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Article in Chinese | WPRIM | ID: wpr-934406


Objective:To investigate the diagnostic value of fluorescence quantitative method and G6PD/6PGD ratio method in glucose-6-phosphate dehydrogenase (G6PD) deficiency and the type of gene mutation.Methods:A total of 1 201 patients (711 males and 490 females) with suspected G6PD deficiency in Shanghai Children′s Hospital were collected from June 2018 to March 2021. Fluorescence quantification method, G6PD/6PGD ratio method and multicolor melting curve were used to detects enzyme activity, ratio and gene mutation type. Comparison of each index and evaluation of its diagnostic efficiency were performed.Results:Among 1 201 suspicious samples, 163 cases (135 males and 28 females) were finally diagnosed. 156 cases were diagnosed by fluorescence quantitative method with a detection rate of 95.71%, and 140 cases were diagnosed by G6PD/6PGD ratio method with a detection rate of 85.89%. enzymatic activity of G6PD and ratio of G6PD/6PGD in male were significantly lower than female, and the differences were statistically significant ( U=642.5, 734.5, P<0.001). 112 cases received G6PD gene mutation detection and 92 cases were diagnosed, 74 were hemizygous mutations, 1 were homozygous mutations, 15 were heterozygous mutations, and 2 were compound heterozygous mutations. Among 15 cases of heterozygous mutations, 11 cases were diagnosed by fluorescence quantitative method, the diagnosed rate was 73.33%, 4 cases were diagnosed by G6PD/6PGD ratio method, and the diagnosed rate was 26.67%. A total of 7 mutation sites were detected and the proportions were c.1388G>A (32.22%), c.1376G>T (30.00%), c.871G>A (13.33%), c.1024C>T (11.11%). c.95A>G (7.78%), c.487G>A (4.44%), c.392G>T (1.11%). The enzymatic activities of c.1376G>T and c.1024C>T, c.487G>A were statistically significant ( P<0.001,0.015); the G6PD/6PGD ratios of c.1024C>T and c.1388G>A, c.1376G>T were statistically significant ( P=0.017,0.002,0.011,0.013). Fluorescence quantitative method had sensitivity of 100%, specificity of 95.65%, and the area under the curve (AUC) is 0.972. The sensitivity of the G6PD/6PGD ratio method was 100%, the specificity was 94.57%, and the AUC was 0.979. The sensitivity of fluorescence quantitative method combined with G6PD/6PGD ratio was 96.7%, the specificity was 100%, and the AUC was 0.992. Conclusions:Compared with fluorescence quantification, the G6PD/6PGD ratio method might not be able to diagnose female heterozygotes effectively; The panel of G6PD fluorescence quantification and G6PD/6PGD ratio was helpful to reduce the missed diagnosis. Combined with gene mutation analysis, it could improve the diagnosis rate of G6PD deficiency in the children.

Acta Pharmaceutica Sinica B ; (6): 558-580, 2022.
Article in English | WPRIM | ID: wpr-929314


Hepatocellular carcinoma (HCC) is an aggressive human cancer with increasing incidence worldwide. Multiple efforts have been made to explore pharmaceutical therapies to treat HCC, such as targeted tyrosine kinase inhibitors, immune based therapies and combination of chemotherapy. However, limitations exist in current strategies including chemoresistance for instance. Tumor initiation and progression is driven by reprogramming of metabolism, in particular during HCC development. Recently, metabolic associated fatty liver disease (MAFLD), a reappraisal of new nomenclature for non-alcoholic fatty liver disease (NAFLD), indicates growing appreciation of metabolism in the pathogenesis of liver disease, including HCC, thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment. In this review, we introduce directions by highlighting the metabolic targets in glucose, fatty acid, amino acid and glutamine metabolism, which are suitable for HCC pharmaceutical intervention. We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment. Furthermore, opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.

Article in Chinese | WPRIM | ID: wpr-928701


OBJECTIVE@#To explore the genotype mutation characteristics of patients with glucose-6-phosphate dehydrogenase(G6PD) deficiency in Wuhan.@*METHODS@#A total of 1 321 neonates with positive screening and outpatients were received G6PD mutation detection, 12 kinds of common G6PD mutation in Chinese people was detected by using multicolor melting curve analysis (MMCA) method, for those with negative results, the enzyme activity and clinical information were analyzed, sequencing was recommended after informed consent when it is necessary.@*RESULTS@#Among 1321 patients, a total of 768 mutations were detected out, with a detection rate of 58.1%. A total of 18 types of G6PD genotypes were identified, including c.1388G>A, c.1376G>T, c.95G>A, c.1024C>T, c.871G>A, c.392G>T, c.487G>A, c.1360C>T, c.1004C>A, c.517T>C, c.592C>T, c.94C>G, c.152C>T, c.320A>G, c.1028A>G, c.1316G>A, c.1327G>C and c.1376G>C, including 683 male hemizygotes, 3 female homozygotes, 80 female heterozygotes and 2 female compound heterozygous.@*CONCLUSION@#A total of 18 types of G6PD mutations are identified in the reaserch, and c.94C>G, c.1028A>G and c.1327G>C are first reported in Chinese population. The most common G6PD mutation types in Wuhan are c.1388G>A, c.1376G>T, c.95G>A.

Asian People/genetics , Female , Genotype , Glucosephosphate Dehydrogenase/genetics , Glucosephosphate Dehydrogenase Deficiency/genetics , Heterozygote , Humans , Infant, Newborn , Male , Mutation
Autops. Case Rep ; 11: e2021285, 2021. graf
Article in English | LILACS | ID: biblio-1249016


Acquired Hemophagocytic Lymphohistiocytosis is a rare and deadly syndrome resulting from an overactive immune system, with uncontrolled activation of macrophages and lymphocytes, hypercytokinemia, and systemic inflammatory response. A 75-year-old male presented with typical anginal pain and was diagnosed with the acute coronary syndrome, which required a percutaneous transluminal coronary angioplasty. Instead of resolving the symptoms, the patient began to exhibit pyrexia and worsening altered sensorium with progressing renal failure, anemia, thrombocytopenia and respiratory failure. This constellation of symptoms caused the patient to require mechanical ventilation and hemodialysis. Upon laboratory analysis, hyperferritinemia provided an indication to the diagnosis of acquired hemophagocytic lymphohistiocytosis. After the initiation of dexamethasone, the patient made a significant recovery and was discharged from the hospital.

Humans , Male , Aged , Lymphohistiocytosis, Hemophagocytic/complications , Hyperferritinemia/diagnosis , Dexamethasone/therapeutic use , Acute Coronary Syndrome/complications , Glucosephosphate Dehydrogenase Deficiency
Chinese Journal of Endemiology ; (12): 927-931, 2021.
Article in Chinese | WPRIM | ID: wpr-909127


Objective:To study the incidence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and the gene carrying status of newborns in Guangxi Zhuang Autonomous Region (Guangxi for short), so as to provide theoretical basis for clinical genetic counseling and accurate diagnosis.Methods:A total of 63 606 newborns who underwent G6PD screening in Guangxi Neonatal Disease Screening Center from January 2017 to December 2018 were selected as study subjects; heel blood was collected to prepare dry blood spots. Fluorescence quantitative analysis was used in the preliminary screening, and the newborns with positive preliminary screening were recalled by telephone; further diagnosis was carried out via the G6PD/6-phosphogluconate dehydrogenase (6PGD) ratio method and genetic testing, the diagnosis rate of the two methods of newborns with positive preliminary screening were compared and analyzed, and genetic mutation testing was conducted.Results:Among 63 606 newborns who underwent G6PD preliminary screening, 4 267 newborns with G6PD positive were detected, and the positive rate of preliminary screening was 6.7%. Among them, the positive rates of preliminary screening of males and females were 10.3% (3 508/33 988) and 2.6% (759/29 618), respectively. The positive rate of preliminary screening of males was significantly higher than that of females ( P < 0.01). A comparative analysis of 777 newborns (519 males and 258 females) that underwent G6PD/6PGD ratio method and genetic testing at the same time as the recall showed that the diagnosis rate of the two methods for male newborns was the same, both of which were 95.6% (496/519). Among female newborns, 168 and 236 confirmed cases were detected by G6PD/6PGD ratio method and genetic testing, respectively, and the diagnosis rates were 65.1% (168/258) and 91.5% (236/258), respectively. The results of genetic mutation testing showed that the five common genotypes in Guangxi were c.1388 G>A, c.1376 G>T, c.95 A>G, c.871 G>A, and c.1024 C>T, respectively. Conclusions:The positive rate of G6PD preliminary screening of newborns in Guangxi is relatively high. It is recommended that G6PD/6PGD ratio method and genetic testing should be performed at the same time for diagnosis of female newborns with positive preliminary screening to avoid missed diagnosis and misdiagnosis.

Article in Chinese | WPRIM | ID: wpr-873086


Objective::To discuss the effect of Qingzao Jiufei Tang on enzymatic activity and regulatory factor of glucose 6-phosphatedehydrogenase(G6PD) in pentose phosphate energy metabolism pathway in lung cancer. Method::Fifty male C57BL6J mice were randomly divided into five groups. Animal models were induced through axillary injection with Lewis cells. The Qingzao Jiufei Tang group was given drugs (11, 5.5, 2.8 g·kg-1·d-1) two weeks before modeling, the cyclophosphamide(CTX) group was intraperitoneally injected with CTX (50 mg·kg-1), and the model group was intraperitoneally injected with the same volume of saline after molding. At 14 d after modeling, the mice were sacrificed, and the tumor tissues were collected. The enzymatic activity of G6PD, content of reactive oxygen species (ROS) were detected by enzyme-linked immunosorbent assay(ELISA) method. Expressions of gp91phox and p22phox mRNA were detected by real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) method. Result::Compared with the model group, the enzymatic activity of G6PD in high-dose group, medium-dose group and low-dose group were reduced obviously (P<0.05, P<0.01). Content of ROS, mRNA expressions of gp91phox and p22phox in high-dose group, medium-dose group and low-dose group were reduced obviously (P<0.01). Conclusion::Qingzao Jiufei Tang may inhibit the expression of G6PD by inhibiting the expression of gp91 phox, p22phox oxidase, and then reduce content of ROS, so as to reduce the energy metabolism and hyperplasia of lung cancer cells.

Article in Chinese | WPRIM | ID: wpr-837499


Objective To analyze the incidence of neonatal glucose-6-phosphate dehydrogenase (G6PD) deficiency in Huangshi area, and to provide guidance for neonatal disease screening. Methods Fluorescence immunoassay was used to detect G6PD activity in an initial screening. Children who were positive in the first screening were recalled for a second screening. Second screening positive children were recalled for G6PD gene testing. Results A total of 105 newborns were positive in the first screening, for a positive rate of 0.21%. A total of 93 cases were recalled, and the recall rate was 88.60%. There were 77 cases positive in the second screening, and the positive rate was 82.80%. A total of 65 patients were recalled, of which 49 neonates were diagnosed, 1 was normal, and 15 refused gene testing. The incidence rate was 0.10%. Conclusion The incidence of newborn G6PD deficiency in Huangshi area is relatively low, which is consistent with the disease distribution trend of “south high-north low”.

Biosci. j. (Online) ; 35(6): 1979-1984, nov./dec. 2019. ilus, tab
Article in English | LILACS | ID: biblio-1049178


G6PD deficiency is associated with erythrocyte deficiency in the X-chromosome enzyme. It causes a hematologic syndrome called hemolytic anemia that connects G6PD deficiency with X-linked condition. In the Middle East, including Saudi Arabia, G6PD deficiency is the most dominant genetic blood disorders. It results in higher rates of mortality and morbidity due to its incurable long-lasting nature and prevalence of physical and psychological incapacities. In this study, an attempt was made to evaluate the prevalence of G6PD deficiency among the Saudi population in Riyadh city. A cross-sectional retrospective study was conducted at King Saud University Medical City in Riyadh, Saudi Arabia. The population of the study comprised randomly chosen males and females who visited the hospital from January 2017 to January 2018. Statistical analyses were performed using SPSS, and descriptive analysis was used to find the frequency of G6PD-deficient patients. Out of the 209 patients, 62.2% were males (n=130) and 37.8% were females (n=79). Twenty males and 6 females were found to have G6PD deficiency, with the male to female ratio being 1:3. Out of the total 130 male participants, 20 patients were found to be enzyme deficient and 6 patients of 79 female patients were found to be G6PD deficient. There were 38.4% (n=10) patients with G6PD level <4 units/gram hemoglobin, 26.9% (n=7) patients had G6PD levels of 4.1­7.0 units/gram hemoglobin, and 34.6% (n=9) patients had >7 units/gram hemoglobin. Among the G6PD patients, 23.07% patients were severely anemic, and 5 (19.2%) patients were reported to have high bilirubin. The present study revealed the G6PD prevalence to be 12.4% among the Saudi population; this value is significantly higher than that found in France, Spain, India, and Singapore. In the Saudi population, males are more vulnerable to G6PD-deficient than females. Hence, attention should be paid to G6PD-deficient patients while prescribing antimalarial medication. Such patients may be advised to avoid certain foods to minimize the risk of having hemolytic episodes.

A deficiência de G6PD está associada à deficiência de eritrócitos na enzima do cromossomo X. Causa uma síndrome hematológica chamada anemia hemolítica que conecta a deficiência de G6PD à condição ligada ao X. No Oriente Médio, incluindo a Arábia Saudita, a deficiência de G6PD é o distúrbio genético do sangue mais dominante. Isso resulta em maiores taxas de mortalidade e morbidade devido à sua natureza incurável e duradoura e à prevalência de incapacidades físicas e psicológicas. Neste estudo, foi feita uma tentativa de avaliar a prevalência de deficiência de G6PD entre a população saudita na cidade de Riade. Um estudo retrospectivo transversal foi realizado na cidade médica da Universidade King Saud, em Riade, na Arábia Saudita. A população do estudo compreendeu homens e mulheres escolhidos aleatoriamente que visitaram o hospital entre janeiro de 2017 e janeiro de 2018. As análises estatísticas foram realizadas com o SPSS e a análise descritiva foi utilizada para determinar a frequência de pacientes com deficiência de G6PD. Dos 209 pacientes, 62,2% eram do sexo masculino (n = 130) e 37,8% eram do sexo feminino (n = 79). Verificou-se que 20 homens e 6 mulheres apresentavam deficiência de G6PD, sendo a proporção homem/mulher de 1:3. Do total de 130 participantes do sexo masculino, 20 pacientes apresentaram deficiência de enzima e 6 de 79 pacientes do sexo feminino apresentaram deficiência de G6PD. Havia 38,4% (n = 10) pacientes com nível de G6PD < 4 unidades/grama de hemoglobina, 26,9% (n = 7) pacientes tinham níveis de G6PD de 4,1-7,0 unidades/grama de hemoglobina e 34,6% (n = 9) pacientes tinham > 7 unidades/grama de hemoglobina. Entre os pacientes com G6PD, 23,07% eram severamente anêmicos e cinco (19,2%) pacientes relataram ter alta bilirrubina. O presente estudo revelou que a prevalência de G6PD é de 12,4% na população saudita; esse valor é significativamente maior que o encontrado na França, Espanha, Índia e Cingapura. Na população saudita, os homens são mais vulneráveis à deficiência de G6PD do que as mulheres. Portanto, deve-se prestar atenção aos pacientes com deficiência de G6PD durante a prescrição de medicamentos antimaláricos. Esses pacientes podem ser aconselhados a evitar certos alimentos para minimizar o risco de episódios hemolíticos.

Glucosephosphate Dehydrogenase , Hemolysis , Anemia, Hemolytic
Arch. endocrinol. metab. (Online) ; 63(3): 228-234, May-June 2019. tab, graf
Article in English | LILACS | ID: biblio-1011164


ABSTRACT Objective Hyperthyroidism causes many injuries in its target organs and the consequences are reflected systemically. As systemic alterations in hyperthyroidism at earlier stages have received partial attention, this study aimed to investigate systemic redox and inflammatory status at an early stage of T4-induced hyperthyroidism. Materials and methods Male Wistar rats were assigned to control and hyperthyroid groups (n = 7/group). The hyperthyroid group received L-thyroxine (12 mg/L) in their drinking water for 14 days whereas control group received only the vehicle. Body weight was measured on the 1st and 14th day of the protocol. On the 14th day, animals were anaesthetized. Blood was then collected from the retro-orbital venous plexus and then the animals were euthanised. The blood was separated into plasma and erythrocytes. Plasma was used to measure ROS levels, sulfhydryl compounds, IL-10, TNF-α and LDH levels; erythrocytes were used for the analysis of thioredoxin reductase activity, glutaredoxin content, and pentose cycle enzymes (total G6PD, G6PD and 6PGD). Results Hyperthyroid animals presented body weight gain and final body weight reduction, which was associated with increased ROS levels and decreased sulfhydryl content in plasma. Thioredoxin reductase activity, glutaredoxin content, and pentose cycle enzymes levels in erythrocytes, as well as IL-10, TNF-α and LDH plasma levels were unaltered. Conclusion Taken together, our results suggest an impairment in corporal mass associated with systemic oxidative stress at this stage of hyperthyroidism. Meanwhile, the pentose cycle was not influenced and systemic inflammation and tissue damage seem to be absent at this stage of hyperthyroidism.

Animals , Male , Rats , Oxidative Stress/drug effects , Erythrocytes/metabolism , Hyperthyroidism/metabolism , Oxidation-Reduction , Pentoses , Thyroxine , Rats, Wistar , Disease Models, Animal , Erythrocytes/drug effects , Hyperthyroidism/blood , Antioxidants/metabolism
Chinese Journal of Endemiology ; (12): 878-882, 2019.
Article in Chinese | WPRIM | ID: wpr-824068


Objective To investigate the prevalence of glucose-6-phosphate dehydrogenase (G6PD) gene mutation in newborns of Hainan Province,and to provide reference for prevention and treatment of G6PD deficiency in this region.Methods Neonatal disease screening filter paper dry blood spots from all midwifery agencies were collected in 18 cities (counties) in Hainan Province from January to June 2016,G6PD activity screening test was conducted at Neonatal Disease Screening Center,Hainan Women and Children's Medical Center,and the enzyme activity was normal when fluorescence value > 1 600,and enzyme deficiency when fluorescence value ≤ 1 600.Referred to "China's Major Birth Defects and Genetic Diseases Survey and Biological Resources Collection",women newborns (3 371 cases) with fluorescence values ≤2 200 and men newborns (1 620 cases) with fluorescence values ≤ 1 700 were included in the study.Molecular screening was performed using multicolor melting curve analysis (MMCA),and the distribution and mutation characteristics of G6PD gene mutants were analyzed.Results Among the 4 991 newborns,2 111 cases with G6PD gene mutation,and the detection rate was 42.30% (2 111/4 991).A total of 27 G6PD gene mutants were found,including 14 single mutants and 13 composite mutants.The mutation detection rates of c.1376 G>T (21.42%,1 069/4 991),c.1388 G>A (11.54%,576/4 991),c.95 A>G (2.40%,120/4 991) and c.871 G>A (2.24%,112/4 991) were higher.The mutation detection rate (61.54%,136/221) of Baisha County (inland area) was the highest,and the mutation detection rate (22.15%,64/289) of Wenchang City (coastal area) was the lowest.The mutation detection rate (49.88%,628/1 259) of the Li nationality was the highest.A total of 873 female heterozygotes were detected,including 13 gene mutants,of which 44.67% (390/873) with normal enzyme activity.The c.86 C>T heterozygous mutation was first detected in a sample of Li female with normal enzyme activity.Conclusions Hainan Province is the high incidence area of G6PD gene mutation,the most common mutations are c.1376 G>T,c.1388 G>A,c.95 A>G and c.871 G>A in newborns.Inland area is the high incidence area,and Li nationality is the high incidence population.

Chinese Journal of Endemiology ; (12): 878-882, 2019.
Article in Chinese | WPRIM | ID: wpr-800943


Objective@#To investigate the prevalence of glucose-6-phosphate dehydrogenase (G6PD) gene mutation in newborns of Hainan Province, and to provide reference for prevention and treatment of G6PD deficiency in this region.@*Methods@#Neonatal disease screening filter paper dry blood spots from all midwifery agencies were collected in 18 cities (counties) in Hainan Province from January to June 2016, G6PD activity screening test was conducted at Neonatal Disease Screening Center, Hainan Women and Children's Medical Center, and the enzyme activity was normal when fluorescence value > 1 600, and enzyme deficiency when fluorescence value ≤1 600. Referred to "China's Major Birth Defects and Genetic Diseases Survey and Biological Resources Collection", women newborns (3 371 cases) with fluorescence values ≤2 200 and men newborns (1 620 cases) with fluorescence values ≤1 700 were included in the study. Molecular screening was performed using multicolor melting curve analysis (MMCA), and the distribution and mutation characteristics of G6PD gene mutants were analyzed.@*Results@#Among the 4 991 newborns, 2 111 cases with G6PD gene mutation, and the detection rate was 42.30% (2 111/4 991). A total of 27 G6PD gene mutants were found, including 14 single mutants and 13 composite mutants. The mutation detection rates of c.1376 G>T (21.42%, 1 069/4 991), c.1388 G>A (11.54%, 576/4 991), c.95 A>G (2.40%, 120/4 991) and c.871 G>A (2.24%, 112/4 991) were higher. The mutation detection rate (61.54%, 136/221) of Baisha County (inland area) was the highest, and the mutation detection rate (22.15%, 64/289) of Wenchang City (coastal area) was the lowest. The mutation detection rate (49.88%, 628/1 259) of the Li nationality was the highest. A total of 873 female heterozygotes were detected, including 13 gene mutants, of which 44.67% (390/873) with normal enzyme activity. The c.86 C>T heterozygous mutation was first detected in a sample of Li female with normal enzyme activity.@*Conclusions@#Hainan Province is the high incidence area of G6PD gene mutation, the most common mutations are c.1376 G>T, c.1388 G>A, c.95 A>G and c.871 G>A in newborns. Inland area is the high incidence area, and Li nationality is the high incidence population.

Article in Chinese | WPRIM | ID: wpr-817949


OBJECTIVE: To analyze the characteristics of gene mutations of glucose-6-phosphate dehydrogenase(G6PD)deficiency in the neonates of Zhejiang Province,and discuss the genetic diversity. METHODS: A total of 2242G6PD values and blood stains on dry filter were collected from the children borned in Zhejiang Province with positive screening of G6PD deficiency between March 2015 and September 2017 in Neonatal Metabolic Screening Center of Zhejiang Province. Genomic DNA of the stains were extracted. Thirty-five gene mutation sites were detected by Mass ARRAY technology. The relationship between mutation gene sites and G6PD activity were analyzed by SPSS 22.0,taking PT,c.1388G>A,c.1024C>T,c.95 A>G,c.871G>A and c.392G>T accounted for 92.96%. There were statistically significant differences in G6PD activity of c.1376 G>T,c.1388G>A,c.1024 C>T,c.95A>G(PT has obvious regional characteristics. Using MassARRAY technology to detect specific mutation sites can be a choice as a second-level screening method for G6PD deficiency.

Rev. cuba. med. gen. integr ; 34(3)jul.-set. 2018.
Article in Spanish | LILACS, CUMED | ID: biblio-1093457


Introducción: La presencia de ictericia en la práctica clínica generalmente hace sospechar problemas hepáticos o de vías biliares, siendo el íctero de causa hemolítica menos frecuente. Objetivo: Presentar un caso de íctero hemolítico infrecuente. Caso clínico: Paciente femenina de 47 años que presenta episodio de íctero hemolítico después de la ingestión de medicamentos. Los estudios de función hepáticos fueron normales. Se sospecha y diagnostica déficit de glucosa 6 fosfato deshidrogenasa variante electroforética A-. Conclusiones: Ante la presencia de íctero deben sospecharse posibles causas no hepáticas, como el déficit de glucosa 6 fosfato deshidrogenasa(AU)

Introduction: The presence of jaundice in clinical practice usually causes suspicion of liver or bile duct problems, but hemolytic icterus is a less frequent cause. Objective: To present a case of infrequent hemolytic icterus. Clinical case: A 47-year-old female patient who presented an episode of hemolytic icterus after medication ingestion. Liver function studies were normal. Suspected and diagnosed glucose 6-phosphate dehydrogenase deficiency, electrophoretic variant A-. Conclusions: In the presence of icterus, possible non-hepatic causes should be suspected, such as glucose 6-phosphate dehydrogenase deficiency(AU)

Humans , Glucosephosphate Dehydrogenase Deficiency , Hemolysis , Jaundice/epidemiology
Rev. bioméd. (México) ; 29(1): 13-24, ene.-abr. 2018. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1003382


Resumen Introducción El daño oxidativo provocado por los radicales libres de oxígeno, está relacionado con el proceso de envejecimiento, con diversas patologías y con el estilo de vida de las personas pero, en el organismo, existen defensas enzimáticas antioxidantes que confieren una debida protección. Objetivo Determinar la actividad enzimática de la glucosa-6-fosfato deshidrogenasa (G6PD), la catalasa (CAT) y la NADH metahemoglobina reductasa (NADH-MR) en una población costarricense de adultos jóvenes y mayores, para establecer el intervalo de referencia y evaluar el efecto de algunas condiciones donde se presenta daño oxidativo. Materiales y métodos Se determinó la actividad enzimática en una población de 110 individuos de entre 19 y 95 años de edad, utilizando el método propuesto por Ernest Beutler. Se estableció el intervalo de referencia de la población y se evaluó el efecto de la edad, patologías de fondo y el fumado, mediante estadística descriptiva. Resultados Conforme avanza la edad, las enzimas NADH-MR y la CAT disminuyeron su actividad eritrocitaria y la G6PD no presentó cambios significativos. No se encontró evidencia de cambio significativo en la actividad enzimática con respecto al hábito de fumado y las condiciones patológicas estudiadas. Conclusiones Es necesario realizar más investigación en factores ambientales y estilo de vida que influyen en la actividad enzimática antioxidante. El tamaño de las poblaciones, la ausencia de métodos estandarizados y las condiciones del ensayo pueden afectar los resultados y su grado de significancia. Por lo tanto, deben estandarizarse las metodologías, de manera que en futuros proyectos se evalúen los resultados de acuerdo con estas condiciones.

Abstract Introduction The oxidative damage caused by free oxygen radicals is related to the aging process, some pathologies and people's lifestyle. However, in the human body there are antioxidant enzymatic defenses that give us an adequate protection. Objective To determine the enzyme activity of glucose-6-phosphate dehydrogenase (G6PD), catalase (CAT) and NADH methemoglobin reductase (NADH-MR), in a Costa Rican population of younger and older adults, in order to establish the reference range and to evaluate the effect of some conditions where oxidative damage occurs. Materials and methods The enzyme activity in a population of 110 individuals aged 19-95 years old was determined using the method proposed by Ernest Beutler. The population reference range was established and the effect of age, background pathologies and smoking were evaluated, using descriptive statistics. Results As age advances the enzyme NADH-MR and CAT decreased erythrocyte activity and G6PD presented no significant changes. Evidence of a significant change in the enzyme activity, with respect to the smoking habit and the pathological conditions, was not found. Conclusions It is necessary to carry out more research in terms of lifestyle and environmental factors, that influence the antioxidant enzyme activity. The size of populations, the absence of standardized methods and the conditions of the test can affect results and their degree of significance. For which methodologies should be standardized, so that in future projects the results can be evaluated according to these conditions.

Article in English | WPRIM | ID: wpr-739648


During cancer progression, cancer cells are repeatedly exposed to metabolic stress conditions in a resource-limited environment which they must escape. Increasing evidence indicates the importance of nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis in the survival of cancer cells under metabolic stress conditions, such as metabolic resource limitation and therapeutic intervention. NADPH is essential for scavenging of reactive oxygen species (ROS) mainly derived from oxidative phosphorylation required for ATP generation. Thus, metabolic reprogramming of NADPH homeostasis is an important step in cancer progression as well as in combinational therapeutic approaches. In mammalian, the pentose phosphate pathway (PPP) and one-carbon metabolism are major sources of NADPH production. In this review, we focus on the importance of glucose flux control towards PPP regulated by oncogenic pathways and the potential therein for metabolic targeting as a cancer therapy. We also summarize the role of Snail (Snai1), an important regulator of the epithelial mesenchymal transition (EMT), in controlling glucose flux towards PPP and thus potentiating cancer cell survival under oxidative and metabolic stress.

Adenosine Triphosphate , Cell Survival , Epithelial-Mesenchymal Transition , Glucose , Glucosephosphate Dehydrogenase , Homeostasis , Metabolism , NADP , Oxidative Phosphorylation , Pentose Phosphate Pathway , Reactive Oxygen Species , Snails , Stress, Physiological , United Nations
Journal of Medical Postgraduates ; (12): 697-702, 2018.
Article in Chinese | WPRIM | ID: wpr-818046


Objective Clear cell renal cell carcinoma (ccRCC) accounts for more than 80% of malignant kidney tumors and its pathogenesis has not been elucidated. Our previous studies showed a positive correlation of Glucose-6-phosphate dehydrogenase (G6PD) with the development, progression and poor prognosis of ccRCC. In this study, we first established a G6PD defect ccRCC stable cell line, detected the influence of G6PD knockdown on ccRCC migration, and provided a cell model for further studies on the functional and molecular mechanisms of G6PD in ccRCC.Methods Using the OligoEngine RNAi software, we designed siRNA targeting the human G6PD gene 3′ non-coding region and negative control siRNA sequences, inserted the double-stranded siRNA into the pSR-GFP/Neo expression vector through Bgl Ⅱ and Hind Ⅲ enzyme loci, and constructed Caki-1-G6PD siRNA and Caki-1-negative control cell lines, followed by transfection and G418 screening of the Caki-1 cells. We measured the expression and enzyme activity of G6PD in the cells by real-time RT-PCR, determined the cell migration phenotypes by Transwell assay, and detected the expressions of p-STAT3 and STAT3 by Western blot.Results Morphologically normal Caki-1-G6PD siRNA and Caki-1-negative control cells were seen under the fluorescence microscope. With GFP expression as a marker, the transfection efficiency rate of the cells was 45-55%. The density of the adherent cells at 48 hours was 90% and their transfection efficiency rate was over 60%. Compared with the Caki-1-negative control cells, the Caki-1-G6PD siRNA cells showed significant decreases in the expressions of Caki-1-G6PD mRNA and protein (P<0.01), enzyme activity (P<0.05), relative count of migratory cells (64.0±4.2 vs 30.0±2.9, P<0.01), and the ratio of p-STAT3/STAT3 (0.45±0.05 vs 0.24±0.01, P<0.01).Conclusion The Caki-1-G6PD siRNA cell line with stable G6PD knockdown and a lower migration ability was first successfully constructed, and the decreased migration ability induced by G6PD knockdown is associated with the STAT3 signal, which is contributive to an insight into the functional and molecular mechanisms of G6PD in the development and progression of ccRCC as well as to finding intervention targets for the treatment of ccRCC.

Rev. MED ; 25(2): 7-21, jul.-dic. 2017. tab, graf
Article in Spanish | LILACS | ID: biblio-977031


RESUMEN La deficiencia de la Glucosa 6 Fosfato Deshidrogenasa es un desorden hereditario del metabolismo ligado al cromosoma X, considerada como la enfermedad metabólica de mayor frecuencia a nivel mundial con más de 400 millones de individuos afectados, es la causa más común de anemia hemolítica no autoinmune de origen metabólico. La prevalencia calculada para Colombia según la organización mundial de la salud se encuentra entre 3 - 7%, pero los reportes de estudios poblacionales son escasos, creando la necesidad de incluir esta deficiencia en un programa de tamizaje neonatal, más cuando aproximadamente un 11 % de la población es afrodescendiente, que sin contar con el mestizaje, puede ofrecer una frecuencia mayor de la deficiencia en ciertas regiones del país. El presente estudio brinda entonces, una panorámica general de la prevalencia de esta enzimopatía eritrocitaria, en población con anemia hemolítica crónica o episódica de naturaleza no inmune, procedentes de diferentes lugares del territorio nacional. Comprende la valoración de 3837 muestras durante el periodo 1998 al 2016, un total de 1801 controles y 2036 individuos (982 hombres/1054 mujeres, Rango de edad: 1 semana a 91 años) con hallazgos sugerentes de esta condición metabólica. Los resultados encontrados, ofrecen una prevalencia del 7 % de la deficiencia con grados variables de actividad residual. El rango general de los grupos control osciló entre 3,31 - 9,98 Ul/gr HB, contrastante contra el grupo de afectados (n=144) que ofreció un valor de 0,0 - 2,97, el 67 % (n=96) correspondiente a varones afectados. Estos hallazgos evidencian la importancia de incluir dentro de un programa de detección neonatal, esta enzimo-patía eritrocitaria.

ABSTRACT Deficiency of Glucose-6 -Phosphate Dehydrogenase is an inherited disorder of X-linked metabolism, as the metabolic disease of the world's largest frequency with more than 400 million affected individuals, is the most common cause of non-autoimmune hemolytic anemia of metabolic origin. The prevalence calculated for Colombia according to the world health organization is between 3 and 7%, but the reports of population studies are scarce, creating the need to include this deficiency in a neonatal screening program, closer to 11% population is Afro-descendant that without the miscegenation, can offer a greater frequency of deficiency in certain regions of the country. The present study provides an overview of the prevalence of erythrocyte enzyme disease in the population with chronic or episodic hemolytic anemia of non-immune nature from different parts of the national territory. lt comprises the evaluation of 3837 samples during the period 1998 to 2016, a total of 1801 controls and 2036 individuals (982 men / 1054 women, age range: 1 week to 91 years) with suggestive findings of this metabolic condition. The results found, offer a prevalence of 7% of the deficiency with variable degrees of residual activity. The overall range of the control groups ranged from 3.31 - 9.98 lU / g HB, contrasting against the group of affected (n = 144) who offered a value of 0.0 - 2.97, 67% = 96 ) corresponds to affected males. These findings highlight the importance of including this erythrocyte enzyme disease in a neonatal screening program.

RESUMO A deficiência de glucose-6-fosfato desidrogenase é uma desordem hereditária do metabolismo ligado ao X, como a doença metabólica da maior freqüência do mundo com mais de 400 milhões de indivíduos afetados, é a causa mais comum de anemia hemolítica não autoimune de origem metabólica. A prevalência calculada para a Colômbia de acordo com a organização mundial de saúde é entre 3 e 7%, mas os relatórios de estudos populacionais são escassos, criando a necessidade de incluir esta deficiência em um programa de triagem neonatal, perto de 11% a população é afro-descendente que sem a miscigenação, pode oferecer uma maior frequência de deficiência em certas regiões do país. O presente estudo fornece uma visão geral da prevalência de doença enzimática de eritrócitos na população com anemia hemolítica crônica ou episódica de natureza não imune de diferentes partes do território nacional. Compreende a avaliação de 3837 amostras durante o período de 1998 a 2016, um total de 1801 controles e 2036 indivíduos (982 homens / 1054 mulheres, faixa etária: 1 semana a 91 anos) com achados sugestivos desta condição metabólica. Os resultados encontrados, oferecem uma prevalência de 7% da deficiência com graus variáveis de atividade residual. O intervalo geral dos grupos de controle variou de 3,31 a 9,98 Ul / g de HB, contrastando com o grupo de afetados (n = 144) que ofereceu um valor de 0,0-297, 67% = 96) corresponde a machos afetados. Esses achados destacam a importância de incluir esta doença enzimática de eritrócitos em um programa de triagem neonatal.

Humans , Anemia, Hemolytic , Colombia , Oxidative Stress , Glucose-6-Phosphate , Acetoin Dehydrogenase
Article in English | LILACS | ID: biblio-1043313


ABSTRACT The aim of this study has been to study whether the top-down method, based on the average value identified in the Brazilian Hospitalization System (SIH/SUS), is a good estimator of the cost of health professionals per patient, using the bottom-up method for comparison. The study has been developed from the context of hospital care offered to the patient carrier of glucose-6-phosphate dehydrogenase (G6PD) deficiency with severe adverse effect because of the use of primaquine, in the Brazilian Amazon. The top-down method based on the spending with SIH/SUS professional services, as a proxy for this cost, corresponded to R$60.71, and the bottom-up, based on the salaries of the physician (R$30.43), nurse (R$16.33), and nursing technician (R$5.93), estimated a total cost of R$52.68. The difference was only R$8.03, which shows that the amounts paid by the Hospital Inpatient Authorization (AIH) are estimates close to those obtained by the bottom-up technique for the professionals directly involved in the care.

RESUMO A pesquisa teve por objetivo estudar se o macrocusteio, baseado no valor médio identificado no Sistema de Internação Hospitalar (SIH/SUS), constitui um bom estimador do custo de profissionais de saúde por paciente, tendo como comparação o método de microcusteio. O estudo foi desenvolvido no contexto da assistência hospitalar oferecida ao portador da deficiência de glicose-6-fosfato desidrogenase (dG6PD) do sexo masculino com evento adverso grave devido ao uso da primaquina, na Amazônia Brasileira. O macrocusteio baseado no gasto em serviços profissionais do SIH/SUS, como proxy desse custo, correspondeu a R$60,71, e o microcusteio, baseado nos salários do médico (R$30,43), do enfermeiro (R$16,33) e do técnico de enfermagem (R$5,93), estimou um custo total de R$52,68. A diferença foi de apenas R$8,03, mostrando que os valores pagos pela Autorização de Internação Hospitalar (AIH) são estimadores próximos daqueles obtidos por técnica de microcusteio para os profissionais envolvidos diretamente no cuidado.

Humans , Male , Adult , Primaquine/adverse effects , Hospital Costs/statistics & numerical data , Glucosephosphate Dehydrogenase Deficiency/economics , Glucosephosphate Dehydrogenase Deficiency/drug therapy , Hospitalization/economics , Antimalarials/adverse effects , Patient Care Team/economics , Primaquine/economics , Time Factors , Brazil , Malaria/diet therapy , Malaria/economics , National Health Programs/economics , Antimalarials/economics
Article in Chinese | WPRIM | ID: wpr-514021


Objective To observe the interference of glucose-6-phosphate dehydrogenase (G6PD) deficiency on glycated hemoglobin (HbA1c) detected by three measurement systems.Methods A total of 286 cases of blood and serum samples were collected at Zhongshan Hospital of Sun Yat-Sun University from August 2012 to April 2016.The blood samples were divided into healthy control group (122 cases),diabetes group (82 cases),glucose-6-phosphate dehydrogenase deficiency group (61 cases) and diabetes with G6PD deficiency group (21 cases).The levels of HbA1 c were detected by three measurement systems,including Primus Ultra2,Variant lⅡ Turbo 2.0 and Modular P.The results of HbA1c were converted into the estimated average blood glucose concentration (eAG).The values of A eAG-FPG in different groups were calculated and statistical analysis was performed for evaluation of the differences from the three measurement systems.Results The HbA1c results measured by the three systems and AeAG-FPG values in G6PD deficiency group were all lower than healthy control group(all P <0.05).The measured results were similar in both diabetes group and diabetes with G6PD deficiency group.Conclusion G6PD deficiency may cause false H-bA1c results detected by three measurement systems.In the case of HbA1c for evaluating blood glucose control,the interference of G6PD deficiency should be noticed.

Braz. J. Pharm. Sci. (Online) ; 53(3): e17095, 2017. tab
Article in English | LILACS | ID: biblio-889381


ABSTRACT In this work, the potential chemopreventive activities of Elaeagnus umbellata fruit aqueous (EUFA) and leaf aqueous (EULA) extracts focusing on the modulatory influence of xenobiotic metabolizing enzymes (XMEs), antioxidant enzymes, glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), lactate dehydrogenase (LDH) activity, lipid peroxidation (LP), sulfhydryl groups were investigated in the hepatic and extrahepatic organs of Swiss albino mice (50 and 100 mg/kg body wt given orally for 14 days) and compared with BHA (0.75 % in diet). The modulatory and chemopreventive properties of two different doses EUFA and EULA were observed for cytochrome P450, cytochrome b5, sulfhydryl groups, NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, 7-ethoxyresorufin-deethylase and N,N-dimethylaniline N-oxidase activities in the liver and compared with BHA as a standard. The activities of glutathione S-transferase (GST) and DT-diaphorase (DTD) showed a significant increase in the kidney, forestomach, heart and brain at both doses of EUFA and EULA. The results of EULA-treated groups were found a notable increase in LDH, G6PD, 6PGD, GST and DTD activities. Superoxide dismutase level in liver, kidney and heart exhibited a significant increase at both doses of EULA. Glutathione reductase activity was a remarkable level at high dose of EUFA in liver, kidney and EULA in kidney. Both doses of EUFA were effective in inducing glutathione peroxidase activitiy in heart. The levels of LP at low and high doses of EULA-treated and EUFA-treated were effective in liver and kidney, respectively. The present results demonstrate that significant effects in the level of XMEs and antioxidant enzymes of EUFA and EULA are remarkable for modulating roles and natural chemoprevention properties and therefore is considered for a valuable natural source.

Animals , Mice , Plant Extracts/analysis , Plant Leaves/metabolism , Elaeagnaceae/adverse effects , Antioxidants , Disease Prevention , Phytochemicals/analysis , Fruit/classification