Direct and indirect photodynamic therapy effects on the cellular and molecular components of the tumor microenvironment

Photodynamic therapy (PDT) is a novel cancer treatment. It involves the activation of a photosensitizer (PS) with light of specific wavelength, which interacts with molecular oxygen to generate singlet oxygen and other reactive oxygen species (ROS) that lead to tumor cell death. When a tumor is treated with PDT, in addition to affect cancer cells, the extracellular matrix and the other cellular components of the microenvironment are altered and finally this had effects on the tumor cells survival. Furthermore, the heterogeneity in the availability of nutrients and oxygen in the different regions of a tridimensional tumor has a strong impact on the sensitivity of cells to PDT. In this review, we summarize how PDT affects indirectly to the tumor cells, by the alterations on the extracellular matrix, the cell adhesion and the effects over the immune response. Also, we describe direct PDT effects on cancer cells, considering the intratumoral role that autophagy mediated by hypoxia-inducible factor 1 (HIF-1) has on the efficiency of the treatment.     

Direct and indirect effects of multiple enemies on water strider mating dynamics

Many different measures of range size are used for both empirical and conservation purposes. The possible consequences of the particular methods used in determining observed patterns of results are seldom considered. Using species of butterflies and freshwater molluses in Britain, we investigate the relationship between the range sizes measured by nine different methods and the sets of rare species they distinguish. A comparison of range sizes measured at different scales. Britain and Europe, is also made for the butterflies. We find that for many studies involving range size the various measures of range size are interchangeable. With respect to the identification of rare species the results are not as clear.     

Differentiation of endocrinocytes in the small-intestinal epithelium of albino rats in ontogenesis]

By means of the light microscopy method differentiation and dynamics on contents of endocrinocytes have been studied in epithelium of the initial part of the jejunum, of the caudal part of the ileum and of the middle part between them during pre- and postnatal periods of development. Formation of the endocrine apparatus of the mucous membrane epithelium in the small intestine takes place simultaneously with tissue differentiation of the epithelial layer. The population density of endotheliocytes of the mucous membrane is maximal in the initial part of the jejunum and decreases gradually in the caudal direction. By the 15th day of the postnatal development endocrinocytes in composition of the epithelium in the small intestine reach a high level of the specific differentiation and their amount increases by 1.3 times in comparison with that in newborn animals.     

The role of osmotic factors in the effect of mineral water Naftusia on smooth muscles of the portal vein

The effect of the Krebs solution tonicity on the electrical and mechanical activity of smooth muscles has been studied while adding 1-5% volume of mineral water Naftusya, its artificial salt analog, and distilled water into the above solution. It is shown that effects observed are induced by the medium tonicity changes rather than by biologically active components of the mineral water. The smooth muscle cells of the rat portal vein are sensitive osmometers which affect hypotonic Krebs solution by 1%.     

Direct and indirect effects of kisspeptin on liver oxidant and antioxidant systems in young male rats

Kisspeptin is a recently discovered hypothalamic peptide which plays an important role in the central control of reproductive functions. We have investigated direct and indirect effects of kisspeptin on the liver oxidative stress in young male rats. Twenty‐four rats were divided into four groups (n = 6/group). First group served as control and received saline. Kisspeptin‐10 was administered to the animals in the second group (20 nmol/rat/day), for a period of 7 days. Rats were given only one dose gosereline (0.9 mg/rat), a GnRH agonist in the third group. The last group received kisspeptin‐10 with gosereline. The activities of catalase, superoxide dismutase (SOD), xanthine oxidase (XO), adenosine deaminase (AD) and level of malondialdehyde were studied in liver tissue. Serum samples were separated for total antioxidant capacity (TAC), total oxidant status (TOS), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, blood urea nitrogen (BUN), colesterol, high‐density lipoprotein (HDL) and triglyceride. Kisspeptin increased the activities of SOD and catalase (p < 0.05). When compared to the control group, the levels of malondialdehyde, TOS and AST were lower, but levels of BUN, cholesterole, HDL and AD were higher in the other three groups (p < 0.05). In conclusion, our findings suggest that kisspeptin may have antioxidant and thus protective effects on the liver tissue. Copyright © 2010 John Wiley & Sons, Ltd.     

Direct and indirect effects of leptin on adipocyte metabolism

Leptin is hypothesized to function as a negative feedback signal in the regulation of energy balance. It is produced primarily by adipose tissue and circulating concentrations correlate with the size of body fat stores. Administration of exogenous leptin to normal weight, leptin responsive animals inhibits food intake and reduces the size of body fat stores whereas mice that are deficient in either leptin or functional leptin receptors are hyperphagic and obese, consistent with a role for leptin in the control of body weight. This review discusses the effect of leptin on adipocyte metabolism. Because adipocytes express leptin receptors there is the potential for leptin to influence adipocyte metabolism directly. Adipocytes also are insulin responsive and receive sympathetic innervation, therefore leptin can also modify adipocyte metabolism indirectly. Studies published to date suggest that direct activation of adipocyte leptin receptors has little effect on cell metabolism in vivo, but that leptin modifies adipocyte sensitivity to insulin to inhibit lipid accumulation. In vivo administration of leptin leads to a suppression of lipogenesis, an increase in triglyceride hydrolysis and an increase in fatty acid and glucose oxidation. Activation of central leptin receptors also contributes to the development of a catabolic state in adipocytes, but this may vary between different fat depots. Leptin reduces the size of white fat depots by inhibiting cell proliferation both through induction of inhibitory circulating factors and by contributing to sympathetic tone which suppresses adipocyte proliferation. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.     

Direct and indirect effects of n-species competition

Summary A measure of net interspecific competition is proposed which incorporates both direct and indirect effects between each species pair in a community. Indirect effects of one species on another may be mediated through other species in the community such that changes in the first species induce changes in other species which in turn directly affect the second species. Even in a competitive community these indirect effects are not necessarily always of a competitive nature and may sometimes actually act to oppose the effects of direct competition. Species pairs which are strong competitors in isolation may exhibit little net competition or even appear mutualistic depending on the other species present in the community.An expression for the net competitive effects between species pairs is derived in terms of the elements of the -matrix representation of the direct competitive effects. Examples calculated from the literature suggest that indirect competitive effects may often act to counterbalance direct competition between otherwise strong competitors in natural communities.     

Effect of palytoxin on the sodium-potassium pump: model and simulation

We propose a reaction model for the palytoxin-sodium-potassium (PTX-Na(+)/K(+)) pump complex. The model, which is similar to the Albers-Post model for Na(+)/K(+)-ATPase, is used to elucidate the effect of PTX on Na(+)/K(+)-ATPase during the enzyme interactions with Na(+) and/or K(+) ions. Conformational substates and reactions for the pump are incorporated into the Albers-Post model to represent enzymes with or without bound PTX. A mathematical model based on the reaction scheme is used in simulations modeling experimental studies of PTX-induced ionic currents. Our simulations suggest that (i) extracellular Na(+) as well as K(+) promotes PTX-induced channel blockage; (ii) extracellular K(+) accelerates PTX unbinding; and (iii) K(+) occlusion in the PTX-pump complex is essential for describing the PTX-induced current dynamics.     

Direct and indirect effects of the pRb tumor suppressor on autophagy

Autophagy, an intracellular degradation pathway involved in cell survival or demise, is tightly controlled by complex regulatory mechanisms. A link between the Rb tumor suppressor and autophagy is now emerging. pRb plays a critical role in cell cycle progression and survival as well as the differentiation of certain cell types. Recently, we have reported that during skeletal myogenesis, Rb-deficient myoblasts fuse to form short myotubes that quickly degenerate. Myotube degeneration was associated with increased autophagic flux and inhibition of autophagy rescued the defect leading to long, twitching myotubes. We propose that Rb-loss sensitizes cells to autophagy via direct and indirect mechanisms and we discuss how these might affect cancer progression and response to chemotherapy.     

Direct and indirect effects of the pRb tumor suppressor on autophagy

Autophagy, an intracellular degradation pathway involved in cell survival or demise, is tightly controlled by complex regulatory mechanisms. A link between the Rb tumor suppressor and autophagy is now emerging. pRb plays a critical role in cell cycle progression and survival as well as the differentiation of certain cell types. Recently, we have reported that during skeletal myogenesis, Rb-deficient myoblasts fuse to form short myotubes that quickly degenerate. Myotube degeneration was associated with increased autophagic flux and inhibition of autophagy rescued the defect leading to long, twitching myotubes. We propose that Rb-loss sensitizes cells to autophagy via direct and indirect mechanisms and we discuss how these might affect cancer progression and response to chemotherapy.     

Direct and indirect effects in microcosm communities of protists

Increased complexity in biological communities can increase the variety of interactions among species, but the relative strengths and long-term consequences of various direct and indirect interactions require further investigation. I studied interactions among four species of protists by monitoring their population dynamics when they were cultured either together or in seven different subset communities. Two protists were bacterivores (Chilomonas and Tetrahymena) and two were predators (Actinosphaerium and Euplotes). Actinosphaerium was omnivorous, and could eat both predatory Euplotes and bacterivores. Three indirect effects occurred among the four species of protists, including indirect facilitation of one predator by the other, apparent competition between bacterivores, and indirect facilitation of one bacterivore by the omnivorous predator. Community structure and invasibility depended on both direct and indirect effects; thus both can be mechanisms for assembly rules.     

Direct and indirect effects of termites on savanna tree-seedling growth

Termites are considered to be ecosystem engineers because they modify their biophysical environments. We tested the effects of soil-nutrient alteration in termite-enriched soils compared with termite-free open savannas. We also tested whether non-nutrient alterations (soil disturbance) induced by termites led to changes in tree-seedling growth. Soil samples taken from termite-enriched soils and adjacent open savanna sites in KwaZulu-Natal, South Africa were analyzed for nitrogen, pH, organic carbon and water-holding capacity. Seeds from three dominant tree species, Acacia sieberiana, Celtis africana and Ziziphus mucronata, were grown in soils taken from termite-enriched soils and adjacent savannas. Overall, organic carbon and nitrogen content were higher in termite-enriched soils than in adjacent savannas. We found that these differences in nutrients did not directly affect seedling growth rates or final height. However, C. africana had increased growth rates in compacted termite-enriched soils, while A. sieberiana seedlings were taller in non-compacted soils. We conclude that the indirect effects of disturbance by termites may be as important as the direct effects of increased nutrients for growth of savanna trees.     

Direct and indirect effects of body weight on adult wages

Previous estimates of the association between body weight and wages in the literature have been conditional on education and occupation. In addition to the effect of current body weight status (body mass index (BMI) or obesity) on wages, this paper examines the indirect effect of body weight status in the late-teenage years on wages operating through education and occupation choice. Using the National Longitudinal Survey of Youth 1979 data, for women, we find that a one-unit increase in BMI is directly associated with 1.83% lower hourly wages whereas the indirect BMI wage penalty is not statistically significant. Neither a direct nor an indirect BMI wage penalty is found for men. However, results based on clinical weight classification reveal that the indirect wage penalty occurs to a larger extent at the upper tail of the BMI distribution for both men and women via the pathways of education and occupation outcomes. Late-teen obesity is indirectly associated with 3.5% lower hourly wages for both women and men. These results are important because they imply that the total effect of obesity on wages is significantly larger than has been estimated in previous cross-sectional studies.