Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 98
Filtrar
1.
Braz J Biol ; 83: e242942, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468508

RESUMO

Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.


Assuntos
Estresse Oxidativo , Timerosal , Animais , Peróxido de Hidrogênio/metabolismo , Rim , Masculino , Ratos , Superóxido Dismutase/metabolismo , Timerosal/metabolismo , Timerosal/toxicidade
2.
Braz J Biol ; 83: e243438, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468509

RESUMO

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.


Assuntos
Cisplatino , Peróxido de Hidrogênio , Animais , Antioxidantes , Cisplatino/toxicidade , Flavonoides , Masculino , Estresse Oxidativo , Ratos , Superóxido Dismutase/metabolismo
3.
Braz J Biol ; 83: e247701, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468529

RESUMO

Staphylococcus aureus is an important foodborne pathogen associated to food intoxication and other multiple infections in human being. Its presence in salted food is a serious issue due to its salt tolerance potential. A study was conducted to analyze the presence of enterotoxins producing drug resistance S. aureus in salted sea fish from Gwadar. Freshly persevered samples (n=50) of salted fish were subjected to analyze the presence of S. aureus using 16S rRNA and Nuc genes primers. The isolates were then evaluated for drug resistance and enterotoxins producing potential using specific primers for MecA (methicillin resistance gene), (SEA) staphylococcal enterotoxin A and (SEB) staphylococcal enterotoxin B genes. Total 13/50 (26%) of the samples were found positive for the presence of S. aureus, preliminary confirmed with biochemical profiling and finally with the help of target genes presence. The isolates were found showing 100% resistant to methicillin, which were molecularly confirmed by the presence of MecA gene present in genome. The isolates 5/13 (38%) were positive for SEA and 3/13 (23%) for SEB genes, whereas 2/13 (15%) were confirmed having both SEA and SEB genes in its genome. It was also confirmed that all the isolates were capable to form biofilm over the glass surfaces. It was concluded that the study confirmed the presence of enterotoxigenic methicillin resistance Staphylococcus aurous (MRSA) in salted fish product, that poses gross food safety concern. Preventive and control measures are necessary to handle this serious food safety concern.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Produtos Pesqueiros , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , RNA Ribossômico 16S , Staphylococcus aureus/genética
4.
Ann R Coll Surg Engl ; 103(8): 583-588, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34464561

RESUMO

INTRODUCTION: To analyse the outcomes of major colorectal resections performed during the COVID-19 pandemic, to assess safety and explore all precautionary measures. METHOD: All patients who underwent major elective colorectal resections at St Helens and Knowsley Teaching Hospital NHS Trust between 24th March 2020 (the date that the Royal Colleges of Surgery produced their guidelines re operating during the pandemic) and 17th April 2020 were analysed from a prospectively maintained database. The primary outcome was 7-day mortality and secondary outcomes were the development of a positive COVID-19 test consequent to hospital stay and the overall complication rate. RESULTS: In this 24 day time frame 27 patients (17 males) underwent elective colorectal resections at St Helens and Knowsley NHS Trust. The median age was 69 (41-84) years and median ASA was 2 (1-3). The median Body Mass Index was 30 (21-40.7). Twenty-five patients underwent surgery for cancer and two patients had urgent resections for low-grade sepsis secondary to diverticular colovesical fistulae. 24 patients underwent laparoscopic colorectal resections and 3 patients underwent planned open surgery. 7-day mortality was 0%, and no patients/staff contracted COVID-19 during the post-operative period. The overall complication rate was 14.8%. At a median follow-up of 29 (17-44) days via telephone, there have been no reported COVID-19 related symptoms in any of these patients. CONCLUSION: Our experience demonstrated that it was possible to undertake laparoscopic colorectal resections despite the COVID-19 pandemic posing a major threat to humanity, providing that adequate and stringent precautions are undertaken.


Assuntos
COVID-19 , Colectomia/estatística & dados numéricos , Laparoscopia/estatística & dados numéricos , Pandemias , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido/epidemiologia
5.
Astrobiology ; 20(12): 1405-1412, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32924535

RESUMO

Hydrothermal vents, which are highly plausible habitable environments for life and of interest for some origin-of-life scenarios, may exist on icy moons such as Europa or Enceladus in addition to Earth. Some hydrothermal vent chimney structures are extremely porous and friable, making their reconstruction in the lab challenging (e.g., brucite or saponite in alkaline hydrothermal settings). Here, we present the results from our efforts to reconstruct a simplified chimney structure directly out of mineral powder using binder jet additive manufacturing. Olivine sand was chosen for this initial method development effort since it represents a naturally occurring seafloor material and is inexpensively available in large quantities in powder form. The crystal structure of olivine used for the print was not modified during the process, as confirmed by powder X-ray diffraction (XRD). To characterize the microstructure of our 3D printed precipitates, we used computed tomography (CT) X-ray scan techniques. We also evaluated a chimney precipitate from a sample collected from the Prony Hydrothermal Field (PHF), southern New Caledonia, an alkaline system driven by serpentinization with mineralogy composed of brucite and carbonates. While not directly comparable from a mineralogical point of view, the microstructure and porosity of both precipitates was similar, suggesting that our 3D printing technique may be a valuable tool for future astrobiology research on hydrothermal vent precipitates.

6.
Front Neurol ; 11: 351, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32390937

RESUMO

Endovascular neuromodulation is an emerging technology that represents a synthesis between interventional neurology and neural engineering. The prototypical endovascular neural interface is the StentrodeTM, a stent-electrode array which can be implanted into the superior sagittal sinus via percutaneous catheter venography, and transmits signals through a transvenous lead to a receiver located subcutaneously in the chest. Whilst the StentrodeTM has been conceptually validated in ovine models, questions remain about the long term viability and safety of this device in human recipients. Although technical precedence for venous sinus stenting already exists in the setting of idiopathic intracranial hypertension, long term implantation of a lead within the intracranial veins has never been previously achieved. Contrastingly, transvenous leads have been successfully employed for decades in the setting of implantable cardiac pacemakers and defibrillators. In the current absence of human data on the StentrodeTM, the literature on these structurally comparable devices provides valuable lessons that can be translated to the setting of endovascular neuromodulation. This review will explore this literature in order to understand the potential risks of the StentrodeTM and define avenues where further research and development are necessary in order to optimize this device for human application.

7.
Can J Ophthalmol ; 55(1 Suppl 1): 14-24, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32089161

RESUMO

OBJECTIVE: The purpose of this report is to develop a consensus for Canadian national guidelines specific to a tele-medicine approach to screening for diabetic retinopathy (DR) using evidence-based and clinical data. METHODS: Canadian Tele-Screening Grading Scales for DR and diabetic macular edema (DME) were created primarily based on severity grading scales outlined by the International Clinical Diabetic Retinopathy Disease Severity Scale (ICDR) and the Scottish DR Grading Scheme 2007. Other grading scales used in international screening programs and the clinical expertise of the Canadian Retina Research Network members and retina specialists nationwide were also used in the creation of the guidelines. RESULTS: National Tele-Screening Guidelines for DR and DME with and without optical coherence tomography (OCT) images are proposed. These outline a diagnosis and management algorithm for patients presenting with different stages of DR and/or DME. General guidelines detailing the requirements for imaged retina fields, image quality, quality control, and follow-up care and the role of visual acuity, pupil dilation, OCT, ultra-wide-field imaging, and artificial intelligence are discussed. CONCLUSIONS: Tele-retina screening can help to address the need for timely and effective screening for DR, whose prevalence continues to rise. A standardized and evidence-based national approach to DR tele-screening has been proposed, based on DR/DME grading using two 45° image fields or a single widefield or ultra-wide-field image, preferable use of OCT imaging, and a focus on local quality control measures.

8.
Parasitol Res ; 118(7): 2277-2285, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31119381

RESUMO

Malaria-associated bacteremia accounts for up to one-third of deaths from severe malaria, and non-typhoidal Salmonella (NTS) has been reported as a major complication of severe malarial infection. Patients who develop NTS bacteremia during Plasmodium infection show higher mortality rates than individuals with malaria alone. Systemic bacteremia can be caused by a wound or translocation from epithelial or endothelial sites. NTS is an intestinal pathogen, however the contribution of bacterial translocation from the intestinal tract during Plasmodium infection is not well studied. Here, we investigated the integrity of the intestinal barrier function of P. chabaudi-infected mice using large molecules and Salmonella infection. Intestinal histology and the adaptive immune response to malaria were also studied using light microscopy and flow cytometry. P. chabaudi infection compromised intestinal barrier function, which led to increased intestinal cellular infiltration. In addition, we observed increased serum lipopolysaccharide binding protein and leakage of soluble molecules from the intestine into the blood in infected mice. Plasmodium infection also increased intestinal translocation and dissemination of NTS to the liver. The adaptive immune response to P. chabaudi infection was also significantly impacted by NTS translocation. Reduced B and T cell activation were observed in co-infected animals, suggesting interference in the malaria-specific immune responses by bacteremia. These studies demonstrate that P. chabaudi infection induces failure of the barrier function of the intestinal wall and enhanced intestinal bacterial translocation, affecting anti-malarial immunity.


Assuntos
Imunidade Adaptativa , Malária/imunologia , Plasmodium chabaudi/imunologia , Infecções por Salmonella/imunologia , Salmonella/imunologia , Animais , Bacteriemia , Coinfecção , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal , Intestinos/microbiologia , Intestinos/patologia , Ativação Linfocitária , Malária/complicações , Malária/parasitologia , Malária/patologia , Camundongos , Camundongos Endogâmicos C57BL , Parasitemia , Infecções por Salmonella/complicações , Infecções por Salmonella/microbiologia , Infecções por Salmonella/patologia
10.
PLoS Pathog ; 14(4): e1006960, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29630679

RESUMO

Protection at the peak of Plasmodium chabaudi blood-stage malaria infection is provided by CD4 T cells. We have shown that an increase in Th1 cells also correlates with protection during the persistent phase of malaria; however, it is unclear how these T cells are maintained. Persistent malaria infection promotes protection and generates both effector T cells (Teff), and effector memory T cells (Tem). We have previously defined new CD4 Teff (IL-7Rα-) subsets from Early (TeffEarly, CD62LhiCD27+) to Late (TeffLate, CD62LloCD27-) activation states. Here, we tested these effector and memory T cell subsets for their ability to survive and protect in vivo. We found that both polyclonal and P. chabaudi Merozoite Surface Protein-1 (MSP-1)-specific B5 TCR transgenic Tem survive better than Teff. Surprisingly, as Tem are associated with antigen persistence, Tem survive well even after clearance of infection. As previously shown during T cell contraction, TeffEarly, which can generate Tem, also survive better than other Teff subsets in uninfected recipients. Two other Tem survival mechanisms identified here are that low-level chronic infection promotes Tem both by driving their proliferation, and by programming production of Tem from Tcm. Protective CD4 T cell phenotypes have not been precisely determined in malaria, or other persistent infections. Therefore, we tested purified memory (Tmem) and Teff subsets in protection from peak pathology and parasitemia in immunocompromised recipient mice. Strikingly, among Tmem (IL-7Rαhi) subsets, only TemLate (CD62LloCD27-) reduced peak parasitemia (19%), though the dominant memory subset is TemEarly, which is not protective. In contrast, all Teff subsets reduced peak parasitemia by more than half, and mature Teff can generate Tem, though less. In summary, we have elucidated four mechanisms of Tem maintenance, and identified two long-lived T cell subsets (TemLate, TeffEarly) that may represent correlates of protection or a target for longer-lived vaccine-induced protection against malaria blood-stages.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Memória Imunológica/imunologia , Malária/imunologia , Malária/prevenção & controle , Plasmodium chabaudi/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Interferon gama/biossíntese , Malária/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
11.
Ann R Coll Surg Engl ; 100(1): 37-41, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29046093

RESUMO

Introduction Perianal fistulas are a common problem. Video-assisted anal fistula treatment is a new technique for the management of this difficult condition. We describe our initial experience with the technique to facilitate the treatment of established perianal fistulas. Methods We reviewed a prospectively maintained database relating to consecutive patients undergoing video-assisted anal fistula treatment in a single unit. Results Seventy-eight consecutive patients had their perianal fistulas treated with video-assistance from November 2014 to June 2016. Complete follow-up data were available in 74 patients, with median follow-up of 14 months (interquartile range 7-19 months). There were no complications and all patients were treated as day cases. Most patients had recurrent disease, with 57 (77%) having had previous fistula surgery. At follow-up, 60 (81%) patients reported themselves 'cured' (asymptomatic) including 5 patients with Crohn's disease and one who had undergone 10 previous surgical procedures. Logistical stepwise regression did not demonstrate any statistically significant factors that may have been considered to affect outcome (age, gender, diabetes, previous I&D, Crohn's disease, smoking, type of fistula). Conclusions Our data have shown that video-assisted anal fistula treatment is safe and effective in the management of perianal fistulas in our patients and this suggests it may be applied to all patients regardless of comorbidity, underlying pathology or type of fistula.


Assuntos
Endoscopia Gastrointestinal , Fístula Retal/cirurgia , Cirurgia Vídeoassistida , Endoscopia Gastrointestinal/efeitos adversos , Endoscopia Gastrointestinal/métodos , Endoscopia Gastrointestinal/estatística & dados numéricos , Feminino , Humanos , Masculino , Estudos Prospectivos , Cirurgia Vídeoassistida/efeitos adversos , Cirurgia Vídeoassistida/métodos , Cirurgia Vídeoassistida/estatística & dados numéricos
12.
J Immunol ; 200(2): 643-656, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29237780

RESUMO

Understanding the mechanisms of CD4 memory T cell (Tmem) differentiation in malaria is critical for vaccine development. However, the metabolic regulation of CD4 Tmem differentiation is not clear, particularly in persistent infections. In this study, we investigated the role of fatty acid synthesis (FAS) in Tmem development in Plasmodium chabaudi chronic mouse malaria infection. We show that T cell-specific deletion and early pharmaceutical inhibition of acetyl CoA carboxylase 1, the rate limiting step of FAS, inhibit generation of early memory precursor effector T cells (MPEC). To compare the role of FAS during early differentiation or survival of Tmem in chronic infection, a specific inhibitor of acetyl CoA carboxylase 1, 5-(tetradecyloxy)-2-furoic acid, was administered at different times postinfection. Strikingly, the number of Tmem was only reduced when FAS was inhibited during T cell priming and not during the Tmem survival phase. FAS inhibition during priming increased effector T cell (Teff) proliferation and strongly decreased peak parasitemia, which is consistent with improved Teff function. Conversely, MPEC were decreased, in a T cell-intrinsic manner, upon early FAS inhibition in chronic, but not acute, infection. Early cure of infection also increased mitochondrial volume in Tmem compared with Teff, supporting previous reports in acute infection. We demonstrate that the MPEC-specific effect was due to the higher fatty acid content and synthesis in MPEC compared with terminally differentiated Teff. In conclusion, FAS in CD4 T cells regulates the early divergence of Tmem from Teff in chronic infection.


Assuntos
Ácidos Graxos/biossíntese , Memória Imunológica , Infecções/imunologia , Infecções/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Acetil-CoA Carboxilase/deficiência , Transferência Adotiva , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Sobrevivência Celular/genética , Doença Crônica , Regulação da Expressão Gênica , Interações Hospedeiro-Parasita/imunologia , Infecções/genética , Infecções/microbiologia , Metabolismo dos Lipídeos , Ativação Linfocitária/imunologia , Malária/genética , Malária/imunologia , Malária/metabolismo , Malária/parasitologia , Camundongos , Camundongos Transgênicos , Mitocôndrias/genética , Mitocôndrias/imunologia , Receptor fas/genética , Receptor fas/metabolismo
13.
Chem Commun (Camb) ; 53(90): 12240-12243, 2017 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-29086774

RESUMO

Herein, we developed a straightforward aqueous synthesis of unprecedented alternating peptide-peptoid copolymers via a Ugi four-component reaction applied to dipeptides. Functional peptide-peptoid copolymers as well as block copolymers were produced in a single step in the presence of acrylic acid and carboxylic acid-terminated poly(ethylene glycol). The thermoresponsiveness of these polymers is highlighted.

14.
Int J Colorectal Dis ; 32(1): 119-124, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27695932

RESUMO

BACKGROUND AND AIMS: Evidence has shown that a positive resection margin (R1) is a key determinant of subsequent local recurrence and a poor prognostic factor in rectal cancer. The aim of this study was to evaluate the outcomes and prognosticators in patients with R1 resection of rectal cancer. MATERIAL AND METHODS: Retrospective study of all patients operatively managed within our institution between April 2008 and April 2013 for rectal cancer. Baseline demographics and multiple outcome measures recorded. Overall survival (OS), disease-free survival (DFS) and recurrence were the primary outcome measures. RESULTS: Overall, there were 306 primary rectal cancers. Seventy-six percent were grade T3/4 tumours. OS was 30 months. R1 rate was 16 % (48 patients). Thirty-one patients underwent APR and 17 AR. In patients who responded to neoadjuvant chemotherapy (NAC), overall survival was 55 months, with no extramural venous invasion (EMV) seen in this cohort. In non-responders OS was 29 months, with EMV in 48 %. In patients who did not receive NAC, OS was 23 months, with EMV in 74 %. EMV is a strong predictor for poor survival following R1 (p = 0.001). We also found a correlation between number of positive nodes and OS/DFS (p = 0.004). CONCLUSIONS: In this small cohort of patients with R1 positive rectal cancers, response to NAC is the strongest predictor of poor overall and disease-free survival. In patients who respond to NAC, OS and DFS has been shown to be positive, with a reduced rate of EMV.


Assuntos
Margens de Excisão , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Veias/patologia , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Linfonodos/patologia , Terapia Neoadjuvante , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Neoplasias Retais/tratamento farmacológico
15.
J Mater Chem B ; 4(37): 6228-6239, 2016 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32263635

RESUMO

The development of flexible drug delivery systems that can be tuned as a function of the drug to be delivered and of the target disease is crucial in modern medicine. For this aim, novel amphiphilic poly(ε-caprolactone)-g-poly(ethylene glycol) (PCL-g-PEG) copolymers with well-controlled design were synthesized by thiol-yne photochemistry. The grafting density and the copolymer amphiphilicity were easily controlled via the reaction parameters: concentration, reaction time, PEG length and the molar ratio between PCL and PEG or the photoinitiator in the reaction mixture. The self-assembling behavior of the copolymers was studied and a correlation between the composition of PCL-g-PEG and the nanoaggregate diameter sizes (28 to 73 nm) and critical aggregation concentrations (1.1 to 4.3 mg L-1) was found. The influence of copolymer amphiphilicity on the drug loading was evaluated with various drugs including anticancer drugs (paclitaxel, ABT-199), drugs to overcome multidrug resistance in cancer cells (curcumin, elacridar), an anti-inflammatory drug (dexamethasone) and an antibacterial drug (clofazimine). Finally, the influence of amphiphilicity on curcumin release and toxicity towards MCF-7 cancer cell lines was studied. The impact of the grafting density, PEG length and the overall EG/CL ratio is discussed in detail. Curcumin loaded PCL-g-PEG with lower EG/CL ratios and shorter PEG chains showed higher toxicity compared to their more hydrophilic counterparts.

16.
Am J Trop Med Hyg ; 93(2): 287-92, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26101276

RESUMO

We investigated the circulating plasma levels of Th1- (Interleukin-2 [IL-2], tumor necrosis factor-α [TNF-α], interferon-gamma [IFN-γ]) and Th2-type (IL-4, IL-5, IL-10) cytokines in human immunodeficiency virus (HIV)-infected pregnant women living in a malaria-endemic area. We analyzed samples from 200 pregnant women included in the prevention of pregnancy-associated malaria in HIV-infected women: cotrimoxazole prophylaxis versus mefloquine (PACOME) clinical trial who were followed until delivery. Cytokine concentrations were measured by flow cytometry-based multiplex bead array. Significantly elevated levels of IL-10 and lower levels of TNF-α were observed at delivery compared with inclusion (P = 0.005). At inclusion, the presence of circulating IFN-γ, a higher CD4(+) T cell count and having initiated intermittent preventive treatment of malaria with sulfadoxine pyrimethamine (SP-IPTp) were all associated with a lower likelihood of Plasmodium falciparum infection. At delivery, the inverse relationship between the presence of infection and circulating IFN-γ persisted, although there was a positive association between the likelihood of infection and the presence of circulating TNF-α. Initiation of antiretroviral therapy was associated with elevated IL-5 production. Consistent with our own and others' observations in HIV seronegative subjects, this study shows circulating IL-10 to be a marker of infection with P. falciparum during pregnancy even in HIV-infected women, although plasma IFN-γ may be a marker of anti-malarial protection in such women.


Assuntos
Infecções por HIV/sangue , Malária Falciparum/sangue , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/virologia , Complicações Parasitárias na Gravidez/sangue , Adulto , Antimaláricos/uso terapêutico , Benin/epidemiologia , Combinação de Medicamentos , Feminino , Infecções por HIV/complicações , Humanos , Interleucina-10/sangue , Interleucina-2/sangue , Interleucina-4/sangue , Interleucina-5/sangue , Malária Falciparum/complicações , Malária Falciparum/tratamento farmacológico , Gravidez , Complicações Parasitárias na Gravidez/tratamento farmacológico , Estudos Prospectivos , Pirimetamina/uso terapêutico , Sulfadoxina/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
17.
J Immunol ; 194(11): 5346-54, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25911759

RESUMO

CD4 T cells orchestrate immunity against blood-stage malaria. However, a major challenge in designing vaccines to the disease is poor understanding of the requirements for the generation of protective memory T cells (Tmem) from responding effector T cells (Teff) in chronic parasite infection. In this study, we use a transgenic mouse model with T cells specific for the merozoite surface protein (MSP)-1 of Plasmodium chabaudi to show that activated T cells generate three distinct Teff subsets with progressive activation phenotypes. The earliest observed Teff subsets (CD127(-)CD62L(hi)CD27(+)) are less divided than CD62L(lo) Teff and express memory genes. Intermediate (CD62L(lo)CD27(+)) effector subsets include the most multicytokine-producing T cells, whereas fully activated (CD62L(lo)CD27(-)) late effector cells have a terminal Teff phenotype (PD-1(+), Fas(hi), AnnexinV(+)). We show that although IL-2 promotes expansion, it actually slows terminal effector differentiation. Using adoptive transfer, we show that only early Teff survive the contraction phase and generate the terminal late Teff subsets, whereas in uninfected recipients, they become both central and effector Tmem. Furthermore, we show that progression toward full Teff activation is promoted by increased duration of infection, which in the long-term promotes Tem differentiation. Therefore, we have defined markers of progressive activation of CD4 Teff at the peak of malaria infection, including a subset that survives the contraction phase to make Tmem, and show that Ag and cytokine levels during CD4 T cell expansion influence the proportion of activated cells that can survive contraction and generate memory in malaria infection.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Memória Imunológica/imunologia , Malária/imunologia , Plasmodium chabaudi/imunologia , Subpopulações de Linfócitos T/imunologia , Transferência Adotiva , Animais , Linfócitos T CD4-Positivos/citologia , Diferenciação Celular/imunologia , Citocinas/biossíntese , Interferon gama/biossíntese , Interleucina-2/imunologia , Subunidade alfa de Receptor de Interleucina-7/metabolismo , Selectina L/metabolismo , Ativação Linfocitária/imunologia , Proteína 1 de Superfície de Merozoito/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Subpopulações de Linfócitos T/citologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
18.
Plant Dis ; 99(2): 292, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30699593

RESUMO

Andrographis paniculata (Family Acanthaceae), also called Kalmegh, is a medicinal herb in India well-known for its various pharmaceutical properties (1). In August 2012, during a survey in the northern parts of India, several Kalmegh plants in Barabanki District of Uttar Pradesh Province showed typical virus-like symptoms along with prominent lethal leaf yellowing. The infected plants initially showed some chlorotic streaks, which later turned completely yellow, ultimately leading to premature death. Mechanical/sap inoculation failed to transmit the pathogen. Based on the symptomology, a heavy infestation of whiteflies (Bemisia tabaci) in the infected fields, and lack of mechanical transmission, the association of a begomovirus was suspected. The disease incidence was calculated to be about 15 to 20% on the basis of plant population. Twenty samples from naturally infected plants of A. paniculata were collected from various field locations. Total genomic DNA from the symptomatic and non-symptomatic samples was isolated by the modified CTAB method (4). The initial PCR-based detection was performed using begomovirus coat protein gene specific primers (forward 5'-ATGGCGAAGCGACCAG-3' and reverse 5'-TTAATTTGTGACCGAATCAT-3'), which generated an amplicon of 771 bp in most of the (17/20) symptomatic samples. No amplification was obtained in healthy or non-symptomatic plant samples. The full-length genome was amplified via rolling-circle amplification (RCA) according to the manufacturer's instructions using random hexamer primers and φ29 DNA polymerase. A portion of the RCA product (1 µl) was subjected to digestion with different restriction enzymes, out of which BamHI yielded DNA fragments of approximately 2.7 and 1.3 kb, corresponding to DNA-A and ß satellite molecules, respectively. These fragments were eluted from the gel and cloned into the suitable restriction site of pGreen0029 vector. The positive clones were checked by restriction digestion. Twelve out of 20 clones were found to be positive and sequenced. The complete genome sequences of DNA A (2,754 bp) and ß (1,366 bp) satellites were deposited in the GenBank database with the accession numbers KM359406 and KM359407, respectively. The absence of DNA-B molecule was ascertained, as no PCR amplification was detected with DNA-B-specific primers. Sequence analysis showed highest nucleotide identity (90%) with Catharanthus yellow mosaic virus (CYMV) (HE580234) and ≤85% identity with other begomoviruses of the database. Sequence analysis of the associated betasatellite showed 96% identity with Andrographis yellow vein leaf curl betasatellite (KC967282). CYMV was first reported on Catharanthus roseus with no associated betasatellite from Pakistan (2). However, this is the first report of CYMV along with a betasatellite infecting A. paniculata in India. Recently a begomovirus (Eclipta yellow vein virus) infection was reported on A. paniculata in association with Andrographis yellow vein leaf curl betasatellite from India for the first time (3); now the crop has also become a host of CYMV. Thus, this study highlights the spread of CYMV from its preliminary host to a new host plant (A. paniculata), across the South Asian countries. Therefore, it is important to take measures for the management of its transmitting vector so as to curtail the spread of the virus to new economically and commercially important crops. References: (1) S. Akbar. Altern. Med. Rev. 16:1, 2011. (2) M. Ilyas et al. Arch. Virol. 158:505, 2013. (3) A. Khan and A. Samad. Plant Dis. 98:698, 2014. (4) S. P. S. Khanuja et al. Plant Mol. Biol. Rep. 17:1, 1999.

19.
Plant Dis ; 99(3): 419, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30699728

RESUMO

Sweet basil (Ocimum basilicum), a member of the Lamiaceae, is used as an ornamental as well as a culinary herb. It is a rich source of the phenolic compound methyl chavicol and is used as a traditional medicinal plant in India, where the crop is grown on ~2,500 ha annually (4). The species is native to India, where it has been cultivated for >5,000 years. During the rainy season, August of 2013, a severe leaf blight was observed on 30- to 45-day-old sweet basil plants in experimental fields (approximately 5 ha) at the CSIR-CIMAP and adjoining areas in Lucknow. Initial symptoms comprised small, irregular, necrotic lesions that coalesced into a leaf blight. Infected parts of the leaves turned black during wet and humid conditions. The incidence of symptoms ranged from 20 to 30%. Infected leaf samples were cut into small pieces and surface-sterilized with 1% sodium hypochlorite for 1 min, followed by two rinses in sterilized, distilled water. The leaf pieces were then blotted dry with sterilized filter paper, placed onto potato dextrose agar (PDA), and incubated at 28°C for 3 to 5 days. Blackish-brown fungal colonies developed. Microscopic examination revealed the presence of brown conidiophores that were cylindrical, septate, unbranched, and straight or geniculate near the apex. Conidia were three-septate, mostly curved at the third cell from the base, which was usually larger and darker than the other cells; intermediate cells were brown or dark brown; terminal cells were subhyaline or pale brown and 16 to 23.5 × 8.5 to 11.5 µm (the average size of 100 conidia was 19.9 × 10.18 µm). On the basis of these characteristics, the fungus was identified as Cochliobolus lunatus (anamorph Curvularia lunata (Wakk.) Boedijin) (1,2). The identification was confirmed by sequencing the internal spacer (ITS) region of ribosomal DNA (rDNA). Genomic DNA was extracted from five fungal isolates, using the 5 Prime Archive Pure DNA Cell/Tissue kit, and subjected to a polymerase chain reaction (PCR) assay with the universal primers ITS1 and ITS4 (5). The amplified product was cloned and sequenced. An NCBI-BLASTn search showed greatest homology (98% similarity) with the ITS sequence of C. lunatus (GenBank Accession No. DQ836800). The sequence was deposited in Genbank (KM272001). A pathogenicity test was carried out using 10, 30-day-old sweet basil (cv. CIM Soumya) plants in pots, by spraying a spore suspension (105 spores/ml) onto the leaves of each plant. Five plants treated similarly with sterilized, distilled water served as a control treatment. The plants were kept at 27 ± 2°C and 85 ± 3% RH for 8 to 10 days. Small, irregular, necrotic lesions appeared after 4 days on all inoculated leaves, while leaves of control plants remained asymptomatic. Fungi re-isolated from inoculated leaves resembled C. lunatus on the basis of microscopic and sequence data, fulfilling Koch's postulates. The fungus was not re-isolated from the control plants. C. guatemalensis has been reported to cause a leaf spot on sweet basil in Korea (3). To our knowledge, this is the first report of a sweet basil leaf blight caused by C. lunatus in India. C. lunatus has the potential to reduce the yield of sweet basil. References: (1) L. M. Liu et al. Plant Dis. 98:686, 2014. (2) D. S. Manamgoda et al. Fungal Divers. 56:131, 2012. (3) J. H. Park et al. Plant Dis. 96:580, 2012. (4) H. A. A. Taie et al. Not. Bot. Hort. Agrobot. Cluj. Napoca 38:119, 2010. (5) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, San Diego, 1990.

20.
Plant Dis ; 99(1): 155, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30699758

RESUMO

Andrographis paniculata (family Acanthaceae), also known as "King of Bitters" or Kalmegh, is an important medicinal plant used for the treatment of various diseases. It has antimicrobial, antiviral, anti-inflammatory, hepatoprotective, antidiabetic, antihyperglycemic, and antioxidant properties (1). During June 2014, while performing a routine survey of the commercial trial fields of Kalmegh at Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, India, typical phytoplasma disease symptoms such as virescence, proliferation, and witches' broom along with little leaf and stunted growth were observed. The disease incidence was estimated to be approximately 7 to 10%. To ascertain the presence of phytoplasma, 16 samples of leaves were collected from nine different field sites, and total genomic DNA was extracted from the symptomatic and symptomless Kalmegh plants by the CTAB method. Direct and nested PCR assays were performed targeting the 16S rDNA using generic phytoplasma primer pairs P1/P6 followed by R16F2n/R16R2 (2). Resulting bands of the expected size (1.5 kb and 1.2 kb, respectively) were amplified from symptomatic plants. No amplification was observed with DNA from asymptomatic plant samples. The purified nested PCR products were cloned into E. coli DH5α, using the pGEM-T Easy vector (Promega, United States) and sequenced with primers M13For/M13Rev using an automatic sequencer (ABI Prism, Perkin Elmer) at CIMAP. The sequence was analyzed by BLASTn and found to share 99% similarity with Echinacea witches'-broom phytoplasma and Sesame phyllody phytoplasma strain (GenBank Accession Nos. JF340080 and KF612966, respectively), which belong to the 16SrII-D group. The sequence was deposited in NCBI as GenBank Accession No. KM359410. A phylogenetic tree using MEGA v5.0 (4) was constructed with 16S rDNA; consensus sequences of phytoplasmas belonging to distinct groups revealed that the present phytoplasma clustered with the 16SrII group. iPhyClassifier software was used to perform sequence comparison and generate a virtual restriction fragment length polymorphism (RFLP) profile (5). On the basis of iPhyClassifier, the 16S rDNA sequence analysis of our isolate showed 99.2% similarity with that of the 'Candidatus Phytoplasma australasiae' reference strain (GenBank Accession No. Y10097), which belongs to 16Sr group II. The virtual RFLP pattern of F2n/R2 fragment was most similar to the 16SrII-D subgroup (similarity coefficient of 0.91) but showed a difference in profile with HpaI, HhaI, and MseI enzymes. Several bacterial/fungal and viral diseases have been reported on A. paniculata (3); however, to our knowledge, this is the first report of witches' broom disease in India and the first record of a 16SrII-D group phytoplasma on Kalmegh. Its presence in Kalmegh is of great significance due to its commercial interest. References: (1) S. Akbar. Altern. Med. Rev. 16:1, 2011. (2) D. E. Gundersen and M. Lee. Phytopathol. Mediterr. 35:144, 1996. (3) A. Khan and A. Samad. Plant Dis. 98:698, 2014. (4) K. Tamura et al. Mol. Biol. Evol. 28:2731, 2011. (5) Y. Zhao et al. Int. J. Syst. Evol. Microbiol. 59:2582, 2009.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...