Coinfection and cross-reaction of dengue and COVID-19: a case series analysis

ABSTRACT Background: The risk of possible cross-reactions between serological tests, together with the clinical similarities between dengue fever and COVID-19, can delay diagnosis and increase the risk of both COVID-19 transmission and worsening. The present study aimed to determine the possibility of cross-reactions among rapid serological tests based on clinical symptoms. Methods: Patients with COVID-19, confirmed by RT-PCR and clinical criteria for diagnosing dengue, were recruited consecutively between September 2020 and August 2021 and underwent rapid immunochromatographic diagnostic (RID) tests for AgNS1, IgM, and IgG. Patients who tested positive for acute-phase dengue IgM and AgNS1 underwent a follow-up test after 12-30 days for diagnostic confirmation. Results: A total of 43 patients were included, 38 of whom required hospital admission, and 8 received intensive care. Seven patients tested positive on the RID tests, comprising 2 NS1 positive (coinfection), one reactive for IgM and IgG (coinfection), three reactive for IgM not confirmed (false-positive), and one reactive for IgG due to previous infection. Two of the 3 patients with coinfection died. Fever, myalgia, headache, and cough were the most common clinical symptoms, while lymphopenia was the most prevalent laboratory finding. Conclusions: Cross-reactivity was found in only three patients and coinfection in another three patients, two of whom died of severe COVID-19 manifestations.

Simultaneous liquid chromatography- tandem mass spectrometry method to quantify epicatechin and procyanidin B2 in rat plasma after oral administration of Trichilia catigua (catuaba) extract and its application to a pharmacokinetic study

Abstract Trichilia catigua A. Juss., Meliaceae, known as catuaba in Brazil, is traditionally used for the treatment of stress, sexual impotence and memory deficits. To our knowledge, there is no analytical method described in literature for simultaneous quantification of catuaba extract marker substances in biological matrices. The aim of this study was to develop and validate a bioanalytical method by LC-MS/MS to quantify epicatechin and procyanidin B2 in rat plasma after administration of standardized extract of T. catigua. Chromatographic separation was achieved with a C18 column, methanol and 0.1% aqueous formic acid at a flow rate of 0.25 ml/min. Detection was performed using electrospray ionization in negative mode. The lower limits of quantification were 5 ng/ml and 12.5 ng/ml for procyanidin B2 and epicatechin, respectively. Intra- and inter-day assays variability were less than 15%. The extraction recovery was 104% for epicatechin and 74% for procyanidin B2 using one-step liquid-liquid extraction with ethyl acetate. Epicatechin and PB2 were detected in plasma up to 300 min after oral administration of 400 mg/kg of standardized extract of T. catigua in rats. This rapid and sensitive method for the analysis of the epicatechin and procyanidin B2 in rat plasma can be applied to pharmacokinetic studies.

Rare α0-thalassemia deletions detected by MLPA in five unrelated Brazilian patients

Abstract Alpha-thalassemias are among the most common genetic diseases in the world. They are characterized by hypochromic and microcytic anemia and great clinical variability, ranging from a practically asymptomatic phenotype to severe anemia, which can lead to intrauterine or early neonatal death. Deletions affecting the α-globin genes, located on chromosome 16p13.3, are the main causes of α-thalassemia. Multiplex ligation-dependent probe amplification (MLPA) can be used to detect rearrangements that cause α-thalassemia, particularly large deletions involving the whole α cluster and/or deletions in the HS-40 region. Here, MLPA was used to investigate the molecular basis of α-thalassemia in five unrelated patients, three of whom had Hb H disease. In addition to the -α3.7 deletion identified in the patients with Hb H disease, four different α0 deletions removing 15 to 225 kb DNA segments were found: two of them remove both the α genes, one affects only the regulatory element (HS-40) region, and another one extends over the entire α cluster and the HS-40 region. These results illustrate the diversity of α-thalassemia deletions in the Brazilian population and highlight the importance of molecular investigation in cases that present with microcytosis and hypochromia without iron deficiency and normal or reduced Hb A2 levels..

Characterization of intestinal absorption of C-glycoside flavonoid vicenin-2 from Lychnophora ericoides leafs in rats by nonlinear mixed effects modeling

AbstractVicenin-2 (apigenin-6,8-di-C-β-d-glucopyranoside) is present in hydroalcoholic extracts of the Brazilian species Lychnophora ericoides Mart., Asteraceae, leaves, and the biological effects of this compound have been demonstrated including anti-inflammatory, antioxidant and anti-tumor effects in rat models. Given the potential of this compound as a pharmacological agent, the aims of this investigation were to evaluate the extent of intestinal absorption of vicenin-2, and to determine the intestinal permeation profile using an in situ single-pass intestinal perfusion technique. A validated HPLC–UV method was applied to measure the amount of unabsorbed vicenin-2 in the gut after an oral administration of 180 mg kg-1 in five rats. A nonlinear mixed effects model was used to determine the absorption pharmacokinetic parameters assuming a first order absorption and active secretion processes for this compound, wherein the active secretion was characterized by a zero-order process. The population pharmacokinetic parameters obtained were 0.274 min-1 for the first-order absorption rate constant, 16.3% min-1 for the zero-order rate constant; the final percentage of the original dose that was absorbed in vivo was 40.2 ± 2.5%. These parameters indicated that vicenin-2 was rapidly absorbed in the small intestine. In contrast to literature information indicating no absorption of vicenin-2 in Caco-2 cells, our results suggested that vicenin-2 can be absorbed in the small intestine of rats. The finding supports further investigation of vicenin-2 as a viable oral phytopharmaceutical agent for digestive diseases.

Recovery of drug residues in equipment and utensils used by compounding pharmacies after standard cleaning procedure / Recuperação de resíduos de drogas em equipamentos e utensílios utilizados por farmácias de manipulação após o procedimento de limpeza padrão

Compounding pharmacies have been cited by some athletes as being responsible for compounding capsules contaminated with drugs banned by the International Olympic Committee (IOC). Therefore, the present study was carried out to quantify the amount of residue remaining in the equipment and utensils used for compounding capsules after standard cleaning procedures. For this purpose, captopril (CAP) and acetylsalicylic acid (ASA) were used since these are hard to clean, in addition to hydrochlorothiazide (HTZ) as a banned drug by the IOC. The amounts of residues found in the equipment were: 181.0 ± 91.8, 1208 ± 483.8 and 431.7 ± 71.3 ppm for ASA, CAP and HTZ, respectively. The continuous compounding of these drugs, followed each time by the standard cleaning procedure, showed a linear accumulation of residues for ASA (r²=0.96) and CAP (r²= 0.88). The residues quantified were greater than the FDA limit for impurities for CAP (>0.1%) but not for HTZ. However, the HTZ residue may be detected in the urine of athletes on IOC tests. Therefore, it was concluded that compounding pharmacies should therefore improve their cleaning procedures and test these in order to attain limits below 10 ppm, thereby avoiding the contamination of other products...

As farmácias de manipulação têm sido citadas por alguns atletas como sendo responsáveis pela manipulação de cápsulas contaminadas com fármacos proibidos pelo Comitê Olímpico Internacional (COI). Portanto, o presente estudo foi realizado para quantificar o montante de resíduo remanescente nos equipamentos e utensílios usados para manipular cápsulas após o procedimento padrão de limpeza. Para este propósito, o captopril (CAP) e o ácido acetilsalicílico (ASA) foram usados por serem fármacos de difícil remoção e a hidroclorotiazida (HTZ), por ser um fármaco proibido pelo COI. As quantidades de resíduos encontradas nos equipamentos após a limpeza foram 181,0 ± 91,8, 1208 ± 483,8 e 431,7 ± 71,3 ppm para ASA, CAP e HTZ, respectivamente. A manipulação contínua dos fármacos seguida pelo procedimento de limpeza mostrou acúmulo de resíduo linear para ASA (r²=0,96) e CAP (r²=0,88). A quantidade de resíduo de CAP foi maior que o limite de impureza sugerido pelo FDA (>0,1%), mas não para HTZ, mas mesmo assim, o resíduo de HTZ pode ser detectado na urina dos atletas submetidos aos testes do COI. Em conclusão, as farmácias de manipulação deveriam, portanto, melhorar o procedimentos de limpeza e testá-los para que alcancem limites abaixo de 10 ppm para evitar contaminação nos outros produtos...

Investigating alpha-globin structural variants: a retrospective review of 135000 Brazilian individuals

Background: Brazil has a multiethnic population with a high diversity of hemoglobinopathies. While screenings for beta-globin mutations are far more common, alterations affecting alpha-globin genes are usually more silent and less well known. The aim of this study was to describe the results of a screening program for alpha-globin gene mutations in a representative sample of the Southeastern Brazilian population. Methods: A total of 135,000 individuals, including patients with clinical suspicion of hemoglobinopathies and their family members, randomly chosen individuals submitted to blood tests and blood donors who were abnormal hemoglobin carriers were analyzed. The variants were screened by alkaline and acid electrophoreses, isoelectric focusing and cation-exchange high performance liquid chromatography (HPLC) and the abnormal chains were investigated by reverse-phase high performance liquid chromatography (RP-HPLC). Mutations were identified by molecular analyses, and the oxygen affinity, heme-heme cooperativity and Bohr effect of the variants were evaluated by functional tests. Results: Four new and 22 rare variants were detected in 98 families. Some of these variants were found in co-inheritance with other hemoglobinopathies. Of the rare hemoglobins, Hasharon, Stanleyville II and J-Rovigo were the most common, the first two being S-like and associated with alpha-thalassemia. Conclusion: The variability of alpha-globin alterations reflects the high degree of racial miscegenation and an intense internal migratory flow between different Brazilian regions. This diversity highlights the importance of programs for diagnosing hemoglobinopathies and preventing combinations that may lead to important clinical manifestations in multiethnic populations.

Lack of effect of cell-wall targeted antibacterials on biofilm formation and antifungal susceptibility of Candida species

The use of central venous catheters (CVC) and broad-spectrum antibacterials are among the main risk factors for the development of candidemia in patients admitted to intensive care units (ICU). It is known that some antibacterials increase the resistance of these yeasts to azole antifungals. Thus, the aim of this research was to determine whether yeast present in CVC colonizations previously exposed to cell-wall targeted antibacterials benefit from a reduction in susceptibility to fluconazole and voriconazole, facilitating their ability to form biofilms. Candida albicans, C. tropicalis, C. glabrata, C. parapsilosis and C. guilhermondii were seeded into antibacterial (cefepime, meropenem, vancomycin, and piperacillin-tazobactam) gradient plates produced in Mueller-Hinton Agar. The susceptibility to fluconazole and voriconazole and the biofilm formation of the yeasts were tested before and after exposure to the antibacterials. None of the antibacterials exerted a significant effect on the in vitro susceptibility of the yeasts to the antifungal agents or on their ability to form biofilms. These results suggest that increased candidemia in ICU patients is not attributable to possible alterations in the yeasts, but is more likely caused by a weakening of the patient's general condition after long exposure to infection.

O uso de cateter venoso central (CVC) e antibióticos de amplo espectro estão entre os principais fatores de risco para o desenvolvimento da candidemia em pacientes internados em unidades de terapia intensiva (UTI). É conhecido que alguns antibióticos aumentam a resistência das leveduras aos antifúngicos azólicos. Assim, o objetivo deste estudo foi avaliar se leveduras presentes em colonização de CVC expostas a antibióticos que atuam em parede celular se beneficiam de uma redução na suscetibilidade ao fluconazol e voriconazol e se obtêm maior capacidade de formar biofilme. Candida albicans, C. tropicalis, C. glabrata,C. parapsilosis e C. guilhermondii foram semeadas em placas de Mueller-Hinton Agar, com gradientes de antibióticos (cefepima, meropenem, vancomicina e piperacilina-tazobactam). A suscetibilidade e a formação de biofilme das leveduras foram testadas antes e após a exposição aos antibióticos. Nenhum dos antibióticos provocou alterações detectáveis in vitro sobre a suscetibilidade das leveduras aos antifúngicos ou à capacidade de formar biofilme. Estes resultados sugerem que o aumento da candidemia na UTI não seria atribuído a possíveis alterações provocadas nas leveduras e sim pelo enfraquecimento da condição geral do paciente após longa exposição à infecção.

Determination of beta S haplotypes in patients with sickle-cell anemia in the state of Rio Grande do Norte, Brazil

βS haplotypes were studied in 47 non-related patients with sickle-cell anemia from the state of Rio Grande do Norte, Brazil. Molecular analysis was conducted by PCR/RFLP using restriction endonucleases XmnI, HindIII, HincII and HinfI to analyze six polymorphic sites from the beta cluster. Twenty-seven patients (57.5 percent) were identified with genotype CAR/CAR, 9 (19.1 percent) CAR/BEN, 6 (12.8 percent) CAR/CAM, 1 (2.1 percent) BEN/BEN, 2 (4.3 percent) CAR/Atp, 1 (2.1 percent) BEN/Atp and 1 (2.1 percent) with genotype Atp/Atp. The greater frequency of Cameroon haplotypes compared to other Brazilian states suggests the existence of a peculiarity of African origin in the state of Rio Grande do Norte.

Characterization of beta-thalassemia mutations in patients from the state of Rio Grande do Norte, Brazil

35 unrelated individuals were studied for characterization as either heterozygous or homozygous for beta-thalassemia. Molecular analysis was done by PCR/RFLP to detect the mutations most commonly associated with beta-thalassemia (β0IVS-I-1, β+IVS-I-6, and β039). In the patients who showed none of these mutations, the beta-globin genes were sequenced. Of the 31 heterozygous patients, 13 (41.9 percent) had the β+IVS-I-6 mutation, 15 (48.4 percent) the β0IVS-I-1 mutation, 2 (6.5 percent) the β+IVS-I-110 mutation and 1 (3.2 percent) the β+IVS-I-5 mutation. IVS-I-6 was detected in the four homozygotes. The mutation in codon 39, often found in previous studies in Brazil, was not detected in the present case. This is the first study aiming at identifying mutations that determine beta-thalassemia in the state of Rio Grande do Norte.

Hb H disease resulting from the association of an αº-thalassemia allele [-(α)20.5] with an unstable α-globin variant [Hb Icaria]: First report on the occurrence in Brazil

Hb H Disease is caused by the loss or inactivation of three of the four functional a-globin genes. Patients present chronic hemolytic anemia and splenomegaly. In some cases, occasional blood transfusions are required. Deletions are the main cause of this type of thalassemia (α-thalassemia). We describe here an unusual case of Hb H disease caused by the combination of a common αº deletion [-(α)20.5] with a rare point mutation (c.427T > A), thus resulting in an elongated and unstable α-globin variant, Hb Icaria, (X142K), with 31 additional amino-acid residues. Very high levels of Hb H and Hb Bart's were detected in the patient's red blood cells (14.7 and 19.0 percent, respectively). This is the first description of this infrequent association in the Brazilian population.

Identificação e caracterização de variantes novas e raras da hemoglobina humana: [revisão] / Identification of characterization of novel and rare variants of human hemoglobin: [review]

As anormalidades estruturais da hemoglobina estão entre as doenças genéticas mais comumente encontradas nas populações humanas. O Laboratório de Hemoglobinopatias do Departamento de Patologia Clínica da Faculdade de Ciências Médicas da Universidade Estadual de Campinas - Unicamp, localizado em Campinas, no estado de São Paulo, região Sudeste do Brasil, realizou, em seus 27 anos de existência, cerca de 130.000 diagnósticos. Entre as variantes estruturais detectadas, as hemoglobinas S, C e D-Punjab foram, como esperado, as mais freqüentes, porém um número expressivo de outras hemoglobinas anômalas, novas e raras, também foi encontrado. Esses achados estão sumarizados no presente artigo.

Hemoglobin structural abnormalities are among the most commonly found human genetic diseases. The Laboratory of Hemoglobinopathies in the Clinical Pathology Department of the Medical Sciences School of the State University in Campinas - Unicamp, São Paulo, Southeastern Brazil, carried out, in its 27 years of activity, about 130,000 diagnoses. As expected, hemoglobins S, C and D were the most frequently observed variants, but an expressive number of other abnormal, novel and rare hemoglobins, was also detected. These findings are summarized in the present article.

Haptoglobin study in myasthenia gravis / Estudo sobre a haptoglobina na miastenia grave

OBJECTIVE: A cross-sectional study of haptoglobin (Hp) in myasthenia gravis (MG) was designed, with the objective to identify its values and correlate them with different disease status. METHOD: 46 patients were enrolled in the study, all having disease severity established according to the quantitative myasthenia gravis strength scores (QMGSS). Based on the functional scale determined by Myasthenia Gravis Foundation of America (MGFA) recommendations, patients were classified as having: complete stable remission (CSR; n=10); minimal manifestations-0 (MM0; n=6), minimal manifestations-1 (MM1; n=4); pharmacological remission (PR; n=6). Two other groups participated: thymomatous patients (T; n=10) and patients without imunosuppression or thymectomy, until the assessment for Hp (WIT; n=10). Hp dosage was done by immunonephelometry, blindly to clinical data. Student's t-test, Anova test and linear regression were employed for statistical analyses. RESULTS: Statistically significant differences occurred between CSR+MM0xWIT groups (86.62x157.57, p<0.001) and PR+MM1xWIT groups (73.93x157.57, p<0.001). Linear regression showed correlation between Hp levels and QMGSS (r=0.759, p<0.001). CONCLUSION: Our results suggest that Hp may be useful in clinical practice as a disease severity marker in MG.

OBJECTIVO: Desenhou-se estudo transversal sobre a haptoglobina (Hp) na miastenia grave (MG) com o objetivo de identificar seus valores e correlacioná-los a diferentes condições na doença. MÉTODO: 46 pacientes foram incluídos, todos tendo a gravidade da doença estabelecida segundo escores internacionais (QMGSS). Os pacientes tiveram seu estado funcional determinado de acordo com a Myasthenia Gravis Foundation of América (MGFA) e classificados em: remissão completa estável (CSR; n=10); mínima manifestação-0 (MM0; n=6), mínima manifestação-1 (MM1; n=4); remissão farmacológica (PR; n=6). Dois outros grupos participaram: pacientes timomatosos (T; n=10) e pacientes sem imunossupressão ou timectomia, até o momento da inclusão no estudo (WIT; n=10). A dosagem de Hp foi realizada por imunonefelometria, de modo cego quanto à clínica. As análises estatísticas incluíram o teste de Student, Anova e regressão linear. RESULTADOS: Observou-se diferença significativa entre os grupos CSR+MM0xWIT (86,62x157,57, p<0,001) e entre PR+MM1xWIT (73,93x157,57, p<0,001). A regressão linear mostrou correlação positiva entre os valores de Hp e os escores QMGSS (r=0,759, p<0,001). CONCLUSÃO: O estudo sugere que valores altos de Hp se correlacionaram a maior gravidade da MG.

Photodynamic effect of light-emitting diode light on cell growth inhibition induced by methylene blue.

The aim of this study was to propose the use of red light-emitting diode (LED) as an alternative light source for methylene blue (MB) photosensitizing effect in photodynamic therapy (PDT). Its effectiveness was tested against Staphylococcus aureus (ATCC 26923), Escherichia coli (ATCC 26922), Candida albicans (ATCC 90028) and Artemia salina. The maximum absorption of the LED lamps was at a wavelength of 663 nm, at intensities of 2,4,6 and 12 J.cm-2 for 10, 20, 30 and 60 min of exposure, respectively. Assays with and without LED exposure were carried out in plates containing MB at concentrations of 7 to 140.8 (micro) M for microorganisms and 13.35 to 668.5 (micro) M for microorganisms or microcrustaceans.The LED exposure induced more than 93.05%, 93.7% and 93.33% of growth inhibition for concentrations of 42.2 (micro)M for S.aureus (D-value=12.05 min) and 35.2 (micro)M for E.coli (D-value=11.51 min) and C.albicans (D-value=12.18 min), respectively after 20 min of exposure. LED exposure for 1 h increased the cytotoxic effect of MB against A.salina from 27% to 75%.Red LED is a promising light device for PDT that can effectively inhibit bacteria, yeast and microcrustacean growth.

Asociación de hemoglobina S (HbS) y beta talasemia en dos pacientes del Centro Hemato-Oncológico del Hospital Pereira Rossell / Association between S haemoglobin and S-thalassemia in two patients of the Haematologic and Oncologic Centre of the Pereira Rossell Children Hospital

Associación del alelo b S que produce hemoglobina S (HbS) y de un alelo de beta talasemia (btal), ocurre principalmente en poblaciones que tienen simultáneamente ascendencia africana y mediterránea, y provoca un síndrome drepanocítico denominado HbS-beta talasemia. Este síndrome presenta una gran heterogeneidad clínica y genética debida en gran parte al alelo talasémico presente. Los individuos que portan un alelo talasémico b 0 presentan, en general, un curso clínico similar a los homocigotas para el alelo b S de la HbS. En cambio, los que portan un alelo b + presentan un curso clínico variable, dependiendo de la reducción en la síntesis de cadena de beta globina. En este estudio se describe el caso clínico de dos pacientes con HbS-beta talasemia que consultaron en el Centro Hemato-Oncológico Pediátrico del Hospital Pereira Rossell. Se analizó el genotipo de los dos pacientes por medio de secuenciación automática del gen de la beta globina. Se demostró la presencia del alelo talasémico b + IVS-1-110- A en uno de los pacientes y del alelo b 0 codón39 C-T en el otro paciente, por lo cual ambos son heterocigotos compuestos b S/b tal. Se discute la relación entre los datos clínicos y paraclínicos con los resultados del diagnóstico molecular. También se discute la importancia del diagnóstico molecular en relación con la composición y estructura de la población uruguaya.

Molecular characterization of alpha-thalassemia in the Mexican population / Caracterización molecular de talasemia alfa en una población mexicana

Background. α-Thalassemia (α-Thal) has been poorly characterized at the molecular level in Mexico. Methods. 106 consecutive individuals identified in Laboratorios Clínicos de Puebla, with either hypochromia (MCH < 24 pg) and/or microcytosis (MCV < 75 fl in women or < 80 fl in man), without iron deficiency, with or without anemia were investigated in this study, along a 16 month-period, α and β-Thal were looked for, the former were characterized at the molecular level. Results. Out of the 106 consecutive cases with hypochromia and/or microcytosis and normal levels of protoporphyrin zinc complex, 48 cases (45.3%) had thalassemia (37 cases of β-Thal and 11 cases of α-Thal), whereas in 58 cases (54.7%) a definite diagnosis could not be established. Of the α-Thal cases, 8 were heterozygous and two were homozygous for the -α3.7 deletion, whereas one case was heterozygous for the α2Hph allele. Conclusions. Only few of the α-Thal alleles tested were found, thus the α-thalassemic mutations, present in the studied population, seem to be rather heterogeneous.

Antecedentes. En México, la α-talasemia (α-Thal) ha sido pobremente caracterizada a nivel molecular. Mátodos. Se estudiaron 106 individuos consecutivos identificados en los Laboratorios Clínicos de Puebla, con hipocromia (CMH < 24 pg) y lo microcitosis (VCM < 75 fl en mujeres o 80 fl en hombres), sin deficiencia de hierro, con o sin anemia, durante un periodo de 16 meses. Se investigaron α y β-Thal; las primeras fueron caracterizadas a nivel molecular. Resultados. De los 106 casos consecutivos estudiados con hipocromia y/o microcitosis, y niveles normales del complejo de protoporfirina-cinc, 48 casos (45.3%) tenían talasemias (37 de ellos β-Thal y 11 α-Thal), mientras que en 58 casos (54.7%) no pudo establecerse un diagnóstico definitivo. De las talasemias α, ocho casos eran heterocigotos y dos homocigotos para la deleción -α3.7, mientras que sólo un caso resultó heterocigoto para el alelo α2Hph. Conclusiones. De los alelos α-Thal estudiados sólo se encontraron algunos, de lo que se infiere que en la población estudiada esas mutaciones parecen ser bastante heterogáneas.

Alpha-thalassemia, HbS, and beta-globin gene cluster haplotypes in two Afro-Uruguayan sub-populations from northern and southern Uruguay

Hemoglobinopathies are the most common monogenic disorders worldwide; however, they have never been systematically studied from a genetic perspective in Uruguay. In this study, we determined the frequencies of hemoglobin variants in Afro-Uruguayans. A sample of 52 healthy unrelated Afro-Uruguayans from the northern (N = 28) and southern (N = 24) regions of the country was analyzed. Eight individuals (15.4 percent) were heterozygous for -alpha3,7thalassemia; seven of them (29.2 percent) were originally from the southern region, whereas one of them (3.6 percent) was from the northern region; the differences between both regions were statistically significant (p = 0.016 +/-0.003). The only structural mutation detected was betaS, which is typical of African populations. Four individuals (10 percent) were heterozygous for betaS, three of them (13.6 percent) from the South, and one (5.6 percent) from the North. The betaS haplotypes were analyzed in eight individuals: two were homozygous betaS/betaS, two were heterozygous betaS/betathal, and four were heterozygous betaS/betaª. This haplotype distribution (60 percent Bantu, 20 percent Benin, and 20 percent Bantu A2) is in agreement with historical records reporting a predominantly Bantu origin for the enslaved Africans brought to Uruguay. Even though this is a preliminary study, due to the small sample size, our results are suggestive of a relatively high incidence of hemoglobinopathies in the Afro-Uruguayan population.

Polycythemia and Hb Coimbra [beta 99 (G1) Asp -> Glu] in Brazil

We report the clinical and laboratory findings concerning three unrelated Brazilian patients investigated for polycythemia, whose definitive diagnosis could only be established after the presence of Hb Coimbra (b99 Asp ® Glu) was demonstrated. This illustrates the importance of properly investigating hereditary hemoglobinopathies in cases of erythrocytosis because in some populations variants with high oxygen affinity may be more frequent than expected but go undetected when conventional electrophoresis is used as the sole detection procedure.

Exatidão das vidrarias volumétricas e impacto sobre a quantificação de metoclopramida em solução oral / Accuracy of volumetric glasses and its impact on the quantitation of metoclopramide oral solution

Este estudo teve por objetivo avaliar o padrão de qualidade das vidrarias volumétricas adquiridas por licitação e impacto nas análises quantitativas de medicamentos. Foram avaliadas pipetas, buretas e balões volumétricos utilizandose metodologia descrita pela international Organization for Standardization (ISO) e realizada análise de teor da solução de metoclopramida gotas. Do total de materiais avaliados 56,36 por cento de balões volumétricos, 30,95 por cento das pipetas e 40,00 por cento de buretas foram reprovados. O maior fornecedor dos materiais, o fabricante G, foi um dos que mostrou menor índice de reprovação, 27,27 por cento para balão, 13,73 por cento para pipetas e 50 por cento para buretas. O medicamento metoclopramida gotas foi usado como exemplo para comparar o resultado utilizando vidraria calibrada e não calibrada na determinação do teor. O resultado mostrou uma diferença de 100,90 ± 1,56 para a vidraria calibrada e de 96,02 ± 2,23 por cento para a não calibrada. Esta diferença pode ser crítica no caso de medicamentos que apresentam o teor próximo à faixa limite de aceitação ou quando o custo da matéria prima é muito elevado. Diante dos resultados podemos observar que dentre os materiais existentes no laboratório, apenas 61,2 por cento deles são passíveis de utilização. Portanto, seria recomendável que fosse feita uma exigência técnica de certificação de qualidade no edital de licitação e uma validação prévia destes materiais antes da efetivação do pagamento, pois mesmo aquelas marcas mais famosas apresentaram desvios de qualidade

Mecanismo de ação do metotrexato e avalição clínica de sua associação com a cloroquina no controle de artrite reumatóide juvenil / Methotrexate action mechanism and clinical assessment of its association with chroquine in juvenile rheumatoid arthritis control

Estudaram-se a eficácia clínica do uso do metotrexato (MTX) e sua associação com a cloroquina (CQ) para o controle da artrite reumatóide juvenil, e o mecanismo bioquímico de inibição celular do MTX. A resposta clínica foi obtida através da avaliação de dor, edma e número de articulações acometidas;a avaliação cinética do MTX no plasma e urina, bem como o estudo dos indicadores de atividade da doença: proteína C-reativa (PCR), substância amilóide A (SAA), velocidade de hemossedimentação (VHS), fibrinogênio e "alfa"-glicoproteína ácida foram feitos em pacientes, cuja idade variou de 12 a 25 anos. Todos os pacientes apresentaram relativo controle da doença e nao mostraram diferença significativa, com relação...