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1.
Front Immunol ; 12: 655122, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34408743

RESUMO

FOXP3+ regulatory T cells (Tregs) are central for maintaining peripheral tolerance and immune homeostasis. Because of their immunosuppressive characteristics, Tregs are a potential therapeutic target in various diseases such as autoimmunity, transplantation and infectious diseases like COVID-19. Numerous studies are currently exploring the potential of adoptive Treg therapy in different disease settings and novel genome editing techniques like CRISPR/Cas will likely widen possibilities to strengthen its efficacy. However, robust and expeditious protocols for genome editing of human Tregs are limited. Here, we describe a rapid and effective protocol for reaching high genome editing efficiencies in human Tregs without compromising cell integrity, suitable for potential therapeutic applications. By deletion of IL2RA encoding for IL-2 receptor α-chain (CD25) in Tregs, we demonstrated the applicability of the method for downstream functional assays and highlighted the importance for CD25 for in vitro suppressive function of human Tregs. Moreover, deletion of IL6RA (CD126) in human Tregs elicits cytokine unresponsiveness and thus may prevent IL-6-mediated instability of Tregs, making it an attractive target to potentially boost functionality in settings of adoptive Treg therapies to contain overreaching inflammation or autoimmunity. Thus, our rapid and efficient protocol for genome editing in human Tregs may advance possibilities for Treg-based cellular therapies.


Assuntos
Edição de Genes/métodos , Subunidade alfa de Receptor de Interleucina-2/genética , Receptores de Interleucina-6/genética , Linfócitos T Reguladores/metabolismo , Buffy Coat/citologia , Sistemas CRISPR-Cas/genética , Fatores de Transcrição Forkhead/metabolismo , Técnicas de Silenciamento de Genes , Células HEK293 , Voluntários Saudáveis , Humanos , Imunoterapia Adotiva/métodos , Cultura Primária de Células , RNA Guia/genética , Fatores de Tempo
2.
Nat Commun ; 12(1): 1970, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33785752

RESUMO

Periods of fasting and refeeding may reduce cardiometabolic risk elevated by Western diet. Here we show in the substudy of NCT02099968, investigating the clinical parameters, the immunome and gut microbiome exploratory endpoints, that in hypertensive metabolic syndrome patients, a 5-day fast followed by a modified Dietary Approach to Stop Hypertension diet reduces systolic blood pressure, need for antihypertensive medications, body-mass index at three months post intervention compared to a modified Dietary Approach to Stop Hypertension diet alone. Fasting alters the gut microbiome, impacting bacterial taxa and gene modules associated with short-chain fatty acid production. Cross-system analyses reveal a positive correlation of circulating mucosa-associated invariant T cells, non-classical monocytes and CD4+ effector T cells with systolic blood pressure. Furthermore, regulatory T cells positively correlate with body-mass index and weight. Machine learning analysis of baseline immunome or microbiome data predicts sustained systolic blood pressure response within the fasting group, identifying CD8+ effector T cells, Th17 cells and regulatory T cells or Desulfovibrionaceae, Hydrogenoanaerobacterium, Akkermansia, and Ruminococcaceae as important contributors to the model. Here we report that the high-resolution multi-omics data highlight fasting as a promising non-pharmacological intervention for the treatment of high blood pressure in metabolic syndrome patients.


Assuntos
Pressão Sanguínea/fisiologia , Peso Corporal/fisiologia , Jejum/fisiologia , Microbioma Gastrointestinal/fisiologia , Síndrome Metabólica/fisiopatologia , Idoso , Akkermansia/fisiologia , Índice de Massa Corporal , Desulfovibrionaceae/fisiologia , Dieta , Fezes/microbiologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/microbiologia , Hipertensão/fisiopatologia , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/microbiologia , Pessoa de Meia-Idade , Ruminococcus/fisiologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/fisiologia
3.
Emerg Radiol ; 28(2): 333-338, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33398711

RESUMO

PURPOSE: Due to the recently emerging shortage in medical staff during the novel corona virus pandemic, several countries have rushed their undergraduate medical students into the emergency department. The accuracy of diagnosing critical findings on X-rays by senior medical students is not well assessed. In this study, we aim to assess the knowledge and accuracy of undergraduate final-year medical students in diagnosing life-threatening emergency conditions on chest x-ray. METHOD: This is a cross-sectional nationwide survey across all medical schools in Jordan. Through an electronic questionnaire, participants were sequentially shown a total of six abnormal X-rays and one normal. For each X-ray, participants were asked to choose the most likely diagnosis, and to grade the degree of self-confidence regarding the accuracy of their answer in a score from 0 (not confident) to 10 (very confident). RESULTS: We included a total of 530 participants. All participants answered at least six out of seven questions correctly, out of them, 139 (26.2%) participants answered all questions correctly. Pneumoperitoneum was the highest correct answer (93.8%), whereas flail chest was the least correctly answered case with only 310 (58.5%) correct answers. Regarding self-confidence for each question, 338 participants (63.8%) reported very high overall self-confidence level. Answers related to tension pneumothorax had the highest confidence level. CONCLUSION: Senior Jordanian medical students showed good knowledge with high confidence levels in diagnosing life-threatening conditions on chest x-rays, supporting their incorporation in the emergency department during pandemics and confirming the reliability of information they can extract.


Assuntos
Competência Clínica , Serviço Hospitalar de Emergência/organização & administração , Radiografia Torácica , Estudantes de Medicina , Adulto , COVID-19/epidemiologia , Estudos Transversais , Feminino , Humanos , Jordânia/epidemiologia , Masculino , Pandemias , SARS-CoV-2 , Inquéritos e Questionários
4.
Sleep Breath ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33118055

RESUMO

BACKGROUND: While several studies assessed the relation between cigarette smoking and sleep, there are still very few studies assessing the effect of nicotine in cigarette smoking on sleep. AIM: This study aimed to compare higher vs lower nicotine levels in cigarette smoking on sleep quality. METHODS: We used data from the recently released dataset for the Randomized Trial of Reduced-Nicotine Standards for Cigarettes. We included three groups in the current study: the least nicotine concentration (i.e., 0.4 mg/g), a moderate nicotine concentration (i.e., 5.2 mg/g), and the highest nicotine concentration (i.e., 15.8 mg/g). For each participant, we included data regarding baseline and the last follow up at 6 weeks, where we compared insomnia, sleep problems, and awakening at night, in addition to different depression and affect scores. RESULTS: A total of 360 patients were included in this study, with a mean age of 42.4 (±13.4) years. For the three nicotine groups (i.e., 0.4 mg/g, 5.2 mg/g, and 15.8 mg/g), we included 119 (33%), 122 (34%), and 119 (33%) participants. Among the high-nicotine-dose group, the number of participants who had worsened sleep was significantly higher than the number of those who had improved sleep (p = 0.01) after 6 weeks of consumption, where 37 (31%) had worsened sleep score after 6 weeks while only 19 (16%) had improved score compared with baseline. CONCLUSION: While previous studies established a relation either between cigarette smoking and sleep or between nicotine patches and sleep, the present study is the first to establish that higher nicotine doses in cigarettes were associated with more sleep disturbances.

5.
Front Immunol ; 11: 253, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32153577

RESUMO

The rise in the prevalence of autoimmune diseases in developed societies has been associated with a change in lifestyle patterns. Among other factors, increased consumption of certain dietary components, such as table salt and fatty acids and excessive caloric intake has been associated with defective immunological tolerance. Dietary nutrients have shown to modulate the immune response by a direct effect on the function of immune cells or, indirectly, by acting on the microbiome of the gastrointestinal tract. FOXP3+ regulatory T cells (Tregs) suppress immune responses and are critical for maintaining peripheral tolerance and immune homeostasis, modulating chronic tissue inflammation and autoimmune disease. It is now well-recognized that Tregs show certain degree of plasticity and can gain effector functions to adapt their regulatory function to different physiological situations during an immune response. However, plasticity of Tregs might also result in conversion into effector T cells that may contribute to autoimmune pathogenesis. Yet, which environmental cues regulate Treg plasticity and function is currently poorly understood, but it is of significant importance for therapeutic purposes. Here we review the current understanding on the effect of certain dietary nutrients that characterize Western diets in Treg metabolism, stability, and function. Moreover, we will discuss the role of Tregs linking diet and autoimmunity and the potential of dietary-based interventions to modulate Treg function in disease.


Assuntos
Dietoterapia , Dieta , Linfócitos T Reguladores/imunologia , Animais , Doenças Autoimunes , Fatores de Transcrição Forkhead/metabolismo , Homeostase , Humanos , Tolerância Imunológica , Microbiota
6.
J Extracell Vesicles ; 10(1): e12022, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33708355

RESUMO

Microglia, the immunocompetent cells of the central nervous system (CNS), play an important role in maintaining cellular homeostasis in the CNS. These cells secrete immunomodulatory factors including nanovesicles and participate in the removal of cellular debris by phagocytosis or autophagy. Accumulating evidence indicates that specifically the cellular exchange of small extracellular vesicles (EVs), participates in physiology and disease through intercellular communication. However, the contribution of microglial-derived extracellular vesicles (M-EVs) to the maintenance of microglia homeostasis and how M-EVs could influence the phenotype and gene function of other microglia subtypes is unclear. In addition, knowledge of canonical signalling pathways of inflammation and immunity gene expression patterns in human microglia exposed to M-EVs is limited. Here, we analysed the effects of M-EVs produced in vitro by either tumour necrosis factor alpha (TNFα) activated or non-activated microglia BV2 cells. We showed that M-EVs are internalized by both mouse and human C20 microglia cells and that the uptake of M-EVs in microglia induced autophagic vesicles at various stages of degradation including autophagosomes and autolysosomes. Consistently, stimulation of microglia with M-EVs increased the protein expression of the autophagy marker, microtubule-associated proteins 1A/1B light chain 3B isoform II (LC3B-II), and promoted autophagic flux in live cells. To elucidate the biological activities occurring at the transcriptional level in C20 microglia stimulated with M-EVs, the gene expression profiles, potential upstream regulators, and enrichment pathways were characterized using targeted RNA sequencing. Inflammation and immunity transcriptome gene panel sequencing of both activated and normal microglia stimulated with M-EVs showed involvement of several canonical pathways and reduced expression of key genes involved in neuroinflammation, inflammasome and apoptosis signalling pathways compared to control cells. In this study, we provide the perspective that a beneficial activity of in vitro cell culture produced EVs could be the modulation of autophagy during cellular stress. Therefore, we use a monoculture system to study microglia-microglia crosstalk which is important in the prevention and propagation of inflammation in the brain. We demonstrate that in vitro produced microglial EVs are able to influence multiple biological pathways and promote activation of autophagy in order to maintain microglia survival and homeostasis.

7.
Front Immunol ; 10: 1141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31214164

RESUMO

Excess salt intake could affect the immune system by shifting the immune cell balance toward a pro-inflammatory state. Since this shift of the immune balance is thought to be beneficial in anti-cancer immunity, we tested the impact of high salt diets on tumor growth in mice. Here we show that high salt significantly inhibited tumor growth in two independent murine tumor transplantation models. Although high salt fed tumor-bearing mice showed alterations in T cell populations, the effect seemed to be largely independent of adaptive immune cells. In contrast, depletion of myeloid-derived suppressor cells (MDSCs) significantly reverted the inhibitory effect on tumor growth. In line with this, high salt conditions almost completely blocked murine MDSC function in vitro. Importantly, similar effects were observed in human MDSCs isolated from cancer patients. Thus, high salt conditions seem to inhibit tumor growth by enabling more pronounced anti-tumor immunity through the functional modulation of MDSCs. Our findings might have critical relevance for cancer immunotherapy.


Assuntos
Imunidade , Neoplasias/imunologia , Neoplasias/metabolismo , Cloreto de Sódio na Dieta/metabolismo , Animais , Apoptose , Biomarcadores , Modelos Animais de Doenças , Progressão da Doença , Xenoenxertos , Humanos , Imuno-Histoquímica , Camundongos , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Neoplasias/patologia
8.
PLoS One ; 13(1): e0191913, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29385188

RESUMO

Research on the relationship between changes in the gut microbiota and human disease, including AIDS, is a growing field. However, studies on the eukaryotic component of the intestinal microbiota have just begun and have not yet been conducted in HIV-infected patients. Moreover, eukaryotic community profiling is influenced by the use of different methodologies at each step of culture-independent techniques. Herein, initially, four DNA extraction protocols were compared to test the efficiency of each method in recovering eukaryotic DNA from fecal samples. Our results revealed that recovering eukaryotic components from fecal samples differs significantly among DNA extraction methods. Subsequently, the composition of the intestinal eukaryotic microbiota was evaluated in HIV-infected patients and healthy volunteers through clone sequencing, high-throughput sequencing of nuclear ribosomal internal transcribed spacers 1 (ITS1) and 2 (ITS2) amplicons and real-time PCRs. Our results revealed that not only richness (Chao-1 index) and alpha diversity (Shannon diversity) differ between HIV-infected patients and healthy volunteers, depending on the molecular strategy used, but also the global eukaryotic community composition, with little overlapping taxa found between techniques. Moreover, our results based on cloning libraries and ITS1/ITS2 metabarcoding sequencing showed significant differences in fungal composition between HIV-infected patients and healthy volunteers, but without distinct clusters separating the two groups. Malassezia restricta was significantly more prevalent in fecal samples of HIV-infected patients, according to cloning libraries, whereas operational taxonomic units (OTUs) belonging to Candida albicans and Candida tropicalis were significantly more abundant in fecal samples of HIV-infected patients compared to healthy subjects in both ITS subregions. Finally, real-time PCR showed the presence of Microsporidia, Giardia lamblia, Blastocystis and Hymenolepis diminuta in different proportions in fecal samples from HIV patients as compared to healthy individuals. Our work revealed that the use of different sequencing approaches can impact the perceived eukaryotic diversity results of the human gut. We also provide a more comprehensive view of the eukaryotic community in the gut of HIV-infected patients through the complementarity of the different molecular techniques used. Combining these various methodologies may provide a gold standard for a more complete characterization of the eukaryotic microbiome in future studies.


Assuntos
Código de Barras de DNA Taxonômico , Infecções por HIV/microbiologia , Intestinos/microbiologia , Microbiota , Estudos de Casos e Controles , Humanos , Reação em Cadeia da Polimerase em Tempo Real
9.
Sci Rep ; 7(1): 16788, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29196717

RESUMO

Herein, the mycobiota was characterized in fecal samples from sick patients and healthy subjects, collected from different geographical locations and using both culturomics and amplicon-based metagenomics approaches. Using the culturomics approach, a total of 17,800 fungal colonies were isolated from 14 fecal samples, and resulted in the isolation of 41 fungal species, of which 10 species had not been previously reported in the human gut. Deep sequencing of fungal-directed ITS1 and ITS2 amplicons led to the detection of a total of 142 OTUs and 173 OTUs from the ITS1 and ITS2 regions, respectively. Ascomycota composed the largest fraction of the total OTUs analyzed (78.9% and 68.2% of the OTUs from the ITS1 and ITS2 regions, respectively), followed by Basidiomycota (16.9% and 30.1% of the OTUs from the ITS1 and ITS2 regions, respectively). Interestingly, the results demonstrate that the ITS1/ITS2 amplicon sequencing provides different information about gut fungal communities compared to culturomics, though both approaches complete each other in assessing fungal diversity in fecal samples. We also report higher fungal diversity and abundance in patients compared to healthy subjects. In conclusion, combining both culturomic and amplicon-based metagenomic approaches may be a novel strategy towards analyzing fungal compositions in the human gut.


Assuntos
DNA Espaçador Ribossômico/análise , Fungos/classificação , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Metagenômica/métodos , Micoses/microbiologia , Ascomicetos/classificação , Ascomicetos/genética , Ascomicetos/isolamento & purificação , Basidiomycota/classificação , Basidiomycota/genética , Basidiomycota/isolamento & purificação , Estudos de Casos e Controles , DNA Fúngico/análise , Fezes/microbiologia , Fungos/genética , Fungos/isolamento & purificação , Microbioma Gastrointestinal , Humanos , Técnicas Microbiológicas , Micobioma , Filogenia , Análise de Sequência de DNA
12.
PLoS One ; 10(3): e0122471, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25811611

RESUMO

MicroRNA 122 (miR-122) is highly expressed in the liver where it influences diverse biological processes and pathways, including hepatitis C virus replication and metabolism of iron and cholesterol. It is processed from a long non-coding primary transcript (~7.5 kb) and the gene has two evolutionarily-conserved regions containing the pri-mir-122 promoter and pre-mir-122 hairpin region. Several groups reported that the widely-used hepatocytic cell line HepG2 had deficient expression of miR-122, previously ascribed to deletion of the pre-mir-122 stem-loop region. We aimed to characterise this deletion by direct sequencing of 6078 bp containing the pri-mir-122 promoter and pre-mir-122 stem-loop region in HepG2 and Huh-7, a control hepatocytic cell line reported to express miR-122, supported by sequence analysis of cloned genomic DNA. In contrast to previous findings, the entire sequence was present in both cell lines. Ten SNPs were heterozygous in HepG2 indicating that DNA was present in two copies. Three validation isolates of HepG2 were sequenced, showing identical genotype to the original in two, whereas the third was different. Investigation of promoter chromatin status by FAIRE showed that Huh-7 cells had 6.2 ± 0.19- and 2.7 ± 0.01- fold more accessible chromatin at the proximal (HNF4α-binding) and distal DR1 transcription factor sites, compared to HepG2 cells (p=0.03 and 0.001, respectively). This was substantiated by ENCODE genome annotations, which showed a DNAse I hypersensitive site in the pri-mir-122 promoter in Huh-7 that was absent in HepG2 cells. While the origin of the reported deletion is unclear, cell lines should be obtained from a reputable source and used at low passage number to avoid discrepant results. Deficiency of miR-122 expression in HepG2 cells may be related to a relative deficiency of accessible promoter chromatin in HepG2 versus Huh-7 cells.


Assuntos
Deleção de Genes , MicroRNAs/genética , Clonagem Molecular , Dosagem de Genes , Haplótipos , Células Hep G2 , Heterozigoto , Humanos , Sequências Repetidas Invertidas , MicroRNAs/química , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas
13.
J Infect Dis ; 211(2): 267-73, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25001460

RESUMO

Vector-borne parasites of the genus Leishmania are responsible for severe human diseases. Cutaneous leishmaniasis, a common form of the disease, is most often caused by the transmission of Leishmania major to humans by female phlebotomine sand flies. Apes are increasingly being seen as a source of zoonotic diseases, including malaria and rickettsiosis. To examine whether gorillas harbor Leishmania species, we screened fecal samples from wild western lowland gorillas (Gorilla gorilla gorilla) in Cameroon for the presence of these pathogens. Of 91 wild gorilla fecal samples, 12 contained Leishmania parasites, and 4 contained phlebotomine sand fly vectors. The molecular identity was determined by running 3 different polymerase chain reaction tests for detection of L. major. Next, fluorescence in situ hybridization was performed to visualize L. major parasites in fecal samples from the gorillas. Both promastigote and amastigote forms of the parasite were found. This work strongly suggests that wild gorillas carry pathogenic Leishmania parasites.


Assuntos
Reservatórios de Doenças , Fezes/parasitologia , Gorilla gorilla/parasitologia , Leishmania major/isolamento & purificação , Animais , DNA de Protozoário/genética , Hibridização in Situ Fluorescente , Reação em Cadeia da Polimerase
14.
Sci Rep ; 4: 6417, 2014 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-25231746

RESUMO

Although gorillas regarded as the largest extant species of primates and have a close phylogenetic relationship with humans, eukaryotic communities have not been previously studied in these populations. Herein, 35 eukaryotic primer sets targeting the 18S rRNA gene, internal transcribed spacer gene and other specific genes were used firstly to explore the eukaryotes in a fecal sample from a wild western lowland gorilla (Gorilla gorilla gorilla). Then specific real-time PCRs were achieved in additional 48 fecal samples from 21 individual gorillas to investigate the presence of human eukaryotic pathogens. In total, 1,572 clones were obtained and sequenced from the 15 cloning libraries, resulting in the retrieval of 87 eukaryotic species, including 52 fungi, 10 protozoa, 4 nematodes and 21 plant species, of which 52, 5, 2 and 21 species, respectively, have never before been described in gorillas. We also reported the occurrence of pathogenic fungi and parasites (i.e. Oesophagostomum bifurcum (86%), Necator americanus (43%), Candida tropicalis (81%) and other pathogenic fungi were identified). In conclusion, molecular techniques using multiple primer sets may offer an effective tool to study complex eukaryotic communities and to identify potential pathogens in the gastrointestinal tracts of primates.


Assuntos
Biomarcadores/metabolismo , Eucariotos/patogenicidade , Fezes/microbiologia , Trato Gastrointestinal/microbiologia , Gorilla gorilla/microbiologia , Microbiota/genética , Animais , Primers do DNA/química , Primers do DNA/genética , Humanos , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 18S/genética , Reação em Cadeia da Polimerase em Tempo Real
15.
Microb Pathog ; 77: 149-54, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25220240

RESUMO

Because of the close genetic relatedness between apes and humans, apes are susceptible to many human infectious agents and can serve as carriers of these pathogens. Consequently, they present a serious health hazard to humans. Moreover, many emerging infectious diseases originate in wildlife and continue to threaten human populations, especially vector-borne diseases described in great apes, such as malaria and rickettsiosis. These wild primates may be permanent reservoirs and important sources of human pathogens. In this special issue, we report that apes, including chimpanzees (Pan troglodytes), bonobos (Pan paniscus), gorillas (Gorilla gorilla and Gorilla beringei), orangutans (Pongo pygmaeus and Pongo abelii), gibbons (Hylobates spp., Hoolock spp. and Nomascus spp) and siamangs (Symphalangus syndactylus syndactylus and Symphalangus continentis), have many bacterial, viral, fungal and parasitic species that are capable of infecting humans. Serious measures should be adopted in tropical forests and sub-tropical areas where habitat overlaps are frequent to survey and prevent infectious diseases from spreading from apes to people.


Assuntos
Bactérias/isolamento & purificação , Transmissão de Doença Infecciosa , Fungos/isolamento & purificação , Hominidae , Parasitos/isolamento & purificação , Vírus/isolamento & purificação , Zoonoses/transmissão , Animais , Reservatórios de Doenças , Humanos , Zoonoses/microbiologia , Zoonoses/parasitologia , Zoonoses/virologia
16.
Intervirology ; 57(5): 248-53, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24993859

RESUMO

OBJECTIVES: Patients with chronic hepatitis B virus (HBV) may exhibit significant liver pathology despite alanine aminotransferase (ALT) and HBV DNA levels below the cutoff values advised by treatment guidelines. We evaluated candidacy for HBV therapy when baseline histopathological changes are taken into consideration. METHODS: Clinical, biochemical, serological, virological, and histopathological (METAVIR score) data of 117 patients with HBeAg-negative chronic HBV genotype D were collected and analyzed. RESULTS: Significant pathology (≥F2 and/or ≥A2) and fibrosis (≥F2 ± ≥A2) were found in 73 (62.4%) and 59 (50.4%) patients, respectively. Based on HBV DNA (>2,000 IU/ml) and ALT levels >2 × 40 U/l (the standard cutoff value), only 31 (26.5%) patients were candidates for therapy. This increased to 58 (49.6%) patients when the new ALT cutoff values (30 U/l for males, and 19 U/l for females) were applied. Relying on either ≥F2 and/or A ≥2 or ≥F2 ± ≥A2 increases the treatment candidacy to 73 (62.4%) and 59 (50.4%) patients, respectively. Also, when compared with standard ALT cutoff values, applying both new ALT cutoff values with either significant pathology or fibrosis increases treatment candidacy to 28 (23.9%) and 42 (35.9%) patients, respectively. CONCLUSION: Liver pathology is more reliable than ALT and HBV DNA in the decision to treat patients with HBeAg-negative chronic HBV genotype D.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/patologia , Fígado/patologia , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Biópsia , Feminino , Genótipo , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/virologia , Humanos , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Carga Viral , Adulto Jovem
17.
Sci Rep ; 4: 4478, 2014 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-24675424

RESUMO

The consumption of insects by apes has previously been reported based on direct observations and/or trail signs in feces. However, DNA-based diet analyses may have the potential to reveal trophic links for these wild species. Herein, we analyzed the insect-diet diversity of 9 feces obtained from three species of African great apes, gorilla (Gorilla gorilla gorilla), chimpanzee (Pan troglodytes) and bonobo (Pan paniscus), using two mitochondrial amplifications for arthropods. A total of 1056 clones were sequenced for Cyt-b and COI gene libraries, which contained 50 and 56 operational taxonomic units (OTUs), respectively. BLAST research revealed that the OTUs belonged to 32 families from 5 orders (Diptera, Isoptera, Lepidoptera, Coleoptera, and Orthoptera). While ants were not detected by this method, the consumption of flies, beetles, moths, mosquitoes and termites was evident in these samples. Our findings indicate that molecular techniques can be used to analyze insect food items in wild animals.


Assuntos
Fezes/parasitologia , Hominidae/parasitologia , Insetos/classificação , Insetos/genética , Isópteros/classificação , Isópteros/genética , Animais , Doenças dos Símios Antropoides/parasitologia , Análise por Conglomerados , Código de Barras de DNA Taxonômico , Genes Mitocondriais , Dados de Sequência Molecular , Filogenia
18.
Ann Saudi Med ; 33(2): 119-23, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23951584

RESUMO

BACKGROUND AND OBJECTIVES: Entecavir is a nucleoside analog used in the treatment of chronic hepatitis B. The efficacy of ETV has not been studied in the Saudi population. The objective of the study was to find undetectable HBV DNA after 48 weeks completion of ETV treatment in real-life versus clinical trial patients. DESIGN AND SETTING: A retrospective study in a tertiary care center in Saudi Arabia of patients treated from 2006 January to 2010 June. PATIENTS AND METHODS: Of 43 eligible patients, 24 patients were treatment-naïve and 19 were treatment refractory. RESULTS: Mean HBV DNA viral load was 51 million IU/mL prior to treatment and decreased to 0.16 million IU/mL at 48 weeks. Mean HBV DNA log10 IU/mL was 6.3 before treatment and decreased to 2.3 log10 IU/mL(P=.001) at 48 weeks. After 48 weeks treatment, ALT significantly decreased from a mean ALT of 88.7 U/L before treatment to 37.5U/L (P=.04). After 48 weeks, the HBV DNA was undetectable in 14 (58.4%) in treatment-naïve patients and in 6 (31.6%) treatment-refractory patients. At 48 weeks 17 (60.7%) of HBeAg-negative patients and 3 (20%) HBeAg-positive patients achieved undetectable HBV DNA (P=.003). When the treatment was extended for a median of 24 months (range 12 months to 60 months), 29 (67.4%) achieved undetectable HBV DNA. Among 29 patients who achieved undetectable HBV DNA, the treatment refractory patients reached undetectability within a mean of 32.4 (18.6) months and treatment-naïve patients in a mean of 18.8 (10.5) months(P=.01). Two (13.3%) of HBeAg-reactive patients converted to HBeAg-negative status and one patient (2.3%)lost HBsAg. CONCLUSION: After treatment with entecavir, HBV DNA undetectable at 48 weeks in 58.4% of naïve patients.The response rate was better in HBeAg-negative and treatment-naïve patients compared to HBeAg-positive and treatment-refractory patients.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Adulto , Biomarcadores/sangue , DNA Viral/sangue , Esquema de Medicação , Feminino , Seguimentos , Guanina/uso terapêutico , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Arábia Saudita , Resultado do Tratamento , Carga Viral
19.
World J Hepatol ; 5(3): 127-32, 2013 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-23556045

RESUMO

AIM: To determine liver transplantation outcomes in Wilson's disease (WD) patients, focusing on neurological manifestations. METHODS: This retrospective study assessed data from 16 WD patients (nine males, 56%) who had liver transplants between 1991 and 2007. Survival, graft function, and neurological complications were assessed during a follow-up period of up to 15 years. In addition, each patient's medical record was reviewed in detail to find the type of Wilson's disease (hepatic or hepatic plus neurological WD), indication for liver transplantation, use of chelating agents prior to transplantation, immediate and long term complications following transplantation, the donor details, and the pathology of explanted liver. RESULTS: End-stage liver disease was the indication for transplantation in all 16 WD patients. Four patients displayed WD-related neurological symptoms in addition to liver disease. Living-related liver transplantation was done in three cases. One patient died on postoperative day 6 due to primary graft non-function. One-year post liver transplant survival was 94%. Neurological manifestations of all four patients disappeared during their follow-up. Four patients developed acute cellular rejection, but all responded to treatment. One patient developed chronic ductopenic rejection after 15 years post-transplantation and their graft failed; this patient is currently waiting for re-transplantation. Fourteen patients (88%) are still living. The long-term average survival is currently 10.5 years, with a current median survival of 8 years. Long-term graft survival is currently 81%. CONCLUSION: Short- and long-term survival in WD patient liver transplantation was excellent, and neurological and psychological WD manifestations disappeared during long-term follow-up.

20.
Ann Saudi Med ; 33(1): 10-2, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23458933

RESUMO

BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) genotype (G) knowledge is essential for determining type, duration and rate of response to antiviral therapy, possible route of HCV transmission, and future vaccine development. Our aim was to study HCV genotypes and to provide precise data on genotype distribution in both genders and different age groups amongst Saudi patients. DESIGN AND SETTING: Genotype data from molecular laboratories at four different tertiary care hospitals in Riyadh from January 2006 until December 2010 were collected and analyzed. PATIENTS AND METHODS: Consecutive data on genotype, sex and age was collected from 1013 Saudi patients. Genotyping was done by selective hybridization of amplicons to HCV genotype-specific oligonucleotides. RESULTS: We found G1 in 262 patients (25.9%), G2 in 44 (4.4 %), G3 in 29 (2.9 %), G4 in 608 (60%), and 3 patients (0.3%) each of G5 and G6. In addition, 64 (6.3%) patients had mixed genotypes, mostly G4 and G1. On subtyping in 191 G1 patients, 67 (35.1%) were G1a, and 124 (64.9 %) G1b. Age distribution showed that 18 (1.7%) were 0-20 years, 173 (17.1 %) 21-40 years, 521 (51.4%) 41-60 years and 301(29.7%) > 60 years. There was no significant difference in frequency of G1, G3 and G4 among the two genders. CONCLUSION: G1 and G4 are the predominant genotypes in Saudi patients infected with HCV (85.9%), with a similar distribution among the two sexes and no significant changes in genotype distribution over the past decade.


Assuntos
Genótipo , Hepacivirus/genética , Hepatite C/virologia , Distribuição por Idade , Feminino , Hepatite C/epidemiologia , Humanos , Masculino , Prevalência , Arábia Saudita/epidemiologia , Distribuição por Sexo , Centros de Atenção Terciária
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