Development in in vitro toxicology

There are three principal pressures driving the development of in vitro toxicology: (1) the need for more efficient testing systems to cope with the large number of xenobiotics currently being developed; (2) public pressure to reduce animal experimentation; and (3) a need for a better understanding of the mechanisms of toxicity. Within this, in vitro toxicology is focused on local, systemic, and target-organ toxicity. It is becoming increasingly apparent that a step or decision-tree approach using input of a variety of experimental data (physicochemical properties, biokinetics, cytotoxicity) provides the most efficient system for predicting toxicity. Examples of the use of in vitro toxicity systems for prediction of systemic toxicity and target-organ (liver) toxicity are presented.Originally presented at ECCP 93.     

Development in in vitro toxicology

There are three principal pressures driving the development of in vitro toxicology: (1) the need for more efficient testing systems to cope with the large number of xenobiotics currently being developed; (2) public pressure to reduce animal experimentation; and (3) a need for a better understanding of the mechanisms of toxicity. Within this, in vitro toxicology is focused on local, systemic, and target-organ toxicity. It is becoming increasingly apparent that a step or decision-tree approach using input of a variety of experimental data (physicochemical properties, biokinetics, cytotoxicity) provides the most efficient system for predicting toxicity. Examples of the use of in vitro toxicity systems for prediction of systemic toxicity and target-organ (liver) toxicity are presented.     

Secular change in menarche in women in Madrid

The age at menarche was estimated by recollection in 1617 women between the ages of 18 and 60 in Madrid and a nearby suburb, Pinto. The population of Pinto is working-class and the Madrid group, taken from residential neighbourhoods , belongs to the upper middle class. In both groups we found a diminution in average age at menarche, from 14.04 to 13.02 years in Madrid and from 14.55 to 13.16 years from about 1935 to about 1965 in Pinto. These changes have been more intense in the group which is less well-off economically, where living conditions have varied much more drastically.     

Changes in the hypothalamic nuclei in in experimental allergy

Summary In rabbits subjected to prolonged sensitization and in which the Arthus phenomenon was induced there was a marked reaction of the hypothalamic nuclei. Staining by Gomori's method indicated a cellular swelling, loss of granules, and protoplasmic vacuolization in the supraoptic nucleus. There was a considerable increase in the size of the cross-sectional area of the cells. The same effects were much less well shown in the paraventricular nucleus. These results show that marked signs of increased neurosecretion developed in the animals at the height of the Arthus phenomenon.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten Éksperimental'noi biologii i Meditsiny, Vol. 55, No. 4, pp. 110–113, April, 1963.     

休克过程中肾上腺髓质素变化的研究进展

Adrenomedullin (AM) is a new peptidergic regulator of vascular function. AM serves as a hormone, which has many biological properties, plays an important role in the many pathophysiological processes, especially shock. This review will highlight the structure, biological properties of AM and the relationship between AM and shock.     

新疆某院2016年住院疾病分类统计分析

目的 分析2016年新疆某院住院疾病分类构成及分布特点,为临床医护人员了解某院疾病的构成及分布提供数据。方法 采集某院2016年住院疾病分类统计数据,进行整理、统计、分析。结果 某院2016年共出院32728人,按系统疾病排序,居于前10位的依次是循环系统疾病、呼吸系统疾病、妊娠分娩及产褥期情况、消化道疾病、内分泌系统疾病、泌尿生殖系统疾病、中毒及损伤,结缔组织及骨骼疾病、神经系统疾病、肿瘤。前10位的系统疾病合计28223人,占出院总数的86.24%,是某院的主流病种。在32728例住院患者中,男性15259占总数的46.62%,女性17469占总数的53.38%,男女之比0.87∶1。前十位系统疾病分类年龄段分析,15~44岁、45~59岁、60岁及以上3个年龄段的住院患者较多,占住院患者疾病分类总数的78.68%。构成比中60岁及以上年龄段比重最大,占总数的39.94%。结论 通过对某院2016年住院疾病的构成分析,可以了解某院医疗辐射区域各系统疾病的构成以及年龄段分布情况,为某院对系统疾病的研究和防治提供可靠的统计数据。     

Economical and rational in vivo and in vitro diagnosis in Basedow hyperthyroidism

Immunogenic hyperthyroidism (Graves' disease) is a life-long ailment. A widespread diagnostic evaluation is essential for unbiased initial values prior to therapy. The major goals of initial investigation are to determine a functional disturbance of the organ, its pathogenesis and morphology. Even a suppressed ultrasensitive bTSH value represents no evidence of overt hyperthyroidism; a positive diagnosis can only be established by the additional presence of increased parameters of circulating free thyroid hormones (fT3, fT4). Evidence of any immunogenic pathogenesis is given by positive thyroid antibody values (TRAK, MAK, TAK). Moreover, the use of sonography (with poor diffuse echo and increased thyroid depth) as well as Tc-99m scan indicating primary autonomy, thyroxine induced hyperthyroidism or painless thyroiditis) may both prove rather useful in a rational and economical diagnosis of Graves' disease.     

Increase in scrotal temperature in car drivers

Several recent studies have reported a gradual decline in sperm production in men. Endocrine disrupters as well as lifestyle have been suggested as risk factors. One lifestyle factor that may affect human fertility is driving a vehicle for a prolonged period. Several authors have suggested that driving position may increase the scrotal temperature. In order to validate this hypothesis we conducted continuous monitoring of scrotal temperature in real conditions, i.e. in men driving a car for a prolonged period. Nine volunteer men were asked to walk outside for 40 min and then to drive a car for 160 min. Scrotal temperatures were measured from thermocouples and values recorded every 2 min on a portable data recorder. Scrotal temperature increased significantly (P < 0.0001) in driving posture after 2 h of driving, reaching a value 1.7-2.2 degrees C higher than that recorded while walking. This link between driving position and increased scrotal temperature indicates a potential exposure of male reproductive function to lifestyle factors.     

Haemophilus influenzae in respiratory pathology in adults

Fifty patients were diagnosed bronchopulmonary Haemophilus infections, because of the production of a purulent sputum, containing at least 10(8) Haemophilus influenzae per ml. Among them were 36 males (average 52 years old) and 14 females (average 58 years old). There was a high percentage (64%) of smokers (over 30 packs/year) within this population, which also included heavy drinkers. The top incidence occurred in winter and spring. Most cases were related to an acute infection in a chronic bronchitis (26 cases). The other cases included 6 cancers, 6 sequelae of tuberculosis, 4 bronchiectasis, 4 asthma, and only 3 pulmonary consolidations. There usually was a low grade fever (only 8 cases reached or went beyond 38 degrees, while in 29 cases the body temperature kept below 38 degrees). The return to a normal temperature was obtained after 4 to 10 days of ampicillin therapy, with no fatal case within this series. The 50 strains were studied by the microbiology laboratory. The minimum inhibitory concentrations showed a peculiar response to ampicillin and erythromycin, and a less dramatic response to chloramphenicol and tetracyclin. Some strains were proved resistant (MIC over 4 micrograms per ml) to cefoxitine and cefamandole.     

Growth in Turkish children in Stockholm

Height, weight and body proportions were studied in 155 Turkish school children born in Sweden, living in a defined area in Stockholm. They were compared with Swedish children matched for sex, age and physical environment, and with a smaller number of Turkish children born in Turkey or in countries other than Turkey and Sweden. Parents' socio-economic levels were extremely low on a Swedish comparison. Growth was correlated to socio-economic background. The study was cross-sectional and longitudinal, combining growth data for key ages from health documents with contemporary data. Turkish schoolchildren under 10 years of age, born in Sweden, were significantly shorter than Swedish children, the difference beginning in the pre-school years. Turkish children born in Turkey were short on arrival in Sweden but soon caught up with the Turkish children born in Sweden. Genetic factors only could not explain the difference in height-for-age between Turkish children born in Sweden and Swedish children. With a longer period of stay in Sweden an increase in height-for-age would be expected.     

Thought disorder in schizophrenia: impairment in contextual processing via integrative failures in cognition

Formal thought disorder is a critical dysfunction in schizophrenia whose cause remains uncertain, but whose explanation may greatly further our understanding of the disease. Thought disorder in patients with schizophrenia has been hypothesized to involve a disturbance in the internal representation of context. Positive symptoms of schizophrenia attributable to thought disorder display a lack of organization that may be accounted for by an absence of normal contextual processing occurring within the operations of the executive system. But the precise nature and pervasiveness of the deficient cognitive operation remain undistinguished. It is proposed here that the assimilatory functions of the brain appear to lack the ability to perform a particular type of integrative operation when presented with heterogeneous information. This deficit involves committing cognitive misattributions through a confusion of mental terms via a process in thought analogous to a linguistic failure to correctly interpret deictic referents. Both proposed deficits in mental deixis and analogous “metarepresentational” deficits in schizophrenia potentially involve a failure to draw information for a conclusion from a separate framework of relations in integrative fashion. These deficits appear to involve a failure to take an interpreted piece of information as an output from a particular mental task and incorporate it into a new operational scheme, and a central attribute to the deficit is that there is a loss of an effective or adequate integration of separate strata of information. Potential neurobiological correlates to such a system based on current knowledge about schizophrenia neurocircuitry, as well as implications for testing, are also discussed.     

Apoptosis and changes in contractile protein pattern in the skeletal muscle in heart failure

Chronic heart failure is characterized as a clinical disorder by exercise intolerance. There are two factors that are independently responsible for the reduced exercise capacity: (a) a shift from myosin heavy chain 1 (MHC1) to MHC2a and MHC2b and (b) muscle atrophy. We have demonstrated, both in experimental models of heart failure and in man, that the more severe the heart failure, the greater the magnitude of skeletal muscle apoptosis. In the monocrotaline treated rat, that develops a severe right‐sided heart failure, the increased number of apoptotic nuclei was paralleled by increasing levels of circulating TNFα. In agreement with some recent observations showing that sphingolipids can mediate programmed cell death, we found that in animals with heart failure and high number of apoptotic nuclei, circulating levels of sphingosine were significantly increased. In a study conducted in patients with heart failure we found a correlation between exercise capacity limitation and skeletal myocytes apoptosis. There was also a correlation between degree of muscle atrophy and magnitude of apoptosis. The shift in MHCs, although with a different mechanism, is also responsible for the reduced exercise capacity in these patients. In fact there is a strong correlation between indices of severity of CHF and MHC composition. Muscle fatigue, appears earlier in patients that have a greater skeletal muscle expression of ‘fast’ MHCs. We have also demonstrated that MHCs shift and apoptosis can be prevented by using angiotensin II converting enzyme inhibitors and angiotensin II receptor blockers.     

Neurodevelopmental differences in confrontational naming in children

Naming disorders have been shown to be a frequently observed characteristic of children with dyslexia and dysphasia. Thus, a measure of confrontational naming can be a valuable diagnostic tool in the assessment of developmental reading and language disorders. The Boston Naming Test (BNT) is one such instrument. Although its diagnostic utility has been demonstrated, a lack of adequate normative data for pediatric populations has limited its usefulness. Thus, this study examined neurodevelopmental differences in confrontational naming within a sample of 70 normal 6‐ to 12‐year‐olds. An analysis of variance (ANOVA) revealed significant between‐group differences for several of the age ranges. Additionally, the BNT was administered to two subtyped groups of developmental dyslexics and to a left‐temporal brain‐tumor control group. An ANOVA showed that the instrument was clinically useful in differentiating the two dyslexic groups.     

Electronic healthcare communications in Vietnam in 2004

BACKGROUND: There is a lack of literature about health information systems (HIS) in "developing" countries, including Vietnam. However, computerization and network development are proceeding in these places, although not in a systematic, transparent way. OBJECTIVE: This is a preliminary overview of HIS's and healthcare communications in Vietnam's four-tiered public healthcare system. It is to indicate the direction that nation might take in order to establish a modern, standards-compliant, national HIS. METHODS: We conducted site visits and interviews in Hanoi and nearby provinces. Additional information was derived from publications of the Vietnamese government and the United Nations. RESULTS: Many of the top-level "central" hospitals have HIS's, although their quality and daily usage varies. Fewer provincial hospitals have networks; district hospitals have a few stand-alone computers, and commune health centers have no computers. Patients often go directly to higher-level providers, due to a widely held perception of better care at such sites. Communications among healthcare units are largely on paper, consisting mostly of administrative matters and some hand-written patient referrals. Telephones are used for discussions of specific matters. Internet connections are almost all dial-up and often belong to individual staff members rather than the healthcare units. Lower-level units derive much of their general medical information from television and newspapers. However, there is considerable interest in computerization among healthcare workers at all levels. CONCLUSION: Familiarization with computerized communications, i.e., training and hardware at all healthcare levels, must be the first step towards a modern healthcare communications network in Vietnam. The skills to do this already exist. The aim of such a network must be to raise the level of information and quality of care at the lower levels. Adherence to international standards, such as HL7, from the beginning would enable the country to bypass many years of haphazard development.     

Phasic spike patterning in rat supraoptic neurones in vivo and in vitro

In vivo, most vasopressin cells of the hypothalamic supraoptic nucleus fire action potentials in a 'phasic' pattern when the systemic osmotic pressure is elevated, while most oxytocin cells fire continuously. The phasic firing pattern is believed to arise as a consequence of intrinsic activity-dependent changes in membrane potential, and these have been extensively studied in vitro . Here we analysed the discharge patterning of supraoptic nucleus neurones in vivo , to infer the characteristics of the post-spike sequence of hyperpolarization and depolarization from the observed spike patterning. We then compared patterning in phasic cells in vivo and in vitro, and we found systematic differences in the interspike interval distributions, and in other statistical parameters that characterized activity patterns within bursts. Analysis of hazard functions (probability of spike initiation as a function of time since the preceding spike) revealed that phasic firing in vitro appears consistent with a regenerative process arising from a relatively slow, late depolarizing afterpotential that approaches or exceeds spike threshold. By contrast, in vivo activity appears to be dominated by stochastic rather than deterministic mechanisms, and appears consistent with a relatively early and fast depolarizing afterpotential that modulates the probability that random synaptic input exceeds spike threshold. Despite superficial similarities in the phasic firing patterns observed in vivo and in vitro , there are thus fundamental differences in the underlying mechanisms.     

Hemodynamics in emotional responses and in emotional stress

In the article, we present experimental data indicating that negative emotional states evoked by electrical stimulation of the ventromedial hypothalamus or by behavioral conflicts are accompanied by a predominance of vascular responses of a presser character possessing the property of summation. In contrast, positive emotional states during a self-stimulation reaction or when animals attain behavioral results satisfying their major biological demands are accompanied by a predominance of pressor-depressor vascular reactions. In individual animals under conditions of experimental emotional stress in conflicting situations of a prolonged character, pronounced disturbances of cardiac-vascular functions occur. Predominantly pressor vascular reactions arise in response to forced stimulation of the ventromedial hypothalamus in such cases. It is shown that changes in vascular tonus plays a leading role in disturbances of AP regulation during stress of immobilization. The most frequent cause of death in animals under such conditions is a progressive fall of AP due to an abrupt decrease in the total peripheral resistance. The resistance of the cardiac-vascular functions to emotional stress is determined to a significant degree by genetic mechanisms.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 74, No. 11, pp. 1535–1545, November, 1988.     

Changes in the adrenals in the sudden death syndrome in infants

Adrenal glands of 52 children dying from a syndrome of sudden death (SSD) and 14 children of the same age dying from acute viral respiratory infections (AVRI) with a long terminal period were studied. The following adrenal changes typical for the SSD were observed: low weight, decrease of the size of the definitive cortex and its zones, the appearance of numerous adenomatous growths in the definitive cortex and so-called giant cells in the fetal cortex, low secretory activity. The appearance of adenomas and giant cells in the presence of organ hypoplasia is a compensatory-hyperplastic adrenal response which attests to a long glucocorticoid deficiency in the SSD. It is suggested that the deficiency of these hormones leads to the metabolic disturbances in various organs, including brain, resulting in the narrowing of the range of homeostatic host responses; this may become the cause of sudden death when the clinical and morphological manifestations of AVRI are insignificant.     

Polarised X-rays in XRF-analysis for improved in vivo detectability of cadmium in man

A technique is described for the in vivo XRF-analysis of cadmium in the kidney cortex of man using plane polarised photons for excitation. The polarised photons are produced by scattering the radiation from an X-ray tube (W anode, 150 kV, 15 mA) in a polymethylmethacrylate disc at a 90 deg angle. The beam paths (X-ray tube to scatterer, scatterer to sample, sample to detector) must represent three mutually orthogonal directions. The minimum detectable concentration for a counting time of 1800 s and a skin-kidney distance of 30 mm is 8 micrograms g-1. This is a factor of 2.5 lower than our earlier method with direct excitation using the 59.5 keV photons from 241Am. The energy imparted has also been lowered from 0.4 to 0.2 mJ. The cadmium concentration in the kidney cortex of six occupationally exposed persons varied between 15 and 170 micrograms g-1.     

Circadian rhythms in metabolic variables in Caenorhabditis elegans

Circadian rhythms govern a wide variety of physiological and metabolic functions in most organisms through neural networks, hormones and gene expression. In this work, we studied the circadian variation in metabolic variables of adult C. elegans such as food consumption, pharyngeal contractions, defecation and oxygen consumption. Feeding behavior was clearly rhythmic under LD conditions, with a non-significant trend under DD conditions. In addition, a daily and circadian variation in muscle contraction of the pharynx was observed. Oxygen consumption also showed a circadian fluctuation with a maximum in the middle of the night (a peak was found around ZT18/CT18). Furthermore, defecation behavior also showed a daily variation in the N2 strain (wild type). This work demonstrates that in the adult nematode C. elegans metabolic variables vary daily. In summary, our results will allow us to take full advantage of this widely used animal model (including research in genetics, ageing and developmental biology) for studies in Chronobiology.