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1.
Biopsychosoc Med ; 15(1): 18, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34641938

RESUMO

BACKGROUND: Environmental psychological factors such as mood states can modify and trigger an organic response; depressive disorder is considered a risk factor for oncological development, leading to alterations both in the genesis and in the progression of the disease. Some authors have identified that personality relates to mood since a high score in neuroticism is associated with intense and long-lasting emotions of stress and therefore with the development of depressive behaviors. The objective of this study was to analyze the relationship between personality and depression in skin cancer patients. METHODS: A total of forty-seven clinically and histopathologically diagnosed patients were scheduled for an hour-long interview, during which they provided informed consent and sociodemographic information. The psychological questionnaires applied were the revised Eysenck Personality Questionnaire and the clinical questionnaire for the diagnosis of the depressive syndrome. RESULTS: The patient's mean age was 66.5 years (SD ± 12.4) and the majority were diagnosed with basal cell carcinoma (70.2%). The frequency of anxious/depressive symptoms was 42.5%, with an increase in depression scores in the female gender (p < 0.001). Furthermore, a difference was found in the neuroticism dimension related to gender, with higher values in women (p = 0.002). Depressive symptomatologic portraits were correlated with the dimensions of neuroticism (p < 0.001, r = 0.705), psychoticism (p = 0.003, r = 0.422) and lying (p = 0.028, r = - 0.321). CONCLUSIONS: Our results support the hypothesis that personality dimensions are related to the presence of anxiety/depressive symptomatology in patients with skin cancer, especially in the female gender. Highlighting the need for future research that delves into the implications at the psychological level, the quality of life, and the biological mechanisms that link personality and depressive symptoms in the development and evolution of skin cancer.

2.
J Ethnopharmacol ; 245: 112183, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31445134

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hydrocotyle umbellata var.bonariensis Lam. (Hb), popularly known in Brazil as acariçoba and outside Brazil Hb by a number of names including marsh-pennywort, and many-flower, has traditionally been used in Ayurvedic medicine in the retardation of aging (Rasayana effect). AIM OF THE STUDY: The present study evaluated the effect of Hb treatment before and during paradoxical sleep deprivation (PSD) and sleep restriction (SR) on learning, memory, and acetylcholinesterase (AChE) brain activity. MATERIAL AND METHODS: Adult Swiss nulliparous female mice were randomly distributed among the experimental groups. The treated groups received the aqueous solution of Hb leaves orally at concentrations of 500 and 1.000 mg/kg. PSD and SR were induced by the multiple platform method, in which the animals remained for 3-days in PSD or 15-days in SR for 22 h per day. The collection of the vaginal epithelium occurred daily to determine the estrous cycle. Body mass gain was determined. The animals were submitted to the passive avoidance test and were then euthanized for the collection of brain tissue and the determination of cerebral cholinesterase activity. RESULTS: The aqueous solution of Hb was associated with a significant reduction in cholinesterase activity at both doses in the SR model, and at the dose of 1.000 mg/kg in the PSD model. Regarding the learning and memory test, the PSD group treated with 1.000 mg/kg presented significant improvement, whereas in the SR experiment none of the treated-groups showed any improvement in learning and memory. In the analysis of SR/PSD interference and/or Hb treatment on the estrous cycle, it was possible to observe that the treatment acted as a protector in the SR group, maintaining a normal cycle. CONCLUSIONS: The analyses showed that Hb was safe to use during periods of SR or PSD, acting as an adaptogen for these situations, in addition to being able to reduce cholinesterase activity, which suggests its neuroprotective action. In relation to the estrous cycle, Hb can act as a protector in SR situations.


Assuntos
Araliaceae , Aprendizagem/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/uso terapêutico , Privação do Sono/tratamento farmacológico , Acetilcolinesterase/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ciclo Estral/efeitos dos fármacos , Feminino , Camundongos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta , Privação do Sono/metabolismo , Privação do Sono/fisiopatologia
3.
Int J Radiat Biol ; 94(9): 838-843, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29939813

RESUMO

PURPOSE: Some phytochemicals have shown the potential of being radiomodifiers, especially phenolic compounds, such as lichenic secondary metabolites. To evaluate the phytochemical usnic acid as a radiomodifier, embryonic cells of molluscs have been used due to their ease of collection, high sensitivity to physical and chemical agents, well-known embryology and low cost for analysis. MATERIALS AND METHODS: This study aimed to assess the radiosensitizing action of usnic acid on Biomphalaria glabrata embryos. Samples were irradiated with 4 Gy of gamma rays from a 60Co source (dose rate 2.906 Gy/h). An acute toxicity test was performed using B. glabrata embryos in the blastula stage, in order to determine the toxicity of usnic acid and to establish the lethal Concentration for 50% (LC50). Subsequently, the radiomodifing capacity of usnic acid was estimated using assays with B. glabrata embryos. RESULTS: Irradiation increased the number of non-viable embryos compared to unirradiated controls. Additionally, it was observed that embryos exposed to a non-toxic concentration of usnic acid (0.6 µg/mL) before irradiation showed a further enhancement in non-viable embryos when compared with exposure to ionizing radiation alone. CONCLUSION: The results presented here indicate that usnic acid makes cells more sensitive to the damaging effects of radiation.


Assuntos
Benzofuranos/farmacologia , Biomphalaria/embriologia , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/efeitos da radiação , Radiossensibilizantes/farmacologia , Animais , Benzofuranos/toxicidade , Radioisótopos de Cobalto , Raios gama , Dose Letal Mediana , Radiossensibilizantes/toxicidade
4.
Scand J Immunol ; 86(1): 40-49, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28426172

RESUMO

It is well established that helper T cell responses influence resistance or susceptibility to Mycobacterium leprae infection, but the role of more recently described helper T cell subsets in determining severity is less clear. To investigate the involvement of Th17 cells in the pathogenesis of leprosy, we determined the immune profile with variant presentations of leprosy. Firstly, IL-17A, IFN-γ and IL-10 were evaluated in conjunction with CD4+ T cell staining by confocal microscopy of lesion biopsies from tuberculoid (TT) and lepromatous leprosy (LL) patients. Secondly, inflammatory cytokines were measured by multiplex assay of serum samples from Multibacillary (MB, n = 28) and Paucibacillary (PB, n = 23) patients and household contacts (HHC, n = 23). Patients with leprosy were also evaluated for leprosy reaction occurrence: LR+ (n = 8) and LR- (n = 20). Finally, peripheral blood mononuclear cells were analysed by flow cytometry used to determine the phenotype of cytokine-producing cells. Lesions from TT patients were found to have more CD4+ IL-17A+ cells than those from LL patients. Higher concentrations of IL-17A and IL-1ß were observed in serum from PB than MB patients. The highest serum IFN-γ concentrations were, however, detected in sera from MB patients that developed leprosy reactions (MB LR+ ). Together, these results indicate that Th1 cells were associated with both the PB presentation and also with leprosy reactions. In contrast, Th17 cells were associated with an effective inflammatory response that is present in the PB forms but were not predictive of leprosy reactions in MB patients.


Assuntos
Mediadores da Inflamação/imunologia , Hanseníase Paucibacilar/imunologia , Hanseníase/imunologia , Mycobacterium leprae/imunologia , Células Th1/imunologia , Células Th17/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Criança , Busca de Comunicante , Feminino , Citometria de Fluxo , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Interferon gama/sangue , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-10/metabolismo , Interleucina-17/sangue , Interleucina-17/imunologia , Interleucina-17/metabolismo , Interleucina-1beta/sangue , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Hanseníase/sangue , Hanseníase/microbiologia , Hanseníase Multibacilar/sangue , Hanseníase Multibacilar/imunologia , Hanseníase Multibacilar/microbiologia , Hanseníase Paucibacilar/sangue , Hanseníase Paucibacilar/microbiologia , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Mycobacterium leprae/fisiologia , Células Th1/metabolismo , Células Th17/metabolismo , Adulto Jovem
5.
Mar Pollut Bull ; 118(1-2): 403-406, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28279503

RESUMO

The Furo of Laura is an economically important river in the Amazon estuary. Thus, in the present study, we evaluated the metal distribution (Al, Cd, Co, Cu, Cr, Fe, Ni, and Mg) in the bottom sediments of this river. The sediments were sampled at four points every 2months for a year with an Ekman-Birge sampler. After microwave acid digestion, the metal levels were determined by optical emission spectrometry with inductively coupled plasma. The particle size and organic matter content influenced the concentration of the metals. The sediments were not enriched by the analyzed metals; the estuary therefore retained the characteristics of an uncontaminated environment, thus serving as a reference environment for comparison.


Assuntos
Monitoramento Ambiental , Estuários , Sedimentos Geológicos/química , Metais Pesados/análise , Poluentes Químicos da Água/análise , Brasil , Tamanho da Partícula , Rios/química
6.
Clin Microbiol Infect ; 21(11): 1027-32, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26166544

RESUMO

The prevalence and management of chronic hepatitis B virus (HBV) infection differ among European countries. The availability and reimbursement of diagnostics and drugs may also vary, determining distinct treatment outcomes. Herein, we analyse differences in medical facilities for the care of patients with chronic HBV infection across Europe. A survey was sent to the members of the ESCMID Study Group for Viral Hepatitis, all of whom are experts in chronic HBV infection management. The comprehensive survey asked questions regarding hepatitis B surface antigen (HBsAg) prevalence, the availability of diagnostics and drugs marketed, and distinct clinical practice behaviours in the management of chronic HBV infection. World Bank data were used to assess the economic status of the countries. With 16 expert physicians responding (69%), the HBsAg prevalence rates were <1% in France, Hungary, Italy, The Netherlands, Portugal, Spain, and the UK, intermediate (1-5%) in Turkey, Romania, and Serbia, and high (>5%) in Albania and Iran. Regarding the availability and reimbursement of HBV diagnostics (HBV DNA and liver stiffness measurement), HBV drugs (interferon, lamivudine, tenofovir, and entecavir), HBV prophylaxis, and duration of HBeAg-positive and HBeAg-negative HBV infection, the majority of high-income and middle-income countries had no restrictions; Albania, Iran and Serbia had several restrictions in diagnostics and HBV drugs. The countries in the high-income group were also the ones with no restrictions in medical facilities, whereas the upper-middle-income countries had some restrictions. The prevalence of chronic HBV infection is much higher in southern and eastern than in western European countries. Despite the availability of European guidelines, policies for diagnostics and treatment vary significantly across European countries.


Assuntos
Acessibilidade aos Serviços de Saúde , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Antivirais/uso terapêutico , Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/estatística & dados numéricos , Uso de Medicamentos , Europa (Continente)/epidemiologia , Feminino , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/epidemiologia , Humanos , Masculino , Estudos Soroepidemiológicos , Inquéritos e Questionários
7.
J Mater Sci Mater Med ; 26(1): 5323, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25577207

RESUMO

The electrochemical behavior and corrosion resistance of Ti-15Mo alloy to applications as biomaterials in solutions 0.15 mol L(-1) Ringer, 0.15 mol L(-1) Ringer plus 0.036 mol L(-1) NaF and 0.036 mol L(-1) NaF (containing 1,500 ppm of fluoride ions, F(-)) were investigated using open-circuit potential, cyclic voltammetry, and electrochemical impedance spectroscopy techniques, X-ray photoelectron spectroscopy and scanning electron microscope. Corrosion resistance and electrochemical stability of the Ti-15Mo alloy decreased in solutions containing F(-) ions. In all cases, there were formation and growth of TiO2 and MoO3 (a protector film), not being observed pitting corrosion, which might enable Ti-15Mo alloys to be used as biomedical implant, at least in the studied conditions, since the electrochemical stability and corrosion resistance of the passive films formed are necessary conditions for osseointegration.


Assuntos
Ligas/química , Cloretos/análise , Corrosão , Eletroquímica , Fluoretos/análise , Ar , Microscopia Eletrônica de Varredura , Espectroscopia Fotoeletrônica , Soluções
8.
Anat Histol Embryol ; 43(4): 310-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24033472

RESUMO

The testicular morphology, spermatogenesis and occurrence of sperm in the ovarian lumen of Trachelyopterus striatulus were studied using anatomical, histological and biometric techniques. A total of 50 catfish (T. striatulus) were captured, measuring 14.9 ± 2.5 cm of standard length, body weight was 81.2 ± 34.5 g and their testes weighed 16.9 ± 6.1 g. The testes of T. striatulus are paired organs, showing two distinct regions: cranial, which shows a compact medial part and with fringes ventrally, and caudal region, which is formed of the seminal vesicle with fringes laterally and two saculiform expansions. The testes presented a length of 35.2 ± 6.9 mm, and the fringes showed a cranial length of 12.1 ± 3.8 mm and caudal length of 6.4 ± 2.6 mm. Histologically, the cranial fringes are spermatogenic and showed cells with significantly different nuclear diameters, ranging from 8.2 ± 1.5 µm (primary spermatogonia) to 1.88 ± 0.3 µm (spermatid). The seminal vesicles and saculiform expansions showed tubules with a simple prismatic secretory epithelium containing spermatozoa and secretion into the lumen. The caudal fringes are exclusively for secretory flow, consisting of tubules with a simple cuboidal epithelium. The common spermatic duct showed a simple cuboidal epithelium and contained spermatozoa with secretion into the lumen. The secretion of the caudal region is acidophilic, with neutral glycoproteins and sialomucin. T. striatulus ovaries showed free spermatozoa or were organized in spermatozeugmata into the ovarian lumen and between the ovuligers lamellae.


Assuntos
Peixes-Gato/anatomia & histologia , Testículo/anatomia & histologia , Animais , Peixes-Gato/fisiologia , Feminino , Masculino , Espermatogênese/fisiologia , Testículo/fisiologia
9.
Genet Mol Res ; 10(4): 4133-46, 2011 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-22179994

RESUMO

Species with a broad distribution rarely have the same genetic make-up throughout their entire range. In some cases, they may constitute a cryptic complex consisting of a few species, each with a narrow distribution, instead of a single-, widely distributed species. These differences can have profound impacts for biodiversity conservation planning. The genetic differentiation of four populations of Aegla longirostri, a freshwater crab found in two geographically isolated basins in Rio Grande do Sul State, Brazil, was investigated by analyzing pentanucleotide multi-loci microsatellites in a heteroduplex assay. Although no morphological differences were evident, we found significant genetic differentiation among the four populations, based on F(ST) values and clustering analysis. This high level of differentiation may be indicative of cryptic species in these populations. If this hypothesis is correct, then the species occurring in the Ibicuí-Mirim River, at the southern limit of the Atlantic Rain Forest, would be under threat, considering its very restricted distribution.


Assuntos
Anomuros/genética , Variação Genética , Repetições de Microssatélites , Animais , Biodiversidade , Brasil , Deriva Genética , Genética Populacional , Geografia
10.
Braz. j. med. biol. res ; 44(2): 123-129, Feb. 2011. tab
Artigo em Inglês | LILACS | ID: lil-573660

RESUMO

We investigated the effect of -174 G/C single-nucleotide polymorphism in the promoter region of the IL6 gene on plasma IL-6 levels and muscle strength, and the relationship between IL-6 levels and muscle strength in elderly women. The sample consisted of 199 elderly residents (73.0 ± 7.8 years old) from rest homes and the community in Belo Horizonte, MG, Brazil. -174 G/C polymorphism was determined by direct sequencing of the product by PCR, and plasma IL-6 concentrations were measured by ELISA. Muscle strength in the knee joint was evaluated using a Biodex System 3 Pro® isokinetic dynamometer. ANCOVA was used to determine the effect of polymorphism on IL-6 levels and muscle strength, and the Pearson correlation coefficient to assess the relationship between IL-6 levels and muscle strength. -174 G/C polymorphism was associated with the plasma IL-6 levels of elderly women (P < 0.01) since homozygotes for the G allele showed high IL-6 levels (GG 3.85 pg/mL, GC + CC 2.13 pg/mL). There was no association of polymorphism on muscle strength (P > 0.05). No association was found between IL-6 levels and knee extensor muscle (r = 0.087, P = 0.306) or flexor (r = -0.011, P = 0.894) strength. An interaction between -174 G/C polymorphism and housing conditions of the sample of elderly women was identified, with the effect of genotype on IL-6 levels being higher in the institutionalized elderly. These results support the evidence that -174 G/C polymorphism of the IL6 gene associates with individual variability of plasma IL-6 levels in elderly women.


Assuntos
Idoso , Feminino , Humanos , /sangue , /genética , Força Muscular/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Teste de Esforço , Genótipo , Contração Isométrica , Articulação do Joelho , Fatores Socioeconômicos
11.
Braz J Med Biol Res ; 44(2): 123-9, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21180882

RESUMO

We investigated the effect of -174 G/C single-nucleotide polymorphism in the promoter region of the IL6 gene on plasma IL-6 levels and muscle strength, and the relationship between IL-6 levels and muscle strength in elderly women. The sample consisted of 199 elderly residents (73.0 ± 7.8 years old) from rest homes and the community in Belo Horizonte, MG, Brazil. -174 G/C polymorphism was determined by direct sequencing of the product by PCR, and plasma IL-6 concentrations were measured by ELISA. Muscle strength in the knee joint was evaluated using a Biodex System 3 Pro® isokinetic dynamometer. ANCOVA was used to determine the effect of polymorphism on IL-6 levels and muscle strength, and the Pearson correlation coefficient to assess the relationship between IL-6 levels and muscle strength. -174 G/C polymorphism was associated with the plasma IL-6 levels of elderly women (P < 0.01) since homozygotes for the G allele showed high IL-6 levels (GG 3.85 pg/mL, GC + CC 2.13 pg/mL). There was no association of polymorphism on muscle strength (P > 0.05). No association was found between IL-6 levels and knee extensor muscle (r = 0.087, P = 0.306) or flexor (r = -0.011, P = 0.894) strength. An interaction between -174 G/C polymorphism and housing conditions of the sample of elderly women was identified, with the effect of genotype on IL-6 levels being higher in the institutionalized elderly. These results support the evidence that -174 G/C polymorphism of the IL6 gene associates with individual variability of plasma IL-6 levels in elderly women.


Assuntos
Interleucina-6/sangue , Interleucina-6/genética , Força Muscular/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Idoso , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Teste de Esforço , Feminino , Genótipo , Humanos , Contração Isométrica , Articulação do Joelho , Fatores Socioeconômicos
12.
Arch Gerontol Geriatr ; 52(3): 322-6, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20627334

RESUMO

An increased circulating level of inflammatory cytokines has been associated with sarcopenia, functional disability, chronic diseases, and mortality in the elderly. Osteoarthritis (OA) is a disease common to this population, the seriousness of articular degeneration has been associated to the increase in some cytokines, IL-6 among them. The aim of the present study was to correlate IL-6 plasma levels with muscle strength, endurance, muscle balance hamstring/quadriceps (H/Q) and physical function in 80 elderly women (71.2 ± 5.3) with knee OA. IL-6 was measured using enzyme-linked immunosorbent assay (ELISA). Quadriceps and hamstring muscle strength, endurance and hamstring-quadriceps muscle balance were assessed using a Biodex system 3 pro(®) isokinetic dynamometer. Physical function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Spearman's correlation coefficient was used to explore the relationship between the outcomes at the significance level of α=0.05. IL-6 was inversely correlated to the endurance of the hamstring muscles (r=-0.232; p=0.03) and muscle balance (H/Q) on the lower right side at 180°/s (r=-0.254; p=0.023). No significant correlation between IL-6, muscle strength and physical function was found. Our results show that elevated levels of IL-6 may possibly contribute to the reduction of the endurance of hamstring muscles and H/Q muscle balance in the elderly studied.


Assuntos
Envelhecimento , Interleucina-6/sangue , Força Muscular/fisiologia , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/fisiopatologia , Idoso , Estudos Transversais , Feminino , Humanos , Resistência Física/fisiologia , Músculo Quadríceps/fisiopatologia
14.
Br J Pharmacol ; 159(8): 1716-23, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20401963

RESUMO

BACKGROUND AND PURPOSE: Compound LASSBio-881 is an orally effective antinociceptive that binds to cannabinoid receptors and is active mainly on the neurogenic component of pain models. We investigated whether transient receptor potential vanilloid subfamily type 1 (TRPV1) channels are involved in the effects of LASSBio-881. EXPERIMENTAL APPROACH: Modulation of capsaicin (CAP)- and low pH-induced currents was evaluated in TRPV1-expressing Xenopus oocytes. In vivo effects were evaluated in CAP-induced acute and inflammatory changes in nociception, as well as in partial sciatic ligation-induced thermal hypernociception. KEY RESULTS: LASSBio-881 inhibited TRPV1 currents elicited by CAP with an IC(50) of 14 microM, and inhibited proton-gated currents by 70% at 20 microM. Functional interaction with CAP was surmountable. Locally applied LASSBio-881 decreased time spent in CAP-elicited nocifensive behaviour by 30%, and given orally it reduced measures of CAP- or carrageenan-evoked thermal hypernociception by 60 and 40% respectively. In addition, LASSBio-881 decreased the paw withdrawal responses to thermal stimuli of animals with sciatic neuropathy 7-11 days after nerve ligation, at a dose of 300 micromol*kg(-1)*day(-1) p.o. At this dose, hyperthermia was not observed within 4 h following oral administration. CONCLUSIONS AND IMPLICATIONS: LASSBio-881 is a TRPV1 antagonist that apparently competes with CAP. Accordingly, LASSBio- 881 inhibited nociception in models of acute, inflammatory and neuropathic pain presumed to involve TRPV1 signalling. These in vivo actions were not hindered by hyperthermia, a common side effect of other TRPV1 antagonists. We propose that the antinociceptive properties of LASSBio-881 are due to TRPV1 antagonism, although other molecular interactions may contribute to the effects of this multi-target drug candidate.


Assuntos
Analgésicos/uso terapêutico , Capsaicina/farmacologia , Hidrazinas/uso terapêutico , Dor/tratamento farmacológico , Nervo Isquiático/cirurgia , Canais de Cátion TRPV/antagonistas & inibidores , Administração Oral , Analgésicos/administração & dosagem , Animais , Feminino , Hidrazinas/administração & dosagem , Camundongos , Dor/induzido quimicamente , Dor/etiologia , Ratos , Ratos Wistar , Xenopus laevis
18.
Int J Mol Med ; 23(6): 733-43, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19424599

RESUMO

The taxane docetaxel is currently the most effective chemotherapeutic drug for the treatment of advanced breast cancer. However, a considerable proportion of breast cancer patients do not respond positively to docetaxel. The mechanisms of docetaxel resistance are poorly understood. Overexpression of ERBB2 occurs in 15-30% of breast tumors and is associated with chemoresistance to a variety of anticancer drugs. In the present study, we sought to identify genes involved in ERBB2-mediated chemoresistance to docetaxel. We generated SAGE libraries from two human mammary cell lines expressing basal (HB4a) and high (C5.2) levels of ERBB2 before and after intensive exposure to docetaxel and identified potential ERBB2 target genes implicated in a variety of cellular processes including cell proliferation, cell adhesion, apoptosis and cytoskeleton organization. Comparison of the transcriptome of the cell lines before and after docetaxel exposure revealed substantially different expression patterns. Twenty-one differentially expressed genes between HB4a and C5.2 cell lines, before and after docetaxel treatment, were further analyzed by qPCR. The alterations in the expression patterns in HB4a and C5.2 cell lines in response to docetaxel treatment observed by SAGE analysis were confirmed by qPCR for the majority of the genes analyzed. Our study provides a comprehensive view of the expression changes induced in two human mammary cells expressing different levels of ERBB2 in response to docetaxel that could contribute to the elucidation of the mechanisms involved in ERBB2-mediated chemoresistance in breast cancer.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Receptor ErbB-2/genética , Taxoides/farmacologia , Transcrição Gênica/efeitos dos fármacos , Western Blotting , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Docetaxel , Resistencia a Medicamentos Antineoplásicos/genética , Eletroforese em Gel de Poliacrilamida , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Reação em Cadeia da Polimerase , Receptor ErbB-2/metabolismo
19.
Eur J Med Chem ; 44(9): 3754-9, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19446931

RESUMO

We have theoretically studied new potential candidates of acetylcholinesterase (AChE) inhibitors designed from cardanol, a non-isoprenoid phenolic lipid of cashew Anacardium occidentale nut-shell liquid. The electronic structure calculations of fifteen molecule derivatives from cardanol were performed using B3LYP level with 6-31G, 6-31G(d), and 6-311+G(2d,p) basis functions. For this study we used the following groups: methyl, acetyl, N,N-dimethylcarbamoyl, N,N-dimethylamine, N,N-diethylamine, piperidine, pyrrolidine, and N,N-methylbenzylamine. Among the proposed compounds we identified that the structures with substitution by N,N-dimethycarbamoyl, N,N-dimethylamine, and pyrrolidine groups were better correlated to rivastigmine, and represent possible AChE inhibitors against Alzheimer disease.


Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Fenóis/química , Fenóis/farmacologia , Doença de Alzheimer/tratamento farmacológico , Anacardium/química , Animais , Elétrons , Electrophorus/metabolismo , Humanos , Modelos Moleculares , Análise de Componente Principal , Relação Estrutura-Atividade
20.
Braz J Med Biol Res ; 42(3): 279-88, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19287907

RESUMO

We evaluated changes in glucose tolerance of 17 progressors and 62 non-progressors for 9 years to improve our understanding of the pathogenesis of type 2 diabetes mellitus. Changes in anthropometric measurements and responses to an oral glucose tolerance test (OGTT) were analyzed. We identified 14 pairs of individuals, one from each group, who were initially normal glucose tolerant and were matched for gender, age, weight, and girth. We compared initial plasma glucose and insulin curves (from OGTT), insulin secretion (first and second phases) and insulin sensitivity indices (from hyperglycemic clamp assay) for both groups. In the normal glucose tolerant phase, progressors presented: 1) a higher OGTT blood glucose response with hyperglycemia in the second hour and a similar insulin response vs non-progressors; 2) a reduced first-phase insulin secretion (2.0 +/- 0.3 vs 2.3 +/- 0.3 pmol/L; P < 0.02) with a similar insulin sensitivity index and a lower disposition index (3.9 +/- 0.2 vs 4.1 +/- 0.2 micromol.kg-1.min-1 ; P < 0.05) vs non-progressors. After 9 years, both groups presented similar increases in weight and fasting blood glucose levels and progressors had an increased glycemic response at 120 min (P < 0.05) and reduced early insulin response to OGTT (progressors, 1st: 2.10 +/- 0.34 vs 2nd: 1.87 +/- 0.25 pmol/mmol; non-progressors, 1st: 2.15 +/- 0.28 vs 2nd: 2.03 +/- 0.39 pmol/mmol; P < 0.05). Theses data suggest that beta-cell dysfunction might be a risk factor for type 2 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Progressão da Doença , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/fisiologia , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Glucose/metabolismo , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco
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