RESUMO
BACKGROUND: Supratentorial intraventricular tumors (SIVTs) are rare lesions of various entities characteristically presenting with hydrocephalus and often posing a surgical challenge due to their deep-seated localization. We aimed to elaborate on shunt dependency after tumor resection, clinical characteristics, and perioperative morbidity. METHODS: We retrospectively searched the institutional database for patients with supratentorial intraventricular tumors treated at the Department of Neurosurgery of the Ludwig-Maximilians-University in Munich, Germany, between 2014 and 2022. RESULTS: We identified 59 patients with over 20 different SIVT entities, most often subependymoma (8/59 patients, 14%). Mean age at diagnosis was 41 ± 3 years. Hydrocephalus and visual symptoms were observed in 37/59 (63%) and 10/59 (17%) patients, respectively. Microsurgical tumor resection was provided in 46/59 patients (78%) with complete resection in 33/46 patients (72%). Persistent postoperative neurological deficits were encountered in 3/46 patients (7%) and generally mild in nature. Complete tumor resection was associated with less permanent shunting in comparison to incomplete tumor resection, irrespective of tumor histology (6% versus 31%, p = 0.025). Stereotactic biopsy was utilized in 13/59 patients (22%), including 5 patients who received synchronous internal shunt implantation for symptomatic hydrocephalus. Median overall survival was not reached and did not differ between patients with or without open resection. CONCLUSIONS: SIVT patients display a high risk of developing hydrocephalus and visual symptoms. Complete resection of SIVTs can often be achieved, preventing the need for long-term shunting. Stereotactic biopsy along with internal shunting represents an effective approach to establish diagnosis and ameliorate symptoms if resection cannot be safely performed. Due to the rather benign histology, the outcome appears excellent when adjuvant therapy is provided.
Assuntos
Neoplasias Encefálicas , Neoplasias do Ventrículo Cerebral , Hidrocefalia , Neoplasias Supratentoriais , Humanos , Adulto , Estudos Retrospectivos , Neoplasias Encefálicas/cirurgia , Procedimentos Neurocirúrgicos , Neoplasias do Ventrículo Cerebral/cirurgia , Neoplasias do Ventrículo Cerebral/complicações , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Hidrocefalia/diagnóstico , Neoplasias Supratentoriais/cirurgia , Derivação VentriculoperitonealRESUMO
MHC class Ia-restricted CD8(+) T cells are important mediators of the adaptive immune response against infections caused by intracellular microorganisms. Whereas antigen-specific effector CD8(+) T cells can clear infection caused by intracellular pathogens, in some circumstances, the immune response is suboptimal and the microorganisms survive, causing host death or chronic infection. Here, we explored the cellular and molecular mechanisms that could explain why CD8(+) T cell-mediated immunity during infection with the human protozoan parasite Trypanosoma cruzi is not optimal. For that purpose, we compared the CD8(+) T-cell mediated immune responses in mice infected with T. cruzi or vaccinated with a recombinant adenovirus expressing an immunodominant parasite antigen. Several functional and phenotypic characteristics of specific CD8(+) T cells overlapped. Among few exceptions was an accelerated expansion of the immune response in adenoviral vaccinated mice when compared to infected ones. Also, there was an upregulated expression of the apoptotic-signaling receptor CD95 on the surface of specific T cells from infected mice, which was not observed in the case of adenoviral-vaccinated mice. Most importantly, adenoviral vaccine provided at the time of infection significantly reduced the upregulation of CD95 expression and the proapoptotic phenotype of pathogen-specific CD8(+) cells expanded during infection. In parallel, infected adenovirus-vaccinated mice had a stronger CD8 T-cell mediated immune response and survived an otherwise lethal infection. We concluded that a suboptimal CD8(+) T-cell response is associated with an upregulation of CD95 expression and a proapoptotic phenotype. Both can be blocked by adenoviral vaccination.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Neuraminidase/imunologia , Vacinas Protozoárias/imunologia , Trypanosoma cruzi/imunologia , Receptor fas/biossíntese , Adenoviridae/genética , Adenoviridae/imunologia , Animais , Anticorpos Antiprotozoários/biossíntese , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Apoptose , Doença de Chagas/imunologia , Doença de Chagas/prevenção & controle , Interferon gama/biossíntese , Proteína 1 de Membrana Associada ao Lisossomo/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Trypanosoma cruzi/patogenicidade , Vacinas Sintéticas/imunologiaRESUMO
MHC-restricted CD8(+) T cells are important during infection with the intracellular protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. Experimental studies performed in the past 25 years have elucidated a number of features related to the immune response mediated by these T cells, which are important for establishing the parasite/host equilibrium leading to chronic infection. CD8(+) T cells are specific for highly immunodominant antigens expressed by members of the trans-sialidase family. After infection, their activation is delayed, and the cells display a high proliferative activity associated with high apoptotic rates. Although they participate in parasite control and elimination, they are unable to clear the infection due to their low fitness, allowing the parasite to establish the chronic phase when these cells then play an active role in the induction of heart immunopathology. Vaccination with a number of subunit recombinant vaccines aimed at eliciting specific CD8(+) T cells can reverse this path, thereby generating a productive immune response that will lead to the control of infection, reduction of symptoms, and reduction of disease transmission. Due to these attributes, activation of CD8(+) T lymphocytes may constitute a path for the development of a veterinarian or human vaccine.
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Linfócitos T CD8-Positivos/imunologia , Imunidade Celular/imunologia , Trypanosoma cruzi/imunologia , Vacinas/imunologia , Doença de Chagas/imunologia , Doença de Chagas/prevenção & controle , HumanosRESUMO
In earlier studies, we reported that a heterologous prime-boost regimen using recombinant plasmid DNA followed by replication-defective adenovirus vector, both containing Trypanosoma cruzi genes encoding trans-sialidase (TS) and amastigote surface protein (ASP) 2, provided protective immunity against experimental infection with a reticulotropic strain of this human protozoan parasite. Herein, we tested the outcome of genetic vaccination of F1 (CB10XBALB/c) mice challenged with myotropic parasite strains (Brazil and Colombian). Initially, we determined that the coadministration during priming of a DNA plasmid containing the murine IL-12 gene improved the immune response and was essential for protective immunity elicited by the heterologous prime-boost regimen in susceptible male mice against acute lethal infections with these parasites. The prophylactic or therapeutic vaccination of resistant female mice led to a drastic reduction in the number of inflammatory infiltrates in cardiac and skeletal muscles during the chronic phase of infection with either strain. Analysis of the electrocardiographic parameters showed that prophylactic vaccination reduced the frequencies of sinus arrhythmia and atrioventricular block. Our results confirmed that prophylactic vaccination using the TS and ASP-2 genes benefits the host against acute and chronic pathologies caused by T. cruzi and should be further evaluated for the development of a veterinary or human vaccine against Chagas disease.
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Trypanosoma cruzi/imunologia , Trypanosoma cruzi/patogenicidade , Animais , Linfócitos T CD8-Positivos/imunologia , Doença de Chagas/prevenção & controle , Feminino , Glicoproteínas/genética , Glicoproteínas/imunologia , Interleucina-12/genética , Interleucina-12/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neuraminidase/genética , Neuraminidase/imunologia , Trypanosoma cruzi/metabolismoRESUMO
Malaria remains a global health challenge, necessitating the development of effective vaccines. The RTS,S vaccination prevents Plasmodium falciparum (Pf) malaria but is ineffective against Plasmodium vivax (Pv) disease. Herein, we evaluated the murine immunogenicity of a recombinant PvCSP incorporating prevalent polymorphisms, adjuvanted with Alhydrogel or Poly I:C. Both formulations induced prolonged IgG responses, with IgG1 dominance by the Alhydrogel group and high titers of all IgG isotypes by the Poly I:C counterpart. Poly I:C-adjuvanted vaccination increased splenic plasma cells, terminally-differentiated memory cells (MBCs), and precursors relative to the Alhydrogel-combined immunization. Splenic B-cells from Poly I:C-vaccinated mice revealed an antibody-secreting cell- and MBC-differentiating gene expression profile. Biological processes such as antibody folding and secretion were highlighted by the Poly I:C-adjuvanted vaccination. These findings underscore the potential of Poly I:C to strengthen immune responses against Pv malaria.
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Adjuvantes de Vacinas , Hidróxido de Alumínio , Imunogenicidade da Vacina , Vacinas Antimaláricas , Malária Vivax , Plasmodium vivax , Poli I-C , Proteínas de Protozoários , Poli I-C/administração & dosagem , Plasmodium vivax/imunologia , Imunidade Humoral , Imunidade Celular , Proteínas de Protozoários/imunologia , Vacinas Antimaláricas/química , Vacinas Antimaláricas/imunologia , Hidróxido de Alumínio/administração & dosagem , Imunoglobulina G/sangue , Masculino , Animais , Plasmócitos/imunologia , Feminino , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/imunologia , Vacinação , Adjuvantes de Vacinas/administração & dosagem , Malária Vivax/prevenção & controleRESUMO
In a rodent (Rattus norvegicus) survey in Buenos Aires province, metacestodes of tapeworms were found encysted in the liver of the host. The aim of this work was the morphological and molecular identification of this parasite. To achieve the molecular characterization of the parasite, ribosomal (28S) and mitochondrial (COI) DNA were amplified and sequenced. Based on both morphological and molecular data using bioinformatic tools, the metacestode was identified as Cysticercus fasciolaris. The adult form of this tapeworm (Taenia taeniaeformis) commonly infects felid and canid mammalian hosts. This is the first report on the molecular identification of Cysticercus fasciolaris in Buenos Aires province (Argentina).
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Cysticercus/anatomia & histologia , Cysticercus/genética , Ratos/parasitologia , Animais , Argentina , Cysticercus/classificação , Cysticercus/isolamento & purificaçãoRESUMO
Listeria monocytogenesis a facultative intracellular pathogen, ubiquitous and aetiological agent of listeriosis. The main way of acquisition is the consumption of contaminated food and can cause serious medical conditions such as septicemia, meningitis and gastroenteritis, especially in children, immunocompromised individuals and seniors and abortions in pregnant women. An increase in cases of listeriosis worldwide has been reported and it is estimated that its prevalence in developed countries is in the range of 2 to 15 cases per one million population. This microorganism is characterized for the transition from the environment into the eukaryotic cell. Several virulence factors have been involved in the intracellular cycle that are regulated, primarily, by the PrfA protein, which in turn is regulated by different mechanisms operating at the transcriptional, translational and post-translational levels. Additionally, other regulatory mechanisms have been described as sigma factor, system VirR/S and antisense RNA, but PrfA is the most important control mechanism and is required for the expression of essential virulence factors for the intracellular cycle.
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Regulação Bacteriana da Expressão Gênica/fisiologia , Listeria monocytogenes/patogenicidade , Transativadores/fisiologia , Fatores de Virulência/fisiologia , Virulência/fisiologia , Feminino , Humanos , Listeria monocytogenes/genética , Masculino , Gravidez , Transativadores/genética , Virulência/genéticaRESUMO
The resistance of gram-negative bacilli is one of the most important areas in modern medicine, however it hasn't been highlighted the role of the third generation cephalosporins and in particularly ceftriaxone in the selection of gram-negative bacilli resistant to these agents. Paradoxically, ceftriaxone, like the rest of the molecules of this generation, whose initial indication were gram- negative infections began to be used as an agent of choice in pneumococcal infections. The broad spectrum activity of this molecule with its favorable pharmacokinetic properties replaces other agents by this antibiotic in the treatment of a wide range of community acquired infections. However, it wasn't considered the action of this cephalosporin on the microbiome, particularly the intestinal flora, which allowed the selection of enterobacteria that by genetic events, especially parental ß-lactamases mutations (TEM-1, TEM-2, SHV-1), developed resistance to third-generation cephalosporins. The decreased susceptibility to penicillin in Streptococcus pneumoniae isolates that stimulated the growing use of ceftriaxone, was one of the main drivers for the development of resistance to third-generation cephalosporins in gram-negative bacilli.
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Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas/efeitos dos fármacos , Ceftriaxona/farmacologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Humanos , Infecções Pneumocócicas/tratamento farmacológico , Streptococcus pneumoniae/efeitos dos fármacosRESUMO
Breast cancer is the most incidental and deadly neoplasm worldwide; in Mexico, very few epidemiologic reports have analyzed the pathological features and its impact on their clinical outcome. Here, we studied the relation between pathological features and the clinical presentation at diagnosis and their impact on the overall and progression-free survival of patients with breast cancer. For this purpose, we collected 199 clinical records of female patients, aged at least 18 years old (y/o), with breast cancer diagnosis confirmed by biopsy. We excluded patients with incomplete or conflicting clinical records. Afterward, we performed an analysis of overall and progression-free survival and associated risks. Our results showed an average age at diagnosis of 52 y/o (24-85), the most common features were: upper outer quadrant tumor (32%), invasive ductal carcinoma (76.8%), moderately differentiated (44.3%), early clinical stages (40.8%), asymptomatic patients (47.8%), luminal A subtype (47.8%). Median overall survival was not reached, but median progression-free survival was 32.2 months (29.75-34.64, CI 95%) associated risk were: clinical stage (p < 0.0001) symptomatic presentation (p = 0.009) and histologic grade (p = 0.02). Therefore, we concluded that symptom presence at diagnosis impacts progression-free survival, and palpable symptoms are related to an increased risk for mortality.
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Neoplasias da Mama , Carcinoma Ductal de Mama , Adulto , Feminino , Humanos , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , México/epidemiologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou maisRESUMO
INTRODUCTION: Multiresistant nosocomial pathogens, especially Gram-negative bacilli (GNB), are a serious problem for public health systems worldwide. Due to their antimicrobial properties, copper alloys have been suggested as an alternative for the control of bacterial burden in surfaces in hospital environment. However, antibiotic multiresistance and copper resistance could be associated in GNB, and there is evidence that both kind of resistance genes (antibiotic and copper) can be located on the same genetic structures. For this reason antibiotic-multiresistant strains could survive in the presence of copper, selecting for bacterial phenotypes resistant to both antibacterial agents. AIM: To evaluate antibacterial activity of copper against nosocomial extended-spectrum ß-lactamases (ESBL) (+) and ESBL (-) GNB, and carbapenems resistant or susceptible strains. MATERIAL AND METHOD: This study included 390 strains of GNB isolated from Chilean hospitals: Acinetobacter baumannii and Pseudomonas aeruginosa resistant (CAR R) and susceptible (CAR S) to carbapenem antibiotics, and Klebsiella pneumoniae and Escherichia coli producers and non-producers of ESBL. Susceptibility levels to cupric sulphate were determined by agar dilution method and statistical analysis were used to determine the significance of the differences in the copper tolerance levels between the strains groups. RESULTS: Statistically superior copper tolerance levels were found in the CAR R and ESBL producing strains of A. baumannii and K. pneumoniae, in relation with the CAR S and ESBL not-producing strains. CONCLUSION: A relation between a diminished susceptibility to ionic copper and to recent generation antimicrobial agents was observed in K. pneumoniae y A. baumannii strains.
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Antibacterianos/farmacologia , Sulfato de Cobre/farmacologia , Cobre/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , beta-Lactamases/metabolismo , Bactérias Gram-Negativas/enzimologia , Bactérias Gram-Negativas/isolamento & purificação , Testes de Sensibilidade MicrobianaRESUMO
Recently, we described a heterologous prime-boost strategy using plasmid DNA followed by replication-defective human recombinant adenovirus type 5 as a powerful strategy to elicit long-lived CD8(+) T-cell-mediated protective immunity against experimental systemic infection of mice with a human intracellular protozoan parasite, Trypanosoma cruzi. In the present study, we further characterized the protective long-lived CD8(+) T cells. We compared several functional and phenotypic aspects of specific CD8(+) T cells present 14 or 98 days after the last immunizing dose and found the following: (i) the numbers of specific cells were similar, as determined by multimer staining or by determining the number of gamma interferon (IFN-γ)-secreting cells by enzyme-linked immunospot (ELISPOT) assay; (ii) these cells were equally cytotoxic in vivo; (iii) following in vitro stimulation, a slight decline in the frequency of multifunctional cells (CD107a(+) IFN-γ(+) or CD107a(+) IFN-γ(+) tumor necrosis factor alpha positive [TNF-α(+)]) was paralleled by a significant increase of CD107a singly positive cells after 98 days; (iv) the expression of several surface markers was identical, except for the reexpression of CD127 after 98 days; (v) the use of genetically deficient mice revealed a role for interleukin-12 (IL-12)/IL-23, but not IFN-γ, in the maintenance of these memory cells; and (vi) subsequent immunizations with an unrelated virus or a plasmid vaccine or the depletion of CD4(+) T cells did not significantly erode the number or function of these CD8(+) T cells during the 15-week period. From these results, we concluded that heterologous plasmid DNA prime-adenovirus boost vaccination generated a stable pool of functional protective long-lived CD8(+) T cells with an effector memory phenotype.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Doença de Chagas/imunologia , Doença de Chagas/prevenção & controle , Memória Imunológica/imunologia , Vacinas Protozoárias/imunologia , Trypanosoma cruzi/imunologia , Vacinação/métodos , Adenoviridae/genética , Animais , Separação Celular , Feminino , Citometria de Fluxo , Vetores Genéticos , Imunização Secundária/métodos , Camundongos , Camundongos Endogâmicos C57BL , Plasmídeos/imunologia , Vacinas de DNA/imunologia , Vacinas Sintéticas/imunologiaRESUMO
CONTEXT: Penstemon gentianoides (Kunth) Poir. and Penstemon campanulatus (Cav.) Willd. (Plantaginaceae) are important medicinal plants in Mexico used by indigenous people for their anti-inflammatory effects and to also reduce rheumatic pains. OBJECTIVE: In addition to radical scavenging activity, the anti-inflammatory activity of the extracts, fractions and compounds of these plants were investigated and reported here for the first time. MATERIALS AND METHODS: The anti-inflammatory activities of MeOH, CH(2)Cl(2), and ethyl acetate extracts and iridoid, flavonoids, and phenylpropanoids from Penstemon gentianoides and P. campanulatus were studied in the TPA-induced mouse ear edema model. In addition, antioxidant activity against DPPH, crocin and ß-carotene were investigated. RESULTS: All extracts were tested and a selection of known compounds significantly (p <0.05) inhibited mouse ear edema. The results showed that CH(2)Cl(2) extracts of roots and stems from P. gentianoides and ethyl acetate extracts of leaves from P. gentianoides and P. campanulatus, as well as luteolin, diosmetin, penstemide and verbascoside produced the most positive results. Of all substances tested, the CH(2)Cl(2) extract of P. gentianoides roots was the most powerful inhibitor (ED(50)=0.07 mg/ear), with activity comparable to that of indomethacin. These extracts, compounds purified, as well as known compounds, inhibited oxidation of ß-carotene and crocin. DISCUSSION AND CONCLUSION: These findings showed that the iridoid monoterpenes, flavonoids and phenylpropanoids present in these plants species may all contribute to the observed anti-inflammatory activity. Additionally, the observed antioxidant activity is correlated with the anti-inflammatory activity of these plants and the phytochemicals derived from them.
Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Penstemon/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/administração & dosagem , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Modelos Animais de Doenças , Edema/tratamento farmacológico , Edema/fisiopatologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Indometacina/farmacologia , Inflamação/fisiopatologia , Iridoides/isolamento & purificação , Iridoides/farmacologia , Masculino , Medicina Tradicional , México , Camundongos , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Solventes/químicaRESUMO
OBJECTIVES: The purpose of this study was (i) to investigate whether nanocomposite poly(methyl-methacrylate)-zinc oxide nanowires (PMMA-ZnO-NWs) have C. albicans antibiofilm activity; (ii) to evaluate the interaction between components of the nanocomposites based on PMMA-ZnO-NWs by Raman spectroscopy; and (iii) to assess ultrastructural alterations. DESIGN: Sixty-eight rectangles (17 PMMA (control) and 51 PMMA-ZnO-NWs (250, 500, 1000 ppm ZnO nanowires) were fabricated. C. albicans ATCC 10231 and a C. albicans clinical strain were tested. Adherence, biofilm formation and ultrastructural alterations were assessed by transmission electron microscopy. Raman mapping images and spectra were analyzed using main component analysis. RESULTS: Nanocomposite PMMA-ZnO-NWs inhibited the formation of C. albicans biofilms 94% at 1000 ppm and 80% at 500 ppm against both C. albicans strains. PMMA-ZnO-NWs induced ultrastructural alterations, including cell wall damage and disorganization of the cytoplasmic membrane, resulting in cell lysis. Raman spectroscopy showed new vibrational modes (300-365-485-600 cm-1) for PMMA and ZnO-NW interactions. CONCLUSIONS: PMMA-ZnO-NWs inhibited C. albicans dose-dependent biofilm formation and led to changes in the structures and cell membrane. Raman spectroscopy showed chemical interactions between ZnO-NWs and PMMA, as suggested by the appearance of new bands at 301 and 485 cm-1.
RESUMO
UNLABELLED: Prostate adenocarcinoma is found in surgical samples without prior diagnosis in 4 to 15% of the patients. In some of them, there is previous suspicion but in others this finding is completely incidental. We present 7 cases of prostate cancer detected in 100 patients who underwent bipolar transurethral resection (TUR) of the prostate due to regular indications. The aim of this paper is to describe patient's characteristics, postoperative outcome, analyze TURP as a diagnostic tool and evaluate therapeutic options for prostate cancer (PCa). METHODS: One hundred patients with bladder outlet obstruction due to benign prostatic hyperplasia (BPH) underwent TURP in FUCDIM between June 2007 and August 2009. In 7 of them, prostate adenocarcinomas were detected. None of the patients underwent TURP only because of increased prostate-specific antigen (PSA). RESULTS: Mean preoperative PSA was 7.6 ng/ml (r= 0.72 -27 ng/ml), 39% of the patients had PSA < 4 ng/ml; 33 (40%) had undergone previous biopsies and 36% of them had 2 or more previous biopsies. Prostate cancer detection global rate was 7%, 3 cases were incidental findings (low PSA and low-risk tumors), 3 patients had increased PSA and several previous biopsies with negative results and 1 had low PSA and aggressive tumor (Gleason 4+3). CONCLUSIONS: TURP patients with prostate cancer are a heterogeneous group. TURP can be both diagnostic and therapeutic when facing patients with obstructive symptoms, high PSA and negative prostate biopsies. There are several therapeutic alternatives for TURP patients with cancer, taking into consideration tumor grade and stage, age, life expectancy and will of the patient. Bipolar TUR, in selected patients, allows to offer optional active surveillance (in these patients PSADT is very useful) and if cancer is not found, it eases the follow up of these patients. Active treatment (surgery or radiotherapy) is indicated in T1a patients with life expectancy longer than 10 years, and in the majority of T1b patients.
Assuntos
Adenocarcinoma/diagnóstico , Doenças Prostáticas/cirurgia , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ressecção Transuretral da PróstataRESUMO
Two years ago, we held an exciting event entitled the São Paulo School of Advanced Sciences on Vaccines (SPSASV). Sixty-eight Ph.D. students, postdoctoral fellows and independent researchers from 37 different countries met at the Mendes Plaza Hotel located in the city of Santos, SP - Brazil to discuss the challenges and the new frontiers of vaccinology. The SPSASV provided a critical and comprehensive view of vaccine research from basics to the current state-of-the-art techniques performed worldwide. For 10 days, we discussed all the aspects of vaccine development in 36 lectures, 53 oral presentations and 2 poster sessions. At the end of the course, participants were further encouraged to present a model of a grant proposal related to vaccine development against individual pathogens. Among the targeted pathogens were viruses (Chikungunya, HIV, RSV, and Influenza), bacteria (Mycobacterium tuberculosis and Streptococcus pyogenes), parasites (Plasmodium falciparum or Plasmodium vivax), and the worm Strongyloides stercoralis. This report highlights some of the knowledge shared at the SPSASV.
RESUMO
Anthropic activity in Antarctica has been increasing considerably in recent years, which could have an important impact on the local microbiota affecting multiple features, including the bacterial resistome. As such, our study focused on determining the antibiotic-resistance patterns and antibiotic-resistance genes of bacteria recovered from freshwater samples collected in areas of Antarctica under different degrees of human influence. Aerobic heterotrophic bacteria were subjected to antibiotic susceptibility testing and PCR. The isolates collected from regions of high human intervention were resistant to several antibiotic groups, and were mainly associated with the presence of genes encoding aminoglycosides-modifying enzymes (AMEs) and extended-spectrum ß-lactamases (ESBLs). Moreover, these isolates were resistant to synthetic and semi-synthetic drugs, in contrast with those recovered from zones with low human intervention, which resulted highly susceptible to antibiotics. On the other hand, we observed that zone A, under human influence, presented a higher richness and diversity of antibiotic-resistance genes (ARGs) in comparison with zones B and C, which have low human activity. Our results suggest that human activity has an impact on the local microbiota, in which strains recovered from zones under anthropic influence were considerably more resistant than those collected from remote regions.
Assuntos
Resistência Microbiana a Medicamentos , Água Doce/microbiologia , Microbiologia da Água , Animais , Regiões Antárticas , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/genética , Farmacorresistência Bacteriana , Meio Ambiente , Genes Bacterianos , Geografia , Humanos , Testes de Sensibilidade Microbiana , Microbiota/efeitos dos fármacos , Reação em Cadeia da Polimerase , beta-Lactamases/metabolismoRESUMO
Plasmodium vivax is the most common species of human malaria parasite found outside Africa, with high endemicity in Asia, Central and South America, and Oceania. Although Plasmodium falciparum causes the majority of deaths, P. vivax can lead to severe malaria and result in significant morbidity and mortality. The development of a protective vaccine will be a major step toward malaria elimination. Recently, a formulation containing the three allelic variants of the P. vivax circumsporozoite protein (PvCSP-All epitopes) showed partial protection in mice after a challenge with the hybrid Plasmodium berghei (Pb) sporozoite, in which the PbCSP central repeats were replaced by the VK210 PvCSP repeats (Pb/Pv sporozoite). In the present study, the chimeric PvCSP allelic variants (VK210, VK247, and P. vivax-like) were fused with the mumps virus nucleocapsid protein in the absence (NLP-CSPR) or presence of the conserved C-terminal (CT) domain of PvCSP (NLP-CSPCT). To elicit stronger humoral and cellular responses, Pichia pastoris yeast was used to assemble them as nucleocapsid-like particles (NLPs). Mice were immunized with each recombinant protein adjuvanted with Poly (I:C) and presented a high frequency of antigen-specific antibody-secreting cells (ASCs) on days 5 and 30, respectively, in the spleen and bone marrow. Moreover, high IgG titers against all PvCSP variants were detected in the sera. Later, these immunized mice with NLP-CSPCT were challenged with Pb/Pv sporozoites. Sterile protection was observed in 30% of the challenged mice. Therefore, this vaccine formulation use has the potential to be a good candidate for the development of a universal vaccine against P. vivax malaria.
RESUMO
Vaccines have had an unquestionable impact on public health during the last century. The most likely reason for the success of vaccines is the robust protective properties of specific antibodies. However, antibodies exert a strong selective pressure and many microorganisms, such as the obligatory intracellular parasite Trypanosoma cruzi, have been selected to survive in their presence. Although the host develops a strong immune response to T. cruzi, they do not clear the infection and instead progress to the chronic phase of the disease. Parasite persistence during the chronic phase of infection is now considered the main factor contributing to the chronic symptoms of the disease. Based on this finding, containment of parasite growth and survival may be one method to avoid the immunopathology of the chronic phase. In this context, vaccinologists have looked over the past 20 years for other immune effector mechanisms that could eliminate these antibody-resistant pathogens. We and others have tested the hypothesis that non-antibody-mediated cellular immune responses (CD4+ Th1 and CD8+ Tc1 cells) to specific parasite antigens/genes expressed by T. cruzi could indeed be used for the purpose of vaccination. This hypothesis was confirmed in different mouse models, indicating a possible path for vaccine development.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Doença de Chagas/imunologia , Vacinas Protozoárias/imunologia , Trypanosoma cruzi/imunologia , Animais , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Doença de Chagas/prevenção & controle , Modelos Animais de Doenças , Imunidade Celular , Camundongos , Trypanosoma cruzi/genéticaRESUMO
Bacterial multi-drugs systems contribute to the development of multi-resistance patterns of Acinetobacter baumannii, a nosocomial pathogen of increasing importance due to its emerging resistance to carbapenems. The multi-resistance phenomena is generated by a combination of mechanisms, one of which the efflux pump system. Many of these multiresistant isolates of A. baumannii harbor genes for the AdeABC multi-drug efflux system, related with resistance to various groups of antibacterial agents, including tygecicline and meropenem. Inhibition of these systems would allow to increase the efficacy of this antimicrobial. This review focuses on the multi-drug efflux pump system of A. baumannii with special emphasis in the AdeABC system.
Assuntos
Acinetobacter baumannii/metabolismo , Antibacterianos/farmacocinética , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana Múltipla/fisiologia , Proteínas de Membrana Transportadoras/metabolismo , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologiaRESUMO
Salmon farming industry in Chile currently uses a significant quantity of antimicrobials to control bacterial pathologies. The main aims of this study were to investigate the presence of transferable sulfonamide- and trimethoprim-resistance genes, sul and dfr, and their association with integrons among bacteria associated to Chilean salmon farming. For this purpose, 91 Gram-negative strains resistant to sulfisoxazole and/or trimethoprim recovered from various sources of seven Chilean salmonid farms and mainly identified as belonging to the Pseudomonas genus (81.0%) were studied. Patterns of antimicrobial resistance of strains showed a high incidence of resistance to florfenicol (98.9%), erythromycin (95.6%), furazolidone (90.1%) and amoxicillin (98.0%), whereas strains exhibited minimum inhibitory concentrations (MIC90) values of sulfisoxazole and trimethoprim of >4,096 and >2,048 µg mL-1, respectively. Strains were studied for their carriage of these genes by polymerase chain reaction, using specific primers, and 28 strains (30.8%) were found to carry at least one type of sul gene, mainly associated to a class 1 integron (17 strains), and identified by 16S rRNA gene sequencing as mainly belonging to the Pseudomonas genus (21 strains). Of these, 22 strains carried the sul1 gene, 3 strains carried the sul2 gene, and 3 strains carried both the sul1 and sul2 genes. Among these, 19 strains also carried the class 1 integron-integrase gene intI1, whereas the dfrA1, dfrA12 and dfrA14 genes were detected, mostly not inserted in the class 1 integron. Otherwise, the sul3 and intI2 genes were not found. In addition, the capability to transfer by conjugation these resistance determinants was evaluated in 22 selected strains, and sul and dfr genes were successfully transferred by 10 assayed strains, mainly mediated by a 10 kb plasmid, with a frequency of transfer of 1.4 × 10-5 to 8.4 × 10-3 transconjugant per recipient cell, and exhibiting a co-transference of resistance to florfenicol and oxytetracycline, currently the most used in Chilean salmon industry, suggesting an antibacterial co-selection phenomenon. This is the first report of the characterization and transferability of integrons as well as sul and dfr genes among bacteria associated to Chilean salmon farms, evidencing a relevant role of this environment as a reservoir of these genes.