Effect of exercise training on liver antioxidant status of deoxycorticosterone acetate salt induced hypertensive rats

Several animal models have been developed to study the pathogenesis of hypertension. Deoxycorticosterone acetate (DOCA) salt induced hypertensive rats are adrenal models used to mimic human Conn's syndrome. Because previous studies showed a beneficial effect of chronic exercise (swimming) on the development of arterial hypertension in spontaneously hypertensive rats (which appears similar to human essential hypertension), we decided to evaluate the effects of swimming on DOCA-salt induced hypertension and liver antioxidant status. Therefore, the aim of this experiment was to study whether the swim training would improve hypertension and liver antioxidant status in DOCA-salt rats. DOCA-salt rats and control Sprague-Dawley rats were trained to swim 1 h/day, 5 days/week for 6 weeks and were sacrificed 48 h after the last exercise period. Systolic blood pressure was recorded before the sacrifice, and liver antioxidant status was evaluated in hepatic homogenates after the sacrifice. Swim exercise did not decrease systolic blood pressure in control and DOCA-salt rats but induced changes in liver activities of antioxidant enzymes, showing that exercise provoked liver oxidative stress in control and DOCA-salt rats. In comparison with our previous studies using spontaneously hypertensive rats, we conclude that the beneficial effects of chronic exercise on systolic blood pressure in rats are dependent on strain and the type of experimental hypertension.     

Expression of p53, or targeting towards EGFR, enhances the oncolytic potency of conditionally replicative adenovirus against neuroblastoma

BACKGROUND: Advanced stage and relapsing neuroblastoma (NB) has a poor prognosis with frequent treatment failures, warranting new treatment options and enhanced local tumor control. Treatment with conditionally replicative adenoviruses (CRAds) has shown effectiveness in various preclinical cancer models, but has not yet been evaluated for local control of NB. Here, we tested the efficacy of the CRAd AdDelta24 and of two AdDelta24 derivatives against NB. Derivative AdDelta24-425S11 infects cells deficient in coxsackie/adenovirus receptor (CAR) via the epidermal growth factor receptor (EGFR). Derivative AdDelta24-p53 expresses the tumor suppressor protein p53 to promote oncolysis. METHODS: Expression of CAR and EGFR, and p53 pathway and DNA damage responses were analyzed in six NB cell lines and two xenografts derived from primary NB using immunohistochemistry, reporter gene transactivation, Western blot and fluorescence-activated cell sorting (FACS) analysis. Efficacy of AdDelta24, AdDelta24-425S11 and AdDelta24-p53 against NB was evaluated in vitro by cell viability analysis and in vivo by monitoring subcutaneous xenograft tumor growth in mice and by histological analysis of treated tumors. RESULTS: Neuroblastoma cell lines were sensitive to oncolysis by AdDelta24, with a higher susceptibility of those with functional p53 and intact DNA damage responses. Compared to AdDelta24, AdDelta24-p53 exhibited enhanced oncolytic potency on all NB cell lines independent of their p53 status and AdDelta24-425S11 was more effective against CAR-low IGR-NB8 cells. Moreover, five daily intratumoral injections of 10(8) plaque-forming units (pfu) of AdDelta24-p53 or AdDelta24-425S11 into subcutaneous IGR-NB8 and IGR-N91 xenografts at an advanced tumor stage yielded significant tumor growth delays (TGD). In contrast, at this dose, AdDelta24 did not cause significant TGD of neuroblastoma xenografts. Injection of AdDelta24-p53 was associated with extensive cell lysis, apoptotic cell death, and fibrous fascicles in the tumors. CONCLUSION: CRAds expressing p53 and targeted towards EGFR appear promising new agents for local control in the treatment of neuroblastoma.     

Clofibric acid or diethylmaleate supplemented diet decrease blood pressure in DOCA-salt treated male Sprague-Dawley rats - relation with liver antioxidant status

The effects of ascorbate and a-tocopherol as antioxidants and as co-operative factors against NADPH-dependent lipid peroxidation in human placental mitochondria have been studied. The addition of ascorbate at low concentration (up to 50 M) to the NADPH-generating system resulted in increasing lipid peroxidation and Fe³⁺ to Fe²⁺ reduction. High concentration of ascorbate (150 M), which produced maximal rate of ascorbate-dependent lipid peroxidation, was found to inhibit almost completely NADPH-dependent lipid peroxidation by maintaining too much iron in its reduced form. Either stimulatory or inhibitory effect of ascorbate on NADPH-dependent lipid peroxidation depends on the appropriate Fe³⁺/Fe²⁺ ratio. -Tocopherol caused a decrease of NADPH-dependent lipid peroxidation, inhibiting completely this process at 150 M concentration. The inhibitory effect of -tocopherol increased rapidly with the increasing ascorbate concentration, almost complete inhibition of NADPH-dependent lipid peroxidation being obtained at 25 M -tocopherol and 50 M ascorbate. This strong inhibitory combined effect of -tocopherol and ascorbate was independent of the Fe³⁺/Fe²⁺ ratio, as a-tocopherol is not able to reduce Fe³⁺ to Fe²⁺ under the conditions employed. These findings suggest that antioxidant effects of ascorbate in placental mitochondria are mediated by recycling of a-tocopherol rather than by strong reduction of Fe³⁺ to Fe²⁺. On the basis of the results obtained, we assume that adequate concentrations of a-tocopherol and ascorbate in placental tissue may prevent the release of lipid peroxide from placental mitochondria and therefore could be protective against the development of preeclampsia.     

Convergence of a cryptic saddle pattern in benthic freshwater fishes

Synopsis Many North American stream fishes have a similar color pattern of four dark saddles against a light background. An interesting feature of the pattern, in addition to its widespread taxonomic distribution, is its consistent configuration. The interval between the first and second saddle is usually the largest, and the last (third) interval is the smallest. All saddled North American freshwater fishes live on uneven, rocky substrates, and nearly all live in flowing water. It is hypothesized that these fishes achieve crypsis through disruptive coloration; the light spaces between the saddles mimic rocks and the dark saddles appear as shadows or gaps between rocks. Saddles are spaced unevenly because rocks in streams are a mixture of sizes; a fish that mimics a series of rocks of similar sizes is more conspicuous than one that mimics rocks of different sizes. The placement of saddles was measured on five North American species. In four of five North American species measured (a sculpin and three darters), the longest spaces are towards the head where the body is also the widest, this is thought to enhance crypsis because pieces of gravel tend to be round or square. In the madtom, the saddle pattern tends more towards even spacing. The madtom may not rely on camouflage to the same extent as other species examined because of decreased predation pressure associated with being nocturnal and possessing sharp spines and venom glands.     

An empirical test for convergence using African barbs (Cypriniformes: Cyprinidae)

Evidence for convergence is often based on overall similarity as interpreted by human eyes. We use geometric morphometrics and an analysis of phylogenetic signal to determine if similarity in form between two sympatric species of cyprinid fishes in a community from the Dja River of Cameroon is due convergence or shared evolutionary history. The two species, Enteromius aspilus and E. guirali, are deep-bodied and are very similar in color and appear to school together. The species co-occur with seven other species of Enteromius that have the more fusiform shape seen in other small barbs across Africa. Phylogenetic analysis of the mitochondrial cytochrome b and COI genes suggests that they are not sister taxa, and there is no phylogenetic signal when the phylogeny is overlaid on shape space. The convergence between the two is likely due to a variety of factors including predator avoidance and crypsis in open water, social mimicry to increase the benefit of the selfish herd effect, and increased protection of E. aspilus via Batesian mimicry of E. guirali, which has a protective dorsal spine.     

Apomorphic and plesiomorphic ITS-1 rDNA patterns in morphologically similar snails (Stylommatophora: Vallonia), with estimates of divergence time

Morphological classification of snail shells is sometimes arbitrary and misleading in correct species delimitation. This topic is investigated in four nominal species of the minute gastropods of the genus Vallonia ( V. pulchella , V. excentrica , V. costata and V. enniensis ). First, individuals are classified according to their shell morphology. Second, variation in ribosomal internal transcribed spacer 1 DNA (ITS-1 rDNA) is analysed. Using a cladistic approach, the nucleotide positions of the ITS-1 are elucidated on apomorphic and plesiomorphic character states (outgroup= Acanthinula aculeata ; Valloniidae). The molecular data yield evidence that the morphospecies V. excentrica is a paraphyletic group, comprising just a loose arrangement of individuals with similar shells. Data on fossil shells and putative divergence time are also elucidated. In the monograph on Vallonia it has been suggested that the split between the branch of V. costata and the branch of V. pulchella , V. excentrica and V. enniensis could have been in the upper Cretaceous. Based on the ITS-1 sequence alignment and the number of variable nucleotide positions, it is suggested that the last common ancestor of both branches lived at some time during the Miocene or even the Pliocene. Therefore, the fossil stem lines of Vallonia should be newly interpreted.     

Regulation of sialic acid transport and catabolism in Haemophilus influenzae

Virulence of nontypeable Haemophilus influenzae (NTHi) is dependent on the decoration of lipooligosaccharide with sialic acid. This sugar must be derived from the host, as NTHi cannot synthesize sialic acids. NTHi can also use sialic acid as a carbon source. The genes encoding the sialic acid transporter and the genes encoding the catabolic activities are localized to two divergently transcribed operons, the siaPT operon and the nan operon respectively. In this study, we identified SiaR as a repressor of sialic acid transport and catabolism in NTHi. Inactivation of siaR resulted in the unregulated expression of the genes in both operons. Unregulated catabolism of sialic acid in the siaR mutant resulted in the reduction of surface sialylation and an increase in serum sensitivity. In addition to SiaR-mediated repression, CRP, the cAMP receptor protein, was shown to activate expression of the siaPT operon but not the nan operon. We describe a model in which SiaR and CRP work to modulate intracellular sialic acid levels. Our results demonstrate the importance of SiaR-mediated regulation to balance the requirement of surface sialylation and the toxic accumulation of intracellular sialic acid.     

Components of variance underlying fitness in a natural population of the great tit Parus major

Traits that are closely associated with fitness tend to have lower heritabilities (h2) than those that are not. This has been interpreted as evidence that natural selection tends to deplete genetic variation more rapidly for traits more closely associated with fitness (a corollary of Fisher's fundamental theorem), but Price and Schluter (1991) suggested the pattern might be due to higher residual variance in traits more closely related to fitness. The relationship between 10 different traits for females, seven traits for males, and overall fitness (lifetime recruitment) was quantified for great tits (Parus major) studied in their natural environment of Wytham Wood, England, using data collected over 39 years. Heritabilities and the coefficients of additive genetic and residual variance (CVA and CVR, respectively) were estimated using an "animal model." For both males and females, a trait's correlation (r) with fitness was negatively related to its h2 but positively related to its CVR. The CVA was not related to the trait's correlation with fitness in either sex. This is the third study using directly measured fitness in a wild population to show the important role of residual variation in determining the pattern of lower heritabilities for traits more closely related to fitness.