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1.
PLoS One ; 19(5): e0302570, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38709749

RESUMO

University students are at high risk of sexually transmitted infections due to the lack of adequate sexual education, as well as multiple associated factors, which lead to risky sexual practices. It is important to update data about sexual behaviors to identify the main factors associated with sexually risky behaviors. The present study aimed to evaluate the current prevalence of sexually risky practices in medical students. A cross-sectional study was conducted among medical students through an anonymous self-administered online questionnaire including demographic characteristics and sexual behaviors. We used descriptive statistics and multivariable regression to analyze the data collected. A total of 1520 undergraduate medical students aged between 18 and 28 years old were included in the study. Sixty percent of the students were sexually active with a higher proportion in men (70%), likewise, they had an earlier sexual debut (16.5 vs 16.9 years old), and a greater number of lifetime sexual partners than women (3.8 vs 2.2). The main sexual activity in both groups was vaginal sex with high use of condoms (75%), however, most of them (67%) reported having unprotected oral sex. Logistic regression analysis showed that condomless sex was associated with having oral sex, anal sex, and being female. The findings of this study showed that medical university students are involved in risky sexual behaviors, the major risk factor was unprotected oral sex. Based on these results, we recommended designing interventions to improve sexual education and preventive approaches from early stages such as in middle school students to mitigate sexually transmitted infections among medical university students.


Assuntos
Assunção de Riscos , Comportamento Sexual , Estudantes de Medicina , Humanos , Masculino , Feminino , Estudantes de Medicina/estatística & dados numéricos , Estudantes de Medicina/psicologia , México/epidemiologia , Adolescente , Adulto , Adulto Jovem , Comportamento Sexual/estatística & dados numéricos , Prevalência , Estudos Transversais , Inquéritos e Questionários , Infecções Sexualmente Transmissíveis/epidemiologia , Sexo sem Proteção/estatística & dados numéricos
2.
Microorganisms ; 11(11)2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38004773

RESUMO

Several species of Acanthamoeba genus are potential pathogens and etiological agents of several diseases. The pathogenic mechanisms carried out by these amoebae in different target tissues have been documented, evidencing the relevant role of contact-dependent mechanisms. With the purpose of describing the pathogenic processes carried out by these protozoans more precisely, we considered it important to determine the emission of extracellular vesicles (EVs) as part of the contact-independent pathogenicity mechanisms of A. culbertsoni, a highly pathogenic strain. Through transmission electronic microscopy (TEM) and nanoparticle tracking analysis (NTA), EVs were characterized. EVs showed lipid membrane and a size between 60 and 855 nm. The secretion of large vesicles was corroborated by confocal and TEM microscopy. The SDS-PAGE of EVs showed proteins of 45 to 200 kDa. Antigenic recognition was determined by Western Blot, and the internalization of EVs by trophozoites was observed through Dil-labeled EVs. In addition, some EVs biological characteristics were determined, such as proteolytic, hemolytic and COX activity. Furthermore, we highlighted the presence of leishmanolysin in trophozites and EVs. These results suggest that EVs are part of a contact-independent mechanism, which, together with contact-dependent ones, allow for a better understanding of the pathogenicity carried out by Acanthamoeba culbertsoni.

3.
Genes (Basel) ; 14(4)2023 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-37107645

RESUMO

BACKGROUND: Ellis-van Creveld syndrome (EvCS) is an autosomal recessive ciliopathy with a disproportionate short stature, polydactyly, dystrophic nails, oral defects, and cardiac anomalies. It is caused by pathogenic variants in the EVC or EVC2 genes. To obtain further insight into the genetics of EvCS, we identified the genetic defect for the EVC2 gene in two Mexican patients. METHODS: Two Mexican families were enrolled in this study. Exome sequencing was applied in the probands to screen potential genetic variant(s), and then Sanger sequencing was used to identify the variant in the parents. Finally, a prediction of the three-dimensional structure of the mutant proteins was made. RESULTS: One patient has a compound heterozygous EVC2 mutation: a novel heterozygous variant c.519_519 + 1delinsT inherited from her mother, and a heterozygous variant c.2161delC (p.L721fs) inherited from her father. The second patient has a previously reported compound heterozygous EVC2 mutation: nonsense mutation c.645G > A (p.W215*) in exon 5 inherited from her mother, and c.273dup (p.K92fs) in exon 2 inherited from her father. In both cases, the diagnostic was Ellis-van Creveld syndrome. Three-dimensional modeling of the EVC2 protein showed that truncated proteins are produced in both patients due to the generation of premature stop codons. CONCLUSION: The identified novel heterozygous EVC2 variants, c.2161delC and c.519_519 + 1delinsT, were responsible for the Ellis-van Creveld syndrome in one of the Mexican patients. In the second Mexican patient, we identified a compound heterozygous variant, c.645G > A and c.273dup, responsible for EvCS. The findings in this study extend the EVC2 mutation spectrum and may provide new insights into the EVC2 causation and diagnosis with implications for genetic counseling and clinical management.


Assuntos
Síndrome de Ellis-Van Creveld , Proteínas de Membrana , Humanos , Feminino , Proteínas de Membrana/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Síndrome de Ellis-Van Creveld/genética , Síndrome de Ellis-Van Creveld/diagnóstico , Linhagem , Mutação , Códon sem Sentido
4.
Foods ; 12(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36673507

RESUMO

Gastric cancer is one of the most common, aggressive, and invasive types of malignant neoplasia. It ranks fifth for incidence and fourth for prevalence worldwide. Products of natural origin, such as propolis, have been assessed for use as new complementary therapies to combat cancer. Propolis is a bee product with antiproliferative and anticancer properties. The concentrations and types of secondary metabolites contained in propolis mainly vary according to the geographical region, the season of the year, and the species of bees that make it. The present study is a systematic review of the main articles related to the effects of propolis against gastric cancer published between 2011 and 2021 in the PubMed and Science Direct databases. Of 1305 articles published, only eight studies were selected; among their principal characteristics was the use of in vitro analysis with cell lines from gastric adenocarcinoma and in vivo murine models of the application of propolis treatments. These studies suggest that propolis arrests the cell cycle and inhibits proliferation, prevents the release of oxidizing agents, and promotes apoptosis. In vivo assays showed that propolis decreased the number of tumors by regulating the cell cycle and the expression of proteins related to apoptosis.

5.
Int J Mol Sci ; 23(19)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36232716

RESUMO

The α-synucleinopathies constitute a subset of neurodegenerative disorders, of which Parkinson's disease (PD) is the most common worldwide, characterized by the accumulation of misfolded α-synuclein in the cytoplasm of neurons, which spreads in a prion-like manner to anatomically interconnected brain areas. However, it is not clear how α-synucleinopathy triggers neurodegeneration. We recently developed a rat model through a single intranigral administration of the neurotoxic ß-sitosterol ß-D-glucoside (BSSG), which produces α-synucleinopathy. In this model, we aimed to evaluate the temporal pattern of levels in oxidative and nitrosative stress and mitochondrial complex I (CI) dysfunction and how these biochemical parameters are associated with neurodegeneration in different brain areas with α-synucleinopathy (Substantia nigra pars compacta, the striatum, in the hippocampus and the olfactory bulb, where α-syn aggregation spreads). Interestingly, an increase in oxidative stress and mitochondrial CI dysfunction accompanied neurodegeneration in those brain regions. Furthermore, in silico analysis suggests a high-affinity binding site for BSSG with peroxisome proliferator-activated receptors (PPAR) alpha (PPAR-α) and gamma (PPAR-γ). These findings will contribute to elucidating the pathophysiological mechanisms associated with α-synucleinopathies and lead to the identification of new early biomarkers and therapeutic targets.


Assuntos
Encéfalo , Complexo I de Transporte de Elétrons , Mitocôndrias , Estresse Oxidativo , Sinucleinopatias , alfa-Sinucleína , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Complexo I de Transporte de Elétrons/metabolismo , Mitocôndrias/metabolismo , Estresse Nitrosativo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Ratos , Sinucleinopatias/metabolismo , Sinucleinopatias/fisiopatologia , alfa-Sinucleína/química , alfa-Sinucleína/metabolismo
6.
Front Immunol ; 13: 946770, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052060

RESUMO

The current pandemic generated by SARS-CoV-2 has led to mass vaccination with different biologics that have shown wide variations among human populations according to the origin and formulation of the vaccine. Studies evaluating the response in individuals with a natural infection before vaccination have been limited to antibody titer analysis and evaluating a few humoral and cellular response markers, showing a more rapid and intense humoral response than individuals without prior infection. However, the basis of these differences has not been explored in depth. In the present work, we analyzed a group of pro and anti-inflammatory cytokines, antibody titers, and cell populations in peripheral blood of individuals with previous SARS-CoV-2 infection using BNT162b2 biologic. Our results suggest that higher antibody concentration in individuals with an earlier disease could be generated by higher production of plasma cells to the detriment of the presence of memory B cells in the bloodstream, which could be related to the high baseline expression of cytokines (IL-6 and IL-10) before vaccination.


Assuntos
COVID-19 , Vacinas Virais , Vacina BNT162 , COVID-19/prevenção & controle , Humanos , Interleucina-10 , Interleucina-6 , Receptores CCR7 , SARS-CoV-2 , Vacinação
7.
Molecules ; 27(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36080417

RESUMO

Infections caused by micro-organisms of the genus Candida are becoming a growing health problem worldwide. These fungi are opportunistic commensals that can produce infections-clinically known as candidiasis-in immunocompromised individuals. The indiscriminate use of different anti-fungal treatments has triggered the resistance of Candida species to currently used therapies. In this sense, propolis has been shown to have potent antimicrobial properties and thus can be used as an approach for the inhibition of Candida species. Therefore, this work aims to evaluate the anti-Candida effects of a propolis extract obtained from the north of Mexico on clinical isolates of Candida species. Candida species were specifically identified from oral lesions, and both the qualitative and quantitative anti-Candida effects of the Mexican propolis were evaluated, as well as its inhibitory effect on C. albicans isolate's germ tube growth and chemical composition. Three Candida species were identified, and our results indicated that the inhibition halos of the propolis ranged from 7.6 to 21.43 mm, while that of the MFC and FC50 ranged from 0.312 to 1.25 and 0.014 to 0.244 mg/mL, respectively. Moreover, the propolis was found to inhibit germ tube formation (IC50 ranging from 0.030 to 1.291 mg/mL). Chemical composition analysis indicated the presence of flavonoids, including pinocembrin, baicalein, pinobanksin chalcone, rhamnetin, and biochanin A, in the Mexican propolis extract. In summary, our work shows that Mexican propolis presents significant anti-Candida effects related to its chemical composition, and also inhibits germ tube growth. Other Candida species virulence factors should be investigated in future research in order to determine the mechanisms associated with antifungal effects against them.


Assuntos
Candida , Própole , Antifúngicos/farmacologia , Candida albicans , Humanos , México , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Própole/química , Própole/farmacologia
8.
Plant Cell ; 34(10): 3512-3542, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-35976122

RESUMO

The liverwort Marchantia polymorpha has been utilized as a model for biological studies since the 18th century. In the past few decades, there has been a Renaissance in its utilization in genomic and genetic approaches to investigating physiological, developmental, and evolutionary aspects of land plant biology. The reasons for its adoption are similar to those of other genetic models, e.g. simple cultivation, ready access via its worldwide distribution, ease of crossing, facile genetics, and more recently, efficient transformation, genome editing, and genomic resources. The haploid gametophyte dominant life cycle of M. polymorpha is conducive to forward genetic approaches. The lack of ancient whole-genome duplications within liverworts facilitates reverse genetic approaches, and possibly related to this genomic stability, liverworts possess sex chromosomes that evolved in the ancestral liverwort. As a representative of one of the three bryophyte lineages, its phylogenetic position allows comparative approaches to provide insights into ancestral land plants. Given the karyotype and genome stability within liverworts, the resources developed for M. polymorpha have facilitated the development of related species as models for biological processes lacking in M. polymorpha.


Assuntos
Embriófitas , Marchantia , Evolução Biológica , Células Germinativas Vegetais , Marchantia/genética , Filogenia
9.
Antioxidants (Basel) ; 10(12)2021 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-34943117

RESUMO

The skin is the main external organ. It protects against different types of potentially harmful agents, such as pathogens, or physical factors, such as radiation. Skin disorders are very diverse, and some of them lack adequate and accessible treatment. The photoaging of the skin is a problem of great relevance since it is related to the development of cancer, while psoriasis is a chronic inflammatory disease that causes scaly skin lesions and deterioration of the lifestyle of people affected. These diseases affect the patient's health and quality of life, so alternatives have been sought that improve the treatment for these diseases. This review focuses on describing the properties and benefits of flavonoids from propolis against these diseases. The information collected shows that the antioxidant and anti-inflammatory properties of flavonoids play a crucial role in the control and regulation of the cellular and biochemical alterations caused by these diseases; moreover, flavones, flavonols, flavanones, flavan-3-ols, and isoflavones contained in different worldwide propolis samples are the types of flavonoids usually evaluated in both diseases. Therefore, the research carried out in the area of dermatology with bioactive compounds of different origins is of great relevance to developing preventive and therapeutic approaches.

10.
Biology (Basel) ; 10(5)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34065939

RESUMO

Infectious diseases are a significant problem affecting the public health and economic stability of societies all over the world. Treatment is available for most of these diseases; however, many pathogens have developed resistance to drugs, necessitating the development of new therapies with chemical agents, which can have serious side effects and high toxicity. In addition, the severity and aggressiveness of emerging and re-emerging diseases, such as pandemics caused by viral agents, have led to the priority of investigating new therapies to complement the treatment of different infectious diseases. Alternative and complementary medicine is widely used throughout the world due to its low cost and easy access and has been shown to provide a wide repertoire of options for the treatment of various conditions. In this work, we address the relevance of the effects of propolis on the causal pathogens of the main infectious diseases with medical relevance; the existing compiled information shows that propolis has effects on Gram-positive and Gram-negative bacteria, fungi, protozoan parasites and helminths, and viruses; however, challenges remain, such as the assessment of their effects in clinical studies for adequate and safe use.

11.
Pathogens ; 9(6)2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32526974

RESUMO

Amoebae of the genus Acanthamoeba are etiological agents of granulomatous amoebic encephalitis (GAE). Recently, through an in vivo GAE model, Acanthamoeba trophozoites were immunolocalized in contact with the peripheral nervous system (PNS) cells-Schwann cells (SC). In this study, we analyzed in greater detail the in vitro early morphological events (1, 2, 3, and 4 h) during the interaction of A. culbertsoni trophozoites (ATCC 30171) with SC from Rattus norvegicus (ATCC CRL-2941). Samples were processed for scanning and transmission electron microscopy as well as confocal microscopy. After 1 h of interaction, amoebae were observed to be adhered to the SC cultures, emitting sucker-like structures associated with micro-phagocytic channels. In addition, evidence of necrosis was identified since edematous organelles as well as multivesicular and multilamellar bodies characteristics of autophagy were detected. At 2 h, trophozoites migrated beneath the SC culture in which necrosis and autophagy persisted. By 3 and 4 h, extensive lytic zones were observed. SC necrosis was confirmed by confocal microscopy. We reported for the first time the induction of autophagic and necrotic processes in PNS cells, associated in part with the contact-dependent pathogenic mechanisms of A. culbertsoni trophozoites.

12.
Breast Cancer ; 27(5): 837-849, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32180141

RESUMO

BACKGROUND: Tumor-infiltrating lymphocytes are an important component of the tumor microenvironment (TME) in breast cancer. They have been linked with tumor pathogenesis in advanced stages. However, little is known about their contribution in early phases. In this study, we analyzed the infiltration of leukocytes and cancer stem cells (CSC) in tumors from patients with early breast cancer. METHODS: Samples of blood and tumor tissue from 30 patients with breast cancer were collected, and the number of dendritic cells (DC), T cells, and CSC were analyzed by flow cytometry. RESULTS: Tumor-infiltrating CD4 and CD8 T cells expressed higher levels of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) compared with peripheral T cells. Regulatory T cells (Treg) were enriched in tumors and overexpressed glucocorticoid-induced TNFR-related protein and CTLA-4. Tumor Treg had a positive correlation with the amount of myeloid DC (mDC) and disease progression. The CD8/Treg ratio was associated with lymph node metastasis and tumor stages. The main subset of DC in early breast tumors was mDC, while plasmacytoid DC were almost absent. CSC were present in most tumors with higher frequencies in patients with lymph node metastasis. CSC were also associated with the amount of tumor-infiltrating Treg. CONCLUSION: Early breast cancer has an inflammatory milieu characterized by mDC, Treg, and CSC infiltration. The frequencies of Treg, CSC and CD8/Treg ratio were associated with disease progression. The composition of leukocytes and the presence of CSC in early breast tumors should be considered for the development of new therapeutic approaches.


Assuntos
Neoplasias da Mama/patologia , Linfócitos T CD8-Positivos/imunologia , Metástase Linfática/imunologia , Células-Tronco Neoplásicas/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/imunologia , Mama/patologia , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Relação CD4-CD8 , Células Dendríticas/imunologia , Feminino , Humanos , Linfonodos/imunologia , Linfonodos/patologia , Linfócitos do Interstício Tumoral , Pessoa de Meia-Idade , Gradação de Tumores , Microambiente Tumoral/imunologia
13.
Nutrients ; 13(1)2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33383693

RESUMO

The use of alternative medicine products has increased tremendously in recent decades and it is estimated that approximately 80% of patients globally depend on them for some part of their primary health care. Propolis is a beekeeping product widely used in alternative medicine. It is a natural resinous product that bees collect from various plants and mix with beeswax and salivary enzymes and comprises a complex mixture of compounds. Various biomedical properties of propolis have been studied and reported in infectious and non-infectious diseases. However, the pharmacological activity and chemical composition of propolis is highly variable depending on its geographical origin, so it is important to describe and study the biomedical properties of propolis from different geographic regions. A number of chronic diseases, such as diabetes, obesity, and cancer, are the leading causes of global mortality, generating significant economic losses in many countries. In this review, we focus on compiling relevant information about propolis research related to diabetes, obesity, and cancer. The study of propolis could generate both new and accessible alternatives for the treatment of various diseases and will help to effectively evaluate the safety of its use.


Assuntos
Doença Crônica/tratamento farmacológico , Própole/farmacologia , Animais , Antineoplásicos/farmacologia , Abelhas , Produtos Biológicos , Geografia , Humanos , Doenças não Transmissíveis , Obesidade , Compostos Fitoquímicos , Ceras/farmacologia
14.
New Phytol ; 223(2): 575-581, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30920664

RESUMO

Methylation of DNA is an epigenetic mechanism for the control of gene expression. Alterations in the regulatory pathways involved in the establishment, perpetuation and removal of DNA methylation can lead to severe developmental alterations. Our understanding of the mechanistic aspects and relevance of DNA methylation comes from remarkable studies in well-established angiosperm plant models including maize and Arabidopsis. The study of plant models positioned at basal lineages opens exciting opportunities to expand our knowledge on the function and evolution of the components of DNA methylation. In this Tansley Insight, we summarize current progress in our understanding of the molecular basis and relevance of DNA methylation in the liverwort Marchantia polymorpha.


Assuntos
Metilação de DNA/genética , Marchantia/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Marchantia/crescimento & desenvolvimento , Modelos Biológicos , RNA de Plantas/metabolismo
15.
Plant Cell Physiol ; 59(12): 2421-2431, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30102384

RESUMO

DNA methylation is an epigenetic mark that ensures silencing of transposable elements (TEs) and affects gene expression in many organisms. The function of different DNA methylation regulatory pathways has been largely characterized in the model plant Arabidopsis thaliana. However, far less is known about DNA methylation regulation and functions in basal land plants. Here we focus on the liverwort Marchantia polymorpha, an emerging model species that represents a basal lineage of land plants. We identified MpMET, the M. polymorpha ortholog of the METHYLTRANSFERASE 1 (MET1) gene required for maintenance of methylation at CG sites in angiosperms. We generated Mpmet mutants using the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein9) system, which showed a significant loss of CG methylation and severe morphological changes and developmental defects. The mutants developed many adventitious shoot-like structures, suggesting that MpMET is required for maintaining differentiated cellular identities in the gametophyte. Even though numerous TEs were up-regulated, non-CG methylation was generally highly increased at TEs in the Mpmet mutants. Closer inspection of CHG methylation revealed features unique to M. polymorpha. Methylation of CCG sites in M. polymorpha does not depend on MET1, unlike in A. thaliana and Physcomitrella patens. Our results highlight the diversity of non-CG methylation regulatory mechanisms in plants.


Assuntos
Divisão Celular/genética , Ilhas de CpG/genética , Metilação de DNA/genética , Marchantia/citologia , Marchantia/genética , Elementos de DNA Transponíveis/genética , Genoma de Planta , Mutação/genética
16.
Int J Dermatol ; 57(8): 965-972, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29855039

RESUMO

Hypohidrotic Ectodermal Dysplasia (HED) is a genetic human disorder which affects structures of ectodermal origin. Although there are autosomal recessive and dominant forms, X-linked (XL) is the most frequent form of the disease. This XL-HED phenotype is associated with mutations in the gene encoding the transmembrane protein ectodysplasin-1 (EDA1), a member of the TNFα-related signaling pathway. The proteins from this pathway are involved in signal transduction from ectoderm to mesenchyme leading to the development of ectoderm-derived structures in the fetus such as hair, teeth, skin, nails, and eccrine sweat glands. The aim of this review was to update the main clinical characteristics of HED regarding to recent molecular advances in the comprehension of all the possible genes involved in this group of disorders since it is known that Eda-A1-Edar signaling has multiple roles in ectodermal organ development, regulating their initiation, morphogenesis, and differentiation steps. The knowledge of the biological mechanisms that generate HED is needed for both a better detection of possible cases and for the design of efficient prevention and treatment approaches.


Assuntos
Displasia Ectodérmica Anidrótica Tipo 1/genética , Ectodisplasinas/genética , Receptor Edar/genética , Proteína de Domínio de Morte Associada a Edar/genética , Quinase I-kappa B/genética , Anodontia/etiologia , Displasia Ectodérmica Anidrótica Tipo 1/complicações , Displasia Ectodérmica Anidrótica Tipo 1/diagnóstico , Displasia Ectodérmica Anidrótica Tipo 1/patologia , Humanos , Hipo-Hidrose/etiologia , Hipotricose/etiologia , Mutação , Transdução de Sinais
17.
Oncotarget ; 8(43): 74233-74243, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-29088781

RESUMO

Identifying founder mutations in BRCA1 and BRCA2 in specific populations constitute a valuable opportunity for genetic screening. Several studies from different populations have reported recurrent and/or founder mutations representing a relevant proportion of BRCA mutation carriers. In Latin America, only few founder mutations have been described. We screened 453 Chilean patients with hereditary breast cancer for mutations in BRCA1 and BRCA2. For recurrent mutations, we genotyped 11 microsatellite markers in BRCA1 and BRCA2 in order to determine a founder effect through haplotype analysis. We found a total of 25 mutations (6 novel) in 71 index patients among which, nine are present exclusively in Chilean patients. Our analysis revealed the presence of nine founder mutations, 4 in BRCA1 and 5 in BRCA2, shared by 2 to 10 unrelated families and spread in different regions of Chile. Our panel contains the highest amount of founder mutations until today and represents the highest percentage (78%) of BRCA1 and BRCA2 mutation carriers. We suggest that the dramatic reduction of Amerindian population due to smallpox and wars with Spanish conquerors, a scarce population increase during 300 years, and the geographic position of Chile constituted a favorable scenario to establish founder genetic markers in our population.

18.
Exp Parasitol ; 183: 150-159, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28917708

RESUMO

Granulomatous amoebic encephalitis (GAE) is a chronic, difficult to resolve infection caused by amphizoic amoebae of the genus Acanthamoeba, which in most cases occurs in immunosuppressed persons or with chronic diseases such as diabetes. In this study, we describe the early events of A. culbertsoni infection of GAE in diabetic mice model. Diabetes was induced in male BALB/c mice, with a dose of streptozotocin (130 mg/kg). Healthy and diabetic mice were inoculated via intranasal with 1 × 106 trophozoites of A. culbertsoni. Then were sacrificed and fixed by perfusion at 24, 48, 72 and 96 h post-inoculation, the brains and nasopharyngeal meatus were processed to immunohistochemical analysis. Invasion of trophozoites in diabetic mice was significantly greater with respect to inoculated healthy mice. Trophozoites and scarce cysts were immunolocalized in respiratory epithelial adjacent bone tissue, olfactory nerve packets, Schwann cells and the epineurium base since early 24 h post-inoculation. After 48 h, trophozoites were observed in the respiratory epithelium, white matter of the brain, subcortical central cortex and nasopharyngeal associated lymphoid tissue (NALT). At 72 h, cysts and trophozoites were immunolocalized in the olfactory bulb with the presence of a low inflammatory infiltrate characterized by polymorphonuclear cells. Scarce amoebae were observed in the granular layer of the cerebellum without evidence of inflammation or tissue damage. No amoebas were observed at 96 h after inoculation, suggesting penetration to other tissues at this time. In line with this, no inflammatory infiltrate was observed in the surrounding tissues where the amoebae were immunolocalized, which could contribute to the rapid spread of infection, particularly in diabetic mice. All data suggest that trophozoites invade the tissues by separating the superficial cells, penetrating between the junctions without causing cytolytic effect in the adjacent cells and subsequently reaching the CNS, importantly, diabetes increases the susceptibility to amoebae infection, which could favor the GAE development.


Assuntos
Acanthamoeba/patogenicidade , Amebíase/etiologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Encefalite/parasitologia , Acanthamoeba/fisiologia , Animais , Encéfalo/parasitologia , Encéfalo/patologia , Cerebelo/parasitologia , Cerebelo/patologia , Suscetibilidade a Doenças , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nasofaringe/parasitologia , Nasofaringe/patologia , Bulbo Olfatório/parasitologia , Bulbo Olfatório/patologia , Inoculações Seriadas , Trofozoítos , Virulência
19.
Gac Med Mex ; 153(3): 371-375, 2017.
Artigo em Espanhol | MEDLINE | ID: mdl-28763076

RESUMO

The 2016 undergraduate medical degree curriculum at the Facultad de Estudios Superiores Iztacala of the Universidad Nacional Autónoma de México (UNAM) is presented. It is the result of a long institutional reflection and academic dialog process of approximately three years, which culminated in its approval by UNAM's Academic Council for the Biology, Chemistry, and Health Sciences areas on January 25, 2016. Its most relevant characteristics are: modular organization, four knowledge areas (biomedical, methodological, socio-psychological, and humanistic and medical practice), and new modules such as Seminar of socio-psycho-biological integration; Genetics and molecular biology; Biochemistry and cellular biology; Pharmacological basis of therapeutics; Infectious diseases, microbiology and parasitology; Medical ethics; Public health; and Evidence-based medicine - clinical epidemiology. To achieve a more flexible curriculum, optional modules were included. To make possible the curricular change, improving the teaching strategies, innovating the learning assessment methods, supporting the training and updating of the teaching staff, and establishing a curriculum development committee for following up and evaluating the program, are necessary. Curricular changes are difficult and complex processes; they suppose challenges and opportunities. It is mandatory to plan them carefully and sensitively to allow a successful transition and avoid conflicts for the students, the teachers and the institution.


Assuntos
Currículo , Educação de Graduação em Medicina/organização & administração , Docentes de Medicina , Humanos , México , Estudantes de Medicina , Ensino/organização & administração
20.
Parasitol Res ; 116(2): 725-733, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27915418

RESUMO

This study was developed in order to describe the early morphological events observed during the invasion of two pathogenic strains of Acanthamoeba (genotype T4); A. castellanii and A. culbertsoni, at the olfactory meatus and cerebral, pulmonary, renal, hepatic and splenic tissues levels, an in vivo invasion study. Histological and immunohistochemical description of the events at 24, 48, 72, and 96 h postintranasal inoculations of BALB/c mice was performed. A. castellanii showed a higher invasion rate than A. culbertsoni, which was only able to reach lung and brain tissue in the in vivo model. The current study supports previous evidence of lack of inflammatory response during the early stages of infection. Acanthamoeba invasion of the CNS and other organs is a slow and contact-dependent process. The early morphological events during the invasion of amoebae include the penetration of trophozoites into different epithelia: olfactory, respiratory, alveolar space, and renal tubule, which resemble the process of amoebae invasion described in corneal tissue. The data suggest that after reaching the nasal epithelium, trophozoites continued invasion, separating and lifting the most superficial cells, then migrating and penetrating between the cell junctions without causing a cytolytic effect on adjacent cells. These results reaffirm the idea that contact-dependent mechanisms are relevant for amoebae of Acanthamoeba genus regardless of the invasion site.


Assuntos
Acanthamoeba/patogenicidade , Amebíase/patologia , Sistema Nervoso Central/parasitologia , Túbulos Renais/parasitologia , Mucosa Nasal/parasitologia , Mucosa Respiratória/parasitologia , Trofozoítos/metabolismo , Animais , Córnea/parasitologia , Modelos Animais de Doenças , Genótipo , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C
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