played a central role in development of research on mosquito-borne pathogen transmission and the development of strategies for mosquito-borne disease prevention

    Vaccines against Tuberculosis: Where Are We and Where Do We Need to Go?

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    In this review we discuss recent progress in the development, testing, and clinical evaluation of new vaccines against tuberculosis (TB). Over the last 20 years, tremendous progress has been made in TB vaccine research and development: from a pipeline virtually empty of new TB candidate vaccines in the early 1990s, to an era in which a dozen novel TB vaccine candidates have been and are being evaluated in human clinical trials. In addition, innovative approaches are being pursued to further improve existing vaccines, as well as discover new ones. Thus, there is good reason for optimism in the field of TB vaccines that it will be possible to develop better vaccines than BCG, which is still the only vaccine available against TB

    Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

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    Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

    Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

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    Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

    <span style="font-size:11.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-GB">Polymeric nanoparticle formulation of Octapeptide (NP-OP): <i style="mso-bidi-font-style:normal">In vitro</i> release and <i style="mso-bidi-font-style:normal">in vivo</i> effect in common marmosets, <i style="mso-bidi-font-style:normal">Callithrix jacchus </i>Linn.</span>

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    1055-1062Octapeptide (OP)/FSH-Receptor Binding Inhibitor-8 (FRBI-8), is a synthetic peptide corresponding to N-terminal sequence of purified fraction of Follicle Stimulating Hormone Binding-Inhibitor (FSHBI), isolated earlier from human ovarian follicular-fluid. In order to avoid the repeated drug-administration, OP-loaded, polymeric polylactide (PLA) nanoparticle formulation (NP-OP), was developed using multiple-emulsion technique. This yielded an average particle size of 120 nm with 70% encapsulation-efficiency. In vitro release profile of NP-OP showed sustained release of OP for 21 days. In vivo anti-fertility studies were conducted in marmosets. Results indicated that control animals conceived in the same cycle while two of three treated animals failed to conceive in treatment cycle. The <i style="mso-bidi-font-style: normal">in vivo studies thus corroborate with in vitro release of OP, demonstrating its anti-fertility activity in 66% of animals. </span
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