Research on the formulation and revision of standard limits for antimony,boron and vanadium in the "Standards for Drinking Water Quality (GB5749-2022)" in China / 中华预防医学杂志

China is rich in antimony, boron, and vanadium mineral resources, which have been detected in environmental water bodies and drinking water. During the revision process of the "Standards for Drinking Water Quality (GB5749-2006)", research and evaluation are focused on three indicators: antimony, boron and vanadium. Vanadium is added and the limit value of boron is adjusted. This study reviews and discusses the technical contents related to the revision of the antimony, boron and vanadium, including the environmental presence levels, exposure status, health effects, and the revision of the standard limits of these three indicators. Suggestions are also made for the implementation of this standard.

Nuclear Factor-κB Signaling Mediates Antimony-induced Astrocyte Activation / 生物医学与环境科学（英文）

Objective@#Antimony (Sb) has recently been identified as a novel nerve poison, although the cellular and molecular mechanisms underlying its neurotoxicity remain unclear. This study aimed to assess the effects of the nuclear factor kappa B (NF-κB) signaling pathway on antimony-induced astrocyte activation.@*Methods@#Protein expression levels were detected by Western blotting. Immunofluorescence, cytoplasmic and nuclear fractions separation were used to assess the distribution of p65. The expression of protein in brain tissue sections was detected by immunohistochemistry. The levels of mRNAs were detected by Quantitative real-time polymerase chain reaction (qRT-PCR) and reverse transcription-polymerase chain reaction (RT-PCR).@*Results@#Antimony exposure triggered astrocyte proliferation and increased the expression of two critical protein markers of reactive astrogliosis, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP), indicating that antimony induced astrocyte activation @*Conclusion@#Antimony activated astrocytes by activating the NF-κB signaling pathway.

Caracterización clínico epidemiológica de la leishmaniosis visceral infantil / Clinical epidemiological characterization of children visceral leishmaniasis

Introducción: La leishmaniosis visceral es la más grave de las formas clínicas de la leishmaniosis, afecta principalmente a los niños y es potencialmente fatal. Objetivo: Exponer la caracterización clínico-epidemiológica de la leishmaniosis visceral en población pediátrica y su respuesta terapéutica. Métodos: Se realizó un estudio retrospectivo, longitudinal y descriptivo en el Hospital Italiano, Ciudad de Djibouti en el período septiembre 2016-agosto 2017. El universo lo conformaron 166 menores de 15 años que ingresaron con diagnóstico de fiebre prolongada sin foco de localización, la muestra fue de 22 niños con diagnóstico confirmado de leishmaniosis visceral. La información se obtuvo de las historias clínicas. Se operacionalizaron 20 variables: sociodemográficas, clínicas, analíticas, terapéuticas y evolutivas. Se utilizó el procesador Epidat 3.1. Los resultados se expresaron en valores absolutos y porcentajes. Resultados: Se diagnosticó leishmaniosis visceral en 13,2 por ciento de niños hospitalizados por fiebre prolongada, 90,9 por ciento de procedencia rural y 59,1 por ciento desnutridos. El 77,3 por ciento de los casos recibió antimoniales, 90,9 por ciento tuvo estadía hospitalaria mayor de 21 días y el 36,4 por ciento se complicó con neumonía. Conclusiones: La leishmaniosis visceral es una entidad relativamente frecuente en niños admitidos por fiebre prolongada en el Hospital Italiano, predominan los varones desnutridos, mayores de cinco años de edad, procedentes de zonas rurales. La fiebre y la esplenomegalia son manifestaciones clínicas constantes, la anemia y la leucopenia los principales hallazgos de laboratorio. La aplicación de antimoniales es el tratamiento electivo, con larga estadía hospitalaria y la neumonía es la complicación más frecuente(AU)

Introduction: Visceral leishmaniasis is the most severe clinical form of leishmaniasis that mainly affects children and is potentially fatal. Objective: To explain the clinical-epidemiological characterization of visceral leishmaniasis in the pediatric population and its therapeutic response. Methods: It was conducted a retrospective, longitudinal and descriptive study in the Italian Hospital, Djibouti City in the period from September 2016 to August 2017. The sample group was formed by 166 children under 15 years old that were admitted with a diagnosis of prolonged fever without localization focus and the sample was of 22 children with confirmed diagnosis of visceral leishmaniasis. The information was obtained from the clinical records. Twenty variables were operationalized: sociodemographic, clinical, analytical, therapeutic and evolutive ones. Epidat 3.1 proccessor was used. The results were expressed in absolute values and percentages. Results: Visceral leishmaniasis was diagnosed in 13.2 percent children that were admitted in hospital due to prolonged fever, 90.9 percent of them were from rural areas and 59.1 percent were undernourished. 77,3 percent of the cases had antimonial treatment, 90.9 percent had hospital stay for more than 21 days and the 36.4 percent had complications due to pneumonia. Conclusions: Visceral leishmaniasis is a relatively frequent entity in children admitted in the Italian Hospital due to prolonged fever with a predominance of undernourished males, older that five years and from rural areas. Fever and splenomegaly are constant clinical manifestations, and anemia and leucopenia are the main laboratory findings. The use of antimonials is the election treatment with long hospital stay, and pneumonia is the most frequent complication(AU)

The heterologous expression of Escherichia coli MutT enzyme is involved in the protection against oxidative stress in Leishmania braziliensis

BACKGROUND Oxidative stress is responsible for generating DNA lesions and the 8-oxoguanine (8-oxoG) is the most commonly lesion found in DNA damage. When this base is incorporated during DNA replication, it could generate double-strand DNA breaks and cellular death. MutT enzyme hydrolyzes the 8-oxoG from the nucleotide pool, preventing its incorporation during DNA replication. OBJECTIVES To investigate the importance of 8-oxoG in Leishmania infantum and L. braziliensis, in this study we analysed the impact of heterologous expression of Escherichia coli MutT (EcMutT) enzyme in drug-resistance phenotype and defense against oxidative stress. METHODS Comparative analysis of L. braziliensis and L. infantum H2O2 tolerance and cell cycle profile were performed. Lines of L. braziliensis and L. infantum expressing EcMutT were generated and evaluated using susceptibility tests to H2O2 and SbIII, cell cycle analysis, γH2A western blotting, and BrdU native detection assay. FINDINGS Comparative analysis of tolerance to oxidative stress generated by H2O2 showed that L. infantum is more tolerant to exogenous H2O2 than L. braziliensis. In addition, cell cycle analysis showed that L. infantum, after treatment with H2O2, remains in G1 phase, returning to its normal growth rate after 72 h. In contrast, after treatment with H2O2, L. braziliensis parasites continue to move to the next stages of the cell cycle. Expression of the E. coli MutT gene in L. braziliensis and L. infantum does not interfere in parasite growth or in susceptibility to SbIII. Interestingly, we observed that L. braziliensis EcMutT-expressing clones were more tolerant to H2O2 treatment, presented lower activation of γH2A, a biomarker of genotoxic stress, and lower replication stress than its parental non-transfected parasites. In contrast, the EcMutT is not involved in protection against oxidative stress generated by H2O2 in L. infantum. MAIN CONCLUSIONS Our results showed that 8-oxoG clearance in L. braziliensis is important to avoid misincorporation during DNA replication after oxidative stress generated by H2O2.

Leishmania infantum induces high phagocytic capacity and intracellular nitric oxide production by human proinflammatory monocyte

BACKGROUND The mechanism of resistance to SbIII in Leishmania is complex, multifactorial and involves not only biochemical mechanisms, but also other elements, such as the immune system of the host. OBJECTIVES In this study, putative changes in the immunological profile of human monocytes infected with wild-type (WT) and antimony (SbIII)-resistant Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum lines were evaluated. METHODS Susceptibility assays WT and SbIII-resistant L. braziliensis and L. infantum were performed using lines THP-1 human monocytic lineage. Phagocytic capacity, cytokine profile, intracellular nitric oxide (NO) production and surface carbohydrate residues profile were performed in peripheral blood monocytes by flow cytometry. FINDINGS The phagocytic capacity and intracellular NO production by classical (CD14++CD16-) and proinflammatory (CD14++CD16+) monocytes were higher in the presence of L. infantum lines compared to L. braziliensis lines. The results also highlight proinflammatory monocytes as the cellular subpopulation of major relevance in a phagocytosis event and NO expression. It is important to note that L. infantum induced a proinflammatory cytokine profile characterised by higher levels of TNF-α in culture supernatant than L. braziliensis. Conversely, both Leishmania lines induce high levels of IL-6 in culture supernatant. Analysis of the expression profile of surface carbohydrates showed that L. braziliensis presents 4.3-fold higher expression of galactose(β1,4)N-acetylglucosamine than L. infantum line. Interestingly, the expression level of α-N-acetylgalactosamine residues was 2-fold lower in the SbIII-resistant L. braziliensis line than its counterpart WT line, indicating differences in surface glycoconjugates between these lines. MAIN CONCLUSIONS Our results showed that L. braziliensis and L. infantum induce different innate immune responses and a highly inflammatory profile, which is characteristic of infection by L. infantum, the species associated with visceral disease.

FLI1 gene influences lesion size and skin test may predict therapeutic response in cutaneous leishmaniasis

Genes associated with wound healing have been shown to be risk factors for cutaneous leishmaniasis (CL) which is caused by Leishmania braziliensis. In this study, we examined whether the genes previously associated with CL influenced the clinical outcome. Patients were genotyped and retrospectively classified as responders, who were cured with a single course of pentavalent antimony (Sbv), or as refractories, who did not respond to Sbv. Patients characterised as responders showed a stronger response to the leishmanin skin test (LST) when compared to the refractory subjects (p = 0.0003). Furthermore, we observed an association between the FLI1 CC genotype and an increased size of ulcers (p = 0.0170). We suggest that the leishmanin skin test may be a predictive tool for therapeutic outcome and reinforce FLI1 as a potential influencer of susceptibility and lesion size in CL.

Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice

Cutaneous leishmaniasis (CL) is a parasitic disease caused by the protozoan Leishmania spp. Pentavalent antimonial agents have been used as an effective therapy, despite their side effects and resistant cases. Their pharmacokinetics remain largely unexplored. This study aimed to investigate the pharmacokinetic profile of meglumine antimoniate in a murine model of cutaneous leishmaniasis using a radiotracer approach. Methods: Meglumine antimoniate was neutron-irradiated inside a nuclear reactor and was administered once intraperitoneally to uninfected and L. amazonensis-infected BALB/c mice. Different organs and tissues were collected and the total antimony was measured. Results: Higher antimony levels were found in infected than uninfected footpad (0.29% IA vs. 0.14% IA, p = 0.0057) and maintained the concentration. The animals accumulated and retained antimony in the liver, which cleared slowly. The kidney and intestinal uptake data support the hypothesis that antimony has two elimination pathways, first through renal excretion, followed by biliary excretion. Both processes demonstrated a biphasic elimination profile classified as fast and slow. In the blood, antimony followed a biexponential open model. Infected mice showed a lower maximum concentration (6.2% IA/mL vs. 11.8% IA/mL, p = 0.0001), a 2.5-fold smaller area under the curve, a 2.7-fold reduction in the mean residence time, and a 2.5-fold higher clearance rate when compared to the uninfected mice. Conclusions: neutron-irradiated meglumine antimoniate concentrates in infected footpad, while the infection affects antimony pharmacokinetics.(AU)

Antimony resistance in Leishmania (Viannia) braziliensis clinical isolates from atypical lesions associates with increased ARM56/ARM58 transcripts and reduced drug uptake

BACKGROUND In addition to the limited therapeutic arsenal and the side effects of antileishmanial agents, drug resistance hinders disease control. In Brazil, Leishmania braziliensis causes atypical (AT) tegumentary leishmaniasis lesions, frequently refractory to treatment. OBJECTIVES The main goal of this study was to characterise antimony (Sb)-resistant (SbR) L. braziliensis strains obtained from patients living in Xakriabá indigenous community, Minas Gerais, Brazil. METHODS The aquaglyceroporin 1-encoding gene (AQP1) from L. braziliensis clinical isolates was sequenced, and its function was evaluated by hypo-osmotic shock. mRNA levels of genes associated with Sb resistance were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Atomic absorption was used to measure Sb uptake. FINDINGS Although clinical isolates presented delayed recovery time in hypo-osmotic shock, AQP1 function was maintained. Isolate 340 accumulated less Sb than all other isolates, supporting the 65-fold downregulation of AQP1 mRNA levels. Both 330 and 340 isolates upregulated antimony resistance marker (ARM) 56/ARM58 and multidrug resistant protein A (MRPA); however, only ARM58 upregulation was an exclusive feature of SbR field isolates. CA7AE seemed to increase drug uptake in L. braziliensis and represented a tool to study the role of glycoconjugates in Sb transport. MAIN CONCLUSIONS There is a clear correlation between ARM56/58 upregulation and Sb resistance in AT-harbouring patients, suggesting the use of these markers as potential indicators to help the treatment choice and outcome, preventing therapeutic failure.

Mucosal leishmaniasis: the experience of a Brazilian referral center

Abstract INTRODUCTION Pentavalent antimonials (Sbv) are the most commonly used drugs for the treatment of mucosal leishmaniasis (ML), despite their high toxicity and only moderate efficacy. The aim of this study was to report therapeutic responses with different available options for ML. METHODS This study was based on a review of clinical records of 35 patients (24 men and 11 women) treated between 2009 and 2015. RESULTS The median age of patients was 63 years, and the median duration of the disease was 24 months. Seventeen patients received Sbv, while nine patients were treated with liposomal amphotericin B (AmB), and another nine patients were treated with fluconazole. Patients treated with AmB received a total median accumulated dose of 2550mg. The mean duration of azole use was 120 days, and the daily dose ranged from 450 to 900mg. At the three-month follow-up visit, the cure rate was 35%, 67%, and 22% for Sbv, AmB, and azole groups, respectively. At the six-month follow-up visit, the cure rates for Sbv, AmB, and azole groups were 71%, 78%, and 33%, respectively. CONCLUSIONS There is a scarcity of effective ML treatment alternatives, and based on our observations, fluconazole is not a valid treatment option.

Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil

BACKGROUND Treatment-refractory visceral leishmaniasis (VL) has become an important problem in many countries. OBJECTIVES We evaluated the antimony-resistance mechanisms of Leishmania infantum isolated from VL patients refractory or responsive to treatment with pentavalent antimony. METHODS Strains isolated from antimony-refractory patients (in vitro antimony-resistant isolates) and antimony-responsive patients (in vitro antimony-sensitive isolates) were examined. Morphological changes were evaluated by transmission electron microscopy after trivalent antimony exposure. P-glycoprotein (P-gp) efflux pump activity was evaluated using the pump-specific inhibitor verapamil hydrochloride, and the role of thiol in trivalent antimony resistance was investigated using the enzymatic inhibitor L-buthionine sulfoximine. FINDINGS Antimony treatment induced fewer alterations in the cellular structure of L. infantum resistant isolates than in that of sensitive isolates. P-gp efflux activity was not involved in antimony resistance in these isolates. Importantly, the resistant isolates contained higher levels of thiol compared to the sensitive isolates, and inhibition of thiol synthesis in the resistant isolates recovered their sensitivity to trivalent antimony treatment, and enhanced the production of reactive oxygen species in promastigotes exposed to the drug. MAIN CONCLUSIONS Our results demonstrate that isolates from patients with antimony-refractory VL exhibited higher thiol levels than antimony-sensitive isolates. This indicates that redox metabolism plays an important role in the antimony-resistance of New World VL isolates.

Study of the Heavy Metals in Fume of Buckshot, Blood Lead Concentration and Self-Rated Health Status of National Clay Shooting Athletes / 대한스포츠의학회지

PURPOSE: This study was conducted to investigate the levels of heavy metals and self-rated health status of the national clay shooting athletes. METHODS: Fourteen subjects' blood lead level and index of liver damage (aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase) were measured. Heavy metal content in training environment was measured by collecting the buckshot fume. In addition, subjects completed a questionnaire assessing self-rated health status (Todai Health Index). RESULTS: Antimony and lead were detected much more than other heavy metals in the air of the shooting range. The average blood lead level of 14 subjects was significantly higher than the upper limit of normal Korean adults. Blood lead level of male is significantly higher than female and training frequency and the total training time per week were positively correlated to the blood lead level. In the result of survey on self-rated health, the higher the blood lead level, the lower the score of the common subjective physical symptoms. By age, the younger the subjects are, the higher the score of the common subjective symptoms. CONCLUSION: Although the level of heavy metals in fume of buckshot and blood lead was high, national clay shooting athletes thought that they are healthy.

Ascorbate peroxidase overexpression protects Leishmania braziliensis against trivalent antimony effects

Ascorbate peroxidase (APX) is a redox enzyme of the trypanothione pathway that converts hydrogen peroxide (H2O2) into water molecules. In the present study, the APX gene was overexpressed in Leishmania braziliensis to investigate its contribution to the trivalent antimony (SbIII)-resistance phenotype. Western blot results demonstrated that APX-overexpressing parasites had higher APX protein levels in comparison with the wild-type line (LbWTS). APX-overexpressing clones showed an 8-fold increase in the antimony-resistance index over the parental line. In addition, our results indicated that these clones were approximately 1.8-fold more tolerant to H2O2 than the LbWTS line, suggesting that the APX enzyme plays an important role in the defence against oxidative stress. Susceptibility tests revealed that APX-overexpressing L. braziliensis lines were more resistant to isoniazid, an antibacterial agent that interacts with APX. Interestingly, this compound enhanced the anti-leishmanial SbIII effect, indicating that this combination represents a good strategy for leishmaniasis chemotherapy. Our data demonstrate that APX enzyme is involved in the development of L. braziliensis antimony-resistance phenotype and may be an attractive therapeutic target in the design of new strategies for leishmaniasis treatment.

Nova proposta para o tratamento da Leishmaniose tegumentar usando antimoniato de meglumina e oxiranos em associação / New proposal for the treatment of cutaneous leishmaniasis using meglumine antimoniate and oxirans in combination

Esta tese porpõe uma nova abordagem para o tratamento da leishmaniose tegumentar com o antimoniato de N-metilglucamina (antimoniato de meglumina - AM) associado a dois derivados oxiranos. O estudo foi conduzido em modelo murino de infecção in vitro e in vivo por Leishmania (Leishmania) amazonensis. Na primeira etapa do estudo foram descritas alterações histológicas causadas por epoxi-α-lapachona, epoximetil-lausona e AM em camundongos BALB/c não infectados, bem como a predição de algumas de suas propriedades farmacocinéticas. Os resultados indicaram que tanto os oxiranos quanto o antimoniato de meglumina induzem alterações histopatológicas nos órgãos analisados. O epoximetil-lausona foi o mais tóxico para o tecido pulmonar, enquanto os danos mais graves no coração foram causados pelo epoxi-α-lapachona. O AM causou alterações leves a moderadas nos tecidos cardíacos e pulmonares, mas sem qualquer efeito detectado nos tecidos cerebrais. Na segunda etapa foi necessário avaliar a eficácia do epoximetil-lausona sobre a infecção de macrófagos e camundongos BALB/c infectados por L.(L.) amazonensis. Em amastigotas intracelulares, o IC50 do epoximetil-lausona foi ligeiramente superior ao do AM (7,41 ± 0,2 e 4,43 ± 0,25 µM, respectivamente), sendo o efeito mais evidente após 48 horas de exposição (18 vezes e 7,4 vezes inferiores, respectivamente).

Os promastigotas também foram afetados pelo composto, porém o IC50 foi seis vezes maior (45,45 ± 5,0µM), indicando sua especificidade sobre os amastigotas intracelulares. A análise de citotoxicidade revelou que o epoximetil-lausona tem um efeito menor (1,7 ×) comparado ao AM (40,05 ± 3,0 e 24,14 ± 2,6 µM). O tratamento com três doses do epoximetil-lausona reduziu a lesão da pata dos animais infectados em 27 %, enquanto a redução obtida com o AM chegou a 31% nas doses baixa e intermediária, e 64% com a dose mais alta, comparado ao grupo controle. Alterações ultraestruturais detectadas nos amastigotas da lesão constataram comprometimento da integridade dos parasitos. Na etapa final deste estudo foi demonstrado o efeito do tratamento com o AM associado aos oxiranos epoxi-α-lapachona e epoximetil-lausona sobre a infecção experimental in vitro e in vivo. Os compostos foram testados individualmente e em combinações, seguindo as razões: 3:1; 1:1 e 1:3 (p/v) sobre macrófagos infectados. Todos os compostos, assim como suas combinações mostraram índices endocíticos muito inferiores ao grupo controle, sendo as maiores reduções obtidas nas razões de 3:1. O tratamento de camundongos BALB/c com os compostos individualmente e combinados nas mesmas razões levou a reduções significativas das lesões. O melhor efeito das combinações foi observado nas razões de 3:1. Os resultados indicaram que a associação do AM com os oxiranos produz um incremento no efeito leishmanicida, e pode ser considerada uma nova abordagem para o tratamento da leishmaniose cutânea. (AU)

Periungual tegumentary leishmaniasis: a diagnostic challenge

Abstract: Periungual and paronychia-like skin lesions can mimic various diseases, setting up a diagnostic challenge that invariably requires correlation with complementary tests. We report a case of an ulcerated tumor of the nailfold diagnosed as leishmaniasis. Although paronychia-like cutaneous leishmaniasis is a rare variant, its epidemiological relevance in Brazil should prompt dermatologists to include it as a plausible diagnosis thus leading to correct work up and treatment.

Leishmaniasis cutáneo-mucosa: presentación de un caso con compromiso medio-facial / Mucocutaneous leishmaniasis: report of a case with midd lefacial commitment / Lehismaniasis mucocutânea: apresentação de um caso com o compromisso mid-facial

La leishmaniasis es una zoonosis parasitaria causada por protozoos. Puede afectar la piel y las mucosas o presentarse como una enfermedad visceral. La variedad mucocutánea conduce a la destrucción parcial o completa de las membranas mucosas de la nariz, las fauces y la faringe. Aproximadamente un 90% de los casos con afectación mucocutánea se producen en Brasil, Bolivia y Perú. En nuestro país afecta en forma endémica a las provincias del norte desde principios del siglo XX. Se relata el caso de un paciente de 53 años con odinodisfagia de aproximadamente 6 meses de evolución, asociado a formaciones granulomatosas medio- faciales, en el que se diagnosticó leishmaniasis cutaneomucosa mediante el rescate de amastigotes en muestras tomadas de lesiones de paladar blando para estudio anatomopatológico con tinción de Giemsa. Se realizó tratamiento con meglumina antimoniato con buena evolución clínica a partir de los quince días de instaurado el mismo.

Leishmaniasis is a parasitic zoonosis caused by protozoa. It can affect skin, mucous membranes or presented as visceral disease. Mucocutaneous variety leads to partial or complete destruction of the mucous membranes of the nose, mouth and pharynx. Approximately, 90% of cases with mucocutaneous involvement occurs in Brazil, Bolivia and Peru. In our country it affects endemic to the northern provinces since the beginning of the century. The case of a 53-year-old patient with odinodisphagia of approximately 6 months of evolution, associated with mid-facial granulomatous formations in which cutaneomucous leishmaniasis was diagnosed by rescue of amastigotes in samples taken from lesions of soft palate for anatomopathological study with Staining of Giemsa. Treatment with meglumina antimonia was carried out with good clinical evolution from the fifteen days of the same establishment.

A leishmaniose é uma zoonose parasitária causada por protozoários. Ele pode afectar a pele e membranas mucosas ou presente como doença visceral. variedade mucocutânea conduz à destruição parcial ou completa das membranas mucosas do nariz, boca e faringe. Aproximadamente 90% dos casos com envolvimento mucocutânea ocorrem no Brasil, Bolívia e Peru. Em nosso país que afeta endêmica para as províncias do norte, desde o início do século XX. O caso de um odinodisfagia 53 anos, aproximadamente, 6 meses evolução associada com formações granulomatosas mediofaciais em que a leishmaniose mucocutânea foi diagnosticada por resgatar amastigotas em amostras tomadas a partir de lesões do palato mole para estudo histopatológico contou Giemsa. O tratamento foi realizado com antimoniato de meglumina com boa evolução clínica a partir de quinze dias introduzidas ele.

Exposure Assessment of Sb2O3 in PET Food Contact Materials / 生物医学与环境科学（英文）

This study was conducted to do exposure assessment of the possible migration of antimony trioxide (Sb2O3) from Polyethylene terephthalate (PET) food contact materials (FCM). Consumption Factor (CF) and Food-type Distribution Factor (fT) were calculated from survey data with reference to the US FDA method. The most conservative migration conditions were obtained by testing Sb migration from PET FCM based on the Chinese national standard of GB/T 5009.101-2003[1]. Migration levels of Sb from PET FCM were tested and migration levels of Sb2O3 were obtained through molecular weight conversion between Sb and Sb2O3. Exposure assessment of Sb2O3 was undertaken. The Chinese Estimated Daily Intake (EDI) of Sb2O3 resulted from PET FCM was 90.7 ng p-1d-1.

Pentoxifilina no tratamento da leishmaniose tegumentar mucosa / Pentoxifylline in the treatment of mucosal tegumentary leishmaniasis

Contexto: No Brasil, a leishmaniose tegumentar é uma das doenças infecciosas que merece maior atenção, especialmente devido a sua alta magnitude e ao risco de ocorrência de deformidades permanentes nos indivíduos acometidos. Ela pode se apresentar nas seguintes formas clínicas: cutânea, disseminada, mucosa ou mucocutânea e difusa. No período de 2009 a 2013 foram registrados, em média, 21.395 casos/ano, distribuídos em todas as Unidades Federativas do Brasil. Algumas pesquisas têm demonstrado sucesso no emprego da pentoxifilina como coadjuvante no tratamento da leishmaniose mucosa, com desfecho de cura em menor tempo quando comparado ao tratamento convencional. Pergunta: Há evidências de que a pentoxifilina é eficaz e segura no tratamento de pacientes com leishmaniose mucosa? Evidências científicas: Após busca em bases de dados da literatura científica, foram encontradas 4 referências sobre o uso da pentoxifilina no tratamento da leishmaniose mucosa (LM): 3 revisões sistemáticas e 1 ensaio clínico randomizado. Uma das revisões se baseou em uma série de casos de 10 pacientes com LM refratária e as outras 2 revisões sistemáticas incluíram o mesmo ensaio clínico randomizado, já selecionado na busca, com 23 pacientes adultos com LM. Tanto a série de casos, quando o ensaio clínico foram realizados na Bahia e incluíram pacientes infectados por L. braziliensis. Em ambos os estudos, a terapia com pentoxifilina associada ao tratamento padrão com antimonial levou a uma taxa de cura maior e mais rápida das lesões do que a terapia com o antimonial isolado. Os membros da CONITEC presentes na reunião do plenário do dia 05/11/2015 - Deliberaram, por unanimidade, por recomendar a ampliação do uso da pentoxifilina 400mg em \r\nassociação ao antimonial para o tratamento da Leishmaniose Tegumentar Mucosa. A Portaria Nº 67, de 19 de novembro de 2015 - Torna pública a decisão de ampliar o uso da pentoxifilina 400 mg em associação ao\r\nantimonial para o tratamento da leishmaniose tegumentar mucosa no âmbito do Sistema Único de Saúde - SUS.

Clinical audit on treatment of mucosal and multiple cutaneous leishmaniasis lesions with pentavalent systemic antimony

Cutaneous leishmaniasis is a parasitic disease spread by the female sandfly occurring throughout the Americas from Texas to Argentina, and in the Old World, particularly the Middle East and North Africa. The condition is diagnosed every year in travelers, immigrants, and military personnel. The treatment mainstay is pentavalent antimony [e.g., sodium stibogluconate]. Not all patients require treatment; many lesions heal spontaneously. The treatment is usually indicated in mucosal, mucocutaneous and multiple active cutaneous lesions. 30 patients of cutaneous leishmaniasis were included from the dermatology ward. The method of data collection was retrospective. The basis of proposal was local guidelines. The audit type was process. The standard set was "100% patients with mucosal and multiple cutaneous leishmaniasis lesions should be treated with pentavalent systemic antimonials"

Avaliação não-clínica da segurança do antimoniato de meglumina em roedores: toxicocinética, toxicidade para o desenvolvimento e efeitos sobre citocromos P450 hepáticos / Non-clinical safety of meglumine antimoniate evaluation in rodents: toxicokinetics, developmental toxicity and effects on liver cytochromes P450

Antimoniais pentavalentes são considerados medicamentos de primeira linha no tratamento das diferentes formas de leishmaniose. O perfil de segurança dos medicamentos à base de antimônio (Sb), entretanto, ainda não foi completamente elucidado. O objetivo deste conjunto de estudos que constam desta tese foi fornecer informações adicionais sobre a segurança de um curso de tratamento com o antimoniato de meglumina (AM). O primeiro estudo investigou o acúmulo e eliminação do Sb do sangue e órgãos de ratos machos adultos tratados com uma dose diária de AM, por um período de 21 dias consecutivos. Foi observado que o antimônio é lentamente eliminado. O segundo estudo avaliou o desenvolvimento pós-natal da prole nascida e amamentada por ratas tratadas na gestação e lactação até o desmame com AM. A transferência de Sb através da placenta e via leite materno para a prole foi determinada. Os resultados mostraram, em geral, que o desenvolvimento pós-natal e a fertilidade dos ratos expostos não foram alterados. Os dados também sugerem que o Sb passa facilmente para o leite e está presente nesta matriz biológica em uma forma química que o torna bem absorvido pelos lactentes. Além disso, nós também investigamos se as atividades das enzimas citocromo P450 hepáticas (CYP), que participam do metabolismo de endo- e xenobióticos, foram alteradas pelo tratamento. Os resultados mostraram que um curso de tratamento de 24 dias com AM causou um consistente declínio das atividades de CYP1A no fígado de camundongos SW e DBA-2, e uma diminuição nas atividades de CYP2B9/10 nas fêmeas de SW, mas não em DBA-2 de ambos os sexos...

Pentavalent antimony compounds are considered as first choice drugs to treat different clinical manifestations of leishmaniasis. The safety profile of antimony-based anti-leishmanial drugs, however, has not been entirely elucidated so far. The objective of the set of experimental studies presented in this thesis was to provide additional information on the safety of a course of treatment with meglumine antimoniate (MA). The first study was an investigation of the accumulation and clearance of antimony (Sb) in the blood and organs of adult male rats treated with a 21-day course of MA. It was observed that residual Sb is slowly eliminated from rat’s organs and blood. The second study evaluated the postnatal development of the offspring born to and nursed by rats treated during gestation and lactation until weaning with MA. The transfer of Sb via placenta and mothers’ milk to the offspring was determined as well. Results showed that offspring postnatal development and fertility remained virtually unaltered after treatment with MA. Data suggested that Sb is transferred into breast milk and is present there in a chemical form that makes this metalloid bioavailable to suckling pups. Furthermore, we investigated whether activities of liver cytochrome P450 enzymes that take part in the metabolism of endogenous and exogenous substances were altered after a course of treatment with MA. It was found that a 24-d course of treatment with MA caused a consistent decline in CYP1A activity in the mouse liver. A decrease of CYP2B9/10 activity was noted in SW females but not in SW males and in DBA-2 of either sex...

The Trend of Leprosy Treatment / 나학회지

Since Mycobacterium Leprae was founded by Dr. Armauer Hansen in 1873, leprosy was proven to infectious disease by a germ not from hereditaty, from a cause, or from sin. For it has no definite method of treatment, made a conclusion at the 1st international leprosy association meeting at Berlin in 1897, isolation is the only way to prevent the disease. So all country started to built a leprosarium and isolated the leprosy patients. Various methods and drugs were used for leprosy treatment including potassium iodide, arsenic, antimony, copper, sera, vaccines and aniline dyes and then X-ray, radium, electric current till 1925. Chaulmoogra oil was introduced to western world in 1854 by Dr. FJ Mouat and used for the leprosy treatment drug. Dr RM Wilson in Kwangju Leprosy Hospital started to use Chaulmoogra oil since 1909 and reported the results of it at JAMA in 1923. But it was replaced to sulfones in 1940'. Mordern treatment started in 1937 when Parke-Davis co. synthesized promin But promin is expensive and have to injection. Then Dapsone delivered from promin and it could be used per oral. Dr. RM Wilson In Aeyang Hospsoital (former Kwangju leposy hospial) started to use Dapson in 1946 with his son Dr. J Wilson. And it was the first episode to use DDS in Korea. When Dr. Cochraine came and visited all the leprosy centers in Korea in 1955 he noticed that some hospital like Aeyangwon and St. Nazarus used DDS but not other hospital. DDS was adopted as main drug of choice in Carville, Loisiana but noticed dapsone resistant bacilli and then WHO recommended the MDT from 1981.