Role for dopamine in malonate-induced damage in vivo in striatum and in vitro in mesencephalic cultures

Defects in mitochondrial energy metabolism have been implicated in the pathology of several neurodegenerative disorders. In addition, the reactive metabolites generated from the metabolism and oxidation of the neurotransmitter dopamine (DA) are thought to contribute to the damage to neurons of the basal ganglia. We have previously demonstrated that infusions of the metabolic inhibitor malonate into the striata of mice or rats produce degeneration of DA nerve terminals. In the present studies, we demonstrate that an intrastriatal infusion of malonate induces a substantial increase in DA efflux in awake, behaving mice as measured by in vivo microdialysis. Furthermore, pretreatment of mice with tetrabenazine (TBZ) or the TBZ analogue Ro 4-1284 (Ro-4), compounds that reversibly inhibit the vesicular storage of DA, attenuates the malonate-induced DA efflux as well as the damage to DA nerve terminals. Consistent with these findings, the damage to both DA and GABA neurons in mesencephalic cultures by malonate exposure was attenuated by pretreatment with TBZ or Ro-4. Treatment with these compounds did not affect the formation of free radicals or the inhibition of oxidative phosphorylation resulting from malonate exposure alone. Our data suggest that DA plays an important role in the neurotoxicity produced by malonate. These findings provide direct evidence that inhibition of succinate dehydrogenase causes an increase in extracellular DA levels and indicate that bioenergetic defects may contribute to the pathogenesis of chronic neurodegenerative diseases through a mechanism involving DA.     

Asthma in children--problems in diagnosis

Bronchial asthma in children may be difficult to diagnose. Education of the parents regarding allergic conditions, specifically bronchial asthma, is exceedingly important in order to assure satisfactory treatment and clinical results. Chest symptoms of unexplained origin in early life should immediately arouse suspicion of allergic disease. Other causes of asthmatic symptoms must be borne in mind and excluded before a positive diagnosis of bronchial asthma is established. Of the many factors to be considered in investigating a child with asthma, a comprehensive history is most essential. The climate to which the patient is exposed and the psychic influences must be taken into account. Physical examination, x-ray films and laboratory procedures should be carefully executed. Skin testing, especially with food allergens, should not be relied upon to give all the information in allergic disease. Some form of diet trial, such as elimination diets, should be used if sensitivity to food is suspected.     

Trends in dental caries in 12-year old children in Croatia

In this epidemiological study the caries status of 12-year-old children was compared over time for the years 1968, 1973, 1980, 1985, 1990, 1991 and 1999. The mean number of decayed, missing and filled teeth (DMFT) decreased from 7.0 in 1968 to 2.6 in 1991. From 1991 to 1999 and increase of DMFT 2.6 in 1991, to 3.5 in 1999) has been seen which is result of war in Croatia and reorganisation of health care delivery system. With the expected continuing decline in the prevalence and severity of oral diseases, one of the main problems in the future seems to be the transition of the oral health care delivery system from a disease-oriented system to a health-oriented one.     

Nuclear conditions in haploid Pelargonium in vivo and in vitro

In the shoot apices of the haploid Pelargonium cultivar Kleine Liebling, all mitoses are haploid (n = 9); however, ca. 20% of the interphase nuclei have DNA contents greater than 2C (up to 4C), indicating a tendency to chromosome endoreduplication in this material. — In internodes in vivo, the few mitoses present are haploid (quite probably, cambium cells); in addition to haploid interphases (1C to 2C DNA contents), endoreduplicated (endopolyploid) nuclei and nuclei in the course of endoreduplication occur with a frequency of ca. 40–50% (DNA contents up to 8C). — When internodes are cultured in vitro, differentiated cells are stimulated to divide, thus forming a population of diploid and tetraploid mitoses in addition to the preexistent meristem (haploid) cell population. In the process of time, diploid and tetraploid mitoses continue to be present in the callus, whilst haploid mitoses may decrease in number and eventually disappear. All mitoses analyzed had euploid chromosome numbers (9, 18 and 36) and their DNA contents were correspondingly 2C, 4C and 8C. Since no extensive chromosome counts were made, aneuploidy in the cultured material cannot be excluded; but, if occurring, it should be rather rare. — Under the experimental conditions used, prolonged culture in vitro leads to the production of nuclei with DNA contents (16C and 32C) greater than those occurring in vivo (8C), due to one and two additional DNA replications respectively beyond the limits attained in vivo. Even in these cultures, however, a population of the meristematic haploid cell line (DNA values 1C to 2C) is still present. — The present results are discussed in their relations with previous works on nuclear conditions in vivo and in vitro and on regeneration processes in cultured tissues in plants.     

Stereoselective metabolism of pentoxifylline in vitro and in vivo in humans

Pentoxifylline increases erythrocyte flexibility, reduces blood viscosity, and inhibits platelet aggregation and is thus used in the treatment of peripheral vascular disease. It is transformed into at least seven phase I metabolites, of which two, M1 and M5, are active. The reduction of the keto group of pentoxifylline to a secondary alcohol in M1 takes place chiefly in erythrocytes, is rapidly reversible, and creates a chiral center. The aims of this study were: to develop HPLC methods to separate the enantiomers of M1, to investigate the kinetics of the reversible biotransformation of pentoxifylline to (R)- and (S)-M1 in hemolysed erythrocyte suspension, and to quantify the formation of the enantiomers of M1 (as well as M4 and M5) after intravenous and oral administration of pentoxifylline to human volunteers. (R)- and (S)-M1 could be separated preparatively on a cellobiohydrolase column, while determination in blood or plasma was by HPLC after chiral derivatization with diacetyl-L-tartaric acid anhydride. The metabolism of pentoxifylline to (R)-M1 in suspensions of hemolysed erythrocytes followed simple Michaelis-Menten kinetics (K(m) = 11 mM), while that to (S)-M1 was best described by a two-enzyme model (K(m) = 1.1 and 132 mM). Studies with inhibitors indicated that the enzymes were of the carbonyl reductase type. At a therapeutic blood concentration of pentoxifylline, the calculated rate of formation of (S)-M1 is 15 times higher than that of the (R)-enantiomer. Back-conversion of M1 to pentoxifylline was 3-4 times faster for the (S)- than for the (R)-enantiomer. In vivo, the R:S plasma concentration ratio of M1 ranged from 0.010-0.025 after intravenous infusion of 300 or 600 mg of pentoxifylline, and from 0.019-0.037 after oral administration of 600 mg. The biotransformation of pentoxifylline to M1 was thus highly stereoselective in favor of the (S)-enantiomer both in vitro and in vivo.     

Biomarkers discovery in cancer--up-dates in methodology

Biomarkers are biomolecules that can indicate normal/pathological processes, or physiological responses to therapy. Due to the serum abundance in proteins, such as albumin and lypo/glycoproteins, biomarkers are difficult to assess. Serum biomarkers identification can contribute to personalized medicine and improve cancer diagnostic and prognostic. The paper summarizes some of the proteomics techniques and the workflow used for protein signatures identification associated to cancer development. Thus, biomarkers validated for prostatic, breast, cervical or lung cancers are presented as examples for clinical application of serum markers. In spite of the continuous research efforts, there are only few validated biomarkers that have proved a good predictive power in cancer. Modern technology and the combination of various techniques used for proteins quantification represent important means for the identification and validation of new biomarkers.     

食品中桔霉素控制方法的研究进展

桔霉素(Citrinin,CIT)是由青霉、曲霉和红曲霉属产生的一种具有肾毒性的真菌毒素。许多食品和饲料中均含有桔霉素,污染范围十分庞大。桔霉素可与其他真菌毒素发生协同作用,如展青霉素(Patulin,PAT)、赭曲霉毒素(Ochratoxin,OTA)等,从而增强其毒性作用,对人及动物健康造成更大的危害。现阶段常用的控制手段主要有物理、化学和生物方法,均取得了一定的成就。本文简单介绍了桔霉素的毒性及污染状况,对桔霉素控制方法的研究进展进行了综述。     

Seasonal variation in alkalinity in pans in Central Africa

Summary The alkalinity and pH of lakes (pans) in Central Africa on Kalahari Sand, varies with the physical nature of the pan. Natural pans show a range of pH from 6.1 to 8.7, and of total alkalinity from 10 mg/l to 580 mg/l. This range is attributable to local soil differences. Some pans have been deepened or have had water pumped into them to provide drinking points for game animals. The alkalinity of pumped pans is determined by the alkalinity of the water pumped into the pan and the time during which this has taken place. All these types of pan show cyclic seasonal variation in alkalinity and pH. The range in these factors is similar from one year to the next. Animals living either in permanent (deepened or pumped) pans or in temporary (natural) pans have to withstand a wide range of alkalinity fluctuation in the course of the year.     

Meiosis in Bovine Oocytes Matured in Vitro and in Vivo

Meiosis in bovine oocytes has; been studied after maturation in vitro or in vivo. Oocytes for in vitro maturation were collected from the ovaries of slaughtered cattle without regard to the phase of the estrous cycle while in vivo maturation was studied in oocytes from gonadotrophin-stimulated heifers at times varying between 6 and 36 h after the beginning of behavioural estrus. Oocytes from slaughtered cattle were classified according to their cumulus complex and ooplasm and were cultured for 6, 12, 18, 24, 36 or 48 h in modified Krebs-Ringer bicarbonate buffer before fixation) for cytogenetic analysis. Oocytes from stimulated heifers were aspirated from follicles or flushed from the oviducts, classified according to cumulus and ooplasm, and fixed within 6 h of collection. Nuclear maturation was more rapid in vitro than in vivo. The largest proportion of oocytes reached maturity (Mil) after 12 to 18 h in culture or 30 to 36 h after the onset of behavioural estrus. Oocytes devoid of cumulus cells or showing signs of vacuolation or degeneration had virtually no capacity for nuclear maturation.     

Inequality in Disability in Bangladesh

Objective

To investigate inequality in disability in Bangladesh.

Methods

The study used both household level and individual level data from a large nationally representative data set, Bangladesh’s Household Income and Expenditure Survey - 2010. Principal component analysis was used to construct a wealth index based on household assets from household level data. Then, using data from 49,809 individuals aged 5 years and over, chi-square tests and logistic regression were performed to test the association between wealth level and disability.

Findings

Women and older people are significantly more likely to report having disabilities than men and younger people. For middle and rich families, respectively, there is a 14 percent lower likelihood of reporting disabilities than for poor families. Changes in the probability of having disabilities are linear with increasing wealth. In addition, the study identifies some significant factors affecting disability, namely, age, sex, education, marital status, and place of residence including divisional differences.

Conclusion

In Bangladesh, worse health among the poor argues for policies prioritizing this group while at the same time giving special attention to women and the elderly.     

Studies in biochemical genetics in Drosophila

The metabolism of the imaginal discs of wild type, miniature, vestigial, and four-jointed varieties of Drosophila was investigated using the Cartesian diver ultramicrorespirometer. Wild type and vestigial wing disc respiration is inhibited by cyanide and azide and thus is mediated by an iron or copper porphyrin system, presumable cytochrome-cytochrome oxidase. Respiration is also inhibited by certain hydroxynaphthoquinones, believed to inactivate some enzyme between cytochromes b and c. The respiration of the vestigial and miniature wing discs is increased to normal by the addition of ascorbic acid and to a lesser extent by p-phenylenediamine and hydroquinone, hence the cytochrome oxidase and cytochrome c systems of vestigial and miniature wing discs are normal and the effects of these genes are on enzymes below cytochrome c in the respiratory chain. The respiratory enzymes of the developing imaginal discs of insects are similar to those of a wide variety of cells from bacteria to mammals. The correlation of these biochemical findings with embryological studies of the discs is discussed.     

Gender differences in fat patterning in children living in Ankara

Body composition is an excellent indicator for assessing obesity and nutritional status of both individuals and populations. Youth obesity has important health and social implications, because a large proportion of adult obesity has its origin in childhood. Numerous studies report that adverse levels of cardiovascular diseases risk factors are associated with adiposity in children. Concerning the Turkish population there is up to now only limited information with regard to adiposity in children. The aim of this study was therefore to determine the anthropometric and body composition characteristics and to investigate sex differences in fat patterning including fat distribution in a group of children living in Ankara. The present study evaluated the body composition of 332 boys and 269 girls aged between 8 and 11 years, attending public schools. It was carried out by a cross-sectional study and was focused on that anthropometric variables, which reflect body fat and fat-free mass. Anthropometric measurements including height, weight, triceps and subscapular skinfolds thickness were carried out on these children. The body mass index (BMI) was also calculated. The measurements were used to estimate the two-compartment model of body composition: fat-free mass (FFM) and body fat (BF) from skinfold equations. The mean fat percentage in boys is highest at 11 years (16.8%) and lowest at 10 years (15.6%). In girls these figures come to 18.2% and 17.1%, respectively. Girls of these age groups have a significantly larger percentage of body fat and skinfold thickness. At this young age there is therefore clear evidence of sexual dimorphism in fat patterning, as girls are showing a greater subcutaneous adiposity, which is mainly contributed by the triceps fat. The body fat (kg) increases in both sexes all over the investigated age groups. The Pearson correlation matrix showed a high significant relation between the anthropometric measurements (p < 0.01). The present study confirms the findings that sexual dimorphism of fat patterning in children is to be seen in the age of 8 - 11 years. It furthermore presents basic data of body composition, which could serve as reference data in other studies on the Turkish population.     

Trends in consanguinity in South India

This study uses data from the 1992-93 National Family Health Survey to assess trends in consanguinity in the South Indian states of Andhra Pradesh, Karnataka, Kerala and Tamil Nadu. In Kerala, the frequency of consanguineous marriages is very low and one type of preferred marriage of the Dravidian marriage system uncle niece marriage--is conspicuously absent. In the other states of South India, consanguinity and the coefficient of inbreeding are high. While no change in consanguinity is observed during the past three to four decades in Karnataka, a definite decline is observed in Andhra Pradesh and Tamil Nadu. Due to recent changes in the demographic and social situation in these states, this decline in consanguinity is likely to continue.     

Oxygen tension in cerebral microvessels in acute anaemia in rats

Using polarographic oxygen microelectrodes, distribution of oxygen tension (pO2) in the rat cerebral arterioles (with a lumen diameter of 8-80 microm) and venules (with a lumen diameter of 8-120 microm) has been studied in acute reduction of haemoglobin concentration in the blood. Isovolumic haemodilution with 5 % albumin solution has been performed stepwise from 14 g/dl (control) to 10 g/dl (step 1), 7 g/dl (step 2) and to 4.6 g/dl (step 3). It was shown that step 1 of haemodilution led to no impairment of oxygen supply to the brain cortex. Step 2 resulted in moderate increase of pO2 in arterioles, whereas in venules oxygen tension fell down substantially (on the average, to 32 mm Hg). Step 3 resulted insignificant increase of pO2 in arterioles. A further fall of pO2 (to 27 mm Hg) in studied venules was recorded. The portion of venules with low pO2 grew to 31% (only 3 % in control). Microregions with a near-to-zero pO2 were recorded in some capillaries. This indicates presence of hypoxic zones in brain tissue. Hypoxic and anoxic microregions originate at this stage of anemia in locations with relatively low and/or impaired blood supply.     

Microparticles in physiological and in pathological conditions

Chronic diseases pose a severe burden to modern National Health Systems. Individuals nowadays have a far more extended lifespan than in the past, but healthy living was only scantily extended. As much as longer life is desirable, it is saddened by chronic diseases and organ malfunctions. One contributor to these problems was recognized to be represented by microparticles (MPs). Our purpose is to better understand MPs, to contrast their ominous threat and possible clinical importance. For this intent we correlated MPs with thrombotic pathologies, hemophilia, malaria, diabetes, cardiovascular diseases, endothelial dysfunctions, pulmonary hypertension, ischemic stroke, pre-eclampsia, rheumatologic diseases-rheumatoid arthritis, polymyositis-dermatomyositis, angiogenesis and tumor progression-cancer; we listed the possibilities of using them to improve transfusion methods, as a marker for acute allograft rejection, in stem cell transplantation, as neuronal biomarkers, to understand gender-specific susceptibility for diseases and to improve vaccination methods and we presented some methods for the detection of MPs.     

Multiple biomarkers study in painters in a shipyard in Korea

Shipbuilding workers are exposed to a variety of genotoxic compounds including polycyclic aromatic hydrocarbons (PAHs). A limited number of studies have been conducted to evaluate biomarkers related to PAH exposure in painters in the shipyard industry. We examined this in 208 workers recruited from a shipyard located in South Korea. Employees were grouped into three exposure groups: (1) 111 painters using coal tar paints, (2) 70 painters using general paints, and (3) 27 on-site controls using no paints. Levels of urinary 1-hydroxypyrene glucuronide (1-OHPG), as internal dose of PAH exposure, were measured by synchronous fluorescence spectroscopy. Glutathione S-transferase (GST) M1 and T1 genotypes were assessed by a multiplex polymerase chain reaction (PCR)-based method, aromatic-DNA adducts in peripheral white blood cells were measured by 32P-postlabeling, and glycophorin A (GPA) variant frequencies in red blood cells were assessed by flow cytometry. Information on demographic characteristics, smoking habits, diet, job title and use of personal protective equipment (e.g. respiratory and dermal) were collected by self-administered questionnaire. Average urinary 1-OHPG levels in coal tar paint (2.24 micromol/mol creatinine) and general paint (1.38 micromol/mol creatinine) users were significantly higher than in on-site controls (0.62 micromol/mol creatinine) (P<0.001). Paint use, irrespective of the type of paints, and smoking (yes/no) were positively associated with urinary 1-OHPG levels, whereas green tea consumption (yes/no) was negatively associated with the 1-OHPG levels. No significant effect in the 1-OHPG levels were observed for the GSTM1 and GSTT1 genotypes. Aromatic-DNA adduct levels tended to be higher in coal tar paint users (P = 0.06) and painters (P = 0.07) compared to on-site controls. No differences in adduct levels were observed, between the two groups of painters, and the combined group showed greater adduct levels than on-site controls (P = 0.05). GPA mutation frequencies measured in 55 individuals with MN heterozygote genotypes were not significantly different among the three exposure groups, and no correlation was observed between urinary 1-OHPG levels and aromatic-DNA adducts or GPA mutation frequency. These results suggest that painters in the shipyard were exposed to significant amounts of PAHs and possibly to other genotoxic aromatic compounds, and that urinary 1-OHPG may be a potential biomarker of PAH exposure in this population.     

Changes in Nightjar Caprimulgus europaeus populations in upland forests in Yorkshire

The Nightjar populations of Yorkshire's upland forests have grown significantly during recent years, probably as a result of a concurrent increase in the available area of suitable habitat due to forest management. In common with other populations it appears that the birds utilize younger, more open plantations. Comparison, based on discriminant analysis, of the habitat characteristics of forest plantations occupied and unoccupied by Nightjars suggests two things. First, that birds are more likely to occupy larger rather than smaller clearings and, second, that the study populations are close to their maxima. However, with continuing rotational felling, the area should continue to support a similar population.     

Changes in aquatic vegetation in Rhine floodplain streams in Alsace in relation to disturbance

Abstract. Changes are described in aquatic vegetation in oligotrophic, groundwater-fed Rhine floodplain streams in Alsace (eastern France), resulting from disturbance. Disturbance factors include changes in nutrients, either permanent ones - effluent from a waste water treatment plant or trout hatcheries - or periodic ones: flooding. Regular inputs of high levels of phosphate and ammonia modified the macrophyte vegetation in these streams. The floristic composition, which was characteristic of oligotrophic waters upstream of the eutrophicated sector, changed to that of a eutrophic situation as originally found downstream. Periodic disturbance by floods which normally occur once a year, irregularly eutrophicates the small streams, causing the development of a mixture of eutrophic and oligotrophic species. Six macrophyte communities are distinguished, indicating different trophic levels. The aquatic vegetation is adapted to the variations of phosphate and ammonia levels. Hence, aquatic macrophytes can be used as bio-indicators of fluctuations in water nutrient levels in relation to the type of disturbance.