Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 270
Filtrar
1.
Sci Total Environ ; 901: 165933, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-37536603

RESUMO

An essential prerequisite to safeguard pollinator species is characterisation of the multifaceted diversity of crop pollinators and identification of the drivers of pollinator community changes across biogeographical gradients. The extent to which intensive agriculture is associated with the homogenisation of biological communities at large spatial scales remains poorly understood. In this study, we investigated diversity drivers for 644 bee species/morphospecies in 177 commercial apple orchards across 33 countries and four global biogeographical biomes. Our findings reveal significant taxonomic dissimilarity among biogeographical zones. Interestingly, despite this dissimilarity, species from different zones share similar higher-level phylogenetic groups and similar ecological and behavioural traits (i.e. functional traits), likely due to habitat filtering caused by perennial monoculture systems managed intensively for crop production. Honey bee species dominated orchard communities, while other managed/manageable and wild species were collected in lower numbers. Moreover, the presence of herbaceous, uncultivated open areas and organic management practices were associated with increased wild bee diversity. Overall, our study sheds light on the importance of large-scale analyses contributing to the emerging fields of functional and phylogenetic diversity, which can be related to ecosystem function to promote biodiversity as a key asset in agroecosystems in the face of global change pressures.

2.
Psychoneuroendocrinology ; 142: 105800, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35598494

RESUMO

Mindfulness-based mental training interventions have become a popular means to alleviate stress and stress-associated health risks. Previous scientific investigations emphasize the importance of exploring the effects of such interventions in naturalistic settings to evaluate their implementation into daily life. Therefore, the current study examined the effects of three distinct mental training modules on a range of measures of daily life experience in the scope of the ReSource Project, a 9-month longitudinal mental training study comparing modules targeting attention and interoception (Presence), socio-affective (Affect) or socio-cognitive abilities (Perspective). We used ecological momentary assessment (EMA) to repeatedly probe levels of stress and stress-coping efficacy combined with stress-reactive cortisol levels, and further explored arousal, affective states, and thought patterns in the daily lives of 289 healthy adults (172 women; 20-55 years). We found increased presence-focused thought and heightened arousal after a training duration of 3-6 months, independent of the type of prior training. Increased coping efficacy emerged specifically after socio-cognitive Perspective training, following 6-9 months of training duration. No training effects were found for subjective stress, stress-reactive cortisol levels, or daily life affect. Our findings corroborate and add ecological validity to previous ReSource findings by showing that they replicate in participants' everyday environment. Regarding endocrine and subjective stress markers, our results suggest caution in generalizing acute laboratory findings to individuals' everyday routines. Overall, the current study provides substantiated insights into how cultivating one's mind through contemplative mental training translates to daily life experience, enhances stress-coping, and may ultimately aide in maintaining health.


Assuntos
Interocepção , Atenção Plena , Adulto , Avaliação Momentânea Ecológica , Feminino , Humanos , Hidrocortisona , Estresse Psicológico
3.
AJNR Am J Neuroradiol ; 43(5): 764-768, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35393363

RESUMO

BACKGROUND AND PURPOSE: Abusive head trauma is the leading cause of morbidity and mortality in young children. Radiology provides valuable information for this challenging diagnosis, but no single neuroimaging finding is independently diagnostic of abusive head trauma. Our purposes were to describe the prevalence of brain and spine neuroimaging findings and to analyze the association of neuroimaging findings with clinical factors to determine which neuroimaging findings may be used as prognostic indicators. MATERIALS AND METHODS: Children with a confirmed abusive head trauma diagnosis between January 2018 to February 2021 were included in this single-center retrospective study. Patient demographics, survival, Glasgow Coma Scale score on admission, length of hospital stay, and intensive care unit stay were examined. Brain neuroimaging findings were categorized as classic and nonclassic findings. Spine MRIs were also assessed for spinal ligamentous injury, compression fracture, and hemorrhage. The χ2 test or the Wilcoxon rank-sum test was used for the analysis. RESULTS: One hundred two children (male/female ratio: 75:27; average age, 9.49; range, 0.27-53.8 months) were included. Subdural hematoma was the most common (83.3%) classic neuroimaging finding. Bridging vein thrombosis was the most common (30.4%) nonclassic neuroimaging finding. Spinal ligamentous injury was seen in 23/49 patients. Hypoxic-ischemic injury was significantly higher in deceased children (P = .0001). The Glasgow Coma Scale score was lower if hypoxic-ischemic injury (P < .0001) or spinal ligamentous injury were present (P = .017). The length of hospital stay was longer if intraventricular hemorrhage (P = .04), diffuse axonal injury (P = .017), hypoxic-ischemic injury (P = .001), or arterial stroke (P = .0003) was present. The intensive care unit stay was longer if intraventricular hemorrhage (P = .02), diffuse axonal injury (P = .01), hypoxic-ischemic injury (P < .0001), or spinal ligamentous injury (P = .03) was present. CONCLUSIONS: Our results may suggest that a combination of intraventricular hemorrhage, diffuse axonal injury, hypoxic-ischemic injury, arterial stroke, and/or spinal ligamentous injury on neuroimaging at presentation may be used as potential poor prognostic indicators in children with abusive head trauma.


Assuntos
Maus-Tratos Infantis , Traumatismos Craniocerebrais , Lesão Axonal Difusa , Traumatismos da Coluna Vertebral , Acidente Vascular Cerebral , Encéfalo , Criança , Maus-Tratos Infantis/diagnóstico , Pré-Escolar , Traumatismos Craniocerebrais/complicações , Lesão Axonal Difusa/complicações , Feminino , Humanos , Lactente , Masculino , Neuroimagem/efeitos adversos , Estudos Retrospectivos , Traumatismos da Coluna Vertebral/diagnóstico por imagem , Acidente Vascular Cerebral/complicações
4.
Sci Rep ; 11(1): 9351, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931689

RESUMO

Cooperative decisions are well predicted by stable individual differences in social values but it remains unclear how they may be modulated by emotions such as fear and anger. Moving beyond specific decision paradigms, we used a suite of economic games and investigated how experimental inductions of fear or anger affect latent factors of decision making in individuals with selfish or prosocial value orientations. We found that, relative to experimentally induced anger, induced fear elicited higher scores on a cooperation factor, and that this effect was entirely driven by selfish participants. In fact, induced fear brought selfish individuals to cooperate similarly to prosocial individuals, possibly as a (selfish) mean to seek protection in others. These results suggest that two basic threat-related emotions, fear and anger, differentially affect a generalized form of cooperation and that this effect is buffered by prosocial value orientation.


Assuntos
Ira/fisiologia , Comportamento Cooperativo , Emoções/fisiologia , Medo/fisiologia , Teoria dos Jogos , Relações Interpessoais , Comportamento Social , Adulto , Feminino , Humanos , Masculino , Valores Sociais
5.
Neuroimage ; 236: 118011, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33852941

RESUMO

The hippocampus is a highly plastic brain structure supporting functions central to human cognition. Morphological changes in the hippocampus have been implicated in development, aging, as well as in a broad range of neurological and psychiatric disorders. A growing body of research suggests that hippocampal plasticity is closely linked to the actions of brain-derived neurotrophic factor (BDNF). However, evidence on the relationship between hippocampal volume (HCV) and peripheral BDNF levels is scarce and limited to elderly and patient populations. Further, despite evidence that BDNF expression differs throughout the hippocampus and is implicated in adult neurogenesis specifically in the dentate gyrus, no study has so far related peripheral BDNF levels to the volumes of individual hippocampal subfields. Besides its clinical implications, BDNF-facilitated hippocampal plasticity plays an important role in regulating cognitive and affective processes. In the current registered report, we investigated how serum BDNF (sBDNF) levels relate to volumes of the hippocampal formation and its subfields in a large sample of healthy adults (N = 279, 160 f) with a broad age range (20-55 years, mean 40.5) recruited in the context of the ReSource Project. We related HCV to basal sBDNF and, in a subsample (n = 103, 57 f), to acute stress-reactive change in sBDNF. We further tested the role of age as a moderator of both associations. Contrary to our hypotheses, neither basal sBDNF levels nor stress-reactive sBDNF change were associated with total HCV or volume of the dentate gyrus/cornu ammonis 4 (DG/CA4) subfield. We also found no evidence for a moderating effect of age on any of these associations. Our null results provide a first point of reference on the relationship between sBDNF and HCV in healthy mid-age, in contrast to patient or aging populations. We suggest that sBDNF levels have limited predictive value for morphological differences of the hippocampal structure when notable challenge to its neuronal integrity or to neurotrophic capacity is absent.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Hipocampo/anatomia & histologia , Adulto , Giro Denteado/anatomia & histologia , Giro Denteado/diagnóstico por imagem , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Proc Biol Sci ; 287(1931): 20200922, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-33043867

RESUMO

Most of the world's crops depend on pollinators, so declines in both managed and wild bees raise concerns about food security. However, the degree to which insect pollination is actually limiting current crop production is poorly understood, as is the role of wild species (as opposed to managed honeybees) in pollinating crops, particularly in intensive production areas. We established a nationwide study to assess the extent of pollinator limitation in seven crops at 131 locations situated across major crop-producing areas of the USA. We found that five out of seven crops showed evidence of pollinator limitation. Wild bees and honeybees provided comparable amounts of pollination for most crops, even in agriculturally intensive regions. We estimated the nationwide annual production value of wild pollinators to the seven crops we studied at over $1.5 billion; the value of wild bee pollination of all pollinator-dependent crops would be much greater. Our findings show that pollinator declines could translate directly into decreased yields or production for most of the crops studied, and that wild species contribute substantially to pollination of most study crops in major crop-producing regions.


Assuntos
Agricultura , Produtos Agrícolas , Polinização , Animais , Abelhas , Abastecimento de Alimentos , Estados Unidos
7.
Neuropsychopharmacology ; 44(10): 1797-1804, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30991416

RESUMO

Brain-derived neurotrophic factor (BDNF) is an essential facilitator of neuronal plasticity. By counteracting the adverse effects of excessive stress-induced glucocorticoid signaling, BDNF has been implicated as a resilience factor to psychopathology caused by chronic stress. Insights into the effects of acute stress on peripheral BDNF levels in humans are inconclusive. The short-term interplay between BDNF and cortisol in response to acute psychosocial stress remains unexplored. Furthermore, it is unknown whether mental training that is effective at reducing cortisol reactivity can also influence BDNF during acute stress. In the current study, we investigated serum BDNF levels during an acute psychosocial stress paradigm, the Trier Social Stress Test (TSST), in 301 healthy participants (178 women, mean age = 40.65) recruited as part of the ReSource Project, a large-scale mental training study consisting of three distinct 3-month training modules. Using a cross-sectional study design, we first examined the relationship between BDNF and salivary cortisol in a control group with no mental training. Subsequent analyses focused on differences in BDNF stress levels between control and mental training groups. We show that serum BDNF is indeed stress-sensitive, characterized by a significant post-stress increase and subsequent decline to recovery. While respective increases in BDNF and cortisol were not associated, we found two indications for an antagonistic relationship. Higher BDNF peaks after stress were associated with steeper cortisol recovery. On the other hand, the magnitude of the cortisol stress response was linked to steeper BDNF recovery after stress. BDNF levels were not modulated by any of the mental training modules. Providing novel evidence for the dynamics of BDNF and cortisol during acute stress, our findings may further inform research on the physiological mechanisms involved in stress chronification and the associated health risks.


Assuntos
Afeto , Atenção , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hidrocortisona/metabolismo , Metacognição , Comportamento Social , Estresse Psicológico/metabolismo , Adulto , Estudos Transversais , Empatia , Feminino , Humanos , Interocepção , Masculino , Meditação , Pessoa de Meia-Idade , Atenção Plena , Motivação , Saliva/química , Estresse Psicológico/psicologia , Adulto Jovem
8.
Sci Rep ; 8(1): 15462, 2018 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-30337580

RESUMO

Daily life stress is an omnipresent phenomenon in modern society. Research has linked prolonged activation of the hypothalamic-pituitary-adrenal axis to psychiatric and somatic diseases. Everyday stressors substantially contribute to these health risks. Despite the notion that the physiological stress response is highly dependent on concurrent psychological processes, investigations associating diurnal cortisol levels with subjective experience have primarily focused on affective states. The impact of everyday cognitive processes including thought content has been largely neglected. To investigate this link, moment-to-moment associations of psychological experience including subjective stress, thought content and affect, and cortisol levels were assessed throughout the daily routines of 289 healthy adult participants. We found that subjective stress interacted with current thought content and affect in predicting cortisol release: more negative and future-directed thoughts were associated with higher cortisol levels after experiencing subjective stress, suggesting an increase in negative future anticipation. Concurrent cortisol rises might reflect proactive coping to adequately prepare for upcoming demands. In the absence of subjective stress, more past-directed thoughts and negative affect were associated with higher cortisol levels. These findings provide evidence for a fundamental link between thought content and daily cortisol activation, and highlight the significant contribution of thought patterns to physiological stress levels.


Assuntos
Atividades Cotidianas , Hidrocortisona/metabolismo , Saliva/metabolismo , Estresse Fisiológico , Estresse Psicológico , Adulto , Feminino , Humanos , Hidrocortisona/análise , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Sci Rep ; 7(1): 11068, 2017 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-28894206

RESUMO

Standard economic theory postulates that decisions are driven by stable context-insensitive preferences, while motivation psychology suggests they are driven by distinct context-sensitive motives with distinct evolutionary goals and characteristic psycho-physiological and behavioral patterns. To link these fields and test how distinct motives could differentially predict different types of economic decisions, we experimentally induced participants with either a Care or a Power motive, before having them take part in a suite of classic game theoretical paradigms involving monetary exchange. We show that the Care induction alone raised scores on a latent factor of cooperation-related behaviors, relative to a control condition, while, relative to Care, Power raised scores on a punishment-related factor. These findings argue against context-insensitive stable preferences and theories of strong reciprocity and in favor of a motive-based approach to economic decision making: Care and Power motivation have a dissociable fingerprint in shaping either cooperative or punishment behaviors.

10.
J Insect Sci ; 17(2)2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28365763

RESUMO

The blue orchard bee, Osmia lignaria (Say), is a solitary bee that is an excellent pollinator of tree fruit orchards. Due to the annual rising costs of honey bee hive rentals, many orchardists are eager to develop management tools and practices to support O. lignaria as an alternative pollinator. Establishing O. lignaria pollination as a sustainable industry requires careful consideration of both bee and orchard management. Here, we test the effect of artificial nest box distribution on in-orchard propagation of O. lignaria in Utah commercial tart cherry orchards. Two nest box distributions were compared across three paired, 1.2-ha plots. One distribution, traditionally employed by O. lignaria consultants, included a centrally located tote for mass-nesting with smaller, surrounding 'satellite' nest boxes at orchard margins. The other distribution was composed of smaller, more equally distributed nest boxes throughout the 1.2-ha plots. Significantly higher propagation of O. lignaria was observed in the latter nest box distribution, although all treatments resulted in bee return exceeding the number of bees initially released. These findings provide support for the use of O. lignaria in tart cherry orchards, and demonstrate how simple changes to bee set-up and management can influence propagation efforts.


Assuntos
Abelhas/fisiologia , Prunus avium/fisiologia , Agricultura/métodos , Animais , Criação de Abelhas/métodos , Polinização , Dinâmica Populacional , Utah
11.
Histochem Cell Biol ; 145(3): 315-26, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26671788

RESUMO

Five different glomerular immunohistochemistry markers were evaluated and compared in four different acute and chronic rat kidney disease models. Progression of glomerular or podocyte damage was shown in the puromycin aminonucleoside nephrosis (PAN) and Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat model. Progression and prevention of glomerular damage was demonstrated in the Zucker diabetic fatty (ZDF) and Dahl salt-sensitive (Dahl SS) rat. Immunohistochemistry was performed for desmin, vimentin, podocin, synaptopodin and Wilms tumor protein-1 (WT-1), and evaluation of glomerular immunohistochemistry markers was done by semiautomated quantitative image analysis. We found desmin and WT-1 as the most sensitive markers for podocyte damage in both acute and chronic glomerular damage followed by vimentin, podocin and synaptopodin. We were able to demonstrate that early podocyte damage as shown by increased desmin and vimentin staining together with either a phenotypic podocyte change or podocyte loss (reduced numbers of WT-1-stained podocytes) drives the progression of glomerular damage. This is followed by a reduction in podocyte-specific proteins such as podocin and synaptopodin. Our report describes the different sensitivity of glomerular or podocyte markers and gives future guidance for the selection of the most sensitive markers for efficacy testing of new drugs as well as for the selection of tissue-based toxicity markers for glomerular or podocyte injury. In addition to functional clinical chemistry markers, desmin and WT-1 immunohistochemistry offers reliable and valuable data on the morphologic state of podocytes.


Assuntos
Desmina/análise , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intracelular/análise , Nefropatias/metabolismo , Proteínas de Membrana/análise , Proteínas dos Microfilamentos/análise , Vimentina/análise , Proteínas WT1/análise , Doença Aguda , Animais , Biomarcadores/análise , Doença Crônica , Imuno-Histoquímica , Masculino , Ratos , Ratos Sprague-Dawley
12.
Transplant Proc ; 47(9): 2791-4, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26680097

RESUMO

Renal transplantation in HIV-positive patients with end-stage renal disease has in recent years become a successful treatment option. We report two patients who underwent renal transplantation using a combination of basiliximab, calcineurin inhibitors, mycophenolate mofetil (MMF), and steroids with a "non-interacting" antiretroviral combination therapy consisting of stavudine or abacavir, lamivudine, and nevirapine. We observed no acute rejection but a BK polyomavirus infection in both patients. In conclusion, a quadruple immunosuppression with an interleukin 2 receptor antagonist, a calcineurin inhibitor, MMF, and steroids appears to be advisable to prevent high rates of acute rejection, but if possible thereafter immunosuppression should be tapered rapidly (eg, MMF stop, prednisolone dose 5 mg/d). The selection of antiretroviral agents should avoid compounds that interact severely with the immunosuppression used.


Assuntos
Rejeição de Enxerto/prevenção & controle , Infecções por HIV/tratamento farmacológico , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim , Adulto , Anticorpos Monoclonais/uso terapêutico , Basiliximab , Inibidores de Calcineurina/uso terapêutico , Quimioterapia Combinada , Feminino , Hospitais Universitários , Humanos , Rim/efeitos dos fármacos , Rim/virologia , Falência Renal Crônica/virologia , Masculino , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Prednisolona/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Esteroides/uso terapêutico
13.
Toxicol In Vitro ; 30(1 Pt B): 429-37, 2015 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-26407524

RESUMO

Drug-induced liver injury (DILI) is a leading cause of acute hepatic failure and a major reason for market withdrawal of drugs. Idiosyncratic DILI is multifactorial, with unclear dose-dependency and poor predictability since the underlying patient-related susceptibilities are not sufficiently understood. Because of these limitations, a pharmaceutical research option would be to reduce the compound-related risk factors in the drug-discovery process. Here we describe the development and validation of a methodology for the assessment of DILI risk of drug candidates. As a training set, 81 marketed or withdrawn compounds with differing DILI rates - according to the FDA categorization - were tested in a combination of assays covering different mechanisms and endpoints contributing to human DILI. These include the generation of reactive metabolites (CYP3A4 time-dependent inhibition and glutathione adduct formation), inhibition of the human bile salt export pump (BSEP), mitochondrial toxicity and cytotoxicity (fibroblasts and human hepatocytes). Different approaches for dose- and exposure-based calibrations were assessed and the same parameters applied to a test set of 39 different compounds. We achieved a similar performance to the training set with an overall accuracy of 79% correctly predicted, a sensitivity of 76% and a specificity of 82%. This test system may be applied in a prospective manner to reduce the risk of idiosyncratic DILI of drug candidates.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Descoberta de Drogas , Avaliação Pré-Clínica de Medicamentos/métodos , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Animais , Calibragem , Glutationa/metabolismo , Humanos , Camundongos , Células NIH 3T3
15.
Environ Entomol ; 42(6): 1166-73, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24128927

RESUMO

We conducted a broad geographic survey in the northwestern United States to quantify production losses in the alfalfa leafcutting bee (Megachile rotundata (F.), Hymenoptera: Megachilidae), a solitary pollinator used extensively in alfalfa seed production. Viable larvae were found in only 47.1% of the nest cells collected at the end of the season. Most of the rest of the cells contained pollen balls (typified by a provision but no larva; 16.7%), unknown causes of mortality (15.5%), or larvae killed by chalkbrood (8.0%). Prevalence of pollen balls was correlated positively with bee release rates and negatively with alfalfa stand age. The unknown mortality was correlated with the U.S. Department of Agriculture-Plant Hardiness Zone, and thus, some of the mortality may be caused by high temperature extremes, although the nesting season degree-days were not correlated with this mortality. Chalkbrood prevalence was correlated with possible nesting-resource or crowding-related factors, such as the number of bees released per hectare and the number of shelters used, but not with nesting board disinfection practices. Vapona is used to control parasitoids when the parent bees are incubated before release, and use of this fumigant was associated with an increase in both chalkbrood and diapausing offspring, although any reason for these correlations are unknown. This survey quantifies the variation in the quality of alfalfa leafcutting bee cocoons produced across much of the U.S. alfalfa seed production area.


Assuntos
Criação de Abelhas , Abelhas/fisiologia , Animais , Feminino , Larva/fisiologia , Masculino , Medicago sativa , Dinâmica Populacional
16.
Toxicol In Vitro ; 27(5): 1589-95, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22954529

RESUMO

Cell-based assays are key tools in drug safety assessment. However, they usually provide only limited information about time-kinetics of a toxic effect and implementing multiple measurements is often complex. To overcome these issues we established an impedance-based approach which is able to differentiate cytostatic from cytotoxic drugs by recording time-kinetics of compound-effects on cells. NIH 3T3 fibroblasts were seeded on xCELLigence® E-plates and impedance was continuously measured over 5 days. The obtained results reflected cytotoxicity and cell proliferation, as confirmed by neutral red uptake in vitro. Based on known toxicants, we established an algorithm able to discriminate cytostatic, cytotoxic and non-toxic compounds based on the shape of the impedance curves. Analyzing impedance curve patterns of additional 37 compounds allowed the identification and differentiation of these distinct effects as results correlated well with previous in vivo findings. We show that impedance-based real-time cell analysis is a convenient tool to characterize and discriminate effects of compounds on cells in a time-dependent and label-free manner. The presented impedance assay could be used to further characterize toxicities observed in vivo or in vitro. Due to the ease of performance it may also be a suitable screening tool.


Assuntos
Bioensaio , Citostáticos/toxicidade , Citotoxinas/toxicidade , Animais , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Impedância Elétrica , Camundongos , Células NIH 3T3 , Vermelho Neutro/metabolismo
17.
Dtsch Med Wochenschr ; 137(38): 1873-7, 2012 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-22971974

RESUMO

Acute kidney injury (AKI) of any origin is a common complication/disease in hospitalized patients, going along with significantly increased mortality and morbidity, as well as hospitalization duration and expenses. Drug-induced AKI is usually seen in patients with concurrent risk factors such as existing kidney disease, dehydration with or without hypotension, older age or diabetes mellitus. In cases with multiple risk factors or therapies the triggering drug is often impossible to define. Hemodynamic alterations, intrinsic tubulointerstitial damages and intrarenal (i. e. tubular) obstructions as a result of drug precipitations are the pathophysiological basis of this disease entity. Clinically the AKI is perceived as the most important problem, due to the development of hyperhydration (including pulmonary edema) and reduced/lacking clearance of toxic metabolites. The prognosis of drug-induced AKI is usually good, especially if the agents are stopped early in the process, but nevertheless some patients experience severe acute AKI requiring dialysis with/without subsequent restoration. Considering and recognizing potential risk factors may help to identify patients at risk and lead to introduction of prophylactic actions. Identification of risk factors and the introduction of prevention strategies should be an integral part of everybody's daily clinical work, especially in intensive care medicine due to the high susceptibility to AKI.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/terapia , Anti-Inflamatórios não Esteroides/efeitos adversos , Comorbidade , Meios de Contraste/efeitos adversos , Diagnóstico Diferencial , Substituição de Medicamentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Necrose do Córtex Renal/induzido quimicamente , Necrose do Córtex Renal/terapia , Testes de Função Renal , Edema Pulmonar/induzido quimicamente , Diálise Renal , Fatores de Risco , Resultado do Tratamento
18.
Int J Tuberc Lung Dis ; 16(8): 1005-14, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22762423

RESUMO

The objective of this review is to report evidence about the efficacy and potential of currently licensed drugs and new molecules beyond pre-clinical development for improving the chemotherapy of tuberculosis (TB). Rifapentine, a rifamycin with low minimum inhibitory concentration, long half-life and potent sterilizing activity in mice did not confirm its potential in a recent short-term clinical trial and is being extensively re-evaluated. Moxifloxacin, a fluoroquinolone, improved the activity of the standard drug regimen when substituted for ethambutol (EMB). It is being studied to shorten the duration of treatment for fully drug-susceptible TB (Remox study). Clofazimine, a fat-soluble dye with experimental activity against TB, but used only for leprosy in the last 50 years, requires further study because it has been included in a successful short 9-month combined drug regimen for the treatment of multidrug-resistant TB. The diarylquinoline TMC207 is the most promising among the new TB drugs because of its experimental and clinical rate of culture conversion. Also exciting, 200 mg daily doses in humans of the nitroimidazo-oxazine PA-824 and the nitro-dihydro-imidazooxazole OPC-67683 were safe and induced a bactericidal effect of respectively 0.098 ± 0.072 log(10) and 0.040 ± 0.056 log(10) per day. The new oxazolidinones PNU-100480 and AZD-5847 might be at least as active as linezolid and much less toxic. SQ109 is an EMB analogue that does not have cross-resistance with EMB and might have synergistic activity in combined regimens. Benzothiazinones and dinitrobenzamides show exciting in vitro anti-microbial activity and deserve careful attention.


Assuntos
Antituberculosos/uso terapêutico , Desenho de Fármacos , Drogas em Investigação/uso terapêutico , Tuberculose/tratamento farmacológico , Animais , Antituberculosos/química , Antituberculosos/farmacologia , Farmacorresistência Bacteriana Múltipla , Quimioterapia Combinada , Drogas em Investigação/química , Drogas em Investigação/farmacologia , Humanos , Tuberculose/diagnóstico , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
19.
Toxicol Appl Pharmacol ; 259(3): 355-65, 2012 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-22293087

RESUMO

INTRODUCTION: Dalcetrapib is a cholesteryl ester transfer protein (CETP) modulator in clinical assessment for cardiovascular outcome benefits. In compliance with regulatory requirements, dalcetrapib was evaluated in rodent 2-year carcinogenesis bioassays. In the mouse bioassay, male mice demonstrated increased liver weight and statistically increased incidences of hepatocellular adenoma/carcinoma. Hepatic cytochrome p450 (Cyp) 2b10 mRNA induction and increased Cyp2b10 enzyme activity signify activation of hepatic nuclear receptor constitutive androstane receptor (CAR), a widely established promoter of rodent-specific hepatic tumors. We therefore monitored hepatic Cyp2b10 mRNA and its enzyme activity in a subset of dalcetrapib-treated male mice from the bioassay. METHODS: Liver samples were obtained from ~1/3 of male mice from each dose group including vehicle-controls (mean and earliest study day of death 678 and 459 respectively). Quantitative real time PCR (qRT-PCR) was performed to determine Cyp2b10 mRNA expression and Cyp1a-, Cyp2b10- and Cyp3a-selective activities were monitored. RESULTS: Cyp2b10 mRNA was strongly induced by dalcetrapib with an expected wide inter-individual variation (5-1421-fold). Group average fold-induction versus vehicle-controls showed a dose-related increase from 48-fold (250mg/kg/day) to 160-fold (750mg/kg/day), which declined slightly at 2000mg/kg/day (97-fold). Cyp enzyme activities showed approximate doubling of total Cyp P450 content per milligram protein and a 9-fold increase in Cyp2b10-selective pentoxyresorufin O-dealkylase activity (750mg/kg/day). DISCUSSION: These data from hepatic Cyp2b10 monitoring are strongly suggestive of CAR activation by dalcetrapib, a mechanism devoid of relevance towards hepatocarcinogenesis in humans; results show feasibility of Cyp2b10 as a surrogate marker for this mechanism at cessation of a carcinogenesis bioassay.


Assuntos
Anticolesterolemiantes/toxicidade , Hidrocarboneto de Aril Hidroxilases/genética , Fígado/efeitos dos fármacos , RNA Mensageiro/metabolismo , Esteroide Hidroxilases/genética , Compostos de Sulfidrila/toxicidade , Amidas , Animais , Anticolesterolemiantes/administração & dosagem , Bioensaio/métodos , Família 2 do Citocromo P450 , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Ésteres , Estudos de Viabilidade , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Reação em Cadeia da Polimerase , Especificidade da Espécie , Compostos de Sulfidrila/administração & dosagem , Fatores de Tempo
20.
Interv Neuroradiol ; 17(4): 486-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22192555

RESUMO

Post-partum cervicocephalic artery dissection (pp-CAD) is a rare and poorly understood condition. To our knowledge, only 21 cases have been reported. Reversible cerebral segmental vasoconstriction (RCSV) was first described by Call and Fleming in 1988, and its association with pp-CAD has only been reported in three cases. However, in those cases it is unclear whether the pp-CAD may have been caused by straining during labor and therefore merely coincidental to the intracranial arteriopathy. We describe a 41-year-old right-handed African-American woman who developed the syndrome of pp-CAD (headaches, trace subarachnoid hemorrhage and diffuse cerebral arteriopathy on angiogram) two weeks after delivery. In this unique case, the patient had fortuitously undergone an MR study twice over a four day period which included the carotid bifurcations. During that time the patient was an inpatient, on bed rest and subject to continuous cardiac monitoring. The interval studies documented a true spontaneous right internal carotid artery dissection occurring without obvious cause. The patient had noted moderate right neck pain developing between the two MR studies but experienced no neurological deficits. Subsequent conventional angiography confirmed the presence of postpartum cerebral arteriopathy and the cervical dissection. The patient was managed conservatively with antiplatelet medication and had an otherwise uneventful course. We hypothesize whether transient arterial wall abnormalities, postpartum hormonal changes or subtle connective tissue aberrations play a similar role in the pathogenesis of these two associated conditions.


Assuntos
Dissecação da Artéria Carótida Interna/diagnóstico , Período Pós-Parto , Vasoespasmo Intracraniano/diagnóstico , Adulto , Anticoagulantes/uso terapêutico , Dissecação da Artéria Carótida Interna/tratamento farmacológico , Angiografia Cerebral , Diagnóstico Diferencial , Feminino , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Síndrome , Tomografia Computadorizada por Raios X , Vasoespasmo Intracraniano/tratamento farmacológico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...