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1.
Eur Rev Med Pharmacol Sci ; 24(8): 4055, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32374004

RESUMO

The article "Long noncoding RNA NORAD promotes the progression of retinoblastoma by sponging miR-136-5p/PBX3 axis, by X.-L. Yang, Y.-J. Hao, B. Wang, X.-L. Gu, X.-X. Wang, J.-F. Sun, published in Eur Rev Med Pharmacol Sci 2020; 24(3):1278-1287. DOI: 10.26355/eurrev_202001_20185. PMID: 32096159" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause.

2.
Eur Rev Med Pharmacol Sci ; 24(3): 1278-1287, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32096159

RESUMO

OBJECTIVE: The specific roles of long noncoding RNAs (lncRNAs) have been found in human cancers, including retinoblastoma (RB). However, the function of lncRNA-NORAD has not been reported in RB. Therefore, the regulatory mechanism of lncRNA-NORAD was investigated in the development of RB. PATIENTS AND METHODS: The experimental tissues were collected from 24 RB patients and 6 patients with ruptured globes. The average age of all patients was 2.78 years (range, 2 months to 11 years). The mRNA and protein expression was measured by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot analysis. The functional mechanism of NORAD was assessed by Cell Counting Kit-8 (CCK-8), transwell, and Dual-Luciferase reporter assays. RESULTS: Upregulation of NORAD and downregulation of miR-136-5p were found in RB. Functionally, knockdown of NORAD and miR-136-5p overexpression restrained RB cell viability, invasion, and migration. In addition, NORAD acts as a ceRNA of miR-136-5p in RB. MiR-136-5p was found to directly target PBX3. Furthermore, knockdown of PBX3 inhibited the progression of RB. More importantly, the NORAD/miR-136-5p axis is involved in RB progression by mediating PBX3. CONCLUSIONS: LncRNA NORAD, serving as a ceRNA of miR-136-5p, accelerates RB progression by upregulation of PBX3.

3.
Anim Reprod Sci ; 207: 52-60, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31208846

RESUMO

This study investigated the effects of isomaltooligosaccharide (IMO) and Bacillus supplementation on sow performance, serum metabolites, and serum and placental oxidative status. Multiparous gestating sows (n = 130) with similar body conditions were randomly allocated to five groups (n = 26) receiving a basal diet (CON group) or a basal diet supplemented with 0.5% IMO (IMO group); 0.5% IMO and 0.02% Bacillus subtilis (IMO + S group); 0.5% IMO and 0.02% Bacillus licheniformis (IMO + L group); or 0.5% IMO, 0.02% Bacillus subtilis, and 0.02% Bacillus licheniformis (IMO + S+L group). There were no significant differences in the litter sizes among all dietary groups. The average piglet birth weight was improved in all treatment groups, and the placental efficiency was greater in the IMO + S and IMO + S+L groups than in the CON group (P < 0.05). The IMO + S+L group had increased the low-density lipoprotein cholesterol and reduced the total cholesterol in umbilical venous serum (P <  0.05). Additionally, the malondialdehyde concentrations were greater in umbilical venous serum of piglets in all treatment groups relative to that in the CON piglets (P <  0.05). The placental total antioxidant capacity was increased in the IMO+L and IMO+S+L groups (P <  0.05). Furthermore, the growth hormone concentration in umbilical venous serum was greater (P <  0.05) in all treatment groups. Overall, IMO and Bacillus supplementation during late gestation resulted in a changed metabolism of sows, improved the placental antioxidant capacity, and increased the growth hormone concentrations in umbilical venous serum, which ultimately improved the piglet birth weight and placental efficiency.


Assuntos
Antioxidantes/metabolismo , Bacillus/fisiologia , Isomaltose/farmacologia , Oligossacarídeos/farmacologia , Placenta/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Ração Animal/microbiologia , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Peso ao Nascer , Análise Química do Sangue/veterinária , Dieta/veterinária , Suplementos Nutricionais , Feminino , Isomaltose/química , Lactação/efeitos dos fármacos , Lactação/metabolismo , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Oligossacarídeos/química , Estresse Oxidativo/efeitos dos fármacos , Placenta/metabolismo , Gravidez , Probióticos , Suínos
4.
Eur Rev Med Pharmacol Sci ; 22(21): 7348-7355, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30468480

RESUMO

OBJECTIVE: To explore the possible role and mechanism of miR-497 in cutaneous squamous cell carcinoma. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to detect miR-497 and FAM114A2 expression level in 38 cases of cutaneous squamous cell carcinoma (CSCC) and 22 normal skin tissues as well as in CSCC cell lines (A431, HSC-5) and normal cells (HaCaT). MiR-497 effects on cell proliferation and cell cycle were examined by CCK8 assays and flow cytometry. Dual luciferase reporter gene assay was performed to detect the regulating relationship between miR-497 and FAM114A2. In addition, the expression of FAM114A2 after overexpression or knockdown of miR-497 was detected by Western blot to evaluate whether miR-497 could regulate proliferation and cell cycle by regulating the expression of FAM114A2. RESULTS: MiR-497mRNA expression in CSCC tissues and cell lines was markedly lower than that in normal tissues and cells. Meanwhile, FAM114A2 mRNA and protein levels in CSCC tissues were markedly higher when compared to than that in normal tissues. miR-497 overexpression or knockdown could inhibit or promote the cell proliferation and cell cycle of A431, HSC-5. The dual luciferase reporter gene assay suggested that FAM114A2 might be a direct target gene of miR-497, and that FAM114A2 expression had a significant negative correlation with miR-497. Overexpression of miR-497 could inhibit FAM114A2 protein expression. Besides, FAM114A2 knockdown reversed the inhibitory effect of low expression of miR-497 on proliferation rate of A431 or HSC-5 cells. CONCLUSIONS: MiR-497 was lowly expressed in squamous cell carcinoma tissues and cells, which can participate in the regulation of cell proliferation through FAM114A2, thus promoting the progression of CSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proliferação de Células , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Cutâneas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Ciclo Celular , Linhagem Celular Tumoral , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Proteínas de Neoplasias/genética , Transdução de Sinais , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia
5.
Zhonghua Yi Xue Za Zhi ; 98(24): 1931-1936, 2018 Jun 26.
Artigo em Chinês | MEDLINE | ID: mdl-29996285

RESUMO

Objective: To investigate current status and problems of internal quality control (IQC) of complete blood count in China so as to perform IQC normally. Methods: The IQC data of complete blood count for five parameters were collected from laboratories participating in national external quality assessment during 2012-2017 (totally 12 times), including WBC, RBC, Hb, Hct and PLT. After confirmation of all data, data for the 12 times were analyzed as follows.The proportions of using different levels of quality control materials were calculated.The 25th, 50th, 75th, 90th percentiles CV of data collected for the 12 times were calculated respectively and the trends of CV were observed over time.The difference of CV among laboratories running three control levels was compared.The CV of each parameter in 2017 was compared with precision requirements based on biological variation, health standards and German Medical Association Directive; The proportions of laboratories using different control rules were calculated. Results: After invalid data was excluded from those IQC data of laboratories for the 12 times external quality assessment (up to 2 402, as low as 1 449) from 2012 to 2017, the residual data (up to 2 332, as low as 1 431, accounting for 96.0%-99.2%) was used for analysis. 61.9%-66.1%, 18.2%-23.6% and 14.3%-17.3% of laboratories ran one, two and three control levels respectively, and the proportions of laboratories running more than two control levels increased from 33.9% to 38.1%. The decrease trend of the 75th, 90th percentiles CV of WBC, RBC, Hb, Hct for three levels, PLT for normal level and the 90th percentiles CV of PLT low level had statistically significance over time (P<0.05); the decrease trend of the 75th percentiles CV of PLT low level and 75th, 90th percentiles CV of PLT high level had no statistically significance over time. The CV had significant difference between low and normal, low and high control level for WBC and PLT, while there were no difference between normal and high control levels. There were no significant difference of CV among three control levels for RBC, Hb, and Hct. Except for the CV of Hct low, normal level and PLT low level, 85% of laboratories for the other parameters could meet the minimum precision requirements based on biological variation; more than 85% laboratories met the requirements of health standards; except for the CV of PLT low level, more than 80% laboratories met the requirements of German Medical Association Directive. The proportion of laboratories using 1(3s)/2(2s) quality control rules increased from 59.2% to 76.0%. Conclusions: During the past 6 years, the CV for IQC has shown a decrease trend over time. However, the control level and quality control rules used by some laboratories do not meet management requirements. The CV of Hct and PLT in a few laboratories do not meet the minimum requirements of the health standards, and need to implement quality improvements fatherly.


Assuntos
Contagem de Células Sanguíneas , Controle de Qualidade , China , Padrões de Referência
6.
BMC Cancer ; 18(1): 281, 2018 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-29530011

RESUMO

BACKGROUND: The primary pulmonary lymphoma (PPL), with a low incidence, was highly misdiagnosed in clinic. The present study analyzes the clinical features, laboratory and imaging data, pathologic characteristics, and summarizes misdiagnosis reasons of PPL cases, aims to provide a better understanding and increase the accuracy of early diagnosis and minimize the misdiagnosis of PPL. METHODS: The clinical data of 19 cases were collected from the first affiliated hospital of Wenzhou medical university (PRC) from April 2010 to May 2016. All cases were confirmed by pathology. The process of misdiagnosis was described. This study retrospectively analyzed the incidence, clinical presentation, laboratory examination, Chest CT scan and diagnosis of the cases. RESULTS: The symptoms of the 19 cases were dyspnea, fever, hemoptysis, chest pain or physical findings without obvious symptoms. Five patients were pneumonia-like, nine patients had lung single nodule or mass and four patients got pleural effusion, which were reported by computed tomography (HRCT) scan. There were 2 cases of Hodgkin lymphoma (HL), and 17 cases of non-Hodgkin lymphoma (NHL). In NHL cases, 12 cases were confirmed mucosa associated lymphoid tissue B lymphoma type, 3 cases were confirmed diffuse large B-cell lymphoma, angioimmunoblastic T-cell lymphoma and ALK positive anaplastic large cell lymphoma were one case separately. Clinical and imaging manifestation of PPL is untypical, but there are still some hints: 1) Fuzzy shadow at the edge of lung mass with air bronchogram; 2) Lung mass shadow stable for a long time; 3) Pneumonia-like changing without infections clinical and lab manifestation. Thirteen patients (68.4%) were misdiagnosed as pneumonia, lung cancer and tuberculosis initially. The term between initial diagnosis and final diagnosis lasted for half a month up to 2 years, with median time of 6 months. Two cases were misdiagnosed as tuberculosis. One case was misdiagnosed as small cell lung cancer. CONCLUSION: Clinical and imaging manifestation of PPL is untypical. Biopsies should be taken actively if the imaging findings don't match the symptoms or the anti-infection treatments to "lung infection" don't work. Accurate diagnosis requires adequate tissue sampling with appropriate ancillary pathologic studies. If clinical manifestation and the diagnosis don't match, repeated biopsy should be ordered.


Assuntos
Erros de Diagnóstico , Doença de Hodgkin/diagnóstico , Neoplasias Pulmonares/diagnóstico , Linfoma não Hodgkin/diagnóstico , Adulto , Idoso , Biópsia , Feminino , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/patologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Tórax/diagnóstico por imagem , Tórax/patologia , Tomografia Computadorizada por Raios X
7.
Eur Rev Med Pharmacol Sci ; 22(5): 1196-1202, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29565474

RESUMO

OBJECTIVE: The use of adipose-derived stem cells (ADSCs) to cure the optic nerve injury was never shown previously. Here, we implanted purified ADSCs into optic nerve injury of rats. MATERIALS AND METHODS: Male Sprague Dawley (SD) rats were used in this study. The vision degeneration was detected by Flash-visual evoked potential (F-VEP) assay. The expression of Macrophage-1 (Mac-1), myeloid differentiation factor 88 (MyD88), and nuclear transcription factor-κB (NF-κB) were studied by Western blot. The expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the optical nerve lysates were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: We found out that ADSC implantation inhibits the amplitude decrease and latency increase of the P1 wave caused by the optic nerve injury. The expression of the inflammation associated proteins of the toll-like receptor 4 (TLR4) signaling pathway, including Mac-1, MyD88, NF-κB, IL-6, and TNF-α, were inhibited in the ADSC therapy group compared to the control group. CONCLUSIONS: Our results indicated that ADSC implantation can inhibit the inflammation after the optic nerve injury and improve the functional vision impairment. These findings suggested ADSC implantation as a translational therapy method for optic nerve injury in clinics.


Assuntos
Tecido Adiposo/citologia , Inflamação/prevenção & controle , Traumatismos do Nervo Óptico/terapia , Transplante de Células-Tronco , Receptor 4 Toll-Like/fisiologia , Animais , Potenciais Evocados Visuais , Masculino , NF-kappa B/fisiologia , Traumatismos do Nervo Óptico/fisiopatologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia
8.
Braz. j. med. biol. res ; 48(6): 515-522, 06/2015. graf
Artigo em Inglês | LILACS | ID: lil-748224

RESUMO

We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each). The model group received 60% (v/v) ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N) and microglia (by Ib1) were conducted. Glutamic acid (Glu) and gamma amino butyric acid (GABA) in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC), and tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05) by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01), and neurons were reduced only in the hippocampal dentate gyrus (P<0.01) in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05), and Glu/GABA, TNF-α, and IL-1β increased (P<0.01) with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.


Assuntos
Animais , Masculino , Etanol/envenenamento , Isoflavonas/uso terapêutico , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Memória Espacial/efeitos dos fármacos , Vasodilatadores/uso terapêutico , Alcoolismo/complicações , Cromatografia Líquida de Alta Pressão , Córtex Cerebral/química , Córtex Cerebral/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Ácido Glutâmico/análise , Interleucina-1beta/análise , Isoflavonas/farmacologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Distribuição Aleatória , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise , Vasodilatadores/farmacologia , Ácido gama-Aminobutírico/análise
9.
Braz J Med Biol Res ; 48(6): 515-22, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25831201

RESUMO

We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each). The model group received 60% (v/v) ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N) and microglia (by Ib1) were conducted. Glutamic acid (Glu) and gamma amino butyric acid (GABA) in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC), and tumor necrosis factor (TNF)-α and interleukin (IL)-1ß were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05) by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01), and neurons were reduced only in the hippocampal dentate gyrus (P<0.01) in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05), and Glu/GABA, TNF-α, and IL-1ß increased (P<0.01) with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.


Assuntos
Etanol/envenenamento , Isoflavonas/uso terapêutico , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Memória Espacial/efeitos dos fármacos , Vasodilatadores/uso terapêutico , Alcoolismo/complicações , Animais , Córtex Cerebral/química , Córtex Cerebral/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ensaio de Imunoadsorção Enzimática , Ácido Glutâmico/análise , Interleucina-1beta/análise , Isoflavonas/farmacologia , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Distribuição Aleatória , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise , Vasodilatadores/farmacologia , Ácido gama-Aminobutírico/análise
10.
Neoplasma ; 60(2): 203-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23259790

RESUMO

Recent studies have shown an indirect link between platelet count and blood vessel metastasis, but this association with lymphatic vessels metastasis has not been established in NSCLC. So we investigated whether an association exists between preoperative platelet count and lymph node metastasis in NSCLC patients. Between January 2001 and January 2011, platelet counts were obtained from 883 NSCLC patients who were resistant to chemotherapy, radiotherapy, and surgery. The preoperative platelet counts, tumor metastasis, and overall survival of NSCLC patients were analyzed for correlations via statistical analysis. Upon considering patients according to their TNM lymph node metastasis stage (N0-N3), multiple comparison analyses revealed that the mean preoperative platelet count of the N0 group was significantly lower than that of the N1-N3. Analysis of variance showed that the preoperative platelet count of patients in stage I was significantly lower than that of those in stages II, III, and IV, with no significant difference among the latter three stages. According to the Kaplan-Meier survival analysis, the overall survival of patients with platelet counts <214.5 × 109/L was significantly longer than that of those with platelet counts ≥214.5 × 109/L. Cox regression analysis indicated that, besides preoperative platelet count, patient age, gender, and TNM stage were independent prognostic factors. In conclusion, preoperative platelet count was significantly associated with metastasis of lymph nodes in NSCLC patients. Preoperative platelet count may be a reliable biomarker of lymph node metastasis possibility and an independent prognostic factor of overall survival in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Contagem de Plaquetas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais
11.
Methods Find Exp Clin Pharmacol ; 32(7): 481-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21069099

RESUMO

A specific, sensitive and simple method was developed to determine the levels of both atorvastatin and ortho-hydroxy atorvastatin in human plasma. The analytes and internal standard pitavastatin were extracted from plasma by liquid-liquid extraction, separated on a Zorbax SB-C18 column, eluted with a mobile phase of water:acetonitrile (45:55 v/v), both containing 5% methanol and 0.01% formic acid. Detection was performed with an electrospray ionization triple quadrupole mass spectrometer in positive ion mode using multiple reaction monitoring. The standard calibration curves of atorvastatin and ortho-hydroxy atorvastatin were linear in the concentration range of 0.2-20 and 0.1-20 ng/mL, respectively. The intra- and inter-day precisions were < 7.7% and the accuracy was within ± 5.9%. The method has been successfully used for the study of the pharmacokinetics of atorvastatin and ortho-hydroxy atorvastatin in Chinese patients with coronary heart disease after a single oral dose of 20 mg atorvastatin. The mean values for the area under the plasma concentration-time curve for atorvastatin and ortho-hydroxy atorvastatin were 63.1 and 46.9 ng.h/mL, respectively.


Assuntos
Ácidos Heptanoicos/farmacocinética , Pirróis/farmacocinética , Área Sob a Curva , Atorvastatina , Cromatografia Líquida de Alta Pressão , Ácidos Heptanoicos/sangue , Humanos , Pirróis/sangue , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Fatores de Tempo
12.
Adv Gerontol ; 16: 30-7, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16075674

RESUMO

A decline in chronic disability prevalence occurred 1982 to 1999 in the U.S. elderly population parallel to declines in severe cognitive impairment. Comparative analysis of factors contributing to the incidence of dementia led us to suggest explanations for this decline. 42,000 disabled and non-disabled individuals aged 65+ participating in National Long Term Care Surveys (NLTCS) were drawn from Medicare enrollment lists to ensure the US population aged 65+ is represented. Severe cognitive impairment (SCI) was defined by the subject not being able to successfully answer any cognitive screen questions in survey interviews. This definition thus covered cases of dementia of different origin and clinical manifestation: Alzheimer's, non-Alzheimer's, stroke-related, vascular etc. Age-specific prevalence of SCI was calculated for 1982, 1984, 1989, 1994 and 1999, and Medicare record physician determined diagnoses of vascular, mixed and Alzheimer's dementia in 1994 and 1999 was determined by gender and age. We found 310,000 fewer severely cognitively impaired elderly in 1999 than in 1982. The average decline in prevalence was from 5.7% to 2.9% for this period. This was associated with a significant decline in mixed but not Alzheimer's dementias. On a gender basis, the male proportional decline was larger than that of female. Several possible explanations of such a surprising trend in elderly age dementias are discussed, including (i) increased proportion of better educated people among the oldest old; (ii) recent declines in stroke rates (these may contribute to decreasing risks of post-stroke dementias); (ii) expanding use of neuro-protective medications working prophylactically for selected dementias. A significant component of disability decline in the U.S. elderly population is the decline in vascular and mixed dementias, but not in Alzheimer's disease alone. Improved medical therapies and better education among the old appear to play important roles in this decline.


Assuntos
Doença de Alzheimer/epidemiologia , Transtornos Cognitivos/epidemiologia , Demência/epidemiologia , Idoso , Doença de Alzheimer/tratamento farmacológico , Transtornos Cognitivos/tratamento farmacológico , Demência/tratamento farmacológico , Feminino , Humanos , Masculino , População , Prevalência , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Estados Unidos/epidemiologia
13.
J Mol Graph Model ; 19(6): 560-70, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11552685

RESUMO

A simple ligand-protein structural optimization and binding evaluation procedure has been routinely used in high-speed ligand-protein docking studies. In this work, we examine whether such an optimization/scoring procedure is useful in indicating possible drug-resistant mutations in proteins. Crystal structures of three wild-type enzymes (HIV-1 protease, HIV-1 reverse transcriptase, and Mycobacterium tuberculosis H37Rv enoyl-ACP reductase) complexed to a variety of inhibitors are studied. Mutations are introduced into these structures by using the molecular modeling software, SYBYL. Structural optimization and scoring of a mutant complex is conducted by a procedure similar to that used in a recent docking study (Wang et al., 1999). The computed results are compared with observed drug resistance data and the profile of nonresistant mutations. Most mutations studied show an energy change in the same direction as those indicated by observed resistance data. 50% of the polar to polar or nonpolar to nonpolar mutations are found to correlate qualitatively with observed drug resistance data. Van der Waals interactions account for most of these changes, which is in agreement with conclusions from structural studies. Substantially larger deviations are found between computed results and observed data for most polar to nonpolar or nonpolar to polar mutations, which result from deficiency in modelling and scoring ligand-protein interactions in our procedure. Our results suggest that an optimization/docking scoring procedure is useful for qualitatively probing polar to polar or nonpolar to nonpolar resistant mutations in addition to its application in screening active compounds. More accurate description of ligand-protein interactions and the use of methods such as free energy perturbation and Poisson-Boltzmann may be needed to further improve the quality of prediction.


Assuntos
Farmacorresistência Bacteriana/genética , Farmacorresistência Viral/genética , Inibidores da Protease de HIV/química , Protease de HIV/química , Transcriptase Reversa do HIV/química , Oxirredutases/química , Inibidores da Transcriptase Reversa/química , Simulação por Computador , Cristalografia por Raios X , Transferência de Energia , Enoil-(Proteína de Transporte de Acila) Redutase (NADH) , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , HIV-1/enzimologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Modelos Moleculares , Estrutura Molecular , Mutagênese , Mycobacterium tuberculosis/enzimologia , Oxirredutases/genética , Conformação Proteica
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