The development of a computer controlled system to simulate in rats,the rapid,frequent changes in oxygen experienced by preterm infants developing retinopathy of prematurity

Preterm infants that develop severe ROP have significantly more fluctuations in their transcutaneous oxygen compared to mild or no ROP, despite the fact that all these infants are kept within clinically 'safe' limits. Current animal models do not accurately reflect this oxygen environment. Our aim was to custom build equipment capable of reproducing the transcutaneous oxygen (TcPO₂) levels recorded by infant cotside monitoring equipment in a rat model and assess the equipment's precision. Using previously published data for therat that translates TcPo₂ into the equivalent inspired FiO, a profile was derived from a datalog of TcPO₂ values recorded every minute for 14 days in an infant that had developed severe ROP. This profile was controlled in the animal chamber by software algorithms which calculated the amount and type of gas to be injected to move oxygen to each new set-point. CO₂ regulation within the chamber was also possible. Absolute differences between the datalog set-points (n=17, 465) and the oxygen sensor were median 0.3% oxygen, IQR 0.2-0.7% oxygen, with 95% of the differences < +/- 2% oxygen. The equipment is capable of reproducing the oxygen environment experienced by a preterm ventilated infant, giving a satisfactory level of precision.     

The developing cervical spinal ventral commissure of the rat: a highly controlled axon-glial system

The floor plate of the neural tube is of major importance in determining axonal behaviour, such that, having crossed, decussating axons do not cross back again. The ventral commissure (VC) of the spinal cord forms immediately ventral to the floor plate shortly after neural tube closure. It is the principal location in which decussating axons cross the midline. It is probably also of major importance in neural tube development, but has received relatively little attention. This study analyses the growth and development of the rat VC and also axon-glial relationships within it throughout the crucial prenatal period of extensive transmedian axon growth, when key biochemical interactions between the two tissues are taking place. The morphometric, stereological and immunohistochemical methods used show that the axonal and glial populations remain in a finely balanced equilibrium throughout a period of almost a hundred-fold growth of both elements. At all stages axons are highly segregated into small bundles of constant size by glial processes, to which they are closely apposed. Thus, glial-axon contact is remarkably precocious, uniquely intimate and persists throughout VC development. This suggests that the relationship between the two tissues is highly controlled through interactions between them. The VC is likely to be the physical basis of a second set of glial-axonal interactions, namely, those which are well known to influence axon crossing behaviour. In mediating these, the extensive axon-glial contact is an ideal arrangement for molecular transfer between them, and is probably the substrate for altering axon responsiveness and ensuring reliable transmedian decussation. The VC is therefore a segregating matrix temporally and spatially specialised for a range of key developmental axon-glial interactions.     

Heart rate changes caused by varying the oxygen supply to isolated hind legs of rats

Summary In a rat with an isolated hind leg circulation perfused with varying tyrode solutions, heart rate (HR) changes were studied in dependence of in the isolated hind leg and of , [K⁺], pH and lactic acid concentration ([Lac]) measured in the venous outflow of the isolated hind leg. In experimental series I the inflow was kept constantly high (either about 65 or 72 kPa). The perfusion pressure alternated between 16 and 24 kPa leading to flow rates in isolated hind legs ( ) from 30 to 50 ml · 100 g⁻¹ · min⁻¹. The depended on the momentary (flow-limited oxygen uptake). The [K⁺] and [Lac], the pH and the remained nearly constant while the was lower at small flow rates. The HR decreases some 4 min after initial enhancement of and . Series II comprised experiments with low flow rates and a medium oxygen supply ( =2.5−17.4 ml · 100 g⁻¹ · min⁻¹), =17.5−62.7 kPa). The ranged between 0.02 and 0.2 ml · 100 g⁻¹ · min⁻¹. The [K⁺] and [Lac], the and the HR increased while the pH decreased. The [Lac] in the outflow showed a strong dependence on oxygen uptake and — at a weak oxygen supply — on the time. Cross-correlation analyses between the parameters confirmed that the HR was best temporally correlated to the [Lac] in the outflow. In series III a 17 min perfusion of normoxic solution ( =65.3 kPa) was followed by perfusion with a hypoxic tyrode solution ( =8.7 kPa). was 30 ml · 100 g⁻¹ · min⁻¹. The [Lac], the and the HR increased accompanied by a decrease in pH. However a HR increase was observed only when the actual values of [Lac], and pH exceeded their normal ranges for a resting muscle. The results support the hypothesis that heart rate is additionally influenced by metabolic muscle receptors measuring lactic acid concentration in working muscle.     

Performance of a dermoscopy-based computer vision system for the diagnosis of pigmented skin lesions compared with visual evaluation by experienced dermatologists

BackgroundIt is often difficult to differentiate early melanomas from benign melanocytic nevi even by expert dermatologists, and the task is even more challenging for primary care physicians untrained in dermatology and dermoscopy. A computer system can provide an objective and quantitative evaluation of skin lesions, reducing subjectivity in the diagnosis.ObjectiveOur objective is to make a low-cost computer aided diagnostic tool applicable in primary care based on a consumer grade camera with attached dermatoscope, and compare its performance to that of experienced dermatologists.Methods and materialsWe propose several new image-derived features computed from automatically segmented dermoscopic pictures. These are related to the asymmetry, color, border, geometry, and texture of skin lesions. The diagnostic accuracy of the system is compared with that of three dermatologists.ResultsWith a data set of 206 skin lesions, 169 benign and 37 melanomas, the classifier was able to provide competitive sensitivity (86%) and specificity (52%) scores compared with the sensitivity (85%) and specificity (48%) of the most accurate dermatologist using only dermoscopic images.ConclusionWe show that simple statistical classifiers can be trained to provide a recommendation on whether a pigmented skin lesion requires biopsy to exclude skin cancer with a performance that is comparable to and exceeds that of experienced dermatologists.     

Behavioral changes induced in rats by exposure to trimethylthiazoline, a component of fox odor

Trimethylthiazoline (TMT), a component of fox feces, has been used in various studies as a natural predator stimulus to induce autonomic and behavioral signs of fear (e.g., higher levels of stress hormones, freezing, and risk assessment). The present study investigated whether 2 further behavioral signs of fear are induced in rats by TMT exposure: potentiation of the acoustic startle response and inhibition of appetitive behavior. In addition, the authors tested the rats for dose dependency of TMT-induced freezing behavior. The study confirmed that behavioral changes observed during TMT exposure are caused by TMT-induced fear and are dose dependent.     

The organization and stability of sleep states in in fullterm, preterm, and small-for-gestational-age infants: a comparative study

Sleep state organization in the neonatal period was compared for groups of fullterm, preterm, and small-for-gestational-age infants. Preterm and small-for-gestational-age groups were found to have greater rates of state change than the fullterm group, and maternal perception of the infants was found to be negatively correlated to rates of state change in the preterm infants. Small-for-gestational-age infants had more active sleep without rapid eye movements than fullterm or preterm infants. The findings are discussed with regard to implications for CNS organization and possible early identification of infants at risk of developmental problems.     

脑发育期甲状腺功能低下大鼠听觉中潜伏期反应的变化

目的：探讨脑发育期甲状腺功能低下（甲低）大鼠听觉中潜伏期反应（MLR）的变化。方法：孕鼠从孕第17天起及其仔鼠出生后起30天内饮含0．03％甲巯咪唑的自来水诱发脑发育期甲低仔鼠;甲低仔鼠生后1～30天腹腔注射左旋甲状腺素[20μg／（kg·d）]进行替代治疗;放射免疫法测定大鼠血清FT3和FT4;计算机平均叠加技术颅表记录大鼠MLR,连续3个月动态观察甲低大鼠波峰潜伏期（PL）、波峰间潜伏期（IPL）和波幅的变化。结果：甲低组大鼠生后第20天时未能引出听觉MLR,生后30～90天的听觉MLR各波PL均明显长于对照组;替代治疗组大鼠MLR除生后20天和生后70天的P。波PL明显短于对照组及生后70天的P“波PL明显长于对照组外,各波PL在生后20-90天与对照组比较差异无显著意义。甲低组大鼠生后30～90天MLR的P0-Pa和Pa—Pb IPL均明显长于对照组;替代治疗组大鼠MLR除生后70天的P0-Pb IPL明显长于对照组外,其余IPL在生后20-90天与对照组比较差异无显著意义。甲低组大鼠生后30～90天MLR各波波幅明显小于对照组;替代治疗组大鼠除生后20天P0和Na波、生后30天P0波的波幅明显大于对照组外,其余各波波幅在生后20～90天与对照组比较差异无显著意义。结论：脑发育期甲低大鼠听觉MLR的发育明显延缓,及早补充甲状腺素能显著改善其脑发育障碍。     

The analgesic effects of automatically controlled rotating acupuncture in rats: mediation by endogenous opioid system

The technique of rotating acupuncture needles has long been used to enhance the effects of acupuncture in Oriental medicine. However, it is difficult to standardize and quantify this stimulation condition. Thus we developed an automatically controlled rotating acupuncture (ACRA) system. The present study was conducted to evaluate the analgesic effects of ACRA using 4 different stimulation conditions (i.e., angle and frequency of rotation: 90 degrees + 1 Hz, 90 degrees + 1/4 Hz, 360 degrees + 1 Hz, and 360 degrees + 1/4 Hz) in Sprague-Dawley rats. Tail-flick latency to a noxious radiant heat stimulus in lightly anesthetized rats was measured before and after 15 min of ACRA stimulation at the Zusanli (ST36) acupoint. ACRA stimulations under all of the conditions above produced more potent analgesic effects than plain acupuncture (PA, acupuncture needle insertion only), but only the 90 degrees + 1/4 Hz ACRA condition showed a statistically significant effect versus PA (P < 0.01). Further, the analgesic effect of 90 degrees + 1/4 Hz ACRA was reversed by pretreatment with naloxone (2 mg/kg, i.p.). These results indicate that the 90 degrees + 1/4 Hz ACRA stimulation has the most potent analgesic effect in rats and that this is mediated by the endogenous opioid system.     

The dynamics of changes in hippocampal GABAergic system in rats exposed to early-life hypoxia-induced seizures

Hypoxia-evoked seizures (H/S) early in life lead to multiple chronic neurological deficits. Here, we present the results of studying GABA release and uptake in hippocampal axon terminals of rats exposed to H/S at 10-12 days of age. We characterized (i) exocytotic release of GABA; (ii) the initial rate of GABA uptake; (iii) the regulation of GABA release by presynaptic GABA(B) receptors. Rats were used for experiments 2, 4 and 8 weeks after H/S. We found that exocytotic [(3)H]GABA release was higher in rats exposed to H/S, and a maximal difference in the release was observed between the control and experimental rats tested 2 weeks after H/S. In contrast, the initial rate of GABA uptake decreased with age, and this tendency was more pronounced in rats exposed to H/S. Using (±)-baclofen and SKF 97541 as agonists of GABA(B) receptor, we revealed that a significant difference in the auto-inhibition of exocytotic [(3)H]GABA release was detected only between the control and experimental adult rats (8 weeks after hypoxia). The inhibitory effect dropped dramatically in the control adults, but only slightly decreased in adult rats exposed to H/S, thus becoming threefold more potent after hypoxic injury. Together, the results show that H/S affects the dynamics of age-dependent changes in the GABAergic system, and that the enhanced GABA(B) receptor-mediated auto-inhibition can be an important factor in weakening the postsynaptic inhibition and in the development of hyperexcitability in rats exposed to H/S.     

The relevance of memory, arousal, and cue factors to developmental changes in spontaneous alternation by rats

Three studies are reported which indicate that memory factors, heightened arousal, and differences in the use of cues are not responsible for the differences in spontaneous alternation (SA) behavior which have been typically found to exist between infant and adult rats. Experiment I examined memory as a factor by reducing intertrial intervals to a minimum. This manipulation did not alter alternation rates at any of the ages studied. Experiment II investigated the effect on alternation of reducing the heightened arousal of young rats by the use of the nonspecific depressant drug chlorpromazine hydrochloride. Alternation rates in both infant and adult rats were again unaffected. Experiment III indicated that 16-day old rats are influenced by the same spatial and olfactory cues that evoke SA in mature animals, but that they tend to use these in a different fashion to adults. The results supported the hypothesis that inhibitory deficiencies in young animals are responsible for the typical perserverative pattern of choices made by these animals in an equal alternative 2-choice T-maze situation.     

充血性心力衰竭犬肾组织内皮素系统表达的变化

目的：观察充血性心力衰竭犬肾脏内皮素系统表达的变化。方法：快速右心室起搏致心力衰竭犬模型,21只犬随机分为对照组、起搏2周组和起搏4周组。测定血液动力学评价心力衰竭严重程度,放射免疫测定法测定血浆内皮素浓度,RT-PCR法检测肾脏皮质和髓质内皮素系统的表达水平。结果：起搏2周组和起搏4周组血浆内皮素浓度均明显升高,起搏2周组肾髓质内皮素B受体表达水平上升,起搏4周组肾皮质和髓质内皮素前体原、内皮素A受体和内皮素B受体的表达均上升,在肾皮质,以内皮素A受体上升幅度较明显,而在肾髓质,则以内皮素B受体上升为显著。结论：在心力衰竭的不同阶段,肾脏内皮素系统表达的改变参与机体水电解质平衡的调节。     

L-thyroxine, cortisol, and diet affect the postnatal development of the facial part of the skull in developing rats

In rats, the effects of L-thyroxine (T4; 0.2 micrograms/g body weight), hydrocortisone (HC; 5 micrograms/g body weight) and mastication on the postnatal development of the facial part of the skull were examined. Administration of T4 and/or HC to rats for 5 consecutive days from day 5 after birth induced a precocious increase in the ratio of the facial length to the head length. The effects of these hormones decreased with the progression of weaning, and after the 20th postnatal day, the hormones had no effects on the postnatal development of either (facial and head) part of the skull. Moreover, these hormones played an additive role in the growth of facial part. On the other hand, continuous suckling from birth to the 30th postnatal day caused a significant decrease in the ratio of the facial length to the head length. These results suggest that increases in the circulating levels of T4 and HC in suckling rats and mastication in the weaning period are involved in development of the postnatal development of the facial part of the skull.     

Role of ATP as a sympathetic nervous system transmitter in the smoothing of rapid arterial pressure changes

Arterial pressure lability and its variations were examined in unrestrained rats following selective elimination of adrenergic or purinergic sympathetic influences on the circulatory system. Both the α₁-andrenoceptor blocker prazosin and the nonselective α-adrenoceptor blocker phentolamine lowered the arterial pressure without affecting its lability. When P_2x purine receptors were desensitized with α,β-methyleneATP, the resulting pronounced hypotension was accompanied by a two-fold increase in the lability of mean arterial pressure. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N^no 11, pp. 461–464, November, 1995 Presented by I. P. Ashmarin, Member of the Russian Academy of Medical Sciences     

Distinctive features of the development of M-1 tumors in rats during changes in the functional condition of the nervous system

Summary It was shown in experiments on rats that small doses of caffeine inhibit the development of the transplanted tumor (sarcoma M-1) by increasing the functional mobility of the nervous system. Large doses of caffeine accelerate the growth of the tumor in connection with the development of the limiting inhibition in the central nervous system.Presented by Academician A. D. Speranskii     

Role of microRNA-29a in the development of diabetic retinopathy by targeting AGT gene in a rat model

Objectives

This study intends to explore the role of microRNA-29a (miRNA-29a) in the development of diabetic retinopathy by targeting AGT gene in a rat model.