Differential expression of cyclooxygenases in hypertrophic scar and keloid tissues

Hypertrophic scar (HS) and keloid (KL) are two forms of an abnormal cutaneous scarring process, mainly characterized by excessive extracellular matrix deposition and fibroblast proliferation. Despite the increased understanding of the molecular and cellular events leading to HS and KL, the pathogenesis of these lesions remains poorly understood. A pivotal role in the formation of abnormal scars has been ascribed to transforming growth factor-β, whose activity appears to be mediated through a link with pathways acting via cyclooxygenases (COX-1 and COX-2). To date, there is no report on the in vivo expression of COX-1 and COX-2 in human HS and KL tissues. Therefore, using immunohistochemistry and Western blot analysis, we investigated 36 cases of KL, 32 cases of HS, and 25 cases of normal skin in order to define the localization and distribution of COX-1 and COX-2 in the tissues of these scar lesions and the overlying epidermis. The results mainly show the following: (a) a significant overexpression of COX-1 in HS tissues and the overlying epidermis as compared with normal skin and KL tissues and (b) a significant overexpression of COX-2 in KL tissue and the overlying epidermis in contrast to normal skin and HS tissues. Our data support the hypothesis that both COXs are involved in the pathogenesis of scar lesions in different ways and, particularly, COX-1 in the formation of HS and COX-2 in the formation of KL. In addition, the overexpression of COX-1 and COX-2 in the epidermis overlying HS and KL tissues, respectively, underlines the importance of epithelial- mesenchymal interactions in the pathogenesis of scar lesion

Nutrição amoniacal com e sem N-Serve: efeitos sobre o crescimento radicular de milho

Under greenhouse conditions, an experiment was made to study the effects of ammonium- N (NH4) 2SO4 with and without the nitrification inhibitor N-Serve on the growth patterns of corn roots. Corn plants were grown for 58 days on pots containing a Brunizem soil material. NH4-N was applied at 13, 28 and 43 days after sowing at 30 µg/g rate. At each of the three dates, plants were harvested and its root fresh and dry weigth, volume, total length and CEC determined. Surface area and average root radius were calculated. Root growth characteristics, throughout the experimental period, were closely related to an exponential model. Regression coefficients were used to calculate relative growth rates of roots. There was a general trend for N-serve to depress the relative growth rate of roots, markedly, total length and surface area. Relative growth rates (R) calculated on dry and fresh weight basis were reduced 20% by N-Serve. These differences were more pronounced at the 43 and 58 days after planting. N-Serve seemed to affect the water relations of the plants. CEC was not affected by the nitrification inhibitor, and decreased only slightly with age.Foi feito um experimento, em casa de vegetação, para avaliar o efeito de uma fonte amoniacal de N (NH4) 2SO4 na ausência ou presença do inibidor de nitrificação N-Serve sobre características do crescimento radicular de milho. Usou-se um solo Brunizem, que foi cultivado em vasos, durante 58 dias. O N (90 µg N-NH4/g solo) foi aplicado parceladamente, aos treze, 28 e 43 dias após plantio, sem (SNS) ou com (CNS) (30 µg/g solo de N-Serve). Em cada data de colheita, foram registrados os pesos fresco e seco das raízes, o seu volume e comprimento total e a CTC. Foram calculados a área superficial e o raio médio. Todas as variáveis de crescimento ajustaram-se de forma altamente significativa a um modelo exponencial. Os tratamentos CNS mostraram taxas de crescimento relativas (R) menores que os tratamentos SNS, sendo que as maiores diferenças ocorreram para comprimento e área superficial. Valores de R baseados em peso fresco e seco, nos tratamentos CNS, foram afetados negativamente em 20%. Essas diferenças foram evidenciadas entre os 43 e 58 dias, não havendo diferenças significativas aos 28 dias. Esses resultados sugerem um efeito de toxidez crônica do NH4, em decorrência de sua absorção contínua num período prolongado

Aspectos climáticos do noroeste fluminense, RJ.

bitstream/CNPS/11829/1/doc_43_2003_noroeste_fluminense.pd

Uso de clorofilometro na avaliação da adubação nitrogenada e potássica no capim Tifton 85.

RESUMO - Objetivou-se com este trabalho aferir o comportamento de um clorofilometro na gramínea forrageira Tifton 85 (Cynodon spp. cv. Tifton 85) e sua relação com a produção de massa seca em resposta à adubação nitrogenada e potássica. No primeiro ensaio de campo realizado foi feita a aplicação de nitrogênio e potássio separados em três tratamentos: 0,75 e 150kg/ha/corte, segundo um delineamento em blocos casualizados, com quatro repetições. Os teores de clorofila total, extraídos da primeira lâmina foliar totalmente expandida, correlacionaram-se bem com as leituras do clorofilometro e foram afetados pelas doses de N e número de cortes. No segundo corte, os teores de clorofila total foram significativamente maiores que no primeiro, enquanto a massa verde seca total da parte aérea respondeu apenas às doses de N, o que sugere a existência de uma produção ?de luxo? de clorofilas. No segundo ensaio, os tratamentos consistiram de cinco doses de N e K: 0; 150; 300; 450 e 600 kg/ha, dispostos na forma de blocos inteiramente casualizados, com quatro repetições e ao final de um período de 28 dias, os teores de clorofila total, as leituras do clorofilometro e a matéria seca de folhas variaram, segundo um modelo quadrático, em resposta às doses de N (entre 0 e 600kg N/ha) sem evidencias de produção de luxo de clorofilas. Embora esta última situação seja provavelmente a situação normal, a melhoria no desempenho do clorofilometro a altos níveis de disponibilidade de N demandará novos estudos com relação às frações nitrogenadas que se acumulam na planta nessas condições. ABSTRACT - The aim of this study was to assess the performance of a chlorophyll meter and its relation to dry matter production of Tifton 85 (Cynodon spp. cv. Tifton 85), in response to nitrogen fertilization. In the first field trial, the total chlorophyll contents extracted from the uppermost fully expanded leaf blade correlated well with chlorophyll meter readings and were affected by N rates and cut number. In the second cut in the first field trial, total chlorophyll contents were higher than the first cut while total dry mass of green shoots responded only to N rates, suggesting that there was a ?luxury? production of chlorophylls. In the second field trial, at the end of a single regrowth period of 28 days, total chlorophyll contents, chlorophyll meter readings and dry leaf biomass varied harmonically, according to a quadratic model of response to N dose (0 - 600kg N/ha), without evidence of a supraoptimal production of chlorophylls. Although this last it is probably the normal situation, the refinement of the chlorophyll meter sensitivity to high levels of soil N availability, will demand news studies in order to clarify the status of the nitrogen fractions accumulated in the plant in these conditions

Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair

The error-free and efficient repair of DNA double-stranded breaks (DSBs) is extremely important for cell survival. RNA has been implicated in the resolution of DNA damage but the mechanism remains poorly understood. Here, we show that miRNA biogenesis enzymes, Drosha and Dicer, control the recruitment of repair factors from multiple pathways to sites of damage. Depletion of Drosha significantly reduces DNA repair by both homologous recombination (HR) and non-homologous end joining (NHEJ). Drosha is required within minutes of break induction, suggesting a central and early role for RNA processing in DNA repair. Sequencing of DNA:RNA hybrids reveals RNA invasion around DNA break sites in a Drosha-dependent manner. Removal of the RNA component of these structures results in impaired repair. These results show how RNA can be a direct and critical mediator of DNA damage repair in human cells

Kaposi's Sarcoma Associated Herpes Virus (KSHV) Induced COX-2: A Key Factor in Latency, Inflammation, Angiogenesis, Cell Survival and Invasion

Kaposi's sarcoma (KS), an enigmatic endothelial cell vascular neoplasm, is characterized by the proliferation of spindle shaped endothelial cells, inflammatory cytokines (ICs), growth factors (GFs) and angiogenic factors. KSHV is etiologically linked to KS and expresses its latent genes in KS lesion endothelial cells. Primary infection of human micro vascular endothelial cells (HMVEC-d) results in the establishment of latent infection and reprogramming of host genes, and cyclooxygenase-2 (COX-2) is one of the highly up-regulated genes. Our previous study suggested a role for COX-2 in the establishment and maintenance of KSHV latency. Here, we examined the role of COX-2 in the induction of ICs, GFs, angiogenesis and invasive events occurring during KSHV de novo infection of endothelial cells. A significant amount of COX-2 was detected in KS tissue sections. Telomerase-immortalized human umbilical vein endothelial cells supporting KSHV stable latency (TIVE-LTC) expressed elevated levels of functional COX-2 and microsomal PGE2 synthase (m-PGES), and secreted the predominant eicosanoid inflammatory metabolite PGE2. Infected HMVEC-d and TIVE-LTC cells secreted a variety of ICs, GFs, angiogenic factors and matrix metalloproteinases (MMPs), which were significantly abrogated by COX-2 inhibition either by chemical inhibitors or by siRNA. The ability of these factors to induce tube formation of uninfected endothelial cells was also inhibited. PGE2, secreted early during KSHV infection, profoundly increased the adhesion of uninfected endothelial cells to fibronectin by activating the small G protein Rac1. COX-2 inhibition considerably reduced KSHV latent ORF73 gene expression and survival of TIVE-LTC cells. Collectively, these studies underscore the pivotal role of KSHV induced COX-2/PGE2 in creating KS lesion like microenvironment during de novo infection. Since COX-2 plays multiple roles in KSHV latent gene expression, which themselves are powerful mediators of cytokine induction, anti-apoptosis, cell survival and viral genome maintainence, effective inhibition of COX-2 via well-characterized clinically approved COX-2 inhibitors could potentially be used in treatment to control latent KSHV infection and ameliorate KS

Lipid (per) oxidation in mitochondria:an emerging target in the ageing process?

Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation. In addition, senescent cells, which are known to contribute significantly to age-related pathologies, are also associated with impaired mitochondrial function and changes in lipid metabolism. Therapeutic targeting of dysfunctional mitochondrial and pathological lipid metabolism is an emerging strategy for alleviating their negative impact during ageing and the progression to age-related diseases. Such therapies could include the use of drugs that prevent mitochondrial uncoupling, inhibit inflammatory lipid synthesis, modulate lipid transport or storage, reduce mitochondrial oxidative stress and eliminate senescent cells from tissues. In this review, we provide an overview of lipid structure and function, with emphasis on mitochondrial lipids and their potential for therapeutic targeting during ageing and age-related disease