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1.
J Neurovirol ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830465

RESUMO

The frequency of central nervous system infections due to herpesvirus have been studied in various populations; however, studies in Mexican mestizo patients are scant. This paper documents the frequency of herpesvirus encephalitis in Mexican mestizo patients from the National Institute of Neurology and Neurosurgery (NINN) of Mexico. To study the frequency of herpetic viral encephalitis at the NINN in the period from 2004 to 2009. We reviewed clinical records from patients with clinically suspected encephalitis; polymerase chain reaction assays were done for detection of herpesviruses in cerebrospinal fluid (CSF) samples. The total number of patients studied was 502; in 59 (12%), the diagnosis of herpetic encephalitis was confirmed by PCR-based testing of CSF. Of them, 21 (36%) were positive for herpes simplex virus type 1, 15 (25%) for Epstein-Barr virus, 10 (17%) for varicella zoster virus, 8 (14%) for cytomegalovirus, 3 (5%) for human herpesvirus 6, and 2 (3%) for herpes simplex virus 2. Our results show a varied frequency of viral encephalitis in mestizo patients due to herpesviruses in a tertiary neurological center and point out the importance of modern molecular technology to reach the etiological diagnosis in cases of encephalitis.

2.
IEEE Trans Med Imaging ; 40(4): 1240-1252, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33434127

RESUMO

We proposed a novel method called HARP-I, which enhances the estimation of motion from tagged Magnetic Resonance Imaging (MRI). The harmonic phase of the images is unwrapped and treated as noisy measurements of reference coordinates on a deformed domain, obtaining motion with high accuracy using Radial Basis Functions interpolations. Results were compared against Shortest Path HARP Refinement (SP-HR) and Sine-wave Modeling (SinMod), two harmonic image-based techniques for motion estimation from tagged images. HARP-I showed a favorable similarity with both methods under noise-free conditions, whereas a more robust performance was found in the presence of noise. Cardiac strain was better estimated using HARP-I at almost any motion level, giving strain maps with less artifacts. Additionally, HARP-I showed better temporal consistency as a new method was developed to fix phase jumps between frames. In conclusion, HARP-I showed to be a robust method for the estimation of motion and strain under ideal and non-ideal conditions.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33517430

RESUMO

AIMS : In this study, we will describe a comprehensive haemodynamic analysis and its relationship to the dilation of the aorta in transposition of the great artery (TGA) patients post-arterial switch operation (ASO) and controls using 4D-flow magnetic resonance imaging (MRI) data. METHODS AND RESULTS : Using 4D-flow MRI data of 14 TGA young patients and 8 age-matched normal controls obtained with 1.5 T GE-MR scanner, we evaluate 3D maps of 15 different haemodynamics parameters in six regions; three of them in the aortic root and three of them in the ascending aorta (anterior-left, -right, and posterior for both cases) to find its relationship with the aortic arch curvature and root dilation. Differences between controls and patients were evaluated using Mann-Whitney U test, and the relationship with the curvature was accessed by unpaired t-test. For statistical significance, we consider a P-value of 0.05. The aortic arch curvature was significantly different between patients 46.238 ± 5.581 m-1 and controls 41.066 ± 5.323 m-1. Haemodynamic parameters as wall shear stress circumferential (WSS-C), and eccentricity (ECC), were significantly different between TGA patients and controls in both the root and ascending aorta regions. The distribution of forces along the ascending aorta is highly inhomogeneous in TGA patients. We found that the backward velocity (B-VEL), WSS-C, velocity angle (VEL-A), regurgitation fraction (RF), and ECC are highly correlated with the aortic arch curvature and root dilatation. CONCLUSION : We have identified six potential biomarkers (B-VEL, WSS-C, VEL-A, RF, and ECC), which may be helpful for follow-up evaluation and early prediction of aortic root dilatation in this patient population.

4.
Viruses ; 13(1)2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33477376

RESUMO

Quinacrine (Qx), a molecule used as an antimalarial, has shown anticancer, antiprion, and antiviral activity. The most relevant antiviral activities of Qx are related to its ability to raise pH in acidic organelles, diminishing viral enzymatic activity for viral cell entry, and its ability to bind to viral DNA and RNA. Moreover, Qx has been used as an immunomodulator in cutaneous lupus erythematosus and various rheumatological diseases, by inhibiting phospholipase A2 modulating the Th1/Th2 response. The aim of this study was to evaluate the potential antiviral effect of Qx against denominated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Vero E6 cells. The cytotoxicity of Qx in Vero E6 cells was determined by the MTT assay. Afterwards, Vero E6 cells were infected with SARS-CoV-2 at different multiplicities of infections (MOIs) of 0.1 and 0.01 in the presence of Qx (0-30 µM) to determinate the half maximal effective concentration (EC50). After 48 h, the effect of Qx against SARS-CoV-2 was assessed by viral cytotoxicity and viral copy numbers, the last were determined by digital real-time RT-PCR (ddRT-PCR). Additionally, electron and confocal microscopy of Vero E6 cells infected and treated with Qx was studied. Our data show that Qx reduces SARS-CoV-2 virus replication and virus cytotoxicity, apparently by inhibition of viral ensemble, as observed by ultrastructural images, suggesting that Qx could be a potential drug for further clinical studies against coronavirus disease 2019 (COVID-19) infection.


Assuntos
Antivirais/farmacologia , Quinacrina/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Linhagem Celular , Chlorocebus aethiops , Microscopia Eletrônica de Transmissão , Células Vero , Carga Viral/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos
5.
Epilepsy Behav ; 115: 107659, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33334719

RESUMO

Transcranial focal stimulation (TFS) is a noninvasive neuromodulation strategy that reduces seizure activity in different experimental models. Nevertheless, there is no information about the effects of TFS in the drug-resistant phenotype associated with P-glycoprotein (Pgp) overexpression. The present study focused on determining the effects of TFS on Pgp expression after an acute seizure induced by 3-mercaptopropionic acid (MPA). P-glycoprotein expression was analyzed by western blot in the cerebral cortex and hippocampus of rats receiving 5 min of TFS (300 Hz, 50 mA, 200 µs, biphasic charge-balanced squared pulses) using a tripolar concentric ring electrode (TCRE) prior to administration of a single dose of MPA. An acute administration of MPA induced Pgp overexpression in cortex (68 ±â€¯13.4%, p < 0.05 vs the control group) and hippocampus (48.5 ±â€¯14%, p < 0.05, vs the control group). This effect was avoided when TFS was applied prior to MPA. We also investigated if TFS augments the effects of phenytoin in an experimental model of drug-resistant seizures induced by repetitive MPA administration. Animals with MPA-induced drug-resistant seizures received TFS alone or associated with phenytoin (75 mg/kg, i.p.). TFS alone did not modify the expression of the drug-resistant seizures. However, TFS combined with phenytoin reduced seizure intensity, an effect associated with a lower prevalence of major seizures (50%, p = 0.03 vs phenytoin alone). Our experiments demonstrated that TFS avoids the Pgp overexpression induced after an acute convulsive seizure. In addition, TFS augments the phenytoin effects in an experimental model of drug-resistant seizures. According with these results, it is indicated that TFS may represent a new neuromodulatory strategy to revert the drug-resistant phenotype.

6.
Gac Med Mex ; 156(5): 458-459, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33372926

RESUMO

A novel chapter in current medical settings is the promotion and attention of esthetic aspects rather than health issues by health professionals. The human aspiration related to the search for personal beauty has generated new scenarios in medical practice. The Committee on Ethics and Transparency in the Physician-Industry Relationship (CETREMI) of the National Academy of Medicine of Mexico has analyzed this phenomenon and has issued recommendations directed both to medical professionals and to producers and potential consumers of esthetic procedures.

7.
Gac Med Mex ; 156(4): 263-264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32831325
8.
Virology ; 549: 85-88, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32858308

RESUMO

Bell's Palsy is the most frequent acute neuropathy of cranial nerves; it has been associated in various reports to herpes viruses. In a prospective study we searched the presence of DNA from five herpes viruses (HSV-1 and 2, VZV, EBV and HHV-6) in 79 patients at the acute phase of Bell's Palsy. Results were related with various parameters; age, gender and clinical outcome. We found the significant presence (p˂0.001) of HSV-1 and VZV in 39% and 42% of patients. However, a large percentage of cases were negative. When comparisons were made between subgroups according to gender and age no differences were found with viral findings nor with clinical outcome of palsy, which was of clinical remission in most cases (78%). Our results suggest that herpes viruses might participate in the complex mechanisms of autoimmunity of Bell's Palsy but not as determinant etiological element.

9.
Pharmaceuticals (Basel) ; 13(7)2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32707662

RESUMO

Glioma is the most frequent and aggressive type of brain neoplasm, being anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM), its most malignant forms. The survival rate in patients with these neoplasms is 15 months after diagnosis, despite a diversity of treatments, including surgery, radiation, chemotherapy, and immunotherapy. The resistance of GBM to various therapies is due to a highly mutated genome; these genetic changes induce a de-regulation of several signaling pathways and result in higher cell proliferation rates, angiogenesis, invasion, and a marked resistance to apoptosis; this latter trait is a hallmark of highly invasive tumor cells, such as glioma cells. Due to a defective apoptosis in gliomas, induced autophagic death can be an alternative to remove tumor cells. Paradoxically, however, autophagy in cancer can promote either a cell death or survival. Modulating the autophagic pathway as a death mechanism for cancer cells has prompted the use of both inhibitors and autophagy inducers. The autophagic process, either as a cancer suppressing or inducing mechanism in high-grade gliomas is discussed in this review, along with therapeutic approaches to inhibit or induce autophagy in pre-clinical and clinical studies, aiming to increase the efficiency of conventional treatments to remove glioma neoplastic cells.

10.
Salud Publica Mex ; 62(3): 255-261, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32520483

RESUMO

OBJECTIVE: To determine distribution, localization and frequency variations of astrocytic tumors (AT) in a Mexican Institute of neurology. MATERIALS AND METHODS: Institutional registries of AT from five decades were analyzed. AT/ Surgical discharges (SD) and AT/Central Nervous System Tumors (CNST) from 1995 to 2014 were compared. RESULTS: Two thousand two hundred and eighty-seven AT (1 356 men and 931 women) were analyzed. The most common glioma was glioblastoma multiforme (GBM), found in young adults with a higher frequency to that reported in other studies. Relation of AT/SD, as well as, relation of AT/CNST was similar between 1995 and 2014. CONCLUSIONS: In general, the frequency of AT worldwide, being higher in the subgroup of young adults with GBM. There was not significant variation in the frequency of AT during the time studied.

12.
Arterioscler Thromb Vasc Biol ; 40(1): e10-e20, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31801375

RESUMO

OBJECTIVE: To assess the relationship between regional wall shear stress (WSS) and oscillatory shear index (OSI) and aortic dilation in patients with bicuspid aortic valve (BAV). Approach and Results: Forty-six consecutive patients with BAV (63% with right-left-coronary-cusp fusion, aortic diameter ≤ 45 mm and no severe valvular disease) and 44 healthy volunteers were studied by time-resolved 3-dimensional phase-contrast magnetic resonance imaging. WSS and OSI were quantified at different levels of the ascending aorta and the aortic arch, and regional WSS and OSI maps were obtained. Seventy percent of BAV had ascending aorta dilation. Compared with healthy volunteers, patients with BAV had increased WSS and decreased OSI in most of the ascending aorta and the aortic arch. In both BAV and healthy volunteers, regions of high WSS matched regions of low OSI and vice versa. No regions of both low WSS and high OSI were identified in BAV compared with healthy volunteers. Patients with BAV with dilated compared with nondilated aorta presented low and oscillatory WSS in the aortic arch, but not in the ascending aorta where dilation is more prevalent. Furthermore, no regions of concomitant low WSS and high OSI were identified when BAV were compared according to leaflet fusion pattern, despite the well-known differences in regional dilation prevalence. CONCLUSIONS: Regions with low WSS and high OSI do not match those with the highest prevalence of dilation in patients with BAV, thus providing no evidence to support the low and oscillatory shear stress theory in the pathogenesis of proximal aorta dilation in the presence of BAV.


Assuntos
Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico , Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas/diagnóstico , Imageamento Tridimensional , Imagem Cinética por Ressonância Magnética/métodos , Fluxo Sanguíneo Regional/fisiologia , Resistência ao Cisalhamento/fisiologia , Adulto , Aorta Torácica/fisiopatologia , Aneurisma da Aorta Torácica/etiologia , Aneurisma da Aorta Torácica/fisiopatologia , Valva Aórtica/fisiopatologia , Feminino , Seguimentos , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Estresse Mecânico
13.
Clin Neurol Neurosurg ; 188: 105588, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31715425

RESUMO

OBJECTIVE: Optic Neuritis (ON) might unfold either as a single intracranial neuritis or as multiple sclerosis, a widespread demyelinating disorder. Different herpes viruses have been proposed as potential participants in the etiology of multiple sclerosis (MS). To analyze the potential presence of herpes viruses in blood and subarachnoid area at the time of ON and contrast the findings according to long-term evolution either as intracranial neuritis or as progression to multiple sclerosis. PATIENTS AND METHODS: In a prospective investigation we searched the presence of DNA from 5 herpes viruses (HSV-1, HSV-2, VZV, EBV and HHV6) in CSF and blood lymphocytes from 54 patients with ON, patients were followed 62 ±â€¯3 months; those who developed MS were separated from those with ephemeral ON. Long-term prognosis of ON was related to DNA findings. RESULTS: As compared with controls, DNA from HSV-1 was significantly more frequent in CSF and blood from cases with ON; VZV and HSV-2 were found only in CSF; EBV was found only in blood samples (p < 0.006). CONCLUSIONS: Our results point out the potential participation of HSV, VZV and EBV in ON; suggesting the intervention of various herpes viruses as triggering agents of autoimmunity. However, the number of positive cases was minor than negative cases. Also, our results suggest that the etiological mechanisms in ON could be similar to those of neuritis of the facial nerve (Bell's palsy).

14.
Eur J Cardiothorac Surg ; 57(5): 896-903, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31821480

RESUMO

OBJECTIVES: Current risk assessment strategies in type B aortic dissection are focused on anatomic parameters, although haemodynamic abnormalities that result in false lumen (FL) pressurization are thought to play a significant role in aortic growth. The objective of this study was to evaluate blood flow of the FL using 4D flow magnetic resonance imaging (MRI) and identify haemodynamic and anatomic factors that independently predict the rate of aortic growth. METHODS: Patients with dissection of the descending thoraco-abdominal aorta (n = 18) were enrolled in a prospective observational study and underwent 4D flow MRI for haemodynamic assessment of the entry tear and FL. Anatomic parameters were obtained by magnetic resonance angiography and baseline computed tomography. False lumen ejection fraction (FL EF) was defined the ratio of retrograde flow rate at the dominant entry tear during diastole over the antegrade systolic flow rate. RESULTS: The median aortic growth rate was 3.5 mm/year (interquartile range 0.5-8.1 mm/year). Entry tear peak velocity was lower in patients with enlarging aortic dimensions (95.5 ± 24.1 vs 128.1 ± 37.4 cm/s, P = 0.039). After adjusting for co-variates FL EF (ß = 0.15, P = 0.004), baseline maximal aortic diameter (ß = 0.37, P = 0.001) and the entry tear distance from the left subclavian artery (ß = 0.07, P = 0.016) were significant predictors of aortic growth rate. CONCLUSIONS: Beyond standard anatomic risk factors, FL EF is an independent predictor of aortic growth rate and may represent an intuitive, non-invasive method to estimate FL pressurization and improve patient-specific risk assessment in patients with type B aortic dissection.

15.
Gac Med Mex ; 155(5): 563-564, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695240

RESUMO

Conflicts of interest are situations in which judgment and integrity of medical decisions or actions are influenced by a secondary interest, often of an economic nature. The Committee of Ethics and Transparency in the Physician-Industry Relationship of the National Academy of Medicine of Mexico recognizes that these conflicts occur in health professionals' daily life, but also in public and private institutions that provide health services, as well as in the academy and in research activities. Therefore, it is necessary to identify conflicting situations and always act in accordance with the patient's interest.


Assuntos
Códigos de Ética , Conflito de Interesses , Comissão de Ética , Ética Médica , Indústria Farmacêutica/ética , Humanos , Seguradoras/ética , Relações Médico-Paciente/ética , Relações Profissional-Família/ética
16.
Pharmaceuticals (Basel) ; 12(3)2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31500285

RESUMO

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Currently, treatment is ineffective and the median overall survival is 20.9 months. The poor prognosis of GBM is a consequence of several altered signaling pathways that favor the proliferation and survival of neoplastic cells. One of these pathways is the deregulation of phosphodiesterases (PDEs). These enzymes participate in the development of GBM and may have value as therapeutic targets to treat GBM. Methylxanthines (MXTs) such as caffeine, theophylline, and theobromine are PDE inhibitors and constitute a promising therapeutic anti-cancer agent against GBM. MTXs also regulate various cell processes such as proliferation, migration, cell death, and differentiation; these processes are related to cancer progression, making MXTs potential therapeutic agents in GBM.

17.
J Oncol ; 2019: 2563092, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275378

RESUMO

Background: Glioblastoma is the most common malignant tumor of Central Nervous System. Despite the research in therapeutics, the prognosis is dismal. Malignant glioma stem cells (MGSCs) are a major cause of treatment failure and increasing tumor recurrence. In general, cancer stem cells (CSCs) express prominin-1 (CD133), considered as a potential therapeutic target. In this study, we produced an avian immunotoxin directed against the subpopulation of CD133+ CSCs within a malignant glioma. We used the avian IgY because it has various advantages as increased affinity to mammal antigens and inexpensive obtention of large amounts of specific antibodies (approximately 1 mg/per egg). The design, production, purification and use of IgY anti CD133 immunotoxin constitute an original goal of this research. Methods: The immunodominant peptide of CD133 was designed to immunize hens; also, the extracellular domain of CD133 was cloned to probe the IgY antibodies. In parallel, a recombinant abrin A chain was produced in E. coli in order to join it to the Fc domain of the anti-CD133 IgY to conform the immunotoxin. This anti-CD133 IgY anti-tumor immunotoxin was tested in vitro and in vivo. Results. The cytotoxicity of the immunotoxin in vitro showed that IgY-abrin immunotoxin reduced 55% cell viability. After subcutaneous MGSCs implantation, the animals treated intraperitoneally or intratumorally with the IgY-abrin immunotoxin showed more than 50% decrease of tumor volume. Conclusion: Results showed that the IgY-abrin immunotoxin had cytotoxic activity against CD133+ MGSCs and provides a novel approach for the immunotherapy of glioblastoma.

18.
Gac Med Mex ; 155(3): 319-321, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31219475

RESUMO

Clinical research is the most important tool for the identification of diagnostic and therapeutic strategies that derive in higher efficacy and safety. Despite its significance, successful implementation of clinical research faces numerous difficulties, with one the most relevant being limited availability of resources for the performance of independent clinical trials. Generally, the pharmaceutical industry absorbs the costs associated with most clinical trials; however, this can generate dissociation between subjects of interest and health priorities when economic interest is the main driver of these protocols. In addition to the relevant role played by the pharmaceutical industry, it is important that government agencies favor adequate conditions, both in economic and regulatory aspects, for the implementation of independent clinical research that addresses subjects of medical and therapeutic interest, even if it does not generate corporate economic benefits.


Assuntos
Pesquisa Biomédica/organização & administração , Ensaios Clínicos como Assunto/organização & administração , Indústria Farmacêutica/organização & administração , Pesquisa Biomédica/economia , Ensaios Clínicos como Assunto/economia , Indústria Farmacêutica/economia , Apoio Financeiro , Humanos
19.
Mol Ther ; 27(9): 1612-1620, 2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31204210

RESUMO

Glioblastoma is the most common and malignant tumor of the CNS, with a mean survival of 14 months after diagnosis. Its unfavorable prognosis reveals the need for novel therapies. It is known that radiation can induce a systemic antitumor effect. Tumor cells produce and release microvesicles in response to cell damage such as radiation. Microvesicles contain a plethora of bioactive molecules, including antigens involved in modulation of the immune response. In this study, we characterized and evaluated irradiated C6 cell-derived microvesicles as a therapeutic vaccination in C6 malignant glioma. Cultured C6 glioma cells were irradiated with a single dose of 50 Gy to obtain the microvesicles. Subcutaneous implantation of C6 cells was performed when the tumor reached 2 cm in diameter, and non-irradiated and irradiated C6 cell-derived microvesicles were administered subcutaneously. Tumor growth, apoptosis, and immunophenotypes were determined. Reduction of tumor volume (more than 50%) was observed in the group treated with irradiated C6 cell-derived microvesicles compared with the control (p = 0.03). The percentages of infiltrative helper, cytotoxic, and regulatory T lymphocytes as well as apoptotic cells were increased in tumors from immunized rats compared with controls. These findings make microvesicle-based vaccination a promising immunotherapeutic approach against glioblastoma.


Assuntos
Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Vacinas Anticâncer/imunologia , Micropartículas Derivadas de Células/imunologia , Glioblastoma/imunologia , Glioblastoma/terapia , Animais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Vacinas Anticâncer/administração & dosagem , Linhagem Celular Tumoral , Micropartículas Derivadas de Células/efeitos da radiação , Modelos Animais de Doenças , Glioblastoma/mortalidade , Glioblastoma/patologia , Imunidade , Imunização , Ratos , Resultado do Tratamento , Carga Tumoral/imunologia
20.
Gac Med Mex ; 155(2): 202-203, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31056602

RESUMO

Doctors require flexibility for prescription. However, some limits are laid down both by current knowledge and by restrictions imposed by access and rules and regulations. The Committee for Ethics and Transparency in the Physician-Industry Relationship (CETREMI) of the National Academy of Medicine proposes several suggestions to help patients, which include the selection of the best alternatives for each case, formalization of prescription standards variations (doses, drug indications, etc.) written down in the medical records, and avoidance of fashions, untested novelties, argumentations solely based on advertising or commercial promotion and conflicts of interest.


Assuntos
Ética Médica , Médicos/organização & administração , Padrões de Prática Médica/normas , Comitês Consultivos , Humanos , México , Médicos/ética , Padrões de Prática Médica/ética
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