Origin and pathogenesis of antiphospholipid antibodies

Antiphospholipid antibodies (aPL) are a heterogeneous group of antibodies that are detected in the serum of patients with a variety of conditions, including autoimmune (systemic lupus erythematosus), infectious (syphilis, AIDS) and lymphoproliferative disorders (paraproteinemia, myeloma, lymphocytic leukemias). Thrombosis, thrombocytopenia, recurrent fetal loss and other clinical complications are currently associated with a subgroup of aPL designating the antiphospholipid syndrome. In contrast, aPL from patients with infectious disorders are not associated with any clinical manifestation. These findings led to increased interest in the origin and pathogenesis of aPL. Here we present the clinical features of the antiphospholipid syndrome and review the origin of aPL, the characteristics of experimentally induced aPL and their historical background. Within this context, we discuss the most probable pathogenic mechanisms induced by these antibodies.

Amplification of 9q34 in childhood adrenocortical tumors: a specific feature unrelated to ethnic origin or living conditions

Adrenocortical tumors (ACT) in children under 15 years of age exhibit some clinical and biological features distinct from ACT in adults. Cell proliferation, hypertrophy and cell death in adrenal cortex during the last months of gestation and the immediate postnatal period seem to be critical for the origin of ACT in children. Studies with large numbers of patients with childhood ACT have indicated a median age at diagnosis of about 4 years. In our institution, the median age was 3 years and 5 months, while the median age for first signs and symptoms was 2 years and 5 months (N = 72). Using the comparative genomic hybridization technique, we have reported a high frequency of 9q34 amplification in adenomas and carcinomas. This finding has been confirmed more recently by investigators in England. The lower socioeconomic status, the distinctive ethnic groups and all the regional differences in Southern Brazil in relation to patients in England indicate that these differences are not important to determine 9q34 amplification. Candidate amplified genes mapped to this locus are currently being investigated and Southern blot results obtained so far have discarded amplification of the abl oncogene. Amplification of 9q34 has not been found to be related to tumor size, staging, or malignant histopathological features, nor does it seem to be responsible for the higher incidence of ACT observed in Southern Brazil, but could be related to an ACT from embryonic origin.

Stability of Natural Colorants of Plant Origin

In recent years, there have been studies that show a correlation between the hyperactivity of children and use of artificial food additives, including colorants. This has, in part, led to preference of natural products over products with artificial additives. Consumers have also become more aware of health issues. Natural food colorants have many bioactive functions, mainly vitamin A activity of carotenoids and antioxidativity, and therefore they could be more easily accepted by the consumers. However, natural colorant compounds are usually unstable, which restricts their usage. Microencapsulation could be one way to enhance the stability of natural colorant compounds and thus enable better usage for them as food colorants. Microencapsulation is a term used for processes in which the active material is totally enveloped in a coating or capsule, and thus it is separated and protected from the surrounding environment. In addition to protection by the capsule, microencapsulation can also be used to modify solubility and other properties of the encapsulated material, for example, to incorporate fat-soluble compounds into aqueous matrices. The aim of this thesis work was to study the stability of two natural pigments, lutein (carotenoid) and betanin (betalain), and to determine possible ways to enhance their stability with different microencapsulation techniques. Another aim was the extraction of pigments without the use of organic solvents and the development of previously used extraction methods. Stability of pigments in microencapsulated pigment preparations and model foods containing these were studied by measuring the pigment content after storage in different conditions. Preliminary studies on the bioavailability of microencapsulated pigments and sensory evaluation for consumer acceptance of model foods containing microencapsulated pigments were also carried out. Enzyme-assisted oil extraction was used to extract lutein from marigold (Tagetes erecta) flower without organic solvents, and the yield was comparable to solvent extraction of lutein from the same flowers. The effects of temperature, extraction time, and beet:water ratio on extraction efficiency of betanin from red beet (Beta vulgaris) were studied and the optimal conditions for maximum yield and maximum betanin concentration were determined. In both cases, extraction at 40 °C was better than extraction at 80 °C and the extraction for five minutes was as efficient as 15 or 30 minutes. For maximum betanin yield, the beet:water ratio of 1:2 was better, with possibly repeated extraction, but for maximum betanin concentration, a ratio of 1:1 was better. Lutein was incorporated into oil-in-water (o/w) emulsions with a polar oil fraction from oat (Avena sativa) as an emulsifier and mixtures of guar gum and xanthan gum or locust bean gum and xanthan gum as stabilizers to retard creaming. The stability of lutein in these emulsions was quite good, with 77 to 91 percent of lutein being left after storage in the dark at 20 to 22°C for 10 weeks whereas in spray dried emulsions the retention of lutein was 67 to 75 percent. The retention of lutein in oil was also good at 85 percent. Betanin was incorporated into the inner w1 water phase of a water1-in-oil-inwater2 (w1/o/w2) double emulsion with primary w1/o emulsion droplet size of 0.34 μm and secondary w1/o/w2 emulsion droplet size of 5.5 μm and encapsulation efficiency of betanin of 89 percent. In vitro intestinal lipid digestion was performed on the double emulsion, and during the first two hours, coalescence of the inner water phase droplets was observed, and the sizes of the double emulsion droplets increased quickly because of aggregation. This period also corresponded to gradual release of betanin, with a final release of 35 percent. The double emulsion structure was retained throughout the three-hour experiment. Betanin was also spray dried and incorporated into model juices with different pH and dry matter content. Model juices were stored in the dark at -20, 4, 20–24 or 60 °C (accelerated test) for several months. Betanin degraded quite rapidly in all of the samples and higher temperature and a lower pH accelerated degradation. Stability of betanin was much better in the spray dried powder, with practically no degradation during six months of storage in the dark at 20 to 24 °C and good stability also for six months in the dark at 60 °C with 60 percent retention. Consumer acceptance of model juices colored with spray dried betanin was compared with similar model juices colored with anthocyanins or beet extract. Consumers preferred beet extract and anthocyanin colored model juices over juices colored with spray dried betanin. However, spray dried betanin did not impart any off-odors or off-flavors into the model juices contrary to the beet extract. In conclusion, this thesis describes novel solvent-free extraction and encapsulation processes for lutein and betanin from plant sources. Lutein showed good stability in oil and in o/w emulsions, but slightly inferior in spray dried emulsions. In vitro intestinal lipid digestion showed a good stability of w1/o/w2 double emulsion and quite high retention of betanin during digestion. Consumer acceptance of model juices colored with spray dried betanin was not as good as model juices colored with anthocyanins, but addition of betanin to real berry juice could produce better results with mixture of added betanin and natural berry anthocyanins could produce a more acceptable color. Overall, further studies are needed to obtain natural colorants with good stability for the use in food products.

Serum antigliadin antibody levels as a screening criterion before jejunal biopsy indication for celiac disease in a developing country

The objective of the present study was to determine the efficacy of detection of antigliadin immunoglobulins G and A (IgG and IgA) for the diagnosis of celiac disease in a developing country, since other enteropathies might alter the levels of these antibodies. Three groups were studied: 22 patients with celiac disease (mean age: 30.6 months), 61 patients with other enteropathies (mean age: 43.3 months), and 46 patients without enteropathies (mean age: 96.9 months). Antigliadin IgG and IgA ELISA showed sensitivity of 90.9 and 95.5%, respectively. With the hypothetical values of prevalence ranging from 1:500 to 1:2000 liveborns, the positive predictive value varied from 8.5 to 2.3% for IgG and from 4.8 to 1.1% for IgA. Considering the patients without enteropathies, specificity was 97.8 and 95.7% for IgG and IgA, respectively. In patients with other enteropathies, specificity was 82.0 and 84.1%, respectively. When patients with and without other enteropathies were considered as a whole, specificity was 88.8 and 91.6%, respectively. The specificity of positive IgG or IgA was 93.5% in children without enteropathies and 78.7% in the presence of other enteropathies. The negative predictive value for hypothetical prevalences varying from 1:500 to 1:2000 liveborns was 99.9%. Thus, even in developing countries where the prevalence of non-celiac enteropathies is high, the determination of serum antigliadin antibody levels is a useful screening test prior to the jejunal biopsy in the investigation of intestinal malabsorption.

The origin of cortical neurons

Neurons of the mammalian cerebral cortex comprise two broad classes: pyramidal neurons, which project to distant targets, and the inhibitory nonpyramidal cells, the cortical interneurons. Pyramidal neurons are generated in the germinal ventricular zone, which lines the lateral ventricles, and migrate along the processes of radial glial cells to their positions in the developing cortex in an `inside-out' sequence. The GABA-containing nonpyramidal cells originate for the most part in the ganglionic eminence, the primordium of the basal ganglia in the ventral telencephalon. These cells follow tangential migratory routes to enter the cortex and are in close association with the corticofugal axonal system. Once they enter the cortex, they move towards the ventricular zone, possibly to obtain positional information, before they migrate radially in the direction of the pial surface to take up their positions in the developing cortex. The mechanisms that guide interneurons throughout these long and complex migratory routes are currently under investigation.

Montana and Wyoming territories : embracing most of the country drained by the Madison, Gallatin and upper Yellowstone rivers

Kartta kuuluu A. E. Nordenskiöldin kokoelmaan

The very worst government that any country ever had. Kirkkovaltio ja paavin asema Britannian parlamenttikeskusteluissa Italian yhdistymisprosessin aikana 1858–1861

Tutkielmassa tarkastellaan Britannian parlamentissa käytyä keskustelua Kirkkovaltiosta ja paavin maallisesta vallasta vuosina 1858–1861. Aihetta tarkastellaan kolmen teeman kautta. Nämä teemat ovat Kirkkovaltion ajassa ja paikassa tapahtunut kontekstualisointi, paavin ja katolilaisten Britannialle aiheuttamasta sisäisestä ja ulkoisesta uhasta käyty keskustelu, sekä Kirkkovaltion liittäminen kansainvälisiin suhteisiin. Britannian ja Kirkkovaltion suhdetta 1800-luvun puolivälissä on käsitelty aikaisemmassa tutkimuksessa vain vähän. Suhtautumisen perusasenteena sekä konservatiiveilla että liberaaleilla on pidetty katolilaisvastaisuutta ja Kirkkovaltion lakkauttamisen ajamista. Tutkielmassa pyritään osoittamaan, että Britannian parlamentin jäsenten suhtautuminen oli kuitenkin moniulotteisempaa ja moniäänisempää, kuin pelkkä tiukka katolilaisvastaisuus. Parlamentin jäsenet pyrkivät kontekstualisoimaan Kirkkovaltiota käyttämällä vertauksia sekä Britanniaan ja Sardinian kuningaskuntaan, että erilaisiin historiallisiin tilanteisiin. Keskusteluun osallistuneilla parlamentin jäsenillä oli myös hyvin laaja skaala erilaisia kontakteja Italiaan ja Roomaan, ja he olivat hyvin perillä paavin maallisesta vallasta käydystä yleiseurooppalaisesta kirjallisesta debatista. Osa parlamentin jäsenistä näki paavin ja katolilaiset sekä sisäisenä että ulkoisena uhkana Britannialle, mikä liittyy vahvasti 1800-luvun puolivälin uhkakuvia täynnä olleeseen näkemykseen. Näkemys uhasta tiivistyi keskusteluun uskollisuudenvalan uudistamisesta vuonna 1858. Tässä keskustelussa esiin nousivat erityisesti ääriprotestanttiset, katolilaisvastaiset parlamentin jäsenet. Osa parlamentin jäsenistä näki paavin itsenäisyyden toisaalta myös hyvänä asiana, ja paavin maallisen vallan lakkauttamista uhkana Britannialle. Viimeisessä käsittelyluvussa tutkitaan suhtautumista Kirkkovaltioon kansainvälisten suhteiden tasolla. Britannialla ei ollut virallisia diplomaattisuhteita Kirkkovaltioon, mutta maan epävirallisista suhteista ja niiden kehittämisestä käytiin parlamentissa keskustelua. Parlamentissa keskusteltiin myös Ranskan ja Itävallan merkityksestä Kirkkovaltiolle, sekä Kirkkovaltion mahdollisista aluemenetyksistä tai jopa valtion lakkauttamisesta. Keskustelua käytiin myös brittien värväämisestä paavin armeijaan ja paavia vastustaneen Garibaldin joukkoihin.

A prospective study of hepatitis B virus markers in patients with chronic HBV infection from Brazilian families of Western and Asian origin

The purpose of the present study was to determine the frequency of hepatitis B virus (HBV) markers in families of HBsAg-positive patients with chronic liver disease. Serum anti-HBc, HBsAg and anti-HBs were determined by enzyme immunoassay and four subpopulations were considered: genetically related (consanguineous) and non-genetically related (non-consanguineous) Asian subjects and genetically related and non-genetically related Western subjects. A total of 165 and 186 relatives of Asian and Western origin were enrolled, respectively. The occurrence of HBsAg and anti-HBs antibodies was significantly higher (P < 0.0001) in family members of Asian origin (81.8%) than in family members of Western origin (36.5%). HBsAg was also more frequent among brothers (79.6 vs 8.5%; P < 0.0001), children (37.9 vs 3.3%; P < 0.0001) and other family members (33.9 vs 16.7%; P < 0.0007) of Asian than Western origin, respectivelly. No difference between groups was found for anti-HBs, which was more frequently observed in fathers, spouses and other non-genetic relatives. HBV infection was significantly higher in children of Asian than Western mothers (P < 0.0004). In both ethnic groups, the mothers contributed more to their children's infection than the fathers (P < 0.0001). Furthermore, HBsAg was more frequent among consanguineous members and anti-HBs among non-consanguineous members. These results suggest the occurrence of vertical transmission of HBV among consanguineous members and probably horizontal sexual transmission among non-consanguineous members of a family cluster. Thus, the high occurrence of dissemination of HBV infection characterizes family members as a high-risk group that calls for immunoprophylaxis. Finally, the study showed a high familial aggregation rate for both ethnic groups, 18/19 (94.7%) and 23/26 (88.5%) of the Asian and Western origin, respectively.

An Update on Inter-Country Differences in Recovery and Utilization of Recycled Paper

The use of recovered paper as raw material in the paper and board industry has increased heavily during recent decades. At the same time, growing environmental awareness has raised the interest in recycling and a more sustainable way of living, at least in high-income countries. This paper combines these topics and explores how economic, demographic and environmental factors have affected the recovery and utilization of recycled paper between 1992 and 2010 in a sample of 70 countries. This study updates and extends the previous research on the topic using panel data and panel data estimation methods. The results confirm the roles of economic determinants but also indicate that concern for the environment impacts the recovery of recycled paper particularly in high-income countries. Moreover, the motives for recycling appear to depend on the income level of a country, which is something that future policies should consider.

Intrinsic bent DNA sites in the chromosomal replication origin of Xylella fastidiosa 9a5c

The features of the nucleotide sequences in both replication and promoter regions have been investigated in many organisms. Intrinsically bent DNA sites associated with transcription have been described in several prokaryotic organisms. The aim of the present study was to investigate intrinsic bent DNA sites in the segment that holds the chromosomal replication origin, oriC, of Xylella fastidiosa 9a5c. Electrophoretic behavior analyses, as well as in silico analyses of both the 2-D projection and helical parameters, were performed. The chromosomal segment analyzed contains the initial sequence of the rpmH gene, an intergenic region, the dnaA gene, the oriC sequence, and the 5' partial sequence of the dnaN gene. The analysis revealed fragments with reduced electrophoretic mobility, which indicates the presence of curved DNA segments. The analysis of the helical parameter ENDS ratio revealed three bent DNA sites (b1, b2, and b3) located in the rpmH-dnaA intergenic region, the dnaA gene, and the oriC 5' end, respectively. The chromosomal segment of X. fastidiosa analyzed here is rich in phased AT tracts and in CAnT motifs. The 2-D projection indicated a segment whose structure was determined by the cumulative effect of all bent DNA sites. Further, the in silico analysis of the three different bacterial oriC sequences indicated similar negative roll and twist >34.00° values. The DnaA box sequences, and other motifs in them, may be associated with the intrinsic DNA curvature.

Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country

Myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED). We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome). Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

Brazilian scientific funding agency budgets have not matched the country's economic growth

The growth of the Brazilian economy in recent years has created an atmosphere of optimism in various segments of Brazilian society, with several important international repercussions. In this paper, we analyze in detail how this economic growth is reflected in investments in science and technology made by major academic funding agencies. As a result, we observed a discrepancy in the growth of funding input and the growth of the Brazilian gross domestic product. This fact associated with an increased academic output entails negative consequences for the system. This may be a symptom of an academic community not fully understood by society and vice versa. Finally, we believe that a long-lasting important change in investment policy in science is necessary in order to ensure financial security for the academic system as a whole.

Nasal CPAP in the delivery room for newborns with extremely low birth weight in a hospital in a developing country

The objective of this study was to determine the feasibility of the use of continuous positive airway pressure installed prophylactically in the delivery room (DR-CPAP), for infants with a birth weight between 500 and 1000 g in settings with limited resources. During 23 months, infants with a birth weight between 500 and 1000 g consecutively received DR-CPAP. A total of 33 infants with low birth weight were enrolled, 16 (48.5%) were females. Only 14 (42.4%) received antenatal corticosteroids and only 2 of those 14 (14.3%) infants weighing 500-750 g were not intubated in the delivery room, and apnea was given as the reason for intubation of these patients. Of the 19 infants in the 751-1000 g weight range, 9 (47.4%) were intubated in the delivery room, 6 due to apnea and 3 due to respiratory discomfort. For DR-CPAP to be successful, it is probably necessary for preterm babies to be more prepared at birth to withstand the respiratory effort without the need for intubation. Antenatal corticosteroids and better prenatal monitoring are fundamental for success of DR-CPAP.

Methylmercury inhibits prolactin release in a cell line of pituitary origin

Heavy metals, such as methylmercury, are key environmental pollutants that easily reach human beings by bioaccumulation through the food chain. Several reports have demonstrated that endocrine organs, and especially the pituitary gland, are potential targets for mercury accumulation; however, the effects on the regulation of hormonal release are unclear. It has been suggested that serum prolactin could represent a biomarker of heavy metal exposure. The aim of this study was to evaluate the effect of methylmercury on prolactin release and the role of the nitrergic system using prolactin secretory cells (the mammosomatotroph cell line, GH3B6). Exposure to methylmercury (0-100 μM) was cytotoxic in a time- and concentration-dependent manner, with an LC50 higher than described for cells of neuronal origin, suggesting GH3B6 cells have a relative resistance. Methylmercury (at exposures as low as 1 μM for 2 h) also decreased prolactin release. Interestingly, inhibition of nitric oxide synthase by N-nitro-L-arginine completely prevented the decrease in prolactin release without acute neurotoxic effects of methylmercury. These data indicate that the decrease in prolactin production occurs via activation of the nitrergic system and is an early effect of methylmercury in cells of pituitary origin.

Comparison of volatile and polyphenolic compounds in Brazilian green propolis and its botanical origin Baccharis dracunculifolia

Ethanolic extracts and essential oils from Green Propolis from southeastern Brazil and leaf buds from its botanical origin Baccharis dracunculifolia were analyzed by Reversed Phase High Performance Liquid Chromatography (RP-HPLC), Reversed Phase High Performance Thin Layer Chromatography (RP-HPTLC) and Gas Chromatography - Mass Spectrometry (GC-MS). The essential oils were obtained by hydro-distillation. Both ethanolic extracts and essential oils showed similar chromatographic profiles. Thirteen flavonoids were identified by RP-HPLC and RP-HPTLC analyses in both samples. Twenty-three volatile compounds were identified by GC-MS analyses. Seventeen were present in both essential oils. The major flavonoid compound in both extracts was artepillin C. The major volatile compound in both essential oils was nerolidol. The major compounds identified in this work could be used as chemical markers in order to classify and identify botanical origins of propolis.