Effect of isoflurane, atracurium, fentanyl, and noxious stimulation on bispectral index in pigs

The study reported here was done to determine the relationship between anesthesia depth and bispectral index (BIS) in stimulated pigs. Isoflurane minimal alveolar concentration (MAC) was determined using the tail-clamp method in 16 Yorkshire/Landrace-cross pigs with mean+/-SEM weight of 27.7+/-1.76 kg. One week later, BIS, ECG, heart rate, arterial blood pressure, esophageal temperature, end-tidal CO2 tension and isoflurane concentration, arterial pH, PaO2, PaCO2, plasma bicarbonate concentration, and base excess were determined at each of five isoflurane MAC-multiples: 0.8, 1.0, 1.3, 1.6, and 2.0. Six treatments were studied: isoflurane; isoflurane and atracurium; isoflurane, atracurium, and fentanyl; isoflurane with noxious stimulation; isoflurane and atracurium with noxious stimulation; and isoflurane, atracurium, and fentanyl with noxious stimulation. The noxious stimulus during BIS measurement was the same as that for MAC determination. Each pig was studied three times (n = 8), and order of MAC-multiples and treatments was randomized. Data were evaluated by use of general linear model analysis of variance and linear regression analysis, with statistical significance set at P < 0.05. Significant differences in BIS values were identified between MAC-multiples within each treatment and between treatment 3 compared with treatments 2 and 4. Significant differences also were observed within and between treatments for heart rate, arterial blood pressure, and PaO2. Use of BIS appears reliable for identification of light versus deep anesthesia, but is of limited use for discrimination between isoflurane MAC-multiples of 1 and 1.6. We conclude that, compared with other treatments, atracurium and noxious stimulation had no significant effect on BIS.     

Neurogenic potential of mesenchymal-like stem cells from human amniotic fluid: the influence of extracellular growth factors

Amniotic fluids contain human stem cells, among which mesenchymal stem cells could be isolated. These cells have multipotent differentiation ability and no tumorigenic potential after transplantation in mice. These features make them good candidates for in vitro studies and for therapeutic purposes. The aim of this study was to isolate mesenchymal stem cell-like cultures from different amniotic fluids in order to study in vitro their neurogenic potential and assess if this process could be reproducible and standardized. We focused attention on the possible differential effects of soluble growth factors. Immunophenotypical and molecular characterization showed that the 31 amniotic fluid-derived cultures expressed mesenchymal markers as well as some stemness properties. These cells also appeared to be responsive to purines or acetylcholine showing an intracellular calcium increase, also reported for mesenchymal stem cells derived from other sources. Interestingly, in the presence of retinoic acid, these cells assumed a neuronal-like morphology. In addition, functional and molecular analyses revealed that retinoic acid-treated cells showed immature electric functional properties, the expression of neuronal markers and stemness genes. In conclusion, even if further investigations are required, the results presented here contribute to support the finding that amniotic fluid contains cells able to differentiate in vitro towards neural-like lineage in the presence of retinoic acid. The ability of retinoic acid to induce a possible neuronal progenitor culture makes the model useful to study a possible in vivo transplantation of these cells and to contribute to define the protocols for cell therapy.     

Genetic Variants in FBN-1 and Risk for Thoracic Aortic Aneurysm and Dissection

Objectives

A recent genome wide association study (GWAS) by LeMaire et al. found that two single nucleotide polymorphisms (SNPs), rs2118181 and rs10519177 in the FBN-1 gene (encoding Fibrillin-1), were associated with thoracic aortic dissection (TAD), non-dissecting thoracic aortic aneurysm (TAA), and thoracic aortic aneurysm or dissection (TAAD); the largest effect was observed for the association of rs2118181 with TAD. We investigated whether rs2118181 and rs10519177 were associated with TAD, TAA, and TAAD in the Yale study.

Methods

The genotypes of rs2118181 and rs10519177 were determined for participants in the Yale study: 637 TAAD cases (140 TAD, 497 TAA) and 275 controls from the United States, Hungary, and Greece. The association of the genotypes with TAD, TAA and TAAD were assessed using logistic regression models adjusted for sex, age, study center and hypertension.

Results and Conclusions

In the Yale study, rs2118181 was associated with TAD: compared with non-carriers, carriers of the risk allele had an unadjusted odds ratio for TAD of 1.80 (95% CI 1.15–2.80) and they had odds ratio for TAD of 1.87 (95% CI 1.09–3.20) after adjusting for sex, age, study center and hypertension. We did not find significant differences in aortic size, a potential confounder for TAD, between rs2118181 risk variant carriers and non-carriers: mean aortic size was 5.56 (95% CI: 5.37–5.73) for risk variant carriers (CC+CT) and was 5.48 (95% CI: 5.36–5.61) for noncarriers (TT) (p = 0.56). rs2118181 was not associated with TAA or TAAD. rs10519177 was not associated with TAD, TAA, or TAAD in the Yale study. Thus, the Yale study provided further support for the association of the FBN-1 rs2118181SNP with TAD.     

A dynamometer for evaluation of dynamic muscle work

The validation of a new dynamometer for evaluation of dynamic muscle work is presented. The device was based on a precise measurement of load displacements of any machine using gravitational loads as external resistance. It allowed, through a sensor consisting of an infrared photo interrupter, the calculation of velocity, force and power during concentric, eccentric and stretch-shortening cycle activity. To validate the dynamometer 33 male and female track and field athletes (12 throwers and 21 jumpers) participated in the study. The throwers (4 women and 8 men) were asked to perform half-squat exercises on a slide machine with a load of 100% of the subject's body mass. The day-to-day reproducibility of half-squat exercises gave a correlation coefficient ofr = 0.88, 0.97 and 0.95 for average push-off force (AF), average push-off velocity (AV), and average push-off power (AP) respectively. Comparison of half-squat measurements was performed against jumping and running test evaluation by the jumpers (7 women and 14 men). The interrelationships among the different variables studied demonstrated a strong correlation between AF, AV and AP and sprinting and jumping parameters (r = 0.53–0.97;P < 0.05–0.001). Using values of AF, AV and AP developed in half-squat exercises executed with different loads, ranging from 35% to 210% of the subject's body mass, it was also possible to establish the force-velocity and power-velocity relationships for both male and female jumpers. In any individual case, the maximal error due to the measurement system was calculated to be less than 0.3%, 0.9% and 1.2% for AF, AV, and AP respectively. Given the accuracy of the ergometer, the high reliability found between 2 days of measurements, and the specificity of the results it is suggested that the dynamic dynamometer would be suitable for evaluation of athletes performing specific skills. In addition, because single and multiple joint movements involving appropriate muscle groups can be easily performed, physiological characteristics could be evaluated for both athletic and rehabilitation purposes. Therefore, because of its simplicity of use and application, and its low cost the dynamometer would be suitable for both laboratory and field conditions.     

The oxytocic effect of xylazine on the canine uterus

The effect of xylazine on intrauterine pressure was compared to that of prostaglandin and oxytocin in seven diestrual bitches. Microtipped pressure transducers were surgically implanted in the uteri of four bitches at 30 d diestrus and in three bitches at 60 d diestrus. Uterine contractile force was measured in the awake bitches on Day 1 and Day 2 following implantation. Uterine responses to intravenous prostaglandin (5 mug/kg), oxytocin (0.05 USP units/kg), and xylazine (0.22 mg/kg) were measured. In the 30-d diestrual bitches, prostaglandin and oxytocin increased intrauterine pressure to 67 and 69 mmHg, with the duration of action being 16 and 14 min, respectively. Xylazine increased intra-uterine pressure to 49 mmHg and had a duration of action of 8 min. All results were decreased but similar in the 60-d diestrual bitches. These findings indicate that xylazine, given intravenously, produces a transitory increase in intrauterine pressure in the diestrual bitch.     

Dopamine Receptors in the Human Dura Mater

Dopamine receptors (Dar) were studied as a component of the nervous dopaminergic system in the human dura mater. Dar were stained in several dural zones (vascular, perivascular, intervascular) in different regions (basal, calvarial, tentorial, occipital, frontal, parietal, temporal) of the cranial meninges. Specimens of human dura mater were harvested from autopsies of 10 elderly male subjects (age range, 60-75 years). Dar were labeled with specific (H3) markers, studied with radiobinding techniques (including liquid scintillation), stained for light microscope autoradiography, and measured by means of quantitative analysis of images. All results were evaluated with statistical analysis to identify significant results. More dural Dar were found in the basal region than in the calvarial one. Moreover, Dar are more abundant in the vascular and perivascular dural zone than in the intervascular one. The vascular distribution of Dar seemed to indicate that Dar play a role in the control of meningeal blood vessels. The location and distribution of D1 and D2 receptors in the human cranial dura mater confirmed the presence of a dopaminergic system, which could play an important role in controlling blood flow and/or other functions of meningeal membranes.     

Modifications induced by plasma of gestational hypertensive women on the Na+/K+-ATPase obtained from human placenta

Pyrimidines and purine (deoxy)nucleotides are the building blocks of DNA and RNA. Nucleoside diphosphate sugars, e.g. UDP-glucose, are the reactive intermediates in the synthesis of nearly all glycosidic bonds between sugars.In mammals the requirement for pyrimidines is met by UMP de novo synthesis and, to a greater or lesser extent, by salvage of free nucleosides. The exceptional compartmentation of the de novo synthesis with respect to mitochondrially-bound dihydroorotate dehydrogenase ('DHOdehase' or 'DHODH', EC 1.3.99.11) is one focus of the present work. DHODH activity was determined by the dihydroorotate-dependent oxygen consumption or by the UV absorption of the product orotate with mitochondria isolated from rodent and porcine tissues. For comparison, the cytochrome c and choline-dependent oxygen consumption of mitochondria from different tissues was measured. The highest specific activity of the rat DHODH was found in liver (2.3 × 10-3 µmol/min × mg protein) > kidney > heart. The application of known enzyme inhibitors Brequinar Sodium and Leflunomide for DHODH and sodium cyanide for cytochrome c oxidase verified the specificity of the activity tests used. The relation of DHODH activity versus that of cytochrome c oxidase revealed the lowest ratios in heart mitochondria and the highest in liver mitochondria. Since disorders in the mitochondrial energy metabolism could entail severe impairment of pyrimidine biosynthesis via respiratory-chain coupled DHODH, it is suggested to include improvement of pyrimidine nucleotide status in therapy protocols. (Mol Cell Biochem 174: 125–129, 1997)     

Drivers of extinction risk in African mammals: the interplay of distribution state,human pressure,conservation response and species biology

Although conservation intervention has reversed the decline of some species, our success is outweighed by a much larger number of species moving towards extinction. Extinction risk modelling can identify correlates of risk and species not yet recognized to be threatened. Here, we use machine learning models to identify correlates of extinction risk in African terrestrial mammals using a set of variables belonging to four classes: species distribution state, human pressures, conservation response and species biology. We derived information on distribution state and human pressure from satellite-borne imagery. Variables in all four classes were identified as important predictors of extinction risk, and interactions were observed among variables in different classes (e.g. level of protection, human threats, species distribution ranges). Species biology had a key role in mediating the effect of external variables. The model was 90% accurate in classifying extinction risk status of species, but in a few cases the observed and modelled extinction risk mismatched. Species in this condition might suffer from an incorrect classification of extinction risk (hence require reassessment). An increased availability of satellite imagery combined with improved resolution and classification accuracy of the resulting maps will play a progressively greater role in conservation monitoring.