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1.
Immun Ageing ; 20(1): 51, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821967

RESUMO

BACKGROUND: Adipose-derived stem cells (ADSC) are multipotent cells implicated in tissue homeostasis. Obesity represents a chronic inflammatory disease associated with metabolic dysfunction and age-related mechanisms, with progressive accumulation of senescent cells and compromised ADSC function. In this study, we aimed to explore mechanisms associated with the inflammatory environment present in obesity in modulating ADSC to a senescent phenotype. We evaluated phenotypic and functional alterations through 18 days of treatment. ADSC were cultivated with a conditioned medium supplemented with a pool of plasma from eutrophic individuals (PE, n = 15) or with obesity (PO, n = 14), and compared to the control. RESULTS: Our results showed that PO-treated ADSC exhibited decreased proliferative capacity with G2/M cycle arrest and CDKN1A (p21WAF1/Cip1) up-regulation. We also observed increased senescence-associated ß-galactosidase (SA-ß-gal) activity, which was positively correlated with TRF1 protein expression. After 18 days, ADSC treated with PO showed augmented CDKN2A (p16INK4A) expression, which was accompanied by a cumulative nuclear enlargement. After 10 days, ADSC treated with PO showed an increase in NF-κB phosphorylation, while PE and PO showed an increase in p38MAPK activation. PE and PO treatment also induced an increase in senescence-associated secretory phenotype (SASP) cytokines IL-6 and IL-8. PO-treated cells exhibited decreased metabolic activity, reduced oxygen consumption related to basal respiration, increased mitochondrial depolarization and biomass, and mitochondrial network remodeling, with no superoxide overproduction. Finally, we observed an accumulation of lipid droplets in PO-treated ADSC, implying an adaptive cellular mechanism induced by the obesogenic stimuli. CONCLUSIONS: Taken together, our data suggest that the inflammatory environment observed in obesity induces a senescent phenotype associated with p38MAPK/NF-κB axis, which stimulates and amplifies the SASP and is associated with impaired mitochondrial homeostasis.

2.
Ultrasound Obstet Gynecol ; 59(4): 465-473, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34725869

RESUMO

OBJECTIVES: Improvement in the antenatal diagnosis of placenta accreta spectrum (PAS) would allow preparation for delivery in a referral center, leading to decreased maternal morbidity and mortality. Our objectives were to assess the performance of classic ultrasound signs and to determine the value of novel ultrasound signs in the detection of PAS. METHODS: This was a retrospective cohort study of women with second-trimester placenta previa who underwent third-trimester transvaginal ultrasound and all women with PAS in seven medical centers. A retrospective image review for signs of PAS was conducted by three maternal-fetal medicine physicians. Classic signs of PAS were defined as placental lacunae, bladder-wall interruption, myometrial thinning and subplacental hypervascularity. Novel signs were defined as small placental lacunae, irregular placenta-myometrium interface (PMI), vascular PMI, non-tapered placental edge and placental bulge towards the bladder. PAS was diagnosed based on difficulty in removing the placenta or pathological examination of the placenta. Multivariate regression analysis was performed and receiver-operating-characteristics (ROC) curves were generated to assess the performance of combined novel signs, combined classic signs and a model combining classic and novel signs. RESULTS: A total of 385 cases with placenta previa were included, of which 55 had PAS (28 had placenta accreta, 11 had placenta increta and 16 had placenta percreta). The areas under the ROC curves for classic markers, novel markers and a model combining classic and novel markers for the detection of PAS were 0.81 (95% CI, 0.75-0.88), 0.84 (95% CI, 0.77-0.90) and 0.88 (95% CI, 0.82-0.94), respectively. A model combining classic and novel signs performed better than did the classic or novel markers individually (P = 0.03). An increasing number of signs was associated with a greater likelihood of PAS. With the presence of 0, 1, 2 and ≥ 3 classic ultrasound signs, PAS was present in 5%, 24%, 57% and 94% of cases, respectively. CONCLUSIONS: We have confirmed the value of classic ultrasound signs of PAS. The use of novel ultrasound signs in combination with classic signs improved the detection of PAS. These findings have clinical implications for the detection of PAS and may help guide the obstetric management of patients diagnosed with these placental disorders. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Placenta Acreta , Placenta Prévia , Feminino , Humanos , Placenta/diagnóstico por imagem , Placenta/patologia , Placenta Acreta/patologia , Placenta Prévia/diagnóstico por imagem , Gravidez , Estudos Retrospectivos , Ultrassonografia Pré-Natal
3.
Cancer Immunol Immunother ; 69(9): 1801-1812, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32350590

RESUMO

Immunotherapy as an approach for cancer treatment is clinically promising. CD73, which is the enzyme that produces extracellular adenosine, favors cancer progression and protects the tumor from immune surveillance. While CD73 has recently been demonstrated to be a potential target for glioma treatment, its role in regulating the inflammatory tumor microenvironment has not yet been investigated. Thus, this study explores the immunotherapeutic value of the CD73 blockade in glioblastoma. The immuno-therapeutic value of the CD73 blockade was evaluated in vivo in immunocompetent pre-clinical glioblastoma model. As such, glioblastoma-bearing rats were nasally treated for 15 days with a siRNA CD73-loaded cationic-nanoemulsion (NE-siRNA CD73R). Apoptosis was determined by flow cytometry using Annexin-V staining and cell proliferation was analyzed by Ki67 expression by immunohistochemistry. The frequencies of the CD4+, CD8+, and CD4+CD25highCD39+ (Treg) T lymphocytes; CD11b+CD45high macrophages; CD11b+CD45low-microglia; and CD206+-M2-like phenotypes, along with expression levels of CD39 and CD73 in tumor and tumor-associated immune cells, were determined using flow cytometry, while inflammatory markers associated with tumor progression were evaluated using RT-qPCR. The CD73 blockade by NE-siRNA CD73 was found to induce tumor cell apoptosis. Meanwhile, the population of Tregs, microglia, and macrophages was significantly reduced in the tumor microenvironment, though IL-6, CCL17, and CCL22 increased. The treatment selectively decreased CD73 expression in the GB cells as well as in the tumor-associated-macrophages/microglia. This study indicates that CD73 knockdown using a nanotechnological approach to perform nasal delivery of siRNA-CD73 to CNS can potentially regulate the glioblastoma immune microenvironment and delay tumor growth by inducing apoptosis.


Assuntos
5'-Nucleotidase/antagonistas & inibidores , 5'-Nucleotidase/imunologia , Proliferação de Células/fisiologia , Glioblastoma/imunologia , Glioblastoma/metabolismo , Glioma/imunologia , Glioma/metabolismo , Adenosina/imunologia , Adenosina/metabolismo , Animais , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Imuno-Histoquímica/métodos , Imunoterapia/métodos , Macrófagos/imunologia , Macrófagos/metabolismo , Microglia/imunologia , Microglia/metabolismo , Ratos
4.
J Oral Rehabil ; 45(5): 399-405, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29573454

RESUMO

The determination of the occlusal vertical dimension (OVD) in edentulous patients is based on clinical assessment with high variability. This study tested the hypothesis: The average OVD in edentulous patients with conventional dentures is too low compared to orthodontic norms, when only clinical parameters are used for the determination of the OVD. Edentulous patients with conventional full dentures were enrolled. Clinical parameters were judged by two senior prosthodontists. Digital lateral cephalograms were taken and served to calculate the OVD according to the lower face height angle (ANS-Xi-D) taking tooth-independent facial growth patterns into account. The ANS-Xi-D angle was compared with reference values by applying one-sample mean comparison tests. Thirty-six participants (17 female, 19 male; mean age 65.3 ± 10.6 years) were enrolled in this study. Clinically, the OVD of four dentures was judged too low, in one case too high, and in the other 31 cases as correct. The mean ANS-Xi-D angle was 48.28°±4.86 and statistically not different to the norm value of 49°±4 (n.s.). There was a tendency that the ANS-Xi-D angle was different between participants with different tooth-independent facial growth patterns (ANOVA, P = .0548). Predominantly, clinically sufficient prostheses show adequate ANS-Xi-D angles. Short-face type denture patients are often restored to comply with mesiofacial norms. The determination of the OVD based on lateral cephalography is not recommendable to be a standard diagnostic parameter. Orthodontic norms are derived from dentate cohorts and might not take the continuing facial growth and other confounding factors of edentulous subjects into account.


Assuntos
Cefalometria , Prótese Total , Face/diagnóstico por imagem , Boca Edêntula/diagnóstico por imagem , Língua/diagnóstico por imagem , Idoso , Relação Central , Planejamento de Dentadura , Face/anatomia & histologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Boca Edêntula/fisiopatologia , Propriedades de Superfície , Língua/anatomia & histologia , Dimensão Vertical
5.
Rev Med Liege ; 71(2): 94-100, 2016 Feb.
Artigo em Francês | MEDLINE | ID: mdl-27141653

RESUMO

Despite its high frequency, bipolarity in childhood is little understood and is often diagnosed only after several years of development, and this during a time when the child's psychosocial future is at stake. A proper diagnosis requires recognition of accurate clinical signs. It is therefore essential to furnish clinicians with precise semiological markers. This paper presents a dimensional semiology for use in anamnesis and in clinical observation of the child. These clinical signs enable the identification of a bipolar manic temperament in the child and/or the identification of various different forms of childhood bipolar and depressive disorder. The relevant differential diagnoses and comorbidities are also presented.


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Criança , Psiquiatria Infantil , Diagnóstico Diferencial , Humanos
6.
J Intern Med ; 277(4): 439-46, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24844122

RESUMO

BACKGROUND: Studies have suggested that being slightly overweight but fit is better for cardiovascular health than being somewhat leaner but unfit. Here, we sought to determine the contribution of cardiorespiratory fitness (CRF), relative to the presence of risk factors, to common carotid intima-media thickness (CIMT), a measurement of atherosclerosis and cardiovascular disease risk. METHODS: Data were analysed from a cohort of 7300 German employed individuals aged 46 (±7) years who participated in a preventive health check-up at a specialized prevention centre. In addition to traditional cardiovascular disease risk factor assessment, participants performed an exercise test with spirometry to exhaustion, and common CIMT was measured. Individuals were defined as being fit or unfit based on the median age- and sex-specific relative maximum oxygen consumption. RESULTS: In a multivariable analysis, there was a strong inverse association between CRF and common CIMT. Individuals who were considered fit and did not have any cardiovascular disease risk factors had the lowest common CIMT values (reference group). Those who were unfit and had an increased risk factor level always had the highest common CIMT values. Good CRF partly compensated for the increased common CIMT due to a risk factor. However, unfit individuals without increased risk factor levels had a common CIMT that was not significantly different from that of the reference group, whereas fit individuals who smoked, had a high body mass index, a low HDL cholesterol concentration or a high systolic blood pressure had an increase in common CIMT. CONCLUSION: Cardiorespiratory fitness is a major determinant of common CIMT. Improved CRF does slightly, but not completely, abolish the adverse consequences of cardiovascular disease risk factors on common CIMT.


Assuntos
Doenças Cardiovasculares/epidemiologia , Espessura Intima-Media Carotídea , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Consumo de Oxigênio , Prevenção Primária , Fatores de Risco
7.
Nat Neurosci ; 24(8): 1051-1064, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34155400

RESUMO

Decisions made by mammals and birds are often temporally extended. They require planning and sampling of decision-relevant information. Our understanding of such decision-making remains in its infancy compared with simpler, forced-choice paradigms. However, recent advances in algorithms supporting planning and information search provide a lens through which we can explain neural and behavioral data in these tasks. We review these advances to obtain a clearer understanding for why planning and curiosity originated in certain species but not others; how activity in the medial temporal lobe, prefrontal and cingulate cortices may support these behaviors; and how planning and information search may complement each other as means to improve future action selection.


Assuntos
Algoritmos , Tomada de Decisões , Neurociências , Animais , Humanos
8.
Braz J Med Biol Res ; 54(8): e10850, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34037096

RESUMO

The conversion of adenosine to inosine is catalyzed by adenosine deaminase (ADA) (EC 3.5.4.4), which has two isoforms in humans (ADA1 and ADA2) and belongs to the zinc-dependent hydrolase family. ADA modulates lymphocyte function and differentiation, and regulates inflammatory and immune responses. This study investigated ADA activity in lymphocyte-rich peripheral blood mononuclear cells (PBMCs) in the absence of disease. The viability of lymphocyte-rich PBMCs isolated from humans and kept in 0.9% saline solution at 4-8°C was analyzed over 20 h. The incubation time and biochemical properties of the enzyme, such as its Michaelis-Menten constant (Km) and maximum velocity (Vmax), were characterized through the liberation of ammonia from the adenosine substrate. Additionally, the presence of ADA protein on the lymphocyte surface was determined by flow cytometry using an anti-CD26 monoclonal human antibody, and the PBMCs showed long-term viability after 20 h. The ADA enzymatic activity was linear from 15 to 120 min of incubation, from 2.5 to 12.5 µg of protein, and pH 6.0 to 7.4. The Km and Vmax values were 0.103±0.051 mM and 0.025±0.001 nmol NH3·mg-1·s-1, respectively. Zinc and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) inhibited enzymatic activity, and substrate preference was given to adenosine over 2'-deoxyadenosine and guanosine. The present study provides the biochemical characterization of ADA in human lymphocyte-rich PBMCs, and indicates the appropriate conditions for enzyme activity quantification.


Assuntos
Adenosina Desaminase , Dipeptidil Peptidase 4 , Adenina , Humanos , Leucócitos Mononucleares , Linfócitos
9.
Neuroscience ; 158(2): 845-55, 2009 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-19010398

RESUMO

Stress induced by early life social isolation leads to long-lasting alterations in stress responses and serotonergic activity. Corticotropin-releasing factor (CRF) is a neurotransmitter that mediates stress responses and alters serotonergic activity. We tested the hypothesis that the stress of early life isolation enhances responses to CRF in adulthood by determining the effect of CRF infusions into the dorsal raphe nucleus (dRN) on 5-HT release in the nucleus accumbens (NAc) of adult rats using in vivo microdialysis. Juvenile male rats were either isolated or housed in groups of three for a 3-week period beginning on postnatal day 21 after which, all rats were group-reared for an additional 2 weeks. Following the isolation/re-socialization procedure, infusion of 100 ng CRF into the dRN decreased 5-HT release in the NAc of group-reared rats. This treatment did not significantly affect 5-HT release in the NAc of isolation-reared animals. In contrast, infusion of 500 ng CRF into the dRN transiently increased 5-HT release in the NAc of both group-reared and isolated animals with isolated animals showing a more prolonged serotonergic response. Western blot and immunofluorescent staining for CRF receptors in the dRN showed that CRF(2) receptor levels were increased in the dRN of isolation-reared animals when compared with group-reared rats. Taken together, the results suggest that isolation during the early part of development causes alterations in both CRF receptor levels and CRF-mediated serotonergic activity. These effects may underlie the increased sensitivity to stress observed in isolates.


Assuntos
Hormônio Liberador da Corticotropina/farmacologia , Hormônios/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Isolamento Social/psicologia , Animais , Animais Recém-Nascidos , Comportamento Animal , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica em Archaea/efeitos dos fármacos , Regulação da Expressão Gênica em Archaea/fisiologia , Masculino , Microdiálise , Ratos , Ratos Sprague-Dawley , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Serotonina/metabolismo
10.
Acta Anaesthesiol Scand ; 53(1): 116-20, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19032569

RESUMO

BACKGROUND: Because mobile telephones may support video calls, emergency medical dispatchers may now connect visually with bystanders during pre-hospital cardio-pulmonary resuscitation (CPR). We studied the quality of simulated dispatcher-assisted CPR when guidance was delivered to rescuers by video calls or audio calls from mobile phones. METHODS: One hundred and eighty high school students were randomly assigned in groups of three to communicate via video calls or audio calls with experienced nurse dispatchers at a Hospital Emergency Medical Dispatch Center. CPR was performed on a recording resuscitation manikin during simulated cardiac arrest. Quality of CPR and time factors were compared depending on the type of communication used. RESULTS: The median CPR time without chest compression ('hands-off time') was shorter in the video-call group vs. the audio-call group (303 vs. 331 s; P=0.048), but the median time to first compression was not shorter (104 vs. 102 s; P=0.29). The median time to first ventilation was insignificantly shorter in the video-call group (176 vs. 205 s; P=0.16). This group also had a slightly higher proportion of ventiliations without error (0.11 vs. 0.06; P=0.30). CONCLUSION: Video communication is unlikely to improve telephone CPR (t-CPR) significantly without proper training of dispatchers and when using dispatch protocols written for audio-only calls. Improved dispatch procedures and training for handling video calls require further investigation.


Assuntos
Reanimação Cardiopulmonar/instrumentação , Reanimação Cardiopulmonar/métodos , Telefone Celular/instrumentação , Sistemas de Comunicação entre Serviços de Emergência , Parada Cardíaca/terapia , Gravação em Vídeo/instrumentação , Gravação em Vídeo/métodos , Adolescente , Adulto , Humanos , Ventilação Pulmonar
11.
Anim Genet ; 40(4): 366-76, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19291137

RESUMO

Behavioural indices in vertebrates are under genetic control at least to some extent. In spite of significant behavioural problems in farm animals, information on the genetic background of behaviour is sparse. The aim of this study was to map QTL for behavioural indices in swine under healthy conditions and after infection with Sarcocystis miescheriana, as behaviour can be significantly influenced by disease. This well-described parasite model subsequently leads to acute (day 14 p.i.), subclinical (day 28 p.i.) and chronic disease (day 42 p.i.), allowing the study and comparison of the behaviour of pigs under four different states of health or disease. The study was based on a well-described Pietrain/Meishan F(2) family that has recently allowed the detection of QTL for disease resistance. We have mapped six genome-wide significant and 24 chromosome-wide significant QTL for six behavioural indices in swine. Six of these QTL (i.e. 20% of total QTL) showed effects on behavioural traits of the healthy pigs (day 0). Some of them (QTL on SSC11 and 18) lost influence on behavioural activities during disease, while the effects of others (QTL on SSC5, SSC8) partly remained during the whole experiment, although with different effects on the distinct behavioural indices. The disease model has been of high relevance to detect effects of gene loci on behavioural indices. Considering the importance of segregating alleles and environmental conditions that allow the identification of the phenotype, we conclude that there are indeed QTL with interesting effects on behavioural indices in swine.


Assuntos
Comportamento Animal , Locos de Características Quantitativas , Suínos/fisiologia , Animais , Mapeamento Cromossômico , Cromossomos de Mamíferos , Comportamento Alimentar , Feminino , Masculino , Sarcocystis , Sarcocistose/veterinária , Suínos/parasitologia , Doenças dos Suínos/parasitologia
12.
Mol Neurobiol ; 56(5): 3260-3279, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30117104

RESUMO

Glioblastoma is the worst and most common primary brain tumor. Here, we demonstrated the role of CD73, an enzyme responsible for adenosine (ADO) production, in glioblastoma progression. ADO increased glioma cell viability via A1 receptor sensitization. CD73 downregulation decreased glioma cell migration and invasion by reducing metalloproteinase-2 and vimentin expression and reduced cell proliferation by 40%, which was related to necrosis and sub-G1 phase blockage of cell cycle. Those effects also involved the stimulation of Akt/NF-kB pathways. Additionally, CD73 knockdown or enzyme inhibition potentiated temozolomide cytotoxic effect on glioma cells by decreasing the IC50 value and sensitizing cells to a non-cytotoxic drug concentration. CD73 inhibition also decreased in vivo rat glioblastoma progression. Delivery of siRNA-CD73 or APCP reduced tumor size by 45 and 40%, respectively, when compared with control. This effect was followed by a parallel 95% reduction of ADO levels in cerebrospinal fluid, indicating the role of extracellular ADO in in vivo glioma growth. Treatment did not induce systemic damage or mortality. Altogether, we conclude that CD73 is an interesting target for glioblastoma treatment and its inhibition may provide new opportunities to improve the treatment of brain tumors. Graphical Abstract ᅟ.


Assuntos
5'-Nucleotidase/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Regulação para Baixo/genética , Glioblastoma/genética , Glioblastoma/patologia , 5'-Nucleotidase/antagonistas & inibidores , 5'-Nucleotidase/metabolismo , Adenosina/metabolismo , Animais , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular , Progressão da Doença , Técnicas de Silenciamento de Genes , Glioblastoma/sangue , Glioblastoma/tratamento farmacológico , Humanos , Metaloproteinase 2 da Matriz/metabolismo , NF-kappa B/metabolismo , Invasividade Neoplásica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Receptores Purinérgicos P1/metabolismo , Transdução de Sinais , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Vimentina/metabolismo
13.
Ned Tijdschr Geneeskd ; 160: D302, 2016.
Artigo em Holandês | MEDLINE | ID: mdl-27531247

RESUMO

Online shopping is on the rise and this extends to purchasing of medicines. Patients can deliberately or unwittingly purchase medicines from one of the many illegal suppliers. On this illegal market, erectile dysfunction medicines play a prominent role. We estimate that at least 70% of sildenafil used in the Netherlands is purchased from illegal suppliers. Price cuts on the legal market with the introduction of generics have not made a difference. It is important to gain an insight into the scale of illegal use of medicines and the potential harmful effects we may encounter.

14.
Braz. j. med. biol. res ; 54(8): e10850, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1249328

RESUMO

The conversion of adenosine to inosine is catalyzed by adenosine deaminase (ADA) (EC 3.5.4.4), which has two isoforms in humans (ADA1 and ADA2) and belongs to the zinc-dependent hydrolase family. ADA modulates lymphocyte function and differentiation, and regulates inflammatory and immune responses. This study investigated ADA activity in lymphocyte-rich peripheral blood mononuclear cells (PBMCs) in the absence of disease. The viability of lymphocyte-rich PBMCs isolated from humans and kept in 0.9% saline solution at 4-8°C was analyzed over 20 h. The incubation time and biochemical properties of the enzyme, such as its Michaelis-Menten constant (Km) and maximum velocity (Vmax), were characterized through the liberation of ammonia from the adenosine substrate. Additionally, the presence of ADA protein on the lymphocyte surface was determined by flow cytometry using an anti-CD26 monoclonal human antibody, and the PBMCs showed long-term viability after 20 h. The ADA enzymatic activity was linear from 15 to 120 min of incubation, from 2.5 to 12.5 µg of protein, and pH 6.0 to 7.4. The Km and Vmax values were 0.103±0.051 mM and 0.025±0.001 nmol NH3·mg-1·s-1, respectively. Zinc and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) inhibited enzymatic activity, and substrate preference was given to adenosine over 2′-deoxyadenosine and guanosine. The present study provides the biochemical characterization of ADA in human lymphocyte-rich PBMCs, and indicates the appropriate conditions for enzyme activity quantification.


Assuntos
Humanos , Adenosina Desaminase , Dipeptidil Peptidase 4 , Leucócitos Mononucleares , Adenina , Linfócitos
15.
MMW Fortschr Med ; 147(47): 53, 55-6, 2005 Nov 24.
Artigo em Alemão | MEDLINE | ID: mdl-16370196

RESUMO

Type 2 diabetes does not represent inescapable fate, but is an avoidable disease, when the main prophylactic approach targets the central problem of insulin resistance. This means daily physical exercise, the reduction of the glycemic load in the diet and--provided there are no contraindications--certainly a daily glass of wine.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Frutas , Resistência à Insulina , Síndrome Metabólica/prevenção & controle , Verduras , Levantamento de Peso , Composição Corporal , Índice Glicêmico , Humanos , Estilo de Vida , Síndrome Metabólica/mortalidade , Prognóstico , Taxa de Sobrevida
16.
Br J Pharmacol ; 172(22): 5414-24, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26375494

RESUMO

BACKGROUND AND PURPOSE: Ceftriaxone is a ß-lactam antibiotic and glutamate transporter activator that reduces the reinforcing effects of psychostimulants. Ceftriaxone also reduces locomotor activation following acute psychostimulant exposure, suggesting that alterations in dopamine transmission in the nucleus accumbens contribute to its mechanism of action. In the present studies we tested the hypothesis that pretreatment with ceftriaxone disrupts acute cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens. EXPERIMENTAL APPROACH: Adult male Sprague-Dawley rats were pretreated with saline or ceftriaxone (200 mg kg(-1) , i.p. × 10 days) and then challenged with cocaine (15 mg kg(-1) , i.p.). Motor activity, dopamine efflux (via in vivo microdialysis) and protein levels of tyrosine hydroxylase (TH), the dopamine transporter and organic cation transporter as well as α-synuclein, Akt and GSK3ß were analysed in the nucleus accumbens. KEY RESULTS: Ceftriaxone-pretreated rats challenged with cocaine displayed reduced locomotor activity and accumbal dopamine efflux compared with saline-pretreated controls challenged with cocaine. The reduction in cocaine-evoked dopamine levels was not counteracted by excitatory amino acid transporter 2 blockade in the nucleus accumbens. Pretreatment with ceftriaxone increased Akt/GSK3ß signalling in the nucleus accumbens and reduced levels of dopamine transporter, TH and phosphorylated α-synuclein, indicating that ceftriaxone affects numerous proteins involved in dopaminergic transmission. CONCLUSIONS AND IMPLICATIONS: These results are the first evidence that ceftriaxone affects cocaine-evoked dopaminergic transmission, in addition to its well-described effects on glutamate, and suggest that its ability to attenuate cocaine-induced behaviours, such as psychomotor activity, is due in part to reduced dopaminergic neurotransmission in the nucleus accumbens.


Assuntos
Ceftriaxona/farmacologia , Dopamina/fisiologia , Núcleo Accumbens/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Animais , Cocaína , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Masculino , Atividade Motora/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Núcleo Accumbens/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley
17.
Am J Cardiol ; 57(4): 199-202, 1986 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-3946208

RESUMO

To determine the importance of usual risk factors of coronary artery disease (CAD) in patients with coronary artery spasm, 40 patients with vasospastic angina (VA), normal or nearly normal coronary arteries and without previous myocardial infarction were compared with 2 control groups of 40 patients each, matched for age and sex: 1 group with CAD and 1 without heart disease. Ninety percent of patients with VA were cigarette smokers and 70% were heavy smokers (more than 20 cigarettes daily), compared with 53% and 33% in patients with CAD (p less than 0.001) and 30% and 15% in those without heart disease (p less than 0.001). Except for cigarette smoking, the risk factor profile of patients with VA appeared more like the profile of patients without heart disease than that of patients with CAD. The results suggest that cigarette smoking may play a role in CAD independent of atherosclerosis and possibly favoring coronary artery spasm.


Assuntos
Doença das Coronárias/etiologia , Vasoespasmo Coronário/etiologia , Fumar , Adulto , Fatores Etários , Idoso , Colesterol/sangue , Doença das Coronárias/patologia , Vasoespasmo Coronário/patologia , Vasos Coronários/patologia , Complicações do Diabetes , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Risco , Fatores Sexuais
18.
Am J Cardiol ; 53(1): 1-9, 1984 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-6362383

RESUMO

Exercise tolerance 1, 3 and 8 hours after 80 mg of propranolol, 120 mg of diltiazem and 20 mg of nifedipine, and after 20 minutes of 0.6 mg of sublingual nitroglycerin were compared with placebo in 15 men who had chronic stable angina pectoris. Three hours after drug ingestion, the exercise time was prolonged by 72 +/- 26, 162 +/- 27 and 161 +/- 30 seconds (p less than 0.05) for propranolol, diltiazem and nifedipine, respectively, and by 123 +/- 35 seconds (p less than 0.001) 20 minutes after sublingual nitroglycerin compared with placebo. The onset of ST-segment depression greater than or equal to 0.1 mV was delayed by 120 +/- 34, 203 +/- 29 and 189 +/- 35 seconds (p less than 0.05) and by 79 +/- 23 seconds (p less than 0.05), respectively. After propranolol, the peak rate-pressure product decreased compared with placebo (15.1 +/- 1.1 U [10(-3)] vs 20.0 +/- 1.5 U, p less than 0.01). In contrast, the peak rate-pressure product was greater after diltiazem and nifedipine than after placebo (22.2 +/- 1.3 U [p less than 0.05] and 23.8 +/- 1.4 U [p less than 0.01]). The maximal increase in exercise tolerance was most marked for each drug at 3 hours, but was also significant at 1 hour for nifedipine and at 8 hours for diltiazem. At 3 hours, an increase in exercise time of more than 2 minutes was observed in 4 of 6 patients who had plasma propranolol concentrations greater than 40 ng/ml, 8 of 9 who had a plasma diltiazem concentration greater than 150 ng/ml, and in 7 of 7 who had a plasma nifedipine concentration greater than 90 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Angina Pectoris/tratamento farmacológico , Benzazepinas/uso terapêutico , Diltiazem/uso terapêutico , Hemodinâmica , Nifedipino/uso terapêutico , Propranolol/uso terapêutico , Adulto , Idoso , Angina Pectoris/sangue , Angina Pectoris/fisiopatologia , Ensaios Clínicos como Assunto , Diltiazem/sangue , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Nifedipino/sangue , Esforço Físico , Propranolol/sangue
19.
J Cancer Res Clin Oncol ; 114(2): 204-7, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-3350854

RESUMO

Samples from the L-428 Hodgkin's cell line and from several other lymphoma cell lines were lysed and the soluble proteins were subjected to one- or two-dimensional gel electrophoresis. The separated proteins were transferred to nitrocellulose by the Western Blot technique; antibody reactivity was detected by an immunoperoxidase reaction. Of 152 sera from patients with Hodgkin's disease (HD) 26 (17%) reacted with protein P-65 whereas in the control group, consisting of 35 healthy persons and 20 patients with other malignant diseases only 1 serum was reactive. Thus, the difference between the two groups was highly significant (P less than 0.01). These antibodies were most common in stage III HD. Splenectomy had no effect on the incidence of these antibodies, and there seemed to be no correlation with B-symptoms or with the histological subtype.


Assuntos
Anticorpos/análise , Doença de Hodgkin/imunologia , Proteínas/imunologia , Adulto , Complexo Antígeno-Anticorpo/análise , Humanos
20.
J Refract Surg ; 13(6): 556-67, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9352484

RESUMO

OBJECTIVE: To evaluate the effects of the intrastromal corneal ring, a device developed to reduce myopia, on corneal asphericity in a large set of eye bank eyes. METHODS: Forty-one deturgesced eye bank eyes were implanted with intrastromal corneal rings of five different thicknesses, ranging from 0.25 mm to 0.45 mm. Corneal asphericity, before and after implantation, was examined using two different metrologies. Corneal asphericity profiles were produced from dioptric power data collected from videokeratography. To statistically assess the corneal asphericity differences between exam times for each intrastromal corneal ring thickness, dependent sample confidence intervals (95%) were calculated for the mean differences between preoperative and postoperative measures for each topographic diameter zone. Laser holographic interferometry was used to inspect corneal asphericity in one eye bank eye case study for four intrastromal corneal ring sizes. Wave unit map and geometric zonal spot ray tracing analyses derived from laser holographic interferometry topography were surveyed. RESULTS: Videokeratographic analysis suggested that preoperative corneal shape was prolate, i.e., flattened from central to paracentral cornea. Corneal shape became more prolate with intrastromal corneal ring implantation for all intrastromal corneal ring thicknesses. Laser holographic interferometry demonstrated that prolate asphericity was preserved with the intrastromal corneal ring sizes tested and that optical collection efficiency of the cornea was not diminished. CONCLUSION: Using two different measurement techniques, this eye bank eye study demonstrated that intrastromal corneal rings maintain prolate corneal asphericity.


Assuntos
Córnea/patologia , Substância Própria/cirurgia , Bancos de Olhos , Próteses e Implantes , Topografia da Córnea , Humanos , Interferometria , Lasers , Refração Ocular , Preservação de Tecido
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