Double power-law viscoelastic relaxation of living cells encodes motility trends.

Living cells are constantly exchanging momentum with their surroundings. So far, there is no consensus regarding how cells respond to such external stimuli, although it reveals much about their internal structures, motility as well as the emergence of disorders. Here, we report that twelve cell lines, ranging from healthy fibroblasts to cancer cells, hold a ubiquitous double power-law viscoelastic relaxation compatible with the fractional Kelvin-Voigt viscoelastic model. Atomic Force Microscopy measurements in time domain were employed to determine the mechanical parameters, namely, the fast and slow relaxation exponents, the crossover timescale between power law regimes, and the cell stiffness. These cell-dependent quantities show strong correlation with their collective migration and invasiveness properties. Beyond that, the crossover timescale sets the fastest timescale for cells to perform their biological functions.

Spatial and temporal variation of phytoplankton in a tropical eutrophic river

This study aims to evaluate the environmental factors determining of the changes in phytoplankton structure in spatial (upper, middle and lower course) and seasonal (dry and rainy period) scales in a eutrophic river (Almada River, northeastern Brazil). In the study period, total accumulated rainfall was below of the historic average, resulting in flow reduction, mainly in rainy period. High orthophosphate concentration was found at the sampling sites. Phytoplankton chlorophyll a increased from upstream to downstream. Geitlerinema splendidum (S1) and Chlamydomonas sp. (X2) were the most abundant species in the upper course and several species of diatoms (D), Euglenophyceae (W1, W2) and Chlorophyceae (X1) in the middle and lower course. The functional groups were found to be characteristic of lotic ecosystem, shallow, with low light availability, rich in organic matter and eutrophic environments. We conclude that phytoplankton community structure was sensitive to change of the river flow and nutrient availability in spatial and seasonal scale in a tropical river.(AU)

O objetivo deste estudo foi avaliar os fatores ambientais determinantes das mudanças na estrutura do fitoplâncton em escala espacial (alto, médio e baixo curso) e temporal (seca e chuva) em um rio eutrófico tropical (rio Almada, nordeste do Brasil). No período de estudo, a precipitação acumulada mensal foi abaixo da média histórica, resultando na redução da vazão, principalmente no período chuvoso. A concentração de ortofosfato foi elevada nos pontos de amostragem. A clorofila a do fitoplâncton aumentou de montante para jusante. Geitlerinema splendidum (S1) e Chlamydomomas sp. (X2) foram as espécies mais abundantes no alto curso e várias espécies de diatomáceas (D), Euglenophyceae (W1, W2) e Chlorophyceae (X1) no médio e/ou baixo curso. Os grupos funcionais foram característicos de ambientes lóticos, rasos, com baixa disponibilidade de luz, rico em matéria orgânica e eutrófico. Concluímos que a estrutura da comunidade fitoplanctônica foi sensível às mudanças na vazão e na disponibilidade de nutrientes em escala espacial e temporal em um rio tropical.(AU)

Spatial and temporal variation of phytoplankton in a tropical eutrophic river / Variação espacial e temporal do fitoplâncton em um rio eutrófico tropical

Abstract This study aims to evaluate the environmental factors determining of the changes in phytoplankton structure in spatial (upper, middle and lower course) and seasonal (dry and rainy period) scales in a eutrophic river (Almada River, northeastern Brazil). In the study period, total accumulated rainfall was below of the historic average, resulting in flow reduction, mainly in rainy period. High orthophosphate concentration was found at the sampling sites. Phytoplankton chlorophyll a increased from upstream to downstream. Geitlerinema splendidum (S1) and Chlamydomonas sp. (X2) were the most abundant species in the upper course and several species of diatoms (D), Euglenophyceae (W1, W2) and Chlorophyceae (X1) in the middle and lower course. The functional groups were found to be characteristic of lotic ecosystem, shallow, with low light availability, rich in organic matter and eutrophic environments. We conclude that phytoplankton community structure was sensitive to change of the river flow and nutrient availability in spatial and seasonal scale in a tropical river.

Resumo O objetivo deste estudo foi avaliar os fatores ambientais determinantes das mudanças na estrutura do fitoplâncton em escala espacial (alto, médio e baixo curso) e temporal (seca e chuva) em um rio eutrófico tropical (rio Almada, nordeste do Brasil). No período de estudo, a precipitação acumulada mensal foi abaixo da média histórica, resultando na redução da vazão, principalmente no período chuvoso. A concentração de ortofosfato foi elevada nos pontos de amostragem. A clorofila a do fitoplâncton aumentou de montante para jusante. Geitlerinema splendidum (S1) e Chlamydomomas sp. (X2) foram as espécies mais abundantes no alto curso e várias espécies de diatomáceas (D), Euglenophyceae (W1, W2) e Chlorophyceae (X1) no médio e/ou baixo curso. Os grupos funcionais foram característicos de ambientes lóticos, rasos, com baixa disponibilidade de luz, rico em matéria orgânica e eutrófico. Concluímos que a estrutura da comunidade fitoplanctônica foi sensível às mudanças na vazão e na disponibilidade de nutrientes em escala espacial e temporal em um rio tropical.

Spatial and temporal variation of phytoplankton in a tropical eutrophic river.

This study aims to evaluate the environmental factors determining of the changes in phytoplankton structure in spatial (upper, middle and lower course) and seasonal (dry and rainy period) scales in a eutrophic river (Almada River, northeastern Brazil). In the study period, total accumulated rainfall was below of the historic average, resulting in flow reduction, mainly in rainy period. High orthophosphate concentration was found at the sampling sites. Phytoplankton chlorophyll a increased from upstream to downstream. Geitlerinema splendidum (S1) and Chlamydomonas sp. (X2) were the most abundant species in the upper course and several species of diatoms (D), Euglenophyceae (W1, W2) and Chlorophyceae (X1) in the middle and lower course. The functional groups were found to be characteristic of lotic ecosystem, shallow, with low light availability, rich in organic matter and eutrophic environments. We conclude that phytoplankton community structure was sensitive to change of the river flow and nutrient availability in spatial and seasonal scale in a tropical river.

Spatial and temporal variation of phytoplankton in a tropical eutrophic river

Abstract This study aims to evaluate the environmental factors determining of the changes in phytoplankton structure in spatial (upper, middle and lower course) and seasonal (dry and rainy period) scales in a eutrophic river (Almada River, northeastern Brazil). In the study period, total accumulated rainfall was below of the historic average, resulting in flow reduction, mainly in rainy period. High orthophosphate concentration was found at the sampling sites. Phytoplankton chlorophyll a increased from upstream to downstream. Geitlerinema splendidum (S1) and Chlamydomonas sp. (X2) were the most abundant species in the upper course and several species of diatoms (D), Euglenophyceae (W1, W2) and Chlorophyceae (X1) in the middle and lower course. The functional groups were found to be characteristic of lotic ecosystem, shallow, with low light availability, rich in organic matter and eutrophic environments. We conclude that phytoplankton community structure was sensitive to change of the river flow and nutrient availability in spatial and seasonal scale in a tropical river.

Resumo O objetivo deste estudo foi avaliar os fatores ambientais determinantes das mudanças na estrutura do fitoplâncton em escala espacial (alto, médio e baixo curso) e temporal (seca e chuva) em um rio eutrófico tropical (rio Almada, nordeste do Brasil). No período de estudo, a precipitação acumulada mensal foi abaixo da média histórica, resultando na redução da vazão, principalmente no período chuvoso. A concentração de ortofosfato foi elevada nos pontos de amostragem. A clorofila a do fitoplâncton aumentou de montante para jusante. Geitlerinema splendidum (S1) e Chlamydomomas sp. (X2) foram as espécies mais abundantes no alto curso e várias espécies de diatomáceas (D), Euglenophyceae (W1, W2) e Chlorophyceae (X1) no médio e/ou baixo curso. Os grupos funcionais foram característicos de ambientes lóticos, rasos, com baixa disponibilidade de luz, rico em matéria orgânica e eutrófico. Concluímos que a estrutura da comunidade fitoplanctônica foi sensível às mudanças na vazão e na disponibilidade de nutrientes em escala espacial e temporal em um rio tropical.

Comparative study of the antihypertensive effects of hexane, chloroform and methanol fractions of essential oil of Alpinia zerumbet in rats Wistar / Estudo comparativo do efeito anti-hipertensivo das frações hexânixa, clorofórmica e metanólica do óleo essencial da Alpinia zerumbet

ABSTRACT The aim of this study was to characterize components of the EOAz and its hexane (HFEOAz), chloroform (CFEOAz) and methanol (MFEOAz) fractions, and its antihypertensive effect. EOAz was extracted from leaves by hydrodistillation. Aliquot was subjected to selective desorption with silica gel column and eluted with hexane, chloroform and methanol. The components of the EOAz and fractions were analyzed by gas chromatography coupled with mass spectrometry and nuclear magnetic resonance spectroscopy of hydrogen. Experiments of vascular reactivity were performed with isolated aortic rings of male Wistar rats. Antihypertensive effect was evaluated in hypertensive rats submitted to the inhibition of synthesis of nitric oxide. Blood pressure was measured indirectly by tail plethysmography. MFEOAz showed the lowest EC50 (150.45 µg/mL), 1,8-cineole (27.81%) and terpinen-4-ol (57.35%) as main components. Single administration by nasogastric tube of EOAz, fractions and captopril significantly reduced the blood pressure of hypertensive rats, when compared to animals of the negative control group with distilled water. In conclusion, the potency of the MFEOAz was higher than that of EOAz and other fractions. The antihypertensive effect of EOAz and fractions was similar, higher than the negative control and lower than that of captopril.

RESUMO O objetivo deste estudo foi caracterizar os componentes do óleo essencial das folhas de Alpinia zerumbet (OEAz) e suas frações hexânica (FHOEAz), clorofórmica (FCOEAz) e metanólica (FMOEAz), e seu efeito anti-hipertensivo. OEAz foi extraído das folhas por hidrodestilação. Uma alíquota foi submetida à desadsorção seletiva com coluna de gel de sílica e eluída com hexano, clorofórmio e metanol. Os componentes do OEAz e fracções foram analisadas por cromatografia gasosa acoplada à detector de massa e por espectros de ressonância magnética nuclear de hidrogênio. Experimentos de reatividade vascular foram realizados com anéis aórticos isolados de ratos Wistar machos. Efeito anti-hipertensivo foi avaliado em ratos hipertensos submetidos à inibição da síntese de óxido nítrico. A pressão arterial foi medida indiretamente por pletismografia de cauda. FMOEAz mostrou a menor CE50 (150,45 μg/mL), 1,8-cineol (27,81%) e terpinen-4-ol (57,35%) como componentes principais. A administração em dose única por sonda nasogástrica de OEAz, frações e captopril reduziu significativamente a pressão arterial de ratos hipertensos, quando comparados aos animais do grupo controle negativo com água destilada. Em conclusão, a potência da FMOEAz foi maior que a do OEAz e outras frações. O efeito anti-hipertensivo de OEAz e frações foi semelhante, maior do que o controle negativo e menor do que o captopril.

Pathophysiological, cardiovascular and neuroendocrine changes in hypertensive patients during the hemodialysis session.

The pathophysiological mechanisms of arterial hypertension during hemodialysis (HD) in patients with end-stage renal disease (ESRD) are still poorly understood. The aim of this study is to investigate physiological, cardiovascular and neuroendocrine changes in patients with ESRD and its correlation with changes in blood pressure (BP) during the HD session. The present study included 21 patients with ESRD undergoing chronic HD treatment. Group A (study) consisted of patients who had BP increase and group B (control) consisted of those who had BP reduction during HD session. Echocardiograms were performed during the HD session to evaluate cardiac output (CO) and systemic vascular resistance (SVR). Before and after the HD session, blood samples were collected to measure brain natriuretic peptide (BNP), catecholamines, endothelin-1 (ET-1), nitric oxide (NO), electrolytes, hematocrit, albumin and nitrogen substances. The mean age of the studied patients was 43 ± 4.9 years, and 54.6% were males. SVR significantly increased in group A (P<0.001). There were no differences in the values of BNP, NO, adrenalin, dopamin and noradrenalin, before and after dialysis, between the two groups. The mean value of ET-1, post HD, was 25.9 pg ml(-1) in group A and 13.3 pg ml(-1) in group B (P = < 0.001). Patients with ESRD showed different hemodynamic patterns during the HD session, with significant BP increase in group A, caused by an increase in SVR possibly due to endothelial dysfunction, evidenced by an increase in serum ET-1 levels.

Cytogenetic evaluation of tannery workers in the city of Teresina, northeastern Brazil.

Assessments of chromosomal integrity and structure enable the prevention of diseases associated with the work environment, with the frequencies of chromosomal aberrations and micronuclei often being used as markers in biomonitoring. Owing to their routine manipulation of potentially toxic chemicals, tannery workers as a group merit a more thorough evaluation and discussion. This study investigated chromosomal damage in 30 workers from a tannery in the city of Teresina, the state capital of Piauí, northeast Brazil, and a control group consisting of 30 employees from a nearby accounting firm. The frequencies of chromosomal aberrations (CAs) and binucleated cell micronuclei (MN) were assessed as a measure of damage. Means were compared using the Student t-test and ANOVA-Dunnett test. Our results indicated a higher number of CAs in exposed individuals compared to the control group, including dicentric (P < 0.0001) and tricentric chromosomes (P < 0.001), and those in ring (P < 0.0001) and acentric ring forms (P < 0.001). Assessment of MN frequency demonstrated a similar trend (exposed vs control, P < 0.0001). It was concluded that the tannery workers in this study exhibited a higher incidence of genetic damage than comparable unexposed individuals. However, further research on this subject is needed, particularly in regard to potentially clastogenic agents used in the tanning process.

Effect of dimeticone and pepsin on the bioavailability of metoclopramide in healthy volunteers.

OBJECTIVE: To assess the effect of dimeticone and pepsin on the bioavailability of metoclopramide (CAS 7232-21-5) in healthy volunteers. METHODS: The study was conducted using a randomized, open, 2-period crossover design. The volunteers received single administration of 7-mg conventional metoclopramide capsule and a formulation containing metoclopramide (7 mg) plus dimeticone (40 mg) and pepsin (50 mg), with a 7-day interval between treatments. Serial blood samples were collected before dosing and during 24 h post-treatment. Plasma metoclopramide concentrations were analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The pharmacokinetics parameters AUC(last) and C(max) were obtained from the metoclopramide plasma concentration vs. time curves. RESULTS: Metoclopramide's association was bioequivalent to conventional capsule; 90% CIs for geometric mean treatment ratios of C(max) [108.0% (90% CI, 100.4-116.3%)], AUC(last) [103.3% (90% CI, 99.5-107.4%)] were within the predefined range. The metoclopramide formulations were well tolerated at the administered doses and no significant adverse reactions were observed. Thus, these results confirm the good bioavailability of metoclopramide in the new formulation and rule out any impaired absorption when the drugs are formulated in combination.

Identification of three novel alleles of HLA-DRB1 and HLA-A in the Brazilian population.

Two human leukocyte antigen (HLA)-DRB1 (HLA-DRB1*1376 and -DRB1*1465) and one HLA-A (HLA-A*2471) novel alleles have been identified in individuals from the Brazilian Bone Marrow Donor Registry. DNA sequencing of exon 2 for HLA-DRB1 alleles showed two and five nucleotide substitutions in -DRB1*1376 and -DRB1*1465, compared with closely related alleles, respectively. These substitutions result in a change of amino acid residues in HLA-DRB1*1376 at position 74 (Arg --> Glu) and in -DRB*1465 at positions 47 (Tyr --> Phe), 57 (Asp --> Ser) and 74 (Glu --> Ala). On the other hand, sequence analysis of exons 2 and 3 for HLA-A*2471 showed a single substitution, leading to a single amino acid change at position 151 (His --> Arg). These three novel alleles may have originated from other HLA alleles by gene conversion. However, it is also possible that HLA-A*2471 has evolved from one of the alleles of the HLA-A*2402 group through a point mutation.

Identification of two novel alleles HLA-B*3569 and -B*4450 and confirmation of HLA-A*2631 in the Brazilian population.

Two novel alleles, human leukocyte antigen (HLA)-B*3569, -B*4450 and a confirmatory sequence of HLA-A*2631 were identified during a routine typing for the Brazilian Bone Marrow Donor Registry. Sequence analysis of coding exons 2 and 3 revealed a single nucleotide substitution in HLA-B*3569 and two single nucleotide substitutions in HLA-B*4450, compared with closely related alleles. At the protein level, these substitutions result in a change of a single amino acid residue in each of HLA-B*3569 and -B*4450 at positions 74 (Arg > Pro) and 80 (Thr > Ile), respectively. These variations are located in the highly polymorphic region at the end of the alpha(1) domain of the HLA molecule. It appears that HLA-B*3569 arose from the analogous HLA-B*3510 through a point mutation. However, HLA-B*4450 may have arisen from HLA-B*440301 and -B*4425 by gene conversion.

An open-label efficacy pilot study with pimecrolimus cream 1% in adults with facial seborrhoeic dermatitis infected with HIV.

BACKGROUND: Seborrhoeic dermatitis (SD) is a common dermatosis in human immunodeficiency virus (HIV)-positive patients, many of whom do not respond satisfactorily to conventional topical treatments such as corticosteroids and antifungals. OBJECTIVE: A pilot study to investigate the efficacy and tolerability of pimecrolimus cream 1% in HIV-positive patients with facial SD. METHODS: In a single-centre study, 21 HIV-infected patients with mild to severe SD were treated twice daily with pimecrolimus cream 1% for 14 days. Thereafter, treatment was discontinued and patients followed up for 5 weeks. Skin involvement at baseline and on days 7, 14, 21, 35 and 49 was assessed using a four-point clinical score and digital photography. MAIN OUTCOME MEASURES: Efficacy and safety of pimecrolimus cream 1% treatment and incidence of relapse in the follow-up phase. Results Marked improvement was seen in clinical parameters at day 7, with >or= 90% patients clear of symptoms at day 14. Relapse was observed at day 35 but signs were milder than at baseline. All patients responded to therapy, despite their immunological status. Pimecrolimus did not alter CD4(+) and CD8(+) T-cell counts or viral load during the treatment period. CONCLUSION: Pimecrolimus cream represents a new, effective therapeutic option for facial SD in HIV patients.

HLA-DRB1*04 and DRB1*10 are associated with resistance and susceptibility, respectively, in Brazilian and Vietnamese leprosy patients.

The host genetic background has been considered one of the factors that influence leprosy outcome, a chronic infectious disease caused by Mycobacterium leprae. Genome scans demonstrated that the 6p21 region is associated with leprosy and a substantial number of population-based studies analyzing human leukocyte antigen (HLA) class II loci suggested association of HLA-DR with leprosy. However, some studies lacked robustness as they had limited power. Indeed, experimental designs require increased sample size to achieve adequate power, as well as replication studies with independent samples for confirmation of previous findings. In this work, we analyzed the influence of the HLA-DRB1 locus on leprosy susceptibility per se and disease type using a case-control design carried out in Brazilians (578 cases and 691 controls) and a replication study based on a family design in a Vietnamese population (n=194 families). The results showed that HLA-DRB1*10 is associated with susceptibility to leprosy and HLA-DRB1*04 is associated with resistance, both in the Brazilian and Vietnamese populations suggesting that these alleles play an important role in the activation of cellular immune responses against M. leprae.

Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery.

Third molar extraction is a common procedure frequently accompanied by moderate or severe pain, and involves sufficient numbers of patients to make studies relatively easy to perform. The aim of the present study was to determine the efficacy and safety of the therapeutic combination of 10 mg piroxicam, 1 mg dexamethasone, 35 mg orphenadrine citrate, and 2.5 mg cyanocobalamin (Rheumazin) when compared with 20 mg piroxicam alone (Feldene) in mandibular third molar surgery. Eighty patients scheduled for removal of the third molar were included in this randomized and double-blind study. They received (vo) Rheumazin or Feldene 30 min after tooth extraction and once daily for 4 consecutive days. Pain was determined by a visual analogue scale and by the need for escape analgesia (paracetamol). Facial swelling was evaluated with a measuring tape and adverse effects and patient satisfaction were recorded. There was no statistically significant difference in facial swelling between Rheumazin and Feldene (control group). Both drugs were equally effective in the control of pain, with Rheumazin displaying less adverse effects than Feldene. Therefore, Rheumazin appears to provide a better risk/benefit ratio in the mandibular molar surgery. Since the side effects resulting from nonsteroidal anti-inflammatory drug administration are a severe limitation to the routine use of these drugs in clinical practice, our results suggest that Rheumazin can be a good choice for third molar removal treatment.

Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery

Third molar extraction is a common procedure frequently accompanied by moderate or severe pain, and involves sufficient numbers of patients to make studies relatively easy to perform. The aim of the present study was to determine the efficacy and safety of the therapeutic combination of 10 mg piroxicam, 1 mg dexamethasone, 35 mg orphenadrine citrate, and 2.5 mg cyanocobalamin (Rheumazin®) when compared with 20 mg piroxicam alone (Feldene®) in mandibular third molar surgery. Eighty patients scheduled for removal of the third molar were included in this randomized and double-blind study. They received (vo) Rheumazin or Feldene 30 min after tooth extraction and once daily for 4 consecutive days. Pain was determined by a visual analogue scale and by the need for escape analgesia (paracetamol). Facial swelling was evaluated with a measuring tape and adverse effects and patient satisfaction were recorded. There was no statistically significant difference in facial swelling between Rheumazin and Feldene (control group). Both drugs were equally effective in the control of pain, with Rheumazin displaying less adverse effects than Feldene. Therefore, Rheumazin appears to provide a better risk/benefit ratio in the mandibular molar surgery. Since the side effects resulting from nonsteroidal anti-inflammatory drug administration are a severe limitation to the routine use of these drugs in clinical practice, our results suggest that Rheumazin can be a good choice for third molar removal treatment.

Preliminary notes on yeasts associated with necrotic cactus stems from different localities in Brazil.

The yeast species found in necrotic stems of three columnar cacti (Pilosocereus machrisii, Pilosocereus vilaboensis, and Praecereus euchlorus) at eight localities in Brazil were described and a similarity analysis using Sorensen distances was used to compare the composition of yeast species at these localities. Of 56 necrotic cactus stems sampled, 32 produced yeast colonies. Ten species of yeast or yeast-like microorganisms were identified from 53 isolates, with Pichia cactophila, Candida sonorensis, Geotrichum sp., and Sporopachydermia cereana being the most common. The remaining species occurred in low proportions in the cacti surveyed. The similarity analysis provided a dendogram (UPGMA) that clustered the yeast communities from different cactus species and indicated that host cactus species was unimportant in this clustering.

Phentolamine relaxes human corpus cavernosum by a nonadrenergic mechanism activating ATP-sensitive K+ channel.

To investigate the pharmacodynamics of phentolamine in human corpus cavernosum (HCC) with special attention to the role of the K+ channels. Strips of HCC precontracted with nonadrenergic stimuli and kept in isometric organ bath immersed in a modified Krebs-Henseleit solution enriched with guanethidine and indomethacine were used in order to study the mechanism of the phentolamine-induced relaxation. Phentolamine caused relaxation (approximately 50%) in HCC strips precontracted with K+ 40 mM. This effect was not blocked by tetrodotoxin (1 microM) (54.6+/-4.6 vs 48.9+/-6.4%) or (atropine (10 microM) (52.7+/-6.5 vs 58.6+/-5.6%). However, this relaxation was significantly attenuated by L-NAME (100 microM) (59.7+/-5.8 vs 27.8+/-7.1%; P<0.05; n = 8) and ODQ (100 microM) (62.7+/-5.1 vs 26.8+/-3.9%; P<0.05; n = 8). Charybdotoxin and apamin (K(Ca)-channel blockers) did not affect the phentolamine relaxations (54.6+/-4.6 vs 59.3+/-5.2%). Glibenclamide (100 microM), an inhibitor of K(ATP)-channel, caused a significant inhibition (56.7+/-6.3 vs 11.3+/-2.3%; P<0.05; n = 8) of the phentolamine-induced relaxation. In addition, the association of glibenclamide and L-NAME almost abolished the phentolamine-mediated relaxation (54.6+/-5.6 vs 5.7+/-1.4%; P<0.05; n = 8). The results suggest that phentolamine relaxes HCC by a nonadrenergic-noncholinergic mechanism dependent on nitric oxide synthase activity and activation of K(ATP)-channel.

Interleukin-10 promoter single-nucleotide polymorphisms as markers for disease susceptibility and disease severity in leprosy.

We have determined IL-10 promoter genotypes of five single-nucleotide polymorphisms (SNPs): T-3575A, A-2849G, C-2763A, -A-1082G and C-819T. The haplotype frequencies were defined in healthy subjects compared to leprosy patients, and analyzed for their occurrence in multi- (MB) vs paucibacillary (PB) as severe and mild forms of leprosy, respectively. Haplotypes defined by three SNP positions (-3575, -2849 and -2763) captured significant differences between controls and patients (P=0.04). The haplotype carrying -3575A, -2849G and -2763C was associated with resistance to leprosy and to the development of severe forms of the disease using either a binomial (controls vs cases, P=0.005, OR=0.35, CI=0.13-0.91) or ordinal (controls vs PB vs MB, P=0.006, OR=0.32, CI=0.12-0.83) model. By contrast, the IL-10 haplotype -3575T/-2849A/-2763C was found to be associated with susceptibility to leprosy per se (P=0.027, OR=2.37, CI=1.04-5.39), but not leprosy type. The data suggest that the IL-10 locus contributes to the outcome of leprosy.

Almost 50,000 volunteers participate at Redome, the Brazilian Bone Marrow Donor Registry.

Striking progress has been observed in the number of volunteer donors for hematopoietic stem cell transplantation in the last years in Brazil. By the end of 1998, the number of donors barely reached 4200 but it has grown progressively. It was close to 48,000 by the end of May 1993. It is possible to notice a steady increase from the first (1993 to 2000) to the last years (2001 to 2003). The regulation of each procedure by the Brazilian Health System, with the collaboration of the Hematology Societies, was essential for the success of Redome and for the stem cell transplantation program in Brazil. However, when analyzing these results some problems were detected: 95% of Redome donors come from the south and southeastern regions of the country, while few donors are from the north, northeast, and central parts of Brazil. The different miscegenation of races in different regions and states of Brazil makes this an important issue: to represent the whole Brazilian population, Redome must improve the donor search in such places. It also became clear that several other centers involved in unrelated hematopoietic transplantation must be accredited to avoid a long line of patients with compatible donors a waiting transplantation.

Strong linkage disequilibrium between HLA-B*3913 and DRB1*0807 in Brazilians.

The purpose of this research was to study the HLA-B39 distribution in 2560 healthy, unrelated, randomly selected individuals living in the southeastern region of Brazil (the states of Rio de Janeiro and São Paulo). Molecular methods were used to type HLA class I and II polymorphism: PCR-SSP, PCR-SSO, and PCR-SBT. HLA-B*39 was found in 7% (n = 182) of these individuals. HLA-B*3901, B*3906, and B*3913 were the most common alleles in this group (n = 57, 36, and 24, respectively). B*3913 was found associated with DRB1*0807 and DQB1*0402 in 16 of the 24 individuals and 13 of these were also associated with A*31012. This haplotype segregation was confirmed by family studies. Furthermore, in 5 of the 13 individuals carrying the A*31012, B*3913, DRB1*0807, and DQB1*0402 haplotype, HLA-DPB1*2701 was also present, suggesting that these alleles were found preferentially in cis association. DRB1-DPB1 linkage disequilibrium analysis was performed in 420 of the 2560 individuals and the association of DRB1*0807 with the uncommon DPB1*2701 was found to be highly significant (P <.0001). Because HLA-B*3913 and HLA-DRB1*0807 have been observed only in South American populations, it is possible that interlocus association has been selected to act on the same haplotype to collaborate in the class I and II restricted immune response to local pathogens and functional adaptation. Although numbers are small to predict which ethnic groups of the Brazilian population display this haplotype prevalently, it is possible to speculate that these data may have clinical application, such as in the selection of unrelated donors for bone marrow transplantation.