A noninvasive analysis of urinary musculoskeletal collagen metabolism markers from rhesus monkeys subject to chronic hypergravity

A decrease in load-bearing activity, as experienced during spaceflight or immobilization, affects the musculoskeletal system in animals and humans, resulting in the loss of bone and connective tissue. It has been suggested that hypergravity (HG) can counteract the deleterious effects of microgravity-induced musculoskeletal resorption. However, little consensus information has been collected on the noninvasive measurement of collagen degradation products associated with enhanced load-bearing stress on the skeleton. The purpose of this study is to assess the urinary collagen metabolic profiles of rhesus monkeys (Macaca mulatta) during 1) 2 wk of basal 1 G (pre-HG), 2) 2 wk of HG (2 G), and 3) two periods of post-HG recovery (1 G). Urine was collected over a 24-h period from six individual rhesus monkeys. Hydroxyproline (Hyp) and collagen cross-links (hydroxylysylpyridinoline and lysylpyridinoline) were measured by reverse-phase HPLC. Urinary calcium, measured by atomic absorption, and creatinine were also assayed. The results indicate no changes in nonreducible cross-links and Hyp during HG. Collagen cross-link biomarker levels were significantly elevated during the 2nd wk of HG. Urinary calcium content was significantly lower during HG than during the 1-G control period, suggesting calcium retention by the body. We conclude that there is an adaptation of the nonhuman primate musculoskeletal system during hyperloading and that noninvasive measurements of musculoskeletal biomarkers can be used as indicators of collagen and mineral metabolism during HG and recovery in nonhuman primates

Climate change denial: \u27making ignorance great again\u27

The denial of climate change and its negative consequences for global environments is pervasive in certain corridors of corporate and political power. This agnosia by powerful elites is a substantial contributor to global environmental degradation and destruction. This chapter explores the power of ignorance and argues that political dismissiveness of climate change is a recipe to exploit the environment for political and profitable purposes. Moreover, it argues that ignorance, defined as ‘unjustifiable belief’, provides those in positions of power and entitlement, to assert their own unquestioning expertise within an ideological bias that not only further their political and capital aspirations but endangers the planet

Circadian Changes in Susceptibility of Young Honeybee Workers to Intoxication by Pyrethroid, Carbamate, Organophosphorus, Benzoyl Urea and Pyridine Derivative Insecticides

In the years 2009 and 2010, in the apiaries surrounding Tarnobrzeg and Leżajsk, Poland (close to the Carpathian Mountains) research was carried out on diurnal changes in the sensitivity of young honey bee (Apis mellifera) workers to insecticides from various chemical groups: pyrethroids (esfenvalerate, cyhalothrin, alpha-cypermethrin, beta-cyfluthrin, deltamethrin), derivatives of pyridine (pyriproxyfen), carbamate (pirimicarb), organophosphate (diazinon), and benzoyl urea derivative (teflubenzuron). The analyses consisted of intoxicating subsequent groups of honey bees in 2-hour intervals, for a period of 24 hours with selected xenobiotics. The results received indicate that the honey bee shows a statistically significant susceptibility to insecticides, changing in the diurnal rhythm

Multidrug resistance in tumour cells: characterisation of the multidrug resistant cell line K562-Lucena 1

Multidrug resistance to chemotherapy is a major obstacle in the treatment of cancer patients. The best characterised mechanism responsible for multidrug resistance involves the expression of the MDR-1 gene product, P-glycoprotein. However, the resistance process is multifactorial. Studies of multidrug resistance mechanisms have relied on the analysis of cancer cell lines that have been selected and present cross-reactivity to a broad range of anticancer agents. This work characterises a multidrug resistant cell line, originally selected for resistance to the Vinca alkaloid vincristine and derived from the human erythroleukaemia cell K562. This cell line, named Lucena 1, overexpresses P-glycoprotein and have its resistance reversed by the chemosensitisers verapamil, trifluoperazine and cyclosporins A, D and G. Furthermore, we demonstrated that methylene blue was capable of partially reversing the resistance in this cell line. On the contrary, the use of 5-fluorouracil increased the resistance of Lucena 1. In addition to chemotherapics, Lucena 1 cells were resistant to ultraviolet A radiation and hydrogen peroxide and failed to mobilise intracellular calcium when thapsigargin was used. Changes in the cytoskeleton of this cell line were also observed.<br>A resistência a múltiplos fármacos é o principal obstáculo no tratamento de pacientes com câncer. O mecanismo responsável pela resistência múltipla mais bem caracterizado envolve a expressão do produto do gene MDR-1, a glicoproteína P. Entretanto, o processo de resistência tem fatores múltiplos. Estudos de mecanismos de resistência m��ltipla a fármacos têm dependido da análise de linhagens celulares tumorais que foram selecionadas e apresentam reatividade cruzada a uma ampla faixa de agentes anti-tumorais. Este trabalho caracteriza uma linhagem celular com múltipla resistência a fármacos, selecionada originalmente pela resistência ao alcalóide de Vinca vincristina e derivado da linhagem eritro-leucêmica K562. Esta linhagem celular, denominada Lucena 1, super-expressa a glicoproteína P e tem sua resistência revertida pelos quimio-sensibilizantes verapamil, trifluoperazina e ciclosporinas A, D e G. Ademais, demonstramos que o azul de metileno era capaz de reverter parcialmente a resistência nesta linhagem celular. Em contraste, o uso de 5-flúor-uracil aumentava a resistência de Lucena 1. Adicionalmente aos quimioterápicos, células Lucena 1 eram resistentes radiação ultra-violeta A e peróxido de hidrogênio e deixavam de mobilizar o cálcio intra-celular quando se usava tapsigargina. Mudanças no cito-esqueleto desta linhagem foram também observadas