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1.
An. Fac. Cienc. Méd. (Asunción) ; 56(1): 25-31, 20230401.
Article in Spanish | LILACS | ID: biblio-1426661

ABSTRACT

Objetivos: Determinar la predisposición a recibir esta vacuna contra SARS-CoV-2. Materiales y métodos: Se aplicó un diseño observacional de corte transversal en la población adulta del Paraguay entre mayo y octubre 2022. se aplicó el cuestionario de Kotta et al previamente validado, el cual fue difundido por redes sociales. Resultados: Se incluyeron 303 encuestados, con edad media 34 ± 12 años y predominio del sexo femenino (64,0%). En la muestra, 51,8% padeció COVID-19 y 97,3% ya recibió al menos una dosis de la vacuna. Se detectó que 58,4% aceptada la vacuna, 17,8% vacilaba en recibirla y 23,7% la rechazaba. La aceptación fue más frecuente en los varones (p 0,05). Conclusión: En el momento epidemiológico de disponibilidad universal de la vacuna y habiendo aún sujetos afectados por COVID-19, el rechazo a la misma fue 23,7%.


Objectives: To determine the predisposition to receive this vaccine against SARS-CoV-2. Materials and methods: An observational cross-sectional design was applied in the adult population of Paraguay between May and October 2022. The previously validated questionnaire of Kotta et al was applied, which was disseminated through social networks. Results: 303 respondents were included, with a mean age of 34 ± 12 years and predominance of the female sex (64.0%). In the sample, 51.8% suffered from COVID-19 and 97.3% have already received at least one dose of the vaccine. It was detected that 58.4% accepted the vaccine, 17.8% hesitated to receive it and 23.7% rejected it. Acceptance was more frequent in males (p 0.05). Conclusion: At the epidemiological moment of universal availability of the vaccine and with subjects still affected by COVID-19, rejection of it was 23.7%.


Subject(s)
SARS-CoV-2 , COVID-19 , Vaccines , Surveys and Questionnaires , Dosage , Goals , Methods
3.
Ann. afr. méd. (En ligne) ; 17(1): e5468-e5474, 2023. figures, tables
Article in French | AIM | ID: biblio-1525345

ABSTRACT

Context and objective The dosage of hemoglobin (Hb) is challenging particularly in rural setting. This dosage can be done using "Point of Care" (POC) material within rural areas and emergency situations. The present study aimed to assess the POC HemoCue® Hb 201+. Methods. This was an analytical cross-sectional study comparing the rates of the dosage of Hb carried out on HemoCue® Hb 201+ hemoglobinometer and those obtained with Mindray BC-5150 automaton in Kinshasa University Hospital, Democratic Republic of Congo (DRC). Results. Two hundred subjects were involved in the study. Mean and median Hb rates were 10,438 ± 2,741 g/dl and 10,600 g/dl (IQR: 8,675-12,300 g/dl) by Mindray BC-5150, respectively and mean rate of Hb was 10,5 ± 2,756 g/dl and the median rate was 10,900 g/dl (IQR: 8,775 ­ 12,300 g/dl) by the HemoCue® Hb 201+, respectively. The linear regression revealed a positive relationship between the Hb rates obtained on an automaton Mindray BC- 5150 and those obtained on the HemoCue® Hb 201+. The diagram of Bland Altman showed limits of agreement between automaton Mindray BC- 5150 and HemoCue® Hb 201+. Conclusion. This study showed that the POC HemoCue® Hb 201+ provided similar results to those of the automaton Mindray BC-5150. Thus, HemoCue® Hb 201+ can be used in emergency services or even in medical institutions that do not have or do not meet the conditions for the use of hematology analyzers in the DRC.


Contexte & objectif Le dosage du taux de l'hémoglobine est un véritable défi en milieu rural où les laboratoires sont moins équipés. Et pourtant, cette analyse, réalisée au moyen des équipements plus au moins sophistiqués, permettant de confirmer une anémie, peut être facilitée par l'utilisation des Points of care (POC). Le POC Hemocue® Hb 201+, utilisé dans certains sites pour ce faire, n'a jamais été évalué. L'objectif de la présenté étude était d'évaluer les performances du POC Hemocue® Hb 201+ à Kinshasa /RDC. Méthodes. Il s'agissait d'une étude transversale, analytique comparant les taux d'Hb obtenus sur Hemocue® Hb 201+ et sur Mindray BC-5150 comme référence, aux Cliniques Universitaires de Kinshasa. Résultats. Deux cents sujets ont été inclus. Les taux moyen et médian d'Hb sur l'automate Mindray BC5150 ont été respectivement, de 10,438 ± 2,741 g/dl et de 10,600 g/dl (IQR : 8,675-12,300 g/dl). Le taux moyen d'Hb sur le POC Hemocue® Hb 201 a été de 10,5 ± 2,756 g/dl et le taux médian de 10,900 g/dl (IQR : 8,775 - 12,300 g/dl). La régression linéaire a mis en évidence une relation positive entre les taux d'Hb dosés sur automate Mindray BC- 5150 et ceux dosés sur HemoCue® Hb 201+. Le diagramme de Bland Altman a montré des limites d'accord entre l'automate Mindray BC- 5150 et Hemocue® Hb 201. Conclusion. Cette étude a montré que le POC HemoCue® Hb 201+ fournissait des résultats identiques à ceux de l'automate Mindray BC-5150. Ainsi, l'HemoCue® Hb 201+ peut être utilisé dans les services d'urgence ou dans les institutions médicales ne possédant pas ou ne remplissant pas les conditions d'utilisation des automates d'hématologie en RDC


Subject(s)
Humans , Male , Female , Hemoglobins , Dosage
4.
Rev. Soc. Argent. Diabetes ; 56(2): 43-50, mayo - ago. 2022. ilus
Article in Spanish | LILACS, BINACIS | ID: biblio-1395828

ABSTRACT

Introducción: el uso prolongado de metformina y la carencia de consumo de vitamina B12 (B12) pueden provocar su déficit en pacientes con diabetes mellitus tipo 2 (DM2). Objetivos: analizar la frecuencia de consumo insuficiente de B12 según: características personales, datos antropométricos, de laboratorio y uso de metformina; asociar niveles séricos de cobalamina con dosis y tiempo de metformina; establecer la relación entre la ingesta de B12 y los niveles séricos. Materiales y métodos: diseño transversal. Mediante encuesta de frecuencia de consumo de alimentos fuente de B12 en 200 pacientes tratados con metformina por más de 18 meses. Se analizaron datos clínicos, antropométricos, de laboratorio, tiempo y dosis de metformina, en dos centros de salud de la Provincia de Buenos Aires. Resultados: el porcentual de consumo deficiente fue del 29%. Se registró un 47,5% de desocupación que alcanzó un déficit de ingesta del 32,6%. Se midió B12 sérica en el 65% de la muestra y un 53,8% de los valores fue anormal (0,8% en niveles deficientes o bajos y 23% en niveles normal-bajo), observándose asociación significativa a dosis de metformina ≥1.500 mg. Las deficiencias de consumos de B12 (<2,4 µg/día) fueron casi cuatro veces mayores en el grupo con menor recuento eritrocítico (76,9 % vs 18,5%; p<0,00 ). El volumen corpuscular medio (VCM) y el recuento de plaquetas arrojaron datos estadísticamente significativos. Conclusiones: si bien el 29% de la muestra exhibió consumo vitamínico deficiente, el 90% de los pacientes con déficit sérico registró ingestas adecuadas de B12. Dado que se trató de un diseño transversal, donde no pudo evaluarse causalidad, en pacientes intervenidos farmacológicamente con metformina se sugiere considerar su impacto en situaciones deficitarias.


Introduction: the prolonged use of metformin and the lack of consumption of vitamin B12 can cause its deficit, in T2D. Objectives: to analyze the frequency of insufficient consumption of vitamin B12 according to: personal characteristics, anthropometric and laboratory data, and use of metformin; associate serum cobalamin levels with metformin dose and time; establish a relationship between B12 intake and serum levels. Materials and methods: cross-sectional design. Through a survey of the frequency of consumption of food sources of B12 in 200 patients treated with metformin for more than 18 months. Clinical, anthropometric, laboratory data, time and dose of metformin were analyzed in 2 health centers in the Province of Buenos Aires. Results: the percentage of deficient consumption was 29%. 47.5% of unemployment was registered, which reached an intake deficit of 32.6%. Serum B12 was measured in 65% of the sample where 53.8% of values were abnormal (0.8% in deficient levels) and 23% at levels normal lower cut-off point, with a significant association being observed at doses of metformin ≥1,500 mg. Deficiencies in B12 intake (<2.4 µg/day) were almost 4 times higher in the group with the lowest erythrocyte count (76.9% vs 18.5%; p<0.00 ). The MCV and platelet count yielded statistically significant data. Conclusions: although 29% of the sample exhibited poor vitamin intake, 90% of patients with serum deficiency had adequate intakes of vitamin B12. Given that it is a cross-sectional design, where causality cannot be evaluated, it is suggested: in patients undergoing pharmacological intervention with metformin, consider the impact of this in deficient situations.


Subject(s)
Diabetes Mellitus, Type 2 , Vitamin B 12 , Dosage , Metformin
5.
Medicina UPB ; 41(1): 3-11, mar. 2022. tab
Article in English | LILACS, COLNAL | ID: biblio-1362378

ABSTRACT

Objetivo: este estudio busca describir los individuos evaluados por sobredosis de acetaminofén entre 2019 y 2020 en un centro de referencia de trasplante hepático en Colombia. Metodología: estudio derivado del análisis secundario de historias clínicas entre el 1.º de enero de 2019 y el 31 de diciembre de 2020. Los criterios de inclusión abarcan individuos con ingestión aguda y voluntaria de dosis tóxicas de acetaminofén (>4 g/día). Resultados: sesenta y tres casos, 68% mujeres, 67% menores de 18 años y 54% estudiantes. Reportó historia personal de enfermedad psiquiátrica el 60% y el 35% al menos un intento de suicidio previo. La mediana de dosis de acetaminofén fue 15g, 46% refirieron co-ingesta de otras sustancias y 13% estaba bajo efecto de sustancias psicoactivas. El 57% tenía la intención clara de suicidarse, así como 81% vomitó antes de acudir al servicio de urgencias, 22% recibió medidas de descontaminación y 10% no recibió N - acetilcisteína. Quince individuos desarrollaron lesión hepática aguda, nueve con criterios de severidad. Conclusiones: la población era predominantemente joven, la historia de enfermedad psiquiátrica fue muy prevalente y la mayoría refirieron un evento vital que explicara el comportamiento impulsivo de consumo. Ninguno desarrolló criterios para trasplante hepático, lo cual podría explicarse por la edad de los individuos, los episodios de vómito temprano, y la ausencia de enfermedad hepática crónica o de consumo de sustancias hepatotóxicas.


Objective: this study aims to describe patients with overdose intake of acetaminophen between 2019 and 2020 at a reference center for liver transplantation in Colombia. Methodology: study derived from a secondary analysis of the clinical records between January 1st, 2019, to December 31st, 2020. Inclusion criteria were individuals with voluntary acute ingestion of toxic doses of acetaminophen (>4 g/day). Results: sixty-three cases, 68% women, 67% <18-year-old, and 54% students. 60% had personal history of psychiatric illness and 35% reported at least one previous suicide attempt. The median dose of acetaminophen was 15g, 46% referred to co-ingestion with other substances and 13% were under the effect of any psychoactive substance. 57% had a clear intention of suicide. 81% vomited before the arrival to the emergency room, 22% received decontamination intervention with gastric lavage or activated charcoal, and 10% did not receive any dose of N-Acetylcysteine. Fifteen individuals developed an acute liver injury, nine with severity criteria. Conclusions: the population was predominantly young, the personal history of psychiatric disease was highly prevalent, and most of the cases referred a vital event that explains the impulsive behavior in acetaminophen consumption. None developed criteria for liver transplantation, and this could be explained by the young age of the individuals, the episodes of early vomiting, and the absence of chronic liver disease or hepatotoxic substance consumption.


Objetivo:este estudo busca descrever os indivíduos avaliados por sobredose de acetaminofen entre 2019 e 2020 num centro de referência de transplante hepático na Colômbia. Metodologia: estudo derivado da análise secundário de histórias clínicas entre o dia 1.º de janeiro de 2019 e 31 de dezembro de 2020. Os critérios de inclusão abrangem indivíduos com ingestão aguda e voluntária de dose tóxicas de acetaminofen (>4 g/dia).Resultados:sessenta e três casos, 68% mulheres, 67% menores de 18 anos e 54% estudantes. Reportou história pessoal de doença psiquiátrica, 60% e 35% pelo menos uma tentativa de suicídio prévio. A média de dose de acetaminofen foi de 15g, 46% referiram com ingestão de outras sustâncias e 13% estava sob efeito de sustâncias psicoativas. 57% tinham a intenção clara de suicidar-se, assim como 81% vomitou antes de acudir ao serviço de urgências, 22% receberam medidas de descontaminação e 10% não recebeu N - acetilcisteína. Quinze indivíduos desenvolveram lesão hepática aguda, nove com critérios de severidade. Conclusões: a população era predominantemente jovem, a história de doençapsiquiátrica foi muito prevalente e a maioria referiram um evento vital que explicasse o comportamento impulsivo de consumo. Nenhum desenvolveu critérios para transplantehepático, o qual se poderia explicar pela idade dos indivíduos, os episódios de vómito precoce, e a ausência de doença hepática crónica ou de consumo de sustâncias hepatotóxicas.


Subject(s)
Humans , Acetaminophen , Acetylcysteine , Suicide, Attempted , Vomiting, Anticipatory , Charcoal , Decontamination , Emergency Service, Hospital , Dosage , Gastric Lavage , Liver Diseases , Mental Disorders
6.
Braz. J. Pharm. Sci. (Online) ; 58: e20030, 2022. graf
Article in English | LILACS | ID: biblio-1403680

ABSTRACT

Abstract N-(9,13b-dihydro-1H-dibenzo[c,f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide (DDIAHB) is a new drug developed through molecular modelling and rational drug design by the molecular association of epinastine and salicylic acid. The present study was designed to assess the possible antinociceptive effects of DDIAHB on different pain models in male ICR mice. DDIAHB exerted the reductions of writhing numbers and pain behavior observed during the second phase in the formalin test in a dose-dependent manner. Moreover, DDIAHB increased the latency in the hot-plate test in a dose-dependent manner. Furthermore, intragastric administration DDIAHB caused reversals of decreased pain threshold observed in both streptozotocin-induced diabetic neuropathy and vincristine-induced peripheral neuropathy models. Additionally, intragastric pretreatment with DDIAHB also caused reversal of decreased pain threshold observed in monosodium urate-induced pain model. We also characterized the possible signaling molecular mechanism of the antinociceptive effect-induced by DDIAHB in the formalin model. DDIAHB caused reductions of spinal iNOS, p-STAT3, p-ERK and p-P38 levels induced by formalin injection. Our results suggest that DDIAHB shows an antinociceptive property in various pain models. Moreover, the antinociceptive effect of DDIAHB appear to be mediated by the reductions of the expression of iNOS, p-STAT3, p-ERK and p-P38 levels in the spinal cord in the formalin-induced pain model.


Subject(s)
Animals , Male , Mice , Pain Measurement , Analgesics/adverse effects , Organization and Administration , Pain/classification , Spinal Cord/abnormalities , Pharmaceutical Preparations/administration & dosage , Drug Design , Dosage
7.
Braz. J. Pharm. Sci. (Online) ; 58: e20074, 2022. tab, graf
Article in English | LILACS | ID: biblio-1403714

ABSTRACT

Abstract Morinda lucida leaves are largely used by Congolese traditional healers for the treatment of uncomplicated malaria. The antimalarial activity of their ethanolic extract has been confirmed both in vitro and in vivo. However, the development of relevant formulations for potential clinical application is hampered since the active ingredients contained in this extract exhibit poor water solubility and low oral bioavailability. Hence, this work aims not only to develop self-nanoemulsifying drug delivery systems (SNEDDSs) for oral delivery of the ethanolic extract of Morinda lucida (ML) but also to evaluate its oral antimalarial activity alone and in combination with other Congolese ethanolic plant extracts (Alstonia congensis, Garcinia kola, Lantana camara, Morinda morindoides or Newbouldia laevis). Based on the solubility of these different extracts in various excipients, SNEDDS preconcentrates were prepared, and 200 mg/g of each plant extract were suspended in these formulations. The 4-day suppressive Peter's test revealed a significant parasite growth inhibiting effect for all the extract-based SNEDDS (from 55.0 to 82.4 %) at 200 mg/kg. These activities were higher than those of their corresponding ethanolic suspensions given orally at the same dose (p<0.05). The combination therapy of MLSNEDDS with other extract-based SNEDDS exhibited remarkable chemosuppression, ranging from 74.3 % to 95.8 % (for 100 + 100 mg/kg) and 86.7 % to 95.5 % (for 200 + 200 mg/kg/day). In regard to these findings, SNEDDS suspension may constitute a promising approach for oral delivery of ML alone or in combination with other antimalarial plants.


Subject(s)
Plants/metabolism , Pharmaceutical Preparations/administration & dosage , Plant Extracts/administration & dosage , Morinda/adverse effects , Antimalarials/analysis , In Vitro Techniques/methods , Drug Delivery Systems , Dosage , Malaria/drug therapy
8.
Braz. J. Pharm. Sci. (Online) ; 58: e18965, 2022. tab, graf
Article in English | LILACS | ID: biblio-1364419

ABSTRACT

Abstract The aim of present study was to explore protective and curative effects of Malve neglecta on kidneys. In silco study with network pharmacology was performed to find out potential target organs, genes and cellular cell lines which confirmed kidneys as target organ of phyto-constituents present in Malva neglecta extract. Gentamicin (40 mg/kg, i.p) was given to induce renal toxicity. Prophylactic study was performed with 300-, 600- and 900 mg/kg doses to find out nephro-protective and -curative effects and curative potential was evaluated at 900 mg/kg dose. Renal function biomarkers, blood urea, BUN, serum creatinine and uric acid, and oxidative stress measuring biomarkers, SOD, CAT, GSH and MDA levels in kidney homogenate were quantified at the end of study. Treatment groups showed decrease in blood urea, BUN, serum creatinine and uric acid levels dose dependently and curative group also showed decline in these biomarkers. SOD, CAT, GSH levels were increased and MDA level decreased in treatment groups significantly as compared to toxic control which revealed the role of oxidative stress in renal damage and anti-oxidant power of MN. Data suggested that use of MN along with drugs causing renal toxicity may prove beneficial due to its nephro- protective and curative effects.


Subject(s)
Animals , Male , Rats , Pharmaceutical Preparations , Malva/metabolism , Neglecta , Therapeutics/instrumentation , Gentamicins , Malvaceae/classification , Creatinine/administration & dosage , Dosage/methods , Antioxidants/adverse effects
9.
Braz. J. Pharm. Sci. (Online) ; 58: e18594, 2022. graf
Article in English | LILACS | ID: biblio-1364422

ABSTRACT

Abstract Traditionally dates is consumed as a rich source of iron supplement and the current research discuss the synthesis of silver nanoparticles (AgNPs) using methanolic seed extract of Rothan date and its application over in vitro anti-arthritic, anti-inflammatory and antiproliferative activity against lung cancer cell line (A549). FTIR result of synthesised AgNPs reveals the presence of functional group OH as capping agent. XRD pattern confirms the crystalline nature of the AgNPs with peaks at 38º, 44º, 64º and 81º, indexed by (111), (200), (220) and (222) in the 2θ range of 10-90, indicating the face centered cubic (fcc) structure of metallic Ag. HR- TEM results confirm the morphology of AgNPs as almost spherical with high surface areas and average size of 42 ± 9nm. EDX spectra confirmed that Ag is only the major element present and the Dynamic light scattering (DLS) assisted that the Z-average size was 203nm and 1.0 of PdI value. Zeta potential showed − 26.5mv with a single peak. The results of the biological activities of AgNPs exhibited dose dependent activity with 68.44% for arthritic, antiinflammatory with 63.32% inhibition and anti-proliferative activity illustrated IC50 value of 59.66 µg/mL expressing the potential of AgNPs to combat cancer


Subject(s)
Silver , In Vitro Techniques/methods , Chronology as Topic , Nanoparticles , Phoeniceae/adverse effects , Lung Neoplasms/classification , Seeds , zeta Potential , Spectroscopy, Fourier Transform Infrared , Inhibitory Concentration 50 , Dosage/methods
10.
São Paulo; s.n; s.n; 2022. 63 p. tab, tab.
Thesis in Portuguese | LILACS | ID: biblio-1396298

ABSTRACT

Introdução: Meropenem (MER) e Piperacilina/Tazobactana (PTZ) são agentes antimicrobianos largamente prescritos para pacientes grandes queimados internados em Unidade de Terapia Intensiva (UTI) com infecções nosocomiais causadas por Gram-negativos sensíveis CIM 2 mg/L, Enterobacteriaceae, EB e Non-enterobacteriaceae, NEB. A síndrome da resposta inflamatória sistêmica (SRIS) que ocorre durante o choque séptico no grande queimado pode causar alteração na farmacocinética do paciente em terapia intensiva, de modo que a dose recomendada pode não atingir o alvo desejado contra Gram-negativos de sensibilidade intermediária CIM >2 mg/L. Objetivo: Investigar a efetividade dos beta-lactâmicos piperacilina e meropenem na infusão estendida comparada à infusão intermitente recomendada, para os pacientes sépticos grandes queimados através da abordagem farmacocinética-farmacodinâmica (PK/PD). Ética, casuística e procedimentos: Autor e co-autores declararam não haver conflito de interesse. O protocolo foi aprovado, registro CAAE 07525118.3.0000.0068. No presente protocolo de estudo investigaram-se 36 pacientes sépticos grandes queimados, ambos os gêneros (12F/24M) em terapia intensiva do choque séptico com piperacilina-tazobactana 4,5g q6h ou meropenem 1g q8h. Os pacientes incluídos foram estratificados em dois grupos com base na administração através da infusão intermitente, 0,5 h (G1) ou da infusão estendida, 3 h (G2), ambos com 16 pacientes cada. Duas amostras sanguíneas (1,5mL/cada) foram coletadas no estado de equilíbrio (Steady State), 3ª e 5ª hora do início da infusão. Os níveis séricos de PTZ e MER foram mensurados através de cromatografia líquida, e a farmacocinética (PK) dos dois grupos de pacientes foi comparada aos dados reportados em voluntários sadios. A abordagem PK/PD foi aplicada para avaliação da cobertura do antimicrobiano a partir da estimativa do índice de predição de efetividade (% fΔT>CIM) e da probabilidade de alcançar o alvo terapêutico (PTA) com base no alvo PK/PD recomendado, 100%fΔT>CIM. Resultados e discussão: As características de admissão dos pacientes G1/G2 foram expressas através de mediana e interquartil: Clcr 115 (90-148) / 127 (90-170) ml/min; 30 (24-31) / 27 (24- 33,5) anos, 70 (61-75) / 71 (65-75) kg, 30 (20-42) / 33,9 (18-38,4)% área total de superfície queimada, SAPS3 53 (45-57) / 48 (37,8-59,5). Na admissão dos pacientes na UTI registrou-se G1/G2: trauma térmico (17/16), trauma elétrico (1/2), lesão inalatória (11/11), ventilação mecânica (16/9) e vasopressores foram necessários em 15/8 pacientes, G1/G2. Ocorreram diferentes alterações na farmacocinética dos dois beta-lactâmicos após a infusão estendida versus a infusão intermitente quando comparadas com dados relatados em voluntários sadios. Evidenciou-se prolongamento da meia vida decorrente do aumento do volume de distribuição. Estes resultados impactaram diferentemente a cobertura. O monitoramento de biomarcadores inflamatórios expressos em medianas (G1/G2) evidenciou aumento do PCR: 232/183mg/L e leucocitose (leucócitos 11/14 mil cel/mm3, neutrófilos 9/10 mil cel/mm3) na fase precoce do choque séptico. Relativamente à microbiologia dos isolados, a erradicação dos patógenos ocorreu para todos os pacientes após a infusão estendida contra Gram-negativos sensíveis (CIM: 2 mg/L), e de sensibilidade intermediária (CIM 4mg/L) como a K. pneumoniae e P. aeruginosa, enquanto a infusão intermitente garantiu erradicação de patógenos apenas até CIM 2 mg/L. Conclusão: Evidenciou-se a superioridade da infusão estendida frente à infusão intermitente na cobertura dos dois antimicrobianos, no alvo terapêutico considerado 100%fΔT>CIM. Registraram-se alterações na farmacocinética destes agentes nos pacientes frente aos dados reportados para voluntários sadios. Diferença significativa entre grupos (G1/G2) foi encontrada com relação meia vida biológica, e ao volume de distribuição tanto pata a piperacilina quanto para o meropenem


Background: Meropenem (MER) and Piperacillin/Tazobactam (PTZ), antimicrobial betalactam agents are widely prescribed to burn patients from the Intensive Care Unit (ICU) with nosocomial infections caused by Gram-negative strains. Change in the pharmacokinetics of critically ill patient occurs during the systemic inflammatory response syndrome (SIRS) at the course of septic shock. Then, the recommended dose administered by intermittent infusion, 0.5 hr cannot reach the target against gram-negative strains MIC > 2 mg/L. Subject: To investigate drug effectiveness of the beta-lactams piperacilin and meropenem in extended infusion compared to the recommended intermittent infusion in critically ill septic burn patients using pharmacokinetic-pharmacodynamic (PK/PD) approach. Ethics, Casuistry and Methods: All authors declared there is no conflict of interests. Ethical approval CAAE, register 07525118.3.0000.0068. It was investigated in the study protocol 36 septic burn patients of both genders (12M / 24F), undergoing antimicrobial therapy with PTZ 4.5 g q6h or MER 1g q8h. Based on the chosen antimicrobial therapy and drug infusion prescribed by the physician, patients were stratified in groups with intermittent 0.5h infusion (G1) or with the extended 3h infusion (G2), both groups with 16 patients each. Two blood samples were collected at the steady state (1.5mL / each), at the 3rd and 5th hrs of starting the infusion. Serum levels were measured by liquid chromatography. Pharmacokinetics (PK) of MER or PTZ was compared to data reported in healthy volunteers for both groups of patients. PK/PD approach was applied to estimate the drug effectiveness index (fΔT> MIC) and to assess the probability of target attained (PTA) based on the recommended PK/PD target, 100% fΔT> MIC. Results and discussion: Characteristics of patients admission G1/G2 were: Clcr 115(90- 148)/127(90-170) ml/min; 30(24-31)/27(24-34) yrs, 70(61-75)/71(65-75) kg, 30(20- 42)/33.9(18-38.4)% total burn surface area, SAPS3 53(45-57)/48(37.8-59.5), medians (interquartile): thermal trauma occurred (17/16), electric trauma (1/2), inhalation injury (11/11), mechanical ventilation (9/16) and vasopressors required in 15/8 patients. It was demonstrated that different PK changes occurred for both beta-lactam agents after the extended or intermittent infusion by comparison with data reported in healthy volunteers. PK changes were related to the prolongation of biological half-life and increases on volume of distribution with impact on pharmacodynamics. On the other hand, meropenem total body clearance reduced by 50% at the earlier period of septic shock could be explained by the reduction of MER-transporters expression in the tubular renal secretion, once only patients with renal function preserved were included in the study protocol. Inflammatory biomarkers increased at the earlier period of septic shock: C-rp 232/183mg/L; leukocytes 11/14*103cel/mm3, neutrophils 9/10*103cel/mm3, medians, G1/G2. Clinical and microbiological cure was obtained for all patients of G1 against MIC < 2mg/L after intermittent 0.5 h infusion; while PK/PD target was attained for G2 patients undergoing antimicrobial therapy with MER or PTZ by extended infusion against gram negative strains K. pneumoniae, P. aeruginosa up to MIC 4mg L. Conclusion: Superiority of the extended infusion over intermitent infusion was obtained for the two antimicrobials was evidenced, in the therapeutic target considered 100%fΔT>CIM. Changes in the pharmacokinetics of these agents were recorded in patients compared to data reported for healthy volunteers. A significant difference between groups (G1/G2) was found in relation to biological half-life and volume of distribution for both piperacillin and meropenem


Subject(s)
Piperacillin/analysis , Burns/diagnosis , Meropenem/analysis , Patients/classification , Shock, Septic/complications , Pharmacokinetics , Pharmaceutical Preparations , Cross Infection/complications , Chromatography, Liquid/methods , Critical Illness/classification , Systemic Inflammatory Response Syndrome/diagnosis , Pharmacologic Actions , Enterobacteriaceae , Dosage , Intensive Care Units/classification , Anti-Infective Agents/analysis
11.
Braz. J. Pharm. Sci. (Online) ; 58: e20139, 2022. tab, graf
Article in English | LILACS | ID: biblio-1403755

ABSTRACT

Abstract Compounding pharmacies play an important role not only in compounding personalized formulations, but also preparing drugs at the same concentration and dosage as those from commercial manufacturers. The excipients used in compounding are generally standardized for many drugs, however they do not consider the intrinsic properties, such as the poor water solubility, of each substance. The excipient performance of commercially available compounded furosemide capsules in 7 compounding pharmacies from Manaus was evaluated and compared them to the performance of the reference medicinal product (Lasix® tablets) and 2 batches of capsules made in-house (T2 and T4) with a standardized excipient. All batches were subjected to tests for weight variation, assay, uniformity of dosage units, disintegration and dissolution profile. Of the 7 different compound formulas acquired in the compounding pharmacies, only 2 passed all tests. Most formulas passed the tests for weight determination, disintegration time and assay, however batches from 2 establishments failed in regards to the uniformity of the content and 5 batches failed the dissolution test. The reference medicinal product was approved in all tests, as were the T2 capsules made in-house with drug-excipient ratio 1:2. These results confirm the importance of the excipient composition, especially for poorly soluble drugs.


Subject(s)
Tablets/adverse effects , Capsules/analysis , Excipients/analysis , Furosemide/analysis , Pharmacies/standards , Quality Control , Pharmaceutical Preparations/classification , Good Manipulation Practices , Dosage , Dissolution
12.
São Paulo; s.n; s.n; 2022. 143 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1416818

ABSTRACT

Leptospira spp. constitui um grupo de bactérias espiroquetas gram-negativas englobando espécies saprofíticas, intermediárias e patogênicas, sendo as últimas agentes causadores da leptospirose, doença zoonótica de alcance mundial e endêmica em regiões tropicais em desenvolvimento. O crescente número de espécies identificadas de leptospiras destaca ainda mais sua diversidade genética e mecanismos de virulência únicos, muitos deles com função ainda desconhecida. Esforços para o desenvolvimento de novas vacinas com proteção cruzada e efeito duradouro revelaram possíveis candidatos vacinais que necessitam ser adequadamente validados, sendo assim, há ainda uma urgente necessidade de uma vacina universal contra a leptospirose capaz de controlar e reduzir os surtos cada vez mais frequentes da doença. Adesinas são importantes fatores de virulência em diversos patógenos, constituindo antígenos promissores para o desenvolvimento de vacinas contra a leptospirose, assim como para o desenvolvimento de métodos diagnósticos mais rápidos e precisos. Previamente, foram identificadas três proteínas hipotéticas conservadas em L. interrogans pela técnica de phage display, denominadas arbitrariamente como LepA069, LepA962 e LepA388. A expressão do gene codificador da proteína LepA069 apresentou aumento de aproximadamente 70 % em animais infectados por leptospiras virulentas, representando a primeira evidência funcional desta proteína ainda desconhecida. Porções recombinantes da lipoproteína hipotética LepA962 (LepA962_Nt e LepA962_Phg) foram obtidos, sendo demonstrada a forte interação da proteína LepA962_Phg, contendo a sequência identificada por phage display, com laminina, fibronectina plasmática, colágeno I e fibrinogênio de maneira dose-dependente. Adicionalmente, LepA962_Phg apresentou ligação às células VERO e à sua matriz extracelular secretada, e o soro obtido a partir desta proteína recombinante foi capaz de se ligar à superfície de leptospiras virulentas, indicando que LepA962_Phg pode representar um importante domínio de interação entre as leptospiras e seu hospedeiro. Finalmente, a proteína LepA388 pertencente a uma extensa família de proteínas modificadoras de virulência com função desconhecida (DUF_61), presente apenas nas leptospiras patogênicas mais virulentas, apresentou aumento na expressão de seu gene codificador em animais infectados por leptospiras virulentas de acordo com dados na literatura. Além disso, porções recombinantes da região Nterminal desta proteína apresentaram ligação a laminina, colágenos I e IV, vitronectina e fibronectinas plasmática e celular, principalmente considerando a sequência identificada por phage display. Estes dados reforçam as predições de modelos tridimensionais da proteína LepA388 e de outros membros da família DUF_61, as quais identificam domínios semelhantes a toxinas (como abrina e CARDS) responsáveis pela ligação e internalização celulares nos hospedeiros. Dados recentes sugerem um possível papel citotóxico desempenhado pelas proteínas desta família em leptospiras, as quais podem também ser consideradas potenciais candidatas vacinais e para diagnóstico da leptospirose, devido à sua distribuição restrita em espécies e cepas patogênicas de importância para saúde humana.


Leptospira spp. constitutes a group of gram-negative spirochete bacteria comprising saprophytic, intermediate and pathogenic species, the last being causative agents of leptospirosis, a zoonotic disease of worldwide extent and endemic in developing tropical regions. The growing number of identified leptospiral species further highlights their genetic diversity and unique virulence mechanisms, many of them with unknown function. Efforts to develop new vaccines with cross-protection and long-lasting effect have revealed possible vaccine candidates that need to be properly validated. Therefore, there is still an urgent need for a universal vaccine against leptospirosis capable of controlling and reducing the increasing outbreaks of the disease. Adhesins are important virulence factors in several pathogens, constituting promising antigens for the development of vaccines against leptospirosis, as well as for the development of faster and more accurate diagnostic methods. Previously, three conserved hypothetical proteins in L. interrogans were identified by phage display technique, arbitrarily named as LepA069, LepA962 and LepA388. Expression of the LepA069 encoding gene showed an increase of approximately 70 % in animals infected by virulent leptospires, representing the first functional evidence of this still unknown protein. Recombinant portions of the hypothetical lipoprotein LepA962 (LepA962_Nt and LepA962_Phg) were obtained, demonstrating the strong interaction of the LepA962_Phg protein, containing the sequence identified by phage display, with laminin, plasma fibronectin, collagen I and fibrinogen in a dose-dependent manner. Furthermore, LepA962_Phg showed binding to VERO cells and its secreted extracellular matrix, and the serum obtained from this recombinant protein was able to bind to the surface of virulent leptospires, indicating that LepA962_Phg may represent an important domain of interaction between leptospires and its host. Finally, LepA388 protein belonging to an extensive family of virulence modifying proteins with unknown function (DUF_61), present only in the most virulent pathogenic leptospires, showed an increase in the expression of its encoding gene in animals infected by virulent leptospires according to data in literature. Moreover, recombinant portions of the N-terminal region of this protein showed binding to laminin, collagens I and IV, vitronectin and plasma and cell fibronectins, especially considering the sequence identified by phage display. These data support the predictions of three-dimensional models of the LepA388 protein and other members of the DUF_61 family, which identify toxin-like domains (such as abrin and CARDS) responsible for cellular binding and internalization in hosts. Recent data suggest a possible cytotoxic role played by proteins of this family in leptospires, which can also be considered potential vaccine candidates and antigens for diagnosis, due to their restricted distribution in pathogenic species and strains of importance to human health


Subject(s)
Adhesins, Bacterial/classification , Virulence Factors/adverse effects , Vaccine Development/instrumentation , Leptospira interrogans/metabolism , Virulence , Vaccines/analysis , Dosage , Cell Surface Display Techniques , Leptospirosis/pathology
13.
Braz. J. Pharm. Sci. (Online) ; 58: e19674, 2022. tab, graf
Article in English | LILACS | ID: biblio-1383973

ABSTRACT

Abstract In the present study, free interstitial levels reached by metformin in the liver were investigated in control and diabetic rats by microdialysis. Firstly, a bioanalytical method using an HPLC-UV system to determine the drug concentration in microdialysis samples was validated. The blood glucose levels and biochemical parameters were investigated in control and diabetic animals. Following that, both groups received a dose of 50 mg/kg of metformin iv bolus and the free interstitial levels reached in the liver were assessed by microdialysis. The method was validated according to FDA guidelines being suitable to quantify free concentrations of metformin in the liver of control and diabetics rats. Free exposure to metformin was similar in control and diabetic animals: AUC0-∞ 118.50 ± 40.18 vs 112.93 ± 50.25 µg.h/mL, respectively. The half-life in tissue was similar to that described in the literature for plasma. Hence diabetes induced by streptozotocin after administration of nicotinamide in our study did not damage the renal and hepatic function of the animals. The levels reached in the liver were 1.6 times higher than the free plasma concentrations, demonstrating higher liver penetration of metformin. This is the first investigation in liver interstitial concentration of metformin in control and diabetic rats


Subject(s)
Animals , Male , Rats , Rats, Wistar/classification , Liver/abnormalities , Metformin/adverse effects , Blood Glucose , Pharmaceutical Preparations/analysis , Chromatography, High Pressure Liquid/methods , Microdialysis/instrumentation , Diabetes Mellitus, Experimental/chemically induced , Dosage
14.
Rev. Nutr. (Online) ; 35: e200148, 2022. tab
Article in English | LILACS | ID: biblio-1360809

ABSTRACT

ABSTRACT Objective Dietary supplements use is increasing. Dietary supplements may contain high doses of substances or dangerous ingredient combinations. This article aims to investigate, by analyzing dietary supplements labels, if there are any doping substances or dangerous amounts of any other component in the reviewed dietary supplements. Methods Several brands which possessed their supplements sorted in pre-workout and post-workout were analyzed. 40 dietary supplements with all ingredients described were included. The minimum and maximum dosages of dietary supplements were statistically described as Mean±SD. Results Citrus aurantium extract, Yohimbe extract, Garcinia cambogia extract and Maca root extract were reported in some of the analyzed dietary supplements. Regarding caffeine, the pre-workout group displayed higher mean caffeine (241±86mg) than the post-workout group (183±68mg), and the minimal mean dose was 226±84mg; meanwhile, the maximal mean dose was 242±88mg. Concerning creatine, the pre-workout group displayed lower mean creatine (3106±1079mg) than the post-workout group (4137±4177mg), and the minimal mean dose was 3167±1728mg; meanwhile, the maximal mean dose was 3917±3643mg. The salt content in the post-workout group displayed a much higher mean (2155±4486mg) than the pre-workout group (464±605mg), and the minimal mean dose was 1635±3930mg; meanwhile, the maximal mean dose was 1708±3926g. Conclusions No doping substances were reported in the dietary supplements, but consumption recommendations on the label could lead to excessive consumption of some not yet fully tested ingredients.


RESUMO Objetivo O uso de suplementos alimentares está a aumentar. Estes podem conter altas doses de substâncias ou combinações de ingredientes perigosas. Este artigo procura encontrar, analisando os rótulos dos produtos, se existem substâncias dopantes ou nocivas. Métodos Foram analisadas várias marcas cujos respectivos suplementos foram classificados em pré e pós-treino. Foram incluídos 40 suplementos com todos os ingredientes descritos. A respectiva dose mínima e máxima foi descrita estatisticamente como média ± DP. Resultados Extratos de Citrus aurantium, Yohimbe, Garcinia cambogia e raiz de Maca foram encontrados nos suplementos analisados. O grupo pré-treino apresentou maior média de cafeína (241±86mg) do que o grupo pós-treino (183±68mg), e a dose média mínima foi de 226±84mg, enquanto a dose média máxima foi de 242±88 mg. O grupo pré-treino apresentou menor média de creatina (3106±1079mg) do que o grupo pós-treino (4137±4177mg), e a dose média mínima foi de 3167±1728mg, enquanto a dose média máxima foi de 3917±3643mg. O grupo pós-treino apresentou uma maior média de sal (2155±4486mg) do que o grupo pré-treino (464±605mg), e a dose média mínima foi 1635±3930mg, enquanto a dose média máxima foi de 1708±3926mg. Conclusão Não foram encontradas substâncias dopantes nos suplementos, mas algumas recomendações de consumo nos rótulos poderão levar à sobredose de certos ingredientes menos testados.


Subject(s)
Dietary Supplements/analysis , Dietary Supplements/toxicity , Dosage , Performance-Enhancing Substances , Risk Assessment
15.
Archives of Orofacial Sciences ; : 31-45, 2022.
Article in English | WPRIM | ID: wpr-962521

ABSTRACT

ABSTRACT@#Inappropriate antibiotic prescribing in dentistry has been widely reported but local studies are scarce. We aimed to evaluate antibiotic prescribing practices among dental officers in a public dental primary care clinic against current guidelines: specifically assessing the number, appropriateness, accuracy of prescriptions, type of antibiotics prescribed and repeated prescribing of the same type of antibiotics within a specific duration. A retrospective audit consisting of two cycles (1st cycle: July to September 2018, 2nd cycle: July to September 2019) was carried out by manually collecting relevant data of patients (aged 18 and above) who were prescribed antibiotics from carbon copies of prescription books. Between each cycle, various interventions such as education through a continuous professional development (CPD) session, presentation of preliminary findings and making guidelines more accessible to dental officers were implemented. When the 1st and 2nd cycles were compared, the number of antibiotic prescriptions issued reduced from 194 to 136 (–30.0%) whereas the percentage of appropriate prescriptions increased slightly by 4.1%. Inaccurate prescriptions in terms of dosage and duration decreased (–0.5% and –13.7%, respectively) whilst drug form and frequency of intake increased (+15.7% and +0.7%, respectively). Repeated prescribing of the same antibiotics by the same officer within a period of ≤6 weeks no longer occurred. Amoxicillin and metronidazole were most commonly prescribed in both cycles. Overall, the antibiotic prescribing practices did not closely adhere to current guidelines. However, clinical audit in conjunction with targeted interventions resulted in improvement in the antibiotic prescribing patterns. Thus, further intervention and re-audit is necessary.


Subject(s)
Dosage , Dental Clinics , Clinical Audit
16.
African Health Sciences ; 22(3): 436-441, 2022-10-26. Figures, Tables
Article in English | AIM | ID: biblio-1401445

ABSTRACT

Background: World Health Organization (WHO) advocates use of weight bands in antiretroviral therapy (ART) guidelines. Allometric scaling could be a more reliable method because it uses a non-linear approach in relating dose to body weight. This study evaluates performance of the allometric ¾ power model in comparison to WHO weight band method in children receiving ART. Methods: Records of children receiving (ABC/3TC) + DTG were reviewed. Paediatric ABC/3TC dose was calculated from the adult dose using the allometric ¾ power model and compared to WHO weight band dose. Results: WHO weight band strategy grouped 50.6% of the children in the 25 kg category and therefore received the adult dose of ABC/3TC (600 mg/300 mg); only 1.1% received this dose with allometric scaling. Mean dose (3.8 tablets) for the WHO weight band dosing method was found to be significantly higher (p<0.0001) than for allometric scaling (1.5 tablets). Conclusions: WHO weight bands may result in the 25 kg weight category receiving a much higher dose leading to ADRs. Using allometric scaling, we recommend a weight band strategy that could improve paediatric ABC/3TC dosing


Subject(s)
Body Weight , Antiretroviral Therapy, Highly Active , Dosage , Multidimensional Scaling Analysis , World Health Organization , Child
17.
Ethiop. j. health sci. (Online) ; 32(6): 1101-1106, 2022. tables
Article in English | AIM | ID: biblio-1402262

ABSTRACT

BACKGROUND: Computed Tomography plays a priceless role for diagnostic and therapeutic purpose; however,applying an optimized Computed Tomography Technique to produce qualified image while delivering minimum radiation dose to patients is the common challenge. The main objective of this study was to establish local diagnostic reference levels for adult patients who visited abdominopelvic Computed Tomography examination. METHODS: A total of 158 patients who had taken abdominopelvic Computed Tomography examination from three selectedAmhara region hospitals were investigated. Both prospective and retrospective techniques of data collection were used while collecting the data in the entire sample. Two GE - Optima Computed Tomography 540 (16 slices) and one Phillips ­ Brilliance (64slices), were employed during data collections. Data for patient demographics scan protocols, Computed Tomography dose descriptors and machine specifications were collected and analyzed by using SPSS software version 26. RESULTS: The third quartile estimated computed tomography dose index volume and dose length product, which is the local Diagnostic Reference Levels, were 12 mGy and 1904 cm.mGy respectively. The investigated local Diagnostic Reference Levels of Computed Tomography Dose index volume (mGy) was comparable to other international Diagnostic Reference Levels. However, the third quartile value of dose length product (cm.mGy) was higher than other reported international Diagnostic Reference Levels. CONCLUSION: The values of local Diagnostic Reference Levels presented in this work can be used as a baseline upon which future dose measurements can be compared in Amhara region


Subject(s)
Humans , Patients , Four-Dimensional Computed Tomography , Tomography , Dosage , Patient Outcome Assessment
19.
Rev. colomb. anestesiol ; 49(4): e200, Oct.-Dec. 2021. tab, graf
Article in English | LILACS, COLNAL | ID: biblio-1341236

ABSTRACT

Abstract Introduction Vasopressors are essential in the management of various types of shock. Objective To establish the trend of vasopressors use in the intensive care units (ICU) in a population of patients affiliated with the Colombian Health System, 2010-2017. Methods Observational trial using a population database of patients hospitalized in eleven ICUs in various cities in Colombia. The drugs dispensed to hospitalized patients over 18 years old, from January 2010 until December 2017 were considered. A review and analysis of the vasopressors dispensed per month was conducted, taking into account sociodemographic and pharmacological variables (vasopressor used and daily doses defined per 100/beds/day (DBD). Results 81,348 dispensations of vasopressors, equivalent to 26,414 treatments in 19,186 patients receiving care in 11 hospitals from 7 cities were reviewed. The mean age of patients was 66.3±18.1 years and 52.6 % were males. Of the total number of treatments recorded, 17,658 (66.8 %) were with just one vasopressor. Norepinephrine was the most frequently prescribed drug (75.9 % of the prescriptions dispensed; 60.5 DBD), followed by adrenaline (26.6 %; 41.6 DBD), dopamine (19.4%), dobutamine (16.0 %), vasopressin (8.5 %) and phenylephrine (0.9 %). The use of norepinephrine increased from 2010 to 2017 (+6.19 DBD), whilst the use of other drugs decreased, particularly the use of adrenaline (-60.6 DBD) and dopamine (-10.8 DBD). Conclusions Norepinephrine is the most widely used vasopressor showing a growing trend in terms of its use during the study period, which is supported by evidence in favor of its effectiveness and safety in patients with shock.


Resumen Introducción Los fármacos vasopresores son fundamentales en el manejo de los diferentes tipos de choque. Objetivo Determinar la tendencia de utilización de fármacos vasopresores en unidades de cuidados intensivos (UCI) en una población de pacientes afiliados al Sistema de Salud de Colombia, 2010-2017. Métodos Estudio observacional, a partir de una base de datos poblacional con pacientes hospitalizados en once UCI de diferentes ciudades de Colombia. Se obtuvieron las dispensaciones de pacientes mayores de 18 años hospitalizados desde enero de 2010 hasta diciembre de 2017. Se hizo revisión y análisis de la dispensación mensual de vasopresores. Se consideraron variables sociodemográficas y farmacológicas (medicamento vasopresor usado y dosis diarias definidas por 100 camas/día [DCD]). Resultados Se revisaron 81.348 dispensaciones de vasopresores, equivalentes a 26.414 terapias en 19.186 pacientes atendidos en 11 hospitales de 7 ciudades, cuya edad promedio fue 66,3±18,1 años y el 52,6 % eran hombres. Del total de terapias registradas, 17.658 (66,8 %) fueron con un solo vasopresor. La norepinefrina fue el más comúnmente prescrito (75,9 % de las dispensaciones; 60,5 DCD), seguido por adrenalina (26,6 %; 41,6 DCD), dopamina (19,4 %), dobutamina (16,0 %), vasopresina (8,5 %) y fenilefrina (0,9 %). El uso de norepinefrina se incrementó de 2010 a 2017 (+6,19 DCD), mientras que el de otros fármacos disminuyó, especialmente adrenalina (-60,6 DCD) y dopamina (-10,8 DCD). Conclusiones La norepinefrina es el fármaco vasopresor más utilizado y el que ha demostrado una tendencia de uso incremental durante el periodo de estudio, lo cual está respaldado por evidencia a favor de su efectividad y seguridad en pacientes con choque.


Subject(s)
Humans , Male , Middle Aged , Aged , Shock , Vasoconstrictor Agents , Vasopressins , Intensive Care Units , Phenylephrine , Pharmaceutical Preparations , Dopamine , Epinephrine , Norepinephrine , Dobutamine , Drug Utilization , Dosage , Prescriptions
20.
Hematol., Transfus. Cell Ther. (Impr.) ; 43(4): 468-475, Oct.-Dec. 2021. tab, graf
Article in English | LILACS | ID: biblio-1350824

ABSTRACT

ABSTRACT Introduction: Although the efficacy of hydroxyurea (HU) in inhibiting erythrocyte sickling has been well demonstrated, the action of this drug on human neutrophils and the mechanism by which it improves the manifestations of the disease have not been studied thoroughly. We aimed to investigate the cell viability, along with inflammatory and oxidative markers in the neutrophils of sickle cell anemia (SCA) patients and the effects of HU therapy on these cells, by evaluating the dose-responsiveness. Methods: In the present study, 101 patients (45 men and 56 women, aged 18-69 years) with SCA were divided into groups according to the use or not of HU: the SS group (without HU treatment, n = 47) and the SSHU group (under HU treatment, n = 54). The SSHU group was further stratified into subgroups according to the daily dose of the drug that patients already used: SSHU - 0.5 g (n = 19); SSHU - 1 g (n = 26) and SSHU - 1.5-2 g (n = 9). A control group (AA) comprised 50 healthy individuals. Neutrophils isolated from whole blood were analyzed using Trypan Blue, monoiodotyrosine (MTT) and lactate dehydrogenase (LDH) toxicity assays. Myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and concentrations of interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α) and malonaldehyde (MDA) were also measured. Results: Neutrophils from SCA patients showed membrane fragility and a significant decrease in cell viability when analyzed by Trypan Blue (p < 0.05), MTT (p < 0.001) and LDH (p = 0.011), compared to the AA group. Levels of inflammatory (MPO, TNF-α, and IL-10) and oxidative markers (SOD, GSH-Px, and MDA) were also altered (p < 0.05) in these cells, showing a significant difference in the SSHU-1g and SSHU - 1.5-2 g groups, compared to the SS group. Treatment with HU reverted the levels of all markers to concentrations similar to those in healthy individuals in a positive dose-effect relationship. Conclusion: The HU did not generate a cytotoxic effect on neutrophils in SCA patients, but it modulated their oxidative and inflammatory mechanisms, promoting cytoprotection with a positive dose-effect.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Hydroxyurea , Anemia, Sickle Cell , Tumor Necrosis Factor-alpha , Oxidative Stress , Cytotoxicity, Immunologic , Dosage , Inflammation , Malondialdehyde , Neutrophils
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