Treatment of pediatric myelodysplastic syndromes and juvenile myelomonocytic leukemia: the Brazilian experience in the past decade

Background: Therapy strategies for myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) vary considerably. Objective: To review the treatment of Brazilian children who were diagnosed with MDS or JMML in the past decade and reported to the Brazilian Cooperative Group on Pediatric Myelodysplastic syndromes (BCG-MDS-PED). Results: of 173 children reported to the BCG-MDS-PED from January 1997 to January 2003 with a suspected diagnosis of MDS or JMML, 91 had the diagnosis confirmed after central review of the bone marrow aspirate and biopsy. Information on previous treatments was available for 78 MDS/JMML patients. Treatment varied from different schedules of low-dose (14%) and standard-dose chemotherapy (50%), granulocyte-colony-stimulating factor (G-CSF 7%), interferon (5%), steroids (2%) and erythropoietin (2%) to allogeneic stem-cell transplantation (SCT) (14%). No survival advantage could be demonstrated based on Hasle's classification or based on treatment. Conclusion: This report reflects the current practice in treating Brazilian children with MDS/JMML without specific Cooperative Group guidelines. Treatment modalities were very heterogeneous. The strategies for implementing a national protocol should consider international guidelines and focus on local experience and available resources. (C) 2004 Elsevier Ltd. All rights reserved.

Puberty and growth rate in thoroughbred fillies

We measured progesterone and estradiol levels from birth to the beginning of adult life in 10 Thoroughbred fillies from the Equilia Stud Farm in Avare SP, Brasil. The animals were measured and weighed monthly for the determination of body development and of a possible correlation between the rate of weight and height gain and the onset of detectable sex hormone levels. Jugular blood was collected twice a week and stored at -20 degrees C until assay of progesterone by a solid phase RIA with a sensitivity of 0.32 nmol/L and of estradiol by liquid phase RIA adapted to low levels (3.67 pmol/L). The fillies were born with high serum levels of both hormones,which fell to undetectable levels by the first week of life. A variation in growth rate was observed, with the highest levels occuring from birth to the 3rd month of life, followed by a reduction until 15 mo of life, when fast growth was resumed. The monthly weight gain was 1.5% when the fillies reached puberty and 5.4% during the next month, (P<0.05, Friedman test). During this second period of accelerated growth after the beginning of progesterone production at detectable levels (above 0.318 nmol/L), the parameters of skeletal growth did not differ (P>0.05). The month of onset of puberty was the month of lowest weight gain in the life of the fillies, and it coincided with the highest insolation period. In conclusion, horses, like all other developed vertebrates, have a double pattern of development, with the acceleration observed at puberty depending on sex steroids, which in turn coincides with the highest insolation period. Gonadal activity characterized by serum progesterone levels was low from birth to the onset of puberty. After puberty the progesterone cycles were similar to those of adult animals with a mature hypothalamic-gonadal axis. (C) 1997 by Elsevier B.V.

PARTICIPATION OF OPIOID RECEPTORS IN THE MODULATION OF THE ANALGESIC RESPONSE BY ADRENAL AND GONADAL GLANDS

The involvement of opioid receptors in the analgesic response was evaluated by the tail-immersion test in simultaneously adrenalectomized and ovariectomized female Wistar rats (210-250 g). The reaction time (mean +/- SEM) for tail withdrawal from hot water decreased significantly 2 weeks after surgery (3.52 +/- 0.20 s) when compared to intact animals (6.09 +/- 0.23 s). Hormonal replacement with dexamethasone (50-mu-g/day) did not affect reaction time (3.38 +/- 0.19 s). However, this response was restored by combined adrenal and gonadal steroid substitution (estradiol 5-mu-g/day and progesterone 1.5-mu-g 6 h before the tests) therapy (5.11 +/- 0.45 s in animals treated with dexamethasone plus estradiol and 5.04 +/- 0.43 s in animals treated with dexamethasone plus estradiol plus progesterone). Naloxone (2 mg/kg) decreased the reaction time of animals treated with adrenal and gonadal steroids (5.11 +/- 0.45 vs 4.15 +/- 0.44 s and 5.04 +/- 0.43 vs 3.87 +/- 0.28 s, respectively, before and after naloxone) but failed to decrease it in rats treated with dexamethasone only (3.88 +/- 0.18 vs 4.34 +/- 0.25 s, before and after naloxone). These observations indicate that gonadal steroids are the most important steroid factors involved in the reaction time to tail immersion in hot water and confirm other reports that the opioid pathways modulating the neuronal circuitry require the presence of these hormones.

Flavonoids and lignans from Virola surinamensis twigs and their in vitro activity against Trypanosoma cruzi

Dichloromethane extracts from twigs of Virola surinamensis (Myristicaceae) showed in vitro trypanosomicidal activity against trypomastigote form of Trypanosoma cruzi. The extract, fractionated by preparative circular chromatography and preparative high-performance liquid chromatography yielded two steroids, two lignans, five flavonoids, and one polyketide. Among the isolated compounds, the lignans presented the highest trypanosomicidal activity.

The changing pattern of analgesic and anti-inflammatory drug use in cleft lip and palate repair

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Stereological study of acinar growth in the rat parotid gland induced by isoproterenol

The growth of the rat parotid gland induced by daily treatment with isoproterenol (IPR) for 2 weeks was investigated by stereological methods applied to light microscopy. After 7 days of treatment, the glandular mass presented a 286% growth, with the first 3 days being the period of greatest growth. Total acinar volume exhibited a 363% increase during the period from 0 to 7 days, while acinar-cell volume presented a 468% growth from 0 to 5 days of treatment. on the other hand, total acinar-cell number did not increase during the study period. Thus, under the conditions used, IPR-stimulated gland growth wits essentially hypertrophic. However, a significant increase in the number of bipolar and multipolar mitoses was also observed, especially on the third and fifth days of treatment. As no increase in acinar-cell number occurred during growth, the presence of these mitoses suggests that cell death occurred during gland growth. on this basis, bipolar mitoses may occur to replace cells that probably degenerated during treatment, whereas multipolar mitoses may lead to the occurrence of polyploidy. (C) 1997 Elsevier B.V. Ltd.

Cortisol in saliva and plasma of cattle after ACTH administration and milking

Interest in the measurement of salivary cortisol has increased recently because saliva can be easily collected before and after an imposed stress. This study evaluated the relationship between plasma and salivary concentrations of cortisol following ACTH administration in calves ( experiment 1) and machine milking of adult cows ( experiment 2). A catheter was inserted into the jugular vein of all animals 72 h before the beginning of experiments. Blood and saliva samples were collected before and after ACTH administration (0.6 IU/kg BW) in calves or before and after machine milking of cows. Using a cotton swab, each saliva sample was taken immediately following the blood sample. In general, cortisol profiles were similar in plasma and saliva and correlated in both experiments; however, plasma concentrations were significantly higher than salivary concentrations. In addition, the differences between cortisol concentrations measured in saliva and plasma within each experiment varied substantially between animals and samples. Furthermore, in experiment 2, nearly 10% of salivary samples were below limits of detection. The sharp peaks in cortisol after ACTH administration in both the plasma and saliva were reflected adrenal stimulation. In addition, increases in cortisol in response to milking in both the plasma and saliva suggest that salivary sampling is a reliable option when studying cortisol responses to normal physiological events.

Characterization of the cellular component of polymorphous low-grade adenocarcinoma by immunohistochemistry and electron microscopy

In order to characterize the cellular component of the polymorphous low-grade adenocarcinoma (PLGA) of the salivary gland, a morphological and immunohistochemical study was carried out. Thirty cases of PLGA were studied by light microscopy and immunohistochemistry and five cases by transmission electron microscopy (TEM). The expression of cytokeratins (CKs) 7,8,10,13,14,18,19, vimentin and muscle-specific actin (MSA) was investigated through the streptavidin-biotin method. The majority of tumor cells stained for vimentin, CKs 8,18 and 7. CK 14 was positive in most cells of the papillary and trabecular sub-types. Although the expression of CKs 8,18 and 14 varied among the tumors sub-types, a straight relationship between each histologic pattern and the CK expression could not be delineated. MSA was reactive in only three tumors while CKs 10 and 13 were not detected in any tumor studied. The absence of MSA and the expression of CKs 8,18 and 7, in most of the tumor cells, lead to the hypothesis that myoepithelial cells are not the major cellular component of the PLGA. TEM revealed cells exhibiting microvilli and variable amounts of secretory granules, some of them suggesting an excretory activity. The presence of CKs 8, 18 and 7, added to the secretory granules, indicates that PLGA originates from cells located at the acinar-intercalated duct junction. (C) 1999 Elsevier B.V. Ltd. All rights reserved.

Acylated flavonol glycosides and terpenoids from the leaves of Alibertia sessilis

Two novel acylated flavonol glycosides, along with iridoids, triterpenes, steroids and alpha-tocopherolquinone, were isolated from the leaves of Alibertia sessilis (Rubiaceae). The determination of the structures of the new compounds was based mainly on H-1- and C-13-NMR.

Antifungal constituents from roots of Virola surinamensis

Chromatographic fractionation of the dichloromethane extract from roots of Virola surinamensis yielded two new natural products, 3-epi-juruenolide C and 2'-hydroxy-7,4'-dimethoxyisoflavone, as well as various known steroids, lignans, isoflavones, flavonoids and diarylpropanes. of these, alpha,2'-dihydroxy-4,3'-dimethoxydihydrochal biochanin A and 2'-hydroxy-7,4'-dimethoxyisoflavone displayed antifungal activity against Cladosporium cladosporioides at a minimum amount of 5 mu g, whereas 7-hydroxyflavanone and 7-hydroxy-4'-methoxyisoflavone exhibited an antifungal activity 10-fold higher than the positive control Nystatin. (C) 1999 Elsevier B.V. Ltd. All rights reserved.

THE EFFECT OF SERUM ON IN-VITRO MATURATION, IN-VITRO FERTILIZATION AND STEROIDOGENESIS OF BOVINE OOCYTES COCULTURED WITH GRANULOSA-CELLS

The influence of fetal calf serum alone (FCS) or associated with proestrous (FCS+PCS), estrous (FCS+ECS) or metaestrous (FCS+MCS) cow serum added to the culture medium and of the steroids produced by co-cultured granulosa cells were evaluated in terms of the in vitro maturation (TVM) and fertilization (IVF) of bovine oocytes. Supplementation of the medium with FCS+ECS and FCS+MCS resulted in higher proportions of oocytes that reached metaphase II (96.0% and 93.3%, respectively) and in higher proportions of embryos that reached the four- and eight-cell/morula stages (51.9% and 65.6%, respectively), whereas the supplementation with FCS and FCS+PCS resulted in only 79.2% and 67.5%, respectively, of matured oocytes and 26.7% and 34.3%, respectively, of cleaved embryos. These findings show that the best IVM and IVF were obtained at lower concentrations of estradiol produced by co-cultured granulosa cells (supplementation with FCS+ECS: 10.3 ng/ml and FCS+MCS: 2.1 ng/ml), whereas the worst-results in IVM and IVF occurred at higher concentrations of estradiol that were obtained with FCS (33.1 ng/ml) and FCS+PCS (19.9 ng/ml) supplementation. These data suggest an inhibitory effect of estradiol on resumption of oocyte meiosis in vitro.

Reproductive compatibility and chromosome pairing in the Drosophila buzzatii complex

Fertility (percentage of fertile crosses) and the degree of synapsis in salivary gland chromosomes in isofemale lines of Drosophila buzzatii, D. serido, D. koepferae and D. seriema were analysed. D. buzzatii was completely sterile in intercrosses with strains from the other species except for D. koepferae. The other species intercrossed to a greater or lesser degree, but also differed between crossing directions. Homologous pairing in salivary gland preparations of strains and hybrids conformed with the data on fertility. The lowest degree of synapsis was present in hybrids between D. koepferae and D. buzzatii, D. seriema and D. koepferae and D. koepferae and D. serido. These species also exhibited the lowest degree of reproductive compatibility. Hybrids between D. seriema and D. serido showed an intermediate degree of synapsis (pairing absent in the proximal and distal chromosome ends), as well as fertility greater than that found in the other interspecific crosses. Results of the fertility of crosses involving strains of a single species, compared with data in the literature, indicated that intraspecific divergence occurred in D. serido and D. koepferae.

Rearranged (4 -> 2)-abeo-clerodane and clerodane diterpenes from Aristolochia chamissonis

From stems of Aristolochia chamissonis Duch., five new diterpenes, one rearranged (4 --> 2)-abeo-clerodane and four ent-clerodanes, were isolated. Their structures were determined to be (+)-(4 --> 2)-abeo-kolavelool-3-oic acid, (-)-13-epi-2-oxokolavelool, (-)-2 beta-hydroxykolavelool, (-)-2 beta-hydroperoxykolavelool and (+)- 13-epi-2 alpha-hydroxykolavelool. In addition, lignans, sesquiterpenes, steroids and two known ent-clerodane diterpenes were isolated. (C) 1998 Elsevier B.V. Ltd. All rights reserved.

Cross-reactivity between antigens from Amblyomma cajennense and A-hebraeum (Acari : Ixodidae)

Laboratory animals exposed to feeding ticks develop resistance which is reflected by a decline in tick engorgement weight, egg-laying by adults and reduced egg viability. Serum antibodies from these hosts and their reaction with tick antigens have been detected by different methods, including precipitation techniques, immunofluorescent techniques, ELISA and Western blots. However, little is known about the effects of antibodies on ticks that engorge on resistant hosts, or which tissues of the tick body are possibly immunogenic. Some researchers, using immunohistochemistry, have detected host antibodies in the gut, salivary glands and haemolymph of ticks engorged on resistant animals. The same technique has helped considerably in determining antigenic sites or antibody targets in other arthropods. Consequently, immunohistochemistry techniques were used in this study to detect cross-reactivity between sera raised against Amblyomma cajennense (Fabricius, 1787) with Amblyomma hebraeum (Koch, 1844), and vice versa. The results show the existence of shared antigens between the 2 tick species. In general, our results point more to a 1-way cross-reactivity of A. hebraeum with A. cajennense than a reciprocal cross-reactivity, suggesting that A. hebraeum is more immunogenic than A. cajennense.

Carboxylic acids of marine evaporitic oils from Sergipe-Alagoas Basin, Brazil

A. suite of 10 different marine evaporitic oil samples from Sergipe-Alagoas Basin, Brazil was studied for its biomarker content, in particular its acidic constituents. The oils showed different molecular distributions and relative abundances of n-alkanoic, isoprenoid and hopanoic acids. The observed differences were assigned to the incorporation of immature organic matter in the oils and fractionation along the migration pathway. The diagenetic precursor functionality (alcohol/ether or acid) was proposed based on the comparison of the relative abundances of the neutral and acidic biomarkers (hopanoids, isoprenoids, alkyl-steranes, monoaromatic alkyl-steroids). In the acidic fraction, 3 series of steroid-alkanoic acids and monoaromatic steroid-alkanoic acids (steroid-methanoic, ethanoic and propanoic acids and monoaromatic steroid-methanoic, ethanoic and propanoic acids) were detected, while in the neutral fraction only 2 series of each corresponding class could be observed (methyl and ethyl-steranes and monoaromatic methyl and ethyl-steroids). These carbon shifts suggest that decarboxylation is an important process in the formation of the alkyrsteranes and monoaromatic alkyl-steroids, and we infer that carboxylic acids are the diagenetic precursors of these classes of compounds. When alcohol or ether are the diagenetic precursors (isoprenoids and hopanoids), no significant differences in the molecular distributions between neutral and acidic fractions were observed. (C) 2000 Elsevier B.V. Ltd. All rights reserved.