Effects of 17ß-estradiol on endothelium-dependent relaxation induced by acetylcholine in female rat aorta

Estrogens have been postulated to play an important role in modulation of vascular responses to endogenous reactive substances. The effects of chronic in vivo treatment with 17ß-estradiol on relaxant responses to acetylcholine were investigated in the rat aorta isolated from prepubertal female rats. The selectivity of effects of 17ß-estradiol on acetylcholine-induced relaxation was evaluated using histamine, another endothelium-dependent relaxant in the rat aorta. 17ß-Estradiol significantly enhanced endothelium-dependent relaxation induced by acetylcholine, but did not alter the vascular responses to acetylcholine in endothelium-denuded aortic rings isolated from prepubertal female rats. In contrast, 17ß-estradiol did not change endothelium-dependent relaxation induced by histamine in endothelium-intact aortic rings. The results of the present study demostrate that 17ß-estradiol selectively enhanced acetylcholine-induced endothelium-dependent relaxation in the rat aorta.     

Effects of micromolar concentrations of manganese, copper, and zinc on α1-adrenoceptor-mediating contraction in rat aorta

To determine the influences of the Mn, Cu, and Zn on α₁-adrenoceptor (AR)-mediated vasoconstriction, we investigated their effects on vasoconstriction produced by the α₁-AR agonist phenylephrine in isolated rings of rat thoracic aorta. The cumulative concentration-contraction curves for phenylephrine were obtained in the absence and presence of Mn (0.3, 1, 3 μM), Cu (1, 10, 16 μM), and Zn (0.3, 1, 10 μM). Mn, Cu, and Zn each inhibited phenylephrine-mediated contraction in a dose-dependent manner. The maximal phenylephrine-induced contraction was significantly reduced by the pretreatment of the arterial rings with 10 and 16 μM Cu (p<0.05). The results suggest that variations in the plasma concentrations of metal might lead to changes in α₁-AR-mediated constrictive response.     

Effect of salinity on the distribution of Ponto-Caspian gammarids in a non-native area – environmental and experimental study

The native area of gammarids from the so-called ‘Caspian complex’, Pontogammarus robustoides (G.O. Sars, 1894), Obesogammarus crassus (G.O. Sars, 1894), Dikerogammarus haemobaphes (Eichwald, 1841) and D. villosus (Sowinsky, 1894), is associated with brackish waters. Over the last several decades they have colonized the European inland waters and part of the brackish Baltic Sea. It is believed that anthropogenic increase in the salinity of inland waters facilitated their expansion. However, the influence of salinity on the dispersal of gammarid species outside their native area is not fully understood. We tested the hypothesis that salinity was a major factor in determining distribution, based on the abundance of Gammaridae in three coastal areas of low salinity (brackish Baltic), i.e. 0.3, 3.4 and 7.3 PSU, successfully inhabited by them. Additionally, for the first time, the effect of water salinity on the osmoregulatory capacity of O. crassus was examined under laboratory conditions, for the salinities given above. The experiments showed that similarly as in the case of other Caspian complex species, salinity values of about 7 PSU create better conditions for osmoregulation in O. crassus than lower salinities (i.e. 0.3 and 3.4 PSU). In the environmental part of the study, we observed that only D. villosus achieved a significantly higher abundance in the area of 7.3 PSU. Thus, we concluded that in the range of 0.3–7.3 PSU, salinity is not a key factor governing the distribution of Ponto-Caspian gammarids.     

Moderate hypothermia attenuates α(1)-adrenoceptor-mediated contraction in isolated rat aorta: the role of the endothelium

Moderate hypothermia (25–31 °C) may have a significant influence on vascular tone. We investigated the cellular mechanisms by which moderate hypothermia alters α-adrenoceptor-mediated contraction in rat thoracic aortae. Cyclooxygenase inhibition by indomethacin; nitric oxide (NO) synthase inhibition by l-NAME; potassium channel and endothelium-derived hyperpolarizing factor (EDHF) inhibition by glibenclamide and TEA; G protein inhibition by pertussis toxin; α₂-adrenergic inhibition by yohimbine; and β-adrenergic inhibition by propranolol were assessed for their effect on the contractile response to the α1-adrenoceptor agonist phenylephrine (Phe) in combination with moderate hypothermia (25 °C). Moderate hypothermia produced a shift to the right for the Phe concentration–response curves in endothelium-intact (E+) and endothelium-denuded (E?) aortic rings. The maximal response to Phe in E+ rings was significantly decreased (P < 0.05) at 25 °C compared to 38 °C, whereas there was no significant difference in E? rings. Hypothermia-induced vasorelaxation in E+ rings was attenuated (P < 0.05) following combined pretreatment with l-NAME (10^?4 M) and indomethacin (10^?5 M), whereas other inhibitors had no significant effect. Importantly, the addition of TEA to rings that were pretreated with l-NAME and indomethacin exhibited no further attenuation (P > 0.05) of hypothermia-induced vasorelaxation. The concentrations of cGMP and cAMP, as measured by radioimmunoassay, were significantly increased (P < 0.05) in E+ rings at 25 °C compared to those at 38 °C, whereas there were no significant differences (P > 0.05) in E? rings. The present study demonstrated that rat aortic endothelium is stimulated during moderate hypothermia and that the NO–cGMP and prostacyclin (PGI₂)–cAMP pathways represent endothelium-dependent mechanisms of hypothermia-induced vasorelaxation. In contrast, EDHF may not be associated with hypothermia-induced vasorelaxation.     

Influence of aluminium on the immune system – an experimental study on volunteers

The purpose of this study was to examine whether oral exposure to aluminum (Al) can affect the human immune system. Eighteen healthy volunteers (mean age 42, 28–57 yr) were divided into a test group (9 females, 4 males) and a referent group (3 females, 2 males). Over 6 weeks, the test subjects ingested 10 ml of antacid (aluminum hydroxide, 59 mg Al/ml) three times daily. Aluminum was analyzed in urine before and during the exposure period (ICP-MS). Blood samples were used for analysis of lymphocyte subpopulations, mitogen-induced lymphocyte proliferation and in vitro production and circulating plasma concentrations of immunoglobulin (Ig) A, IgG, IgM, interleukin (IL) -2 and IL-4. Urinary Al concentration in the test subjects was approximately 10- to 20-fold higher than in the referent group during exposure. This indicates that ingestion of an Al-containing antacid is associated with an Al absorption far above that originating from food and drinking water. In both referents and test subjects the lymphocyte subpopulations, lymphocyte proliferation and the in vitro Ig and IL production showed similar, time-dependent changes before as well as during the exposure period. No major differences were seen between the referent and test groups regarding the immune parameters, except for a slightly smaller CD8+CD45R0+ population (primed cytotoxic T-cells), in the exposed individuals as compared to the referents. The results also show that subjects on antacid therapy may constitute a suitable population for studying biological effects of high-dose oral exposure to Al.     

Is the repair of articular cartilage lesion by costal chondrocyte transplantation donor age-dependent? An experimental study in rabbits

The repair of chondral injuries is a very important problem and a subject of many experimental and clinical studies. Different techniques to induce articular cartilage repair are under investigation. In the present study, we have investigated whether the repair of articular cartilage folowing costal chondrocyte transplantation is donor age-dependent. Transplantation of costal chondrocytes from 4- and 24-week old donors, with artificially induced femoral cartilage lesion, was performed on fourteen 20-week-old New Zealand White male rabbits. In the control group, the lesion was left without chondrocyte transplantation. The evaluation of the cartilage repair was performed after 12 weeks of transplantation. We analyzed the macroscopic and histological appearance of the newly formed tissue. Immunohistochemistry was also performed using monoclonal antibodies against rabbit collagen type II. The newly formed tissue had a hyaline-like appearance in most of the lesions after chondrocyte transplantation. Positive immunohistochemical reaction for collagen II was also observed in both groups with transplanted chondrocytes. Cartilage from adult donors required longer isolation time and induced slightly poorer repair. However, hyaline-like cartilage was observed in most specimens from this group, in contrast to the control group, where fibrous connective tissue filled the lesions. Rabbit costal chondrocytes seem to be a potentially useful material for inducing articular cartilage repair and, even more important, they can also be derived from adult, sexually mature animals.     

Effects on the prostate of environmental cadmium exposure – A cross-sectional population study in China

To explore possible effects of environmental cadmium exposure on prostate in humans, and the possible relationship of serum sex hormones to occurrence of clinic signs of tissue changes in the prostate, a case-control study was undertaken in the southeast part of China in 1998. A total of 297 male volunteers from a control area and two cadmium-polluted areas were included as subjects in this study. All the subjects were required to answer a questionnaire and to undergo a complete physical examination including digital-rectal examination (DRE). Blood and urine samples were collected. Serum total prostate specific antigen (PSA), total serum testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured by radioimmunoassay and enzymeimmunoassay method, respectively. The data of urinary cadmium (U-Cd) and blood cadmium (B-Cd) were obtained by atomic absorption spectrometry (AAS) as an indicator of cadmium body burden. Statistical analysis was applied to investigate a possible relation between cadmium exposure and prostate pathological changes. The results show that there is a clear dose-response relationship between cadmium exposure and the prevalence of cases with abnormal PSA. The blood cadmium content in cases with positive DRE was significantly higher than that of subjects with negative DRE (P<0.05). Significant differences in the level of FSH between cases with positive DRE and the normal subjects were also noted (P<0.05). These results indicate that chronic environmental cadmium exposure is associated with injuries to human prostate. A possible relationship to changes in circulating sex hormones needs further investigation.     

Inhibition by triptoquinone-A of LPS- and IL-1β-primed induction of no synthase in rat thoracic aorta

We investigated the effect of triptoquinone-A (TQA), an active principal of Triptergium wilfordii, on the induction of nitric oxide synthase (NOS) promoted by endotoxin (LPS) and interleukin-1β (IL-1β). Prophylactic application of TQA selectively prevented LPS-primed initiation of L-arginine (Arg)-induced relaxation, and cGMP formation of rat thoracic aorta, and LPS-stimulated nitrite production by cultured aortic smooth muscle cells, which appear to be mediated by NOS expressed by LPS in vascular smooth muscle. TQA also prevented IL-1β-triggered initiation of Arg-induced relaxation and nitrite accumulation. These results suggest that TQA prevents LPS- or IL-1β-promoted induction of NOS in vascular smooth muscle, thus inhibiting development of Arg-induced vasorelaxation.     

The combined impact of mechanical factors on the wall stress of the human ascending aorta – a finite elements study

Background

Biomechanical factors influence stress in the aortic wall. The aim of this study was to assess how the diameter and shape of the vessel, blood pressure and longitudinal systolic aortic stretching (SAS) caused by the contraction of the myocardium influence stress in the aortic wall.

Methods

Three computational models of the non-dilated aorta and aneurysms of the ascending aorta and aortic root were created. Then, finite elements analyses were carried out. The models were subjected to blood pressure (120 mmHg and 160 mmHg) and longitudinal systolic aortic stretching (0 mm, 5 mm, 10 mm and 15 mm). The influence of wall elasticity was examined too.

Results

Blood pressure had a smaller impact on the stress than the SAS. An increase in blood pressure from 120 mmHg to 160 mmHg increased the peak wall stress (PWS) on average by 0.1 MPa in all models. A 5 mm SAS caused a 0.1–0.2 MPa increase in PWS in all the models. The increase in PWS caused by a 10 mm and 15 mm SAS was 0.2 MPa and 0.4 MPa in the non-dilated aorta, 0.2–0.3 MPa and 0.3–0.5 MPa in the aneurysm of the ascending aorta, and 0.1–0.2 MPa and 0.2–0.3 MPa in the aortic root aneurysm model, respectively. The loss of elasticity of the aneurysmal wall resulted in an increase of PWS by 0.1–0.2 MPa.

Conclusions

Aortic geometry, wall stiffness, blood pressure and SAS have an impact on PWS. However, SAS had the biggest impact on wall stress. The results of this study may be useful in future patient-specific computational models used to assess the risk of aortic complications.

     

Effect of rosuvastatin on outcomes in chronic haemodialysis patients – design and rationale of the AURORA study

Background

Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular events. Multiple risk factors for atherosclerosis are present in ESRD and may contribute to the increased risk of cardiovascular mortality in this population. In contrast to patients with normal renal function, the benefits of modifying lipid levels on cardiovascular outcomes in patients with ESRD on haemodialysis have yet to be confirmed in large prospective randomised trials. A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events (AURORA) will be the first large-scale international trial to assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis.

Methods

More than 2,750 ESRD patients who have been receiving chronic haemodialysis treatment for at least 3 months have been randomised (1:1), irrespective of baseline lipid levels, to treatment with rosuvastatin 10 mg or placebo. The primary study endpoint is the time to a major cardiovascular event (first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Secondary endpoints include all-cause mortality, major cardiovascular event-free survival time, time to cardiovascular death, time to non-cardiovascular death, cardiovascular interventions, tolerability of treatment and health economic costs per life-year saved. Study medication will be given until 620 subjects have experienced a major cardiovascular event.

Conclusion

Our hypothesis is that results from AURORA will establish the clinical efficacy and tolerability of rosuvastatin in patients with ESRD receiving chronic haemodialysis and guide the optimal management of this expanding population.     

The age of hair matters – the incorporation of cortisol by external contamination is enhanced in distal hair segments of pigs and cattle

Hair cortisol concentration (HCC) is used as an indicator of long-term stress or pathologies in humans and increasingly in animals. Although the main mechanism for the incorporation of cortisol into the hair shaft is by diffusion from blood, cortisol may also be incorporated from external sources by contamination of the hair surface. In farm animals under conventional husbandry conditions and trapped animals, contamination of hair with cortisol-containing body fluids, especially with urine, was shown to be a considerable confounding factor when studying HCCs. We recently found that cattle and pigs exhibit elevated HCCs in distal hair segments and assume that the incorporation of external cortisol is facilitated in these older hair segments. Therefore, the aim of this study was to investigate the effects of urine contamination on HCC in different hair segments of pigs and cattle, and to determine whether different cleaning protocols can prevent contamination effects. In an in vivo experiment in pigs (n = 18) and an in vitro experiment in cattle (n = 12), hairs were repeatedly contaminated with urine of the respective species and then shaved or cut in segments. Cortisol concentrations in hair segments were analysed by enzyme immunoassay after washing with isopropanol and extraction with methanol. Results were compared with HCCs in untreated hairs or hairs treated with water. Moreover, additional bovine hair samples contaminated with urine were subjected to two further cleaning procedures. Contamination with urine generally increased HCCs, and it was demonstrated for the first time that this effect is more pronounced in distal compared to proximal hair segments in both species. The immersion of bovine hair in vitro in water caused a washout of cortisol, which was also more pronounced in distal hair segments. In general, the different cleaning protocols for cattle hair did not prevent contamination effects, so we assume that external cortisol not only adheres but is incorporated into the hair shaft. Structural damage of older, distal hair segments may facilitate permeability of the hair matrix and diffusion of cortisol from and into aqueous solutions. Thus, the validity of HCC as a marker of stress is compromised in animals where soiling of hair with body fluids is a risk factor. Therefore, hair samples should be collected from clean body regions and, if possible, using proximal hair segments.     

Effects of algal diets and temperature on the growth and fatty acid content of the cichlid fish Oreochromis niloticus L. – A laboratory study

The effects of different algal foods and water temperatures on the growth and fatty acid content of the Nile Tilapia, Oreochromis niloticus L., were studied. Four types of algae, given in the same amounts as the control diet, were used as food: Microcystis aeruginosa, colonial and single-celled forms; Arthrospira fusiformis; and Scenedesmus quadricauda. The control group was fed a commercial diet of cichlid pellets, while another group was left unfed. The feeding experiment was run at 25 °C. The condition factor decreased in all algal fed fish groups, except the one fed on Microcystis colonies, whereas the control group showed no significant change. Both food quantity and quality were responsible for this result. Some short-chained fatty acids in the diets could be traced in the long-chained counter-parts in the fish tissue. Both saturated fatty acids and monounsaturated fatty acids were higher in the control vs. treatment groups, whereas the polyunsaturated fatty acids displayed no significant differences amongst any of the treatment groups studied, including the unfed group. Direct quantitative comparison of individual fatty acid in the diet vs. tissue lipids in the fish proved to be difficult due to the great capacity of these tilapias to elongate and desaturate 18 carbon acids into long-chained homologues. The effect of temperature was studied by growing the fish at 16, 20 and 25 °C. All groups were fed commercial cichlid pellets. The level of saturated and monounsaturated fatty acids increased at 20 °C, whereas polyunsaturated fatty acids showed little variation. Docosahexaenoic acid, belonging to the important omega 3 group where the first double bond starts at carbon number three, was highest at 16 °C, resulting in a markedly elevated omega-3/omega-6 ratio at that temperature.     

Effects of short term pollution on the level of fluctuating asymmetry – a case study using damselflies

Fluctuating asymmetry (FA), a measure of developmental stability, has been suggested as a monitoring tool for environmental pollution. However, there have been few investigations into the effects of short term pollution on the level of FA. This paper explores effects of exposing late instar larvae to short term pollution on the level of FA in the wings of adult damselflies. In these insects FA in wing length and in cell patterns have different windows of opportunity in relation to environmental stress. If increased environmental stress is applied after the window of opportunity of one trait had closed, while the window of the other trait was still open then the level of FA of the first trait should not be altered whereas that of the latter should increase. If short term pollution killed part of a population, symmetrical individuals (low FA) should survive better than highly asymmetrical ones, because FA reflects the overall ability of an individual to cope with stress. If the pollution event occurred at a time when the level of FA was already fixed, the level of FA of the remaining population should be lower than that in controls. An experiment was carried out, using 10 artificial ponds, each holding a population of larvae of the damselfly Xanthocnemis zealandica (McLachlan). Damselfly larvae were exposed to carbaryl at a nominal concentration of 100 g l^–1, which reduced emergence success after 10–20 days by ca. 50%. Based on laboratory experiments, it was assumed that despite the high mortality, the short exposure to carbaryl late in the last instar would ensure that the wing cell patterns of the damselflies were not altered by the increased stress. The level of FA in wing length increased in the damselflies surviving the exposure to carbaryl but the level of FA in cell patterns did not differ significantly between the treatment and the control. The effects of differential mortality, as well as the effects of pollution, on the level of FA in traits with different windows of opportunity need further investigation.     

The shape and mobility of the thoracic spine in asymptomatic adults – A systematic review of in vivo studies

A comprehensive knowledge of the thoracic shape and kinematics is essential for effective risk prevention, diagnose and proper management of thoracic disorders and assessment of treatment or rehabilitation strategies as well as for in silico and in vitro models for realistic applications of boundary conditions.After an extensive search of the existing literature, this study summarizes 45 studies on in vivo thoracic kyphosis and kinematics and creates a systematic and detailed database. The thoracic kyphosis over T1–12 determined using non-radiological devices (34°) was relatively less than measured using radiological devices (40°) during standing. The majority of kinematical measurements are based on non-radiological devices. The thoracic range of motion (RoM) was greatest during axial rotation (40°), followed by lateral bending (26°), and flexion (21°) when determined using non-radiological devices during standing. The smallest RoM was identified during extension (13°). The lower thoracic level (T8–12) contributed more to the RoM than the upper (T1–4) and middle (T4–8) levels during flexion and lateral bending. During axial rotation and extension, the middle level (T4–8) contributed the most. Coupled motion was evident, mostly during lateral bending and axial rotation. With aging, the thoracic kyphosis increased by about 3° per decade, whereas the RoM decreased by about 5° per decade for all load directions. These changes with aging mainly occurred in the lower region (T6–12). The influence of sex on thoracic kyphosis and the RoM has been described as partly contradictory. Obesity was found to decrease the thoracic RoM. Studies comparing standing, sitting and lying reported the effect of posture as significant.     

Effects of an anesthetic mixture of medetomidine,midazolam, and butorphanol in rats—strain difference and antagonism by atipamezole

An anesthetic mixture of medetomidine (MED), midazolam (MID), and butorphanol (BUT) hasbeen used in laboratory animals. We previously reported that this anesthetic mixtureproduced closely similar anesthetic effects in BALB/c and C57BL/6J strains. We alsodemonstrated the efficacy of atipamezole (ATI), an antagonist of MED that produced quickrecovery from anesthesia in mice. Anesthetics have various anesthetic effects among animalstrains. However, the differences in the effects of anesthetic mixtures in rats areunclear. In the present study, we first examined effects of the abovementioned anestheticmixture using three different rat strains: Wistar (WST), Sprague-Dawley (SD), and Fischer344 (F344). Second, we examined how different dosages and optimum injection timing of ATIaffected recovery from anesthesia in rats. We used the anesthetic score to measureanesthetic duration and a pulse oximeter to monitor vital signs. We found no significantdifferences in anesthetic duration among the three different strains. However, recoveryfrom anesthesia in the SD strain took significantly longer than in the other strains. Theantagonistic effects of ATI (0.15 mg/kg and 0.75 mg/kg) were equivalent when administeredat 30 min after anesthetic mixture administration. The antagonistic effects of ATI 0.75mg/kg were stronger than those of ATI 0.15 mg/kg at 10 min after anesthetic mixtureadministration. This anesthetic mixture is a useful drug that can induce similaranesthetic effects in three different strains and has an antagonist, ATI, that makes ratsquickly recover from anesthesia. These results may contribute to the welfare of laboratoryanimals.     

Effects of ground water and harvest intensity on alkaline grassland ecosystem dynamics – a simulation study

A model for the alkaline grassland ecosystems, MAGE, was applied to plant communities dominated by three species. Field observations on two communities dominated respectively by Puccinellia tenuiflora and Suaeda corniculata were used to parameterize the model for multiple species interaction. The model behaves reasonably in following the seasonal variations of water content, soluble sodium cation and calcium cation in surface soil, as well as biomass of the plant communities.Simulations were run to investigate the effects of ground water quality, ground water table depth, maximum non-capillary porosity in surface soil and harvest intensity, on ecosystem dynamics. The results indicated that ground water sodium concentration and ground water table depth had primary control on soil alkalization and vegetation status. The improvement of soil conditions by vegetation is limited to an extent with moderate ground water depth and sodium concentration. Non-capillary pores are critical for vegetation to affect the soil alkalization/de-alkalization process, but the effect of non-capillary pores tends to saturate when maximum non-capillary porosity is greater than 0.1.     

Effects of temperature on growth, development and diapause in the yellow dung fly – against all the rules?

The effects of rearing temperature (and photoperiod) on growth, development, body size, and diapause induction and termination in the yellow dung fly, Scathophaga stercoraria, were investigated by allowing replicate families of larvae to develop in the field along a time sequence approaching the onset of winter. This was supplemented with extensive laboratory rearing. At constant laboratory temperatures, growth rates were maximal between 15°C and 20°C and decreased at higher (25°C) and lower (10°C) temperatures, while the development rate was maximal at 25°C. Perhaps related to this, yellow dung flies reached a given size faster at naturally variable, as opposed to constant, temperatures. In the field, lower temperatures towards the end of the season resulted in larger individuals that grew faster. Adult body size increased as development time, expressed in calendar days, increased, a positive relationship commonly taken for granted in life history theory, but decreased as development time expressed in degree-days increased. The effect of temperature on growth, development and body size can thus change or even reverse if individuals can alter their growth rate independently of development time, and if the physiological effects of temperature are factored out by converting development time into degree-days above a lower development threshold. Therefore, supposedly well-established trends possibly need to be re-examined along these lines. Pupal winter diapause towards the end of the season was highly reversible by temperature. Pre- and post-winter emergence patterns together suggest that the minimum time for yellow dung flies to successfully complete development, at any time of the year, is about 230–250 degree-days. Received: 2 September 1996 / Accepted: 26 February 1997