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Sample records for glucose-6-phosphate dehydrogenase g-6-pd

  1. Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency in patients ...

    African Journals Online (AJOL)

    This is a study of Glucose-6-phosphate dehydrogenase(G6PD) deficiency in sickle cell anaemia patients attending the haematology clinic of the Jos University Teaching Hospital (JUTH), Jos- Nigeria. The prevalence of G6PD deficiency among the 130 sickle cell anaemia patients studied was found to be 18.5%. G6PD ...

  2. G6PD Deficiency (Glucose-6-Phosphate Dehydrogenase) (For Parents)

    Science.gov (United States)

    ... genes from one or both parents to a child. The gene responsible for this deficiency is on the X chromosome. G6PD deficiency is most common in males of African heritage. Many females of African heritage are carriers ...

  3. Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among malaria patients in Upper Myanmar.

    Science.gov (United States)

    Lee, Jinyoung; Kim, Tae Im; Kang, Jung-Mi; Jun, Hojong; Lê, Hương Giang; Thái, Thị Lam; Sohn, Woon-Mok; Myint, Moe Kyaw; Lin, Khin; Kim, Tong-Soo; Na, Byoung-Kuk

    2018-03-16

    Glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) deficiency is one of the most common X-linked recessive hereditary disorders in the world. Primaquine (PQ) has been used for radical cure of P. vivax to prevent relapse. Recently, it is also used to reduce P. falciparum gametocyte carriage to block transmission. However, PQ metabolites oxidize hemoglobin and generate excessive reactive oxygen species which can trigger acute hemolytic anemia in malaria patients with inherited G6PD deficiency. A total of 252 blood samples collected from malaria patients in Myanmar were used in this study. G6PD variant was analysed by a multiplex allele specific PCR kit, DiaPlexC™ G6PD Genotyping Kit [Asian type]. The accuracy of the multiplex allele specific PCR was confirmed by sequencing analysis. Prevalence and distribution of G6PD variants in 252 malaria patients in Myanmar were analysed. Six different types of G6PD allelic variants were identified in 50 (7 females and 43 males) malaria patients. The predominant variant was Mahidol (68%, 34/50), of which 91.2% (31/34) and 8.8% (3/34) were males and females, respectively. Other G6PD variants including Kaiping (18%, 9/50), Viangchan (6%, 3/50), Mediterranean (4%, 2/50), Union (2%, 1/50) and Canton (2%, 1/50) were also observed. Results of this study suggest that more concern for proper and safe use of PQ as a radical cure of malaria in Myanmar is needed by combining G6PD deficiency test before PQ prescription. Establishment of a follow-up system to monitor potential PQ toxicity in malaria patients who are given PQ is also required.

  4. Two apparent glucose-6-phosphate dehydrogenase variants in normal XY males: G6PD Alabama.

    Science.gov (United States)

    Prchal, J T; Hall, K; Csepreghy, M; Lilly, M; Berkow, R; Scott, C W

    1988-03-01

    A six-year-old black boy who had transient hemolysis after a viral infection was found to have mildly decreased red cell glucose-6-phosphate dehydrogenase (G6PD) activity (1.25 IU/g hemoglobin). Two G6PD bands, both slightly faster than normal G6PD B, were seen on electrophoresis in both the propositus as well as in his maternal grandfather. This is an unexpected finding, since the G6PD gene is located on the long arm of the X chromosome that is subject to X-chromosome inactivation, and available evidence indicates that it is present as a single functional copy in the human genome. The obvious possibility of duplication of the X chromosome was eliminated by cytogenetic analysis with G-banding. G6PD duplication is unlikely, since peripheral blood granulocytes, platelets, and lymphocytes; cultured skin and bone marrow fibroblasts; and Epstein-Barr virus-stimulated lymphocytes yielded only a single electrophoretic band with mobility identical to the slower band seen in crude red blood cell hemolysate. Study of partially purified red blood cell hemolysate G6PD also yielded a single band with identical mobility. Kinetic studies of the enzyme in the propositus and in three generations of his family identified a unique, previously unpublished G6PD mutant that is herein designated G6PD Alabama. Red blood cells were separated by density gradient into a reticulocyte-enriched, an intermediate, and a dense, older portion. Two distinct enzyme bands were identified on electrophoresis of hemolysate from the reticulocyte-enriched portion, but not from the other two portions. It is postulated that two transcriptional products of the mutant G6PD gene exist; one with a short half-life and detectable only in young red blood cells, and another with a longer half-life present in all cells. The existence of two distinct mutant genes in the genome or a unique post-translational form of the mutant G6PD detected only in reticulocytes cannot be excluded.

  5. Pedigree analysis of glucose-6 phosphate dehydrogenase (G6PD deficiency of a Javanese Chinese family in Indonesia

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    IDG Ugrasena

    2017-02-01

    Full Text Available The molecular and pedigree analyses in a Javanese Chinese family were carried oul on glucose-6-phosphate dehydrogenase deficiencies. By method of  MPTP scanning without the sequencing steps, those variants could be confirmed. Two out of three sons were clinically jaundiced at birth due to G6PD deficiency and identified to have a G to T nucleotide change al 1376th nucleotide 01 the G6PD gene (GI376T, corresponding to G6PD Canton. Another son was also identified to have a C to T nucleotide change at 1311st nucleotide 01 the G6PD gene (CI311T, corresponding to a Silent mutation. Their father was normal, but their mother obsorved to have the heleromutation 01 G1376T (G6PD Canton and C1311T (a Silent mutation.

  6. Prevalence of glucose-6-phosphate dehydrogenase (G6PD deficiency in neonates in Bunda Women's and Children's Hospital, Jakarta, Indonesia

    Directory of Open Access Journals (Sweden)

    Risma Kerina Kaban

    2011-02-01

    Full Text Available Background Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most connnon enzyme deficiency in the world. Itis a risk factor for hyperbilirubinemia in neonates, which can cause serious complications such as bilirubininduced encephalopathy or kernicterus. WHO recommends universal neonatal screening for G6PD deficiency when the frequency exceeds 35% of male newborns. Objective To assess the prevalence of G6PD deficiency among neonates in Bunda Women and C hildren Hospital (Bunda WCH, Jakarta, in order to detennine if there is a need for routine G6PD neonatal screening. Methods This is a cross-sectional and retrospective study; infants' data were obtained from medical records. From January 2009 to May 2010, all neonates in Bunda WCH were screened for G6PD deficiency on the yd day of life. Blood samples were collected using filter papers. We considered a result to be nonnal if it exceeded 3.6 U/g Hb. Results A total 1802 neonates were screened. We found 94 neonates (5.2% with G6PD deficiency. Out of 943 males, 59 (6.26% were G6PD deficient, and out of 859 females, 35 (4.07% were G6PD deficient. We observed that prevalence of G6PD deficiency according to sex distribution was significantly higher in males than females (6.26% vs. 4.07%, P=0.037. There was no significant difference in the risk for severe hyperbilirubinemia between the G6PD deficient infants and the nonnal infants (P=0.804. Conclusions The frequencies of G6PD deficiency were 6.26% of male neonates and 4.07% of female neonates. We recommend universal neonatal screening for G6PD deficiencies in Jakarta since our findings exceed the WHO recommendation for routine testing.

  7. Identification of Mutation of Glucose-6-Phosphate Dehy-drogenase (G6PD) in Iran: Meta- analysis Study.

    Science.gov (United States)

    Moosazadeh, Mahmood; Nekoei-Moghadam, Mahmood; Aliram-Zany, Maryam; Amiresmaili, Mohammadreza

    2013-09-01

    Glucose-6-phosphate dehydrogenase is one of the most common genetic deficiencies, which approximately 400 million people in the world suffer from. According to authors' initial search, numerous studies have been carried out in Iran regarding molecular variants of this enzyme. Thus, this meta-analysis presented a reliable estimation about prevalence of different types of molecular mutations of G6PD Enzyme in Iran. Keywords "glucose 6 phosphate dehydrogenase or G6PD, Mediterranean or Chatham or Cosenza and mutation, Iran or Iranian and their Persian equivalents" were searched in different databases. Moreover, reference list of the published studies were examined to increase sensitivity and to select more studies. After studying titles and abstracts of retrieved articles, excluding the repeated and unrelated ones, and evaluating quality of articles, documents were selected. Data was analyzed using STATA. After performing systematic review, 22 papers were entered this meta-analysis and 1698 subjects were examined concerning G6PD molecular mutation. In this meta-analysis, prevalence of Mediterranean mutation, Chatham mutation and Cosenza mutation in Iran was estimated 78.2%, 9.1% and 0.5% respectively. This meta-analysis showed that in spite of prevalence of different types of G6PD molecular mutations in center, north, north-west and west of Iran, the most common molecular mutations in people with G6PD deficiency in Iran, like other Mediterranean countries and countries around Persian Gulf, were Mediterranean mutation, Chatham mutation and Cosenza mutation. It is also recommended that future studies may focus on races and regions which haven't been taken into consideration up to now.

  8. Glucose-6-phosphate dehydrogenase (G6PD mutations and haemoglobinuria syndrome in the Vietnamese population

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    Day Nick

    2009-07-01

    Full Text Available Abstract Background In Vietnam the blackwater fever syndrome (BWF has been associated with malaria infection, quinine ingestion and G6PD deficiency. The G6PD variants within the Vietnamese Kinh contributing to the disease risk in this population, and more generally to haemoglobinuria, are currently unknown. Method Eighty-two haemoglobinuria patients and 524 healthy controls were screened for G6PD deficiency using either the methylene blue reduction test, the G-6-PDH kit or the micro-methaemoglobin reduction test. The G6PD gene variants were screened using SSCP combined with DNA sequencing in 82 patients with haemoglobinuria, and in 59 healthy controls found to be G6PD deficient. Results This study confirmed that G6PD deficiency is strongly associated with haemoglobinuria (OR = 15, 95% CI [7.7 to 28.9], P G6PD variants were identified in the Vietnamese population, of which two are novel (Vietnam1 [Glu3Lys] and Vietnam2 [Phe66Cys]. G6PD Viangchan [Val291Met], common throughout south-east Asia, accounted for 77% of the variants detected and was significantly associated with haemoglobinuria within G6PD-deficient ethnic Kinh Vietnamese (OR = 5.8 95% CI [114-55.4], P = 0.022. Conclusion The primary frequency of several G6PD mutations, including novel mutations, in the Vietnamese Kinh population are reported and the contribution of G6PD mutations to the development of haemoglobinuria are investigated.

  9. Glucose-6-phosphate dehydrogenase (G6PD)-deficient infants: Enzyme activity and gene variants as risk factors for phototherapy in the first week of life.

    Science.gov (United States)

    Wong, Fei-Liang; Ithnin, Azlin; Othman, Ainoon; Cheah, Fook-Choe

    2017-07-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a recognised cause of severe neonatal hyperbilirubinaemia, and identifying which infants are at risk could optimise care and resources. In this study, we determined if G6PD enzyme activity (EA) and certain gene variants were associated with neonatal hyperbilirubinaemia requiring phototherapy during the first week after birth. Newborn infants with G6PD deficiency and a group with normal results obtained by the fluorescent spot test were selected for analyses of G6PD EA and the 10 commonly encountered G6PD mutations in this region, relating these with whether the infants required phototherapy before discharge from the hospital in the first week. A total of 222 infants with mean gestation and birth weight of 38.3 ± 1.8 weeks and 3.02 ± 0.48 kg, respectively, were enrolled. Of these, n = 121 were deficient with EA ≤6.76 U/g Hb, and approximately half (43%) received phototherapy in the first week after birth. The mean EA level was 3.7 U/g Hb. The EA had good accuracy in predicting phototherapy use, with area under the receiver-operating-characteristic curve of 0.81 ± 0.05. Infants on phototherapy more commonly displayed World Health Organization Class II mutations (deficiency in EA and mutation at c.1388G>A (adjusted odds ratio, 1.5 and 5.7; 95% confidence interval: 1.31-1.76 and 1.30-25.0, respectively) were independent risk factors for phototherapy. Low G6PD EA (G6PD gene variant, c.1388G>A, are risk factors for the need of phototherapy in newborn infants during the first week after birth. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  10. Seizure is a rare presentation for acute hemolysis due to G6PD deficiency. We report a previously healthy boy who presented initially with seizure and cyanosis and subsequently acute hemolysis, due to glucose-6-phosphate dehydrogenase deficiency (G6PD) an

    OpenAIRE

    Afshin FAYYAZI; Ali KHAJEH; Hosein ESFAHANI

    2012-01-01

    Seizure is a rare presentation for acute hemolysis due to G6PD deficiency. We report a previously healthy boy who presented initially with seizure and cyanosis and subsequently acute hemolysis, due to glucose-6-phosphate dehydrogenase deficiency (G6PD) and probably secondary methemoglobinemia, following the ingestion of fava beans.

  11. Genetics Home Reference: glucose-6-phosphate dehydrogenase deficiency

    Science.gov (United States)

    ... deficiency Encyclopedia: Glucose-6-phosphate dehydrogenase test Encyclopedia: Hemolytic anemia Encyclopedia: Newborn jaundice Health Topic: Anemia Health Topic: G6PD Deficiency Health Topic: Newborn Screening Genetic and Rare Diseases Information Center (1 link) Glucose-6-phosphate dehydrogenase ...

  12. Glucose 6 phosphate dehydrogenase deficiency in adults

    International Nuclear Information System (INIS)

    Khan, M.

    2004-01-01

    Objective: To determine the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in adults presented with anemia. Subjects and Methods: Eighteen months admission data was reviewed for G6PD deficiency as a cause of anemia. Anemia was defined by world health organization (WHO) criteria as haemoglobin less than 11.3 gm%. G6PD activity was measured by Sigma dye decolorisation method. All patients were screened for complications of hemolysis and its possible cause. Patients with more than 13 years of age were included in the study. Results: Out of 3600 patients admitted, 1440 were found anaemic and 49 as G6PD deficient. So the frequency of G6PD deficiency in anaemic patients was 3.4% and the overall frequency is 1.36%. G6PD deficiency among males and females was three and six percent respectively. Antimalarials and antibiotics containing sulphonamide group were the most common precipitating factors for hemolysis. Anemia and jaundice were the most common presentations while malaria was the most common associated disease. Acute renal failure was the most severe complication occurring in five patients with two deaths. Conclusion: G6PD deficiency is a fairly common cause of anemia with medicine as common precipitating factor for hemolysis. Such complications can be avoided with early recognition of the disease and avoiding indiscriminate use of medicine. (author)

  13. Glucose 6-phosphate dehydrogenase variants in Japan.

    Science.gov (United States)

    Miwa, S

    1980-01-01

    Fifty-four cases of glucose 6-phosphate dehydrogenase (G6PD) deficiency have so far been reported in Japan. Among them, 21 G6PD variants have been characterized. Nineteen out of the 21 variants were characterized in our laboratory and G6PD Heian and "Kyoto" by others. G6PD Tokyo, Tokushima, Ogikubo, Kurume, Fukushima, Yokohama, Yamaguchi, Wakayama, Akita, Heian and "Kyoto" were classified as Class 1, because all these cases showed chronic hemolytic anemia and severe enzyme deficiency. All these variants showed thermal instability. G6PD Mediterranean-like, Ogori, Gifu and Fukuoka were classified as Class 2, whereas G6PD Hofu, B(-) Chinese, Ube, Konan, Kamiube and Kiwa belonged to Class 3. All the 6 Class 3 variants were found as the results of the screening tests. The incidence of the deficiency in Japanese seems to be 0.1-0.5% but that of the cases which may slow drug-induced hemolysis would be much less. G6PD Ube and Konan appear to be relatively common in Japan.

  14. Prevalence of glucose-6-phosphate dehydrogenase deficiency in ...

    African Journals Online (AJOL)

    Background: Glucose-6-phosphate dehydrogenase (G6PD) is a house keeping enzyme which catalyzes the first step in the hexose monophosphate pathway of glucose metabolism. G6PD deficiency is the commonest hemolytic X-linked genetic disease, which affects approximately 400 million people worldwide.

  15. Glucose-6-phosphate dehydrogenase deficiency in Singapore.

    Science.gov (United States)

    Quak, S H; Saha, N; Tay, J S

    1996-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) in man is an X-linked enzyme. The deficiency of this enzyme is one of the most common inherited metabolic disorders in man. In Singapore, three clinical syndromes associated with G6PD deficiency had been described: severe haemolysis in neonates with kernicterus, haemoglobinuria and "viral hepatitis"-like syndrome. The human G6PD monomer consists of 515 amino acids. Only the tetrameric or dimeric forms composed of a single type subunit are catylitically active. The complete amino acid sequence of G6PD had been elucidated in man and various other animals. The region of high homology among the enzymes of various animals is presumably functionally active. Among the Chinese in Singapore, three common molecular variants had been identified: Canton (nt 1376 G --> T), Kaiping (nt 1388 G --> A) and Mediterranean (nt 563 C --> T) in frequencies of 24%, 21% and 10% respectively. In addition, two common mutants (Gaozhou, nt 95 A --> G and Chinese 5, nt 1024 C --> T) have been detected in Singapore Chinese in low frequencies. In Malays, 6 different deficient variants are known in Singapore (3 new, 1 Mahidol, 1 Indonesian and 1 Mediterranean).

  16. Glucose-6-phosphate dehydrogenase deficiency; the single most ...

    African Journals Online (AJOL)

    Introduction: Glucose- 6-phosphate dehydrogenase deficiency is the most common enzymatic disorder of the red cell and an important risk factor for neonatal jaundice. Methodology: The aim of the study was to determine the incidence of G-6-PD deficiency among jaundiced neonates, and describe the associated morbidity ...

  17. Identification of glucose 6 phosphate dehydrogenase mutations by ...

    African Journals Online (AJOL)

    Identification of glucose 6 phosphate dehydrogenase mutations by single strand conformation polymorphism and gene sequencing analysis. ... Subject: Six DNA samples from Turkish males confirmed to have G-6-PD deficiency where available for the study. Results: One subject was found to have an abnormal mobility shift ...

  18. Biochemical and cytochemical evaluation of heterozygote individuals with glucose-6-phosphate dehydrogenase deficiency

    NARCIS (Netherlands)

    Gurbuz, Nilgun; Aksu, Tevfik Aslan; van Noorden, Cornelis J. F.

    2005-01-01

    The aim of this study was to diagnose heterozygous glucose-6-phosphate dehydrogenase (G6PD) deficient females by an inexpensive cytochemical G6PD staining method that is easy to perform, allowing diagnosis of G6PD deficiency without cumbersome genetic analysis. Three subject groups were included in

  19. The first evaluation of glucose-6-phosphate dehydrogenase deficiency (G6PD) gene mutation in malaria-endemic region at South Central Timor (SCT) district, Eastern Indonesia 2015-2016

    Science.gov (United States)

    Hutagalung, J.; Kusnanto, H.; Supargiyono; Sadewa, A. H.; Satyagraha, A. W.

    2018-03-01

    Primaquine (PQ) is the only licensed drug effective against P. vivax for specific hypnozoites and as a key drug in the malaria elimination stage. However, PQ can cause severe hemolysis in G6PD deficient individuals. Unfortunately, few epidemiological data of these disorders was in Indonesia. This study aimed to assesses the prevalence and genotyping variant of G6PDd among the people on malaria-endemic. Blood samples from 555 unrelated subjects in eastern Indonesia were for G6PDd by quantitative test and PCR-RFLP-DNA sequencing. All protocols followed by Promega, Madison, USA. The prevalence of malaria and anemia was 32.6% (181/555) and 16% (89/555) with P. vivaxdominant species 52.5% (95/181), respectively. Overall, 16.6% (92/555) subjects were G6PD deficient, including 58.7% (54/92) females and 41.3% (38/92). Among the 92 cases G6PD deficient molecularly studied, the genotype variant Vanua Lava (T10883C) were detected dominant and unknown G6PD deficient (T-13.154-C) in 3 cases. It was high G6PD deficient in eastern Indonesia indicate that diagnosis and management of G6PD deficient are necessary. Obligatory anti-malaria doses for G6PD deficient individuals, population screening, are needed on endemic malaria in eastern Indonesia.

  20. Erythrocyte glucose-6-phosphate dehydrogenase from Brazilian opossum Didelphis marsupialis

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    Barretto O.C. de O.

    2006-01-01

    Full Text Available In a comparative study of erythrocyte metabolism of vertebrates, the specific activity of glucose-6-phosphate dehydrogenase (G6PD of the Brazilian opossum Didelphis marsupialis in a hemolysate was shown to be high, 207 ± 38 IU g-1 Hb-1 min-1 at 37ºC, compared to the human erythrocyte activity of 12 ± 2 IU g-1 Hb-1 min-1 at 37ºC. The apparent high specific activity of the mixture led us to investigate the physicochemical properties of the opossum enzyme. We report that reduced glutathione (GSH in the erythrocytes was only 50% higher than in human erythrocytes, a value lower than expected from the high G6PD activity since GSH is maintained in a reduced state by G6PD activity. The molecular mass, determined by G-200 Sephadex column chromatography at pH 8.0, was 265 kDa, which is essentially the same as that of human G6PD (260 kDa. The Michaelis-Menten constants (Km: 55 µM for glucose-6-phosphate and nicotinamide adenine dinucleotide phosphate (Km: 3.3 µM were similar to those of the human enzyme (Km: 50-70 and Km: 2.9-4.4, respectively. A 450-fold purification of the opossum enzyme was achieved and the specific activity of the purified enzyme, 90 IU/mg protein, was actually lower than the 150 IU/mg protein observed for human G6PD. We conclude that G6PD after purification from the hemolysate of D. marsupialis does not have a high specific activity. Thus, it is quite probable that the red cell hyperactivity reported may be explained by increased synthesis of G6PD molecules per unit of hemoglobin or to reduced inactivation in the RBC hemolysate.

  1. Glucose-6-phosphate dehydrogenase activity decreases during storage of leukoreduced red blood cells

    NARCIS (Netherlands)

    Peters, Anna L.; van Bruggen, Robin; de Korte, Dirk; van Noorden, Cornelis J. F.; Vlaar, Alexander P. J.

    2016-01-01

    During storage, the activity of the red blood cell (RBC) antioxidant system decreases. Glucose-6-phosphate dehydrogenase (G6PD) is essential for protection against oxidative stress by producing NADPH. G6PD function of RBC transfusion products is reported to remain stable during storage, but activity

  2. Glucose-6-phosphate dehydrogenase deficiency in Nigerian children.

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    Olatundun Williams

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common human enzymopathy and in Sub-Saharan Africa, is a significant cause of infection- and drug-induced hemolysis and neonatal jaundice. Our goals were to determine the prevalence of G6PD deficiency among Nigerian children of different ethnic backgrounds and to identify predictors of G6PD deficiency by analyzing vital signs and hematocrit and by asking screening questions about symptoms of hemolysis. We studied 1,122 children (561 males and 561 females aged 1 month to 15 years. The mean age was 7.4 ± 3.2 years. Children of Yoruba ethnicity made up the largest group (77.5% followed by those Igbo descent (10.6% and those of Igede (10.2% and Tiv (1.8% ethnicity. G6PD status was determined using the fluorescent spot method. We found that the overall prevalence of G6PD deficiency was 15.3% (24.1% in males, 6.6% in females. Yoruba children had a higher prevalence (16.9% than Igede (10.5%, Igbo (10.1% and Tiv (5.0% children. The odds of G6PD deficiency were 0.38 times as high in Igbo children compared to Yoruba children (p=0.0500. The odds for Igede and Tiv children were not significantly different from Yoruba children (p=0.7528 and 0.9789 respectively. Mean oxygen saturation, heart rate and hematocrit were not significantly different in G6PD deficient and G6PD sufficient children. The odds of being G6PD deficient were 2.1 times higher in children with scleral icterus than those without (p=0.0351. In conclusion, we determined the prevalence of G6PD deficiency in Nigerian sub-populations. The odds of G6PD deficiency were decreased in Igbo children compared to Yoruba children. There was no association between vital parameters or hematocrit and G6PD deficiency. We found that a history of scleral icterus may increase the odds of G6PD deficiency, but we did not exclude other common causes of icterus such as sickle cell disease or malarial infection.

  3. Neonatal jaundice and glucose-6-phosphate dehydrogenase

    OpenAIRE

    Leite, Amauri Antiquera [UNESP

    2010-01-01

    A deficiência de glicose-6-fosfato desidrogenase em neonatos pode ser a responsável pela icterícia neonatal. Este comentário científico é decorrente do relato sobre o tema publicado neste fascículo e que preocupa diversos autores de outros países em relação às complicações em neonatos de hiperbilirrubinemia, existindo inclusive proposições de alguns autores em incluir o teste para identificar a deficiência de glicose-6-fosfato desidrogenase nos recém-nascidos.Glucose-6-phosphate dehydrogenase...

  4. [Glucose-6-phosphate dehydrogenase deficiency in children: a case report].

    Science.gov (United States)

    Verdugo L, Patricia; Calvanese T, Marlene; Rodríguez V, Diego; Cárcamo C, Cassandra

    2014-02-01

    Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) is the most common red blood cell (RBC) enzyme disorder. The decrease as well as the absence of the enzyme increase RBC vulnerability to oxidative stress caused by exposure to certain medications or intake of fava beans. Among the most common clinical manifestations of this condition, acute hemolysis, chronic hemolysis, neonatal hyperbilirubinemia, and an asymptomatic form are observed. To analyze the case of a child who presented hemolytic crisis due to favism. A 2 year and 7 month old boy with a history of hyperbilirubinemia during the newborn period with no apparent cause, no family history of hemolytic anemia or parental consanguinity. He presented a prolonged neonatal jaundice and severe anemia requiring RBC transfusion. An intake of fava beans 48 h prior to onset of symptoms was reported. G6PD qualitative determination was compatible with this enzyme deficiency. G6PD deficiency can be highly variable in its clinical presentation, so it is necessary to keep it in mind during the diagnosis of hemolytic anemia at any age.

  5. Posttranslational regulation of glucose-6-phosphate dehydrogenase activity in tongue epithelium

    NARCIS (Netherlands)

    Biagiotti, E.; Bosch, K. S.; Ninfali, P.; Frederiks, W. M.; van Noorden, C. J.

    2000-01-01

    Expression of glucose-6-phosphate dehydrogenase (G6PD) activity is high in tongue epithelium, but its exact function is still unknown, it may be related;either to the high proliferation rate of this tissue or to protection against oxidative stress. To elucidate its exact role, we localized

  6. Prevalence of glucose-6-phosphate dehydrogenase deficiency and diagnostic challenges in 1500 immigrants in Denmark examined for haemoglobinopathies

    DEFF Research Database (Denmark)

    Warny, Marie; Klausen, Tobias Wirenfeldt; Petersen, Jesper

    2015-01-01

    Similar to the thalassaemia syndromes, glucose-6-phosphate dehydrogenase (G6PD) deficiency is highly prevalent in areas historically exposed to malaria. In the present study, we used quantitative and molecular methods to determine the prevalence of G6PD deficiency in a population of 1508 immigran...

  7. Rasburicase-induced Hemolytic Anemia in an Adolescent With Unknown Glucose-6-Phosphate Dehydrogenase Deficiency.

    Science.gov (United States)

    Akande, Manzilat; Audino, Anthony N; Tobias, Joseph D

    2017-01-01

    Rasburicase, used in the prevention and treatment of tumor lysis syndrome (TLS), may cause hemolytic anemia and methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Although routine screening for G6PD deficiency has been recommended, given the turnaround time for test results and the urgency to treat TLS, such screening may not be feasible. We report a case of rasburicase-induced hemolytic anemia without methemoglobinemia in an adolescent with T-cell lymphoblastic lymphoma, TLS, and previously unrecognized G6PD deficiency. Previous reports of hemolytic anemia with rasburicase are reviewed, mechanisms discussed, and preventative strategies presented.

  8. Glucose 6 phosphatase dehydrogenase (G6PD) and neurodegenerative disorders: Mapping diagnostic and therapeutic opportunities

    OpenAIRE

    Manju Tiwari

    2017-01-01

    Glucose 6 phosphate dehydrogenase (G6PD) is a key and rate limiting enzyme in the pentose phosphate pathway (PPP). The physiological significance of enzyme is providing reduced energy to specific cells like erythrocyte by maintaining co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH). There are preponderance research findings that demonstrate the enzyme (G6PD) role in the energy balance, and it is associated with blood-related diseases and disorders, primarily the anemia resulted f...

  9. Glucose 6-phosphate dehydrogenase: isoenzymatic pattern in Oesophagostomum venulosum, Trichuris ovis and T. suis.

    Science.gov (United States)

    Rodriguez, B; Cutillas, C; German, P; Guevara, D

    1991-12-01

    In the present communication we have studied the isoenzymatic pattern activity of the glucose 6-phosphate dehydrogenase (G6PD) in Oesophagostomum venulosum, Trichuris ovis and T. suis, parasites of Capra hircus (goat), Ovis aries (sheep) and Sus scrofa domestica (pig) respectively, by polyacrylamide gel electrophoresis. Different phenotypes have been observed in the G6PD isoenzymatic pattern activity in males and females of Oesophagostomum venulosum. Furthermore, G6PD activity has been assayed in Trichuris ovis collected from Ovis aries and Capra hircus. No differences have been observed in the isoenzymatic patterns attending to the different hosts. All the individuals exhibited one single band or two bands; this suggests a monomeric condition for G6PD in T. ovis. In T. suis the enzyme G6PD appeared as a single electrophoretic band in about 85.7% of the individuals.

  10. Data mining and pathway analysis of glucose-6-phosphate dehydrogenase with natural language processing

    Science.gov (United States)

    Chen, Long; Zhang, Chunhua; Wang, Yanling; Li, Yuqian; Han, Qiaoqiao; Yang, Huixin; Zhu, Yuechun

    2017-01-01

    Human glucose-6-phosphate dehydrogenase (G6PD) is a crucial enzyme in the pentose phosphate pathway, and serves an important role in biosynthesis and the redox balance. G6PD deficiency is a major cause of neonatal jaundice and acute hemolyticanemia, and recently, G6PD has been associated with diseases including inflammation and cancer. The aim of the present study was to conduct a search of the National Center for Biotechnology Information PubMed library for articles discussing G6PD. Genes that were identified to be associated with G6PD were recorded, and the frequency at which each gene appeared was calculated. Gene ontology (GO), pathway and network analyses were then performed. A total of 98 G6PD-associated genes and 33 microRNAs (miRNAs) that potentially regulate G6PD were identified. The 98 G6PD-associated genes were then sub-classified into three functional groups by GO analysis, followed by analysis of function, pathway, network, and disease association. Out of the 47 signaling pathways identified, seven were significantly correlated with G6PD-associated genes. At least two out of four independent programs identified the 33 miRNAs that were predicted to target G6PD. miR-1207-5P, miR-1 and miR-125a-5p were predicted by all four software programs to target G6PD. The results of the present study revealed that dysregulation of G6PD was associated with cancer, autoimmune diseases, and oxidative stress-induced disorders. These results revealed the potential roles of G6PD-regulated signaling and metabolic pathways in the etiology of these diseases. PMID:28627690

  11. Glucose-6-Phosphate Dehydrogenase Deficiency and Adrenal Hemorrhage in a Filipino Neonate with Hyperbilirubinemia

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    Akira Ohishi

    2013-05-01

    Full Text Available We report on a Filipino neonate with early onset and prolonged hyperbilirubinemia who was delivered by a vacuum extraction due to a prolonged labor. Subsequent studies revealed adrenal hemorrhage and glucose-6-phosphate dehydrogenase (G6PD deficiency. It is likely that asphyxia and resultant hypoxia underlie the occurrence of adrenal hemorrhage and the clinical manifestation of G6PD deficiency and that the presence of the two events explains the early onset and prolonged hyperbilirubinemia of this neonate. Our results represent the importance of examining possible underlying factors for the development of severe, early onset, or prolonged hyperbilirubinemia.

  12. Glucose-6-Phosphate Dehydrogenase: Update and Analysis of New Mutations around the World

    Science.gov (United States)

    Gómez-Manzo, Saúl; Marcial-Quino, Jaime; Vanoye-Carlo, America; Serrano-Posada, Hugo; Ortega-Cuellar, Daniel; González-Valdez, Abigail; Castillo-Rodríguez, Rosa Angélica; Hernández-Ochoa, Beatriz; Sierra-Palacios, Edgar; Rodríguez-Bustamante, Eduardo; Arreguin-Espinosa, Roberto

    2016-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme in the pentose phosphate pathway which produces nicotinamide adenine dinucleotide phosphate (NADPH) to maintain an adequate reducing environment in the cells and is especially important in red blood cells (RBC). Given its central role in the regulation of redox state, it is understandable that mutations in the gene encoding G6PD can cause deficiency of the protein activity leading to clinical manifestations such as neonatal jaundice and acute hemolytic anemia. Recently, an extensive review has been published about variants in the g6pd gene; recognizing 186 mutations. In this work, we review the state of the art in G6PD deficiency, describing 217 mutations in the g6pd gene; we also compile information about 31 new mutations, 16 that were not recognized and 15 more that have recently been reported. In order to get a better picture of the effects of new described mutations in g6pd gene, we locate the point mutations in the solved three-dimensional structure of the human G6PD protein. We found that class I mutations have the most deleterious effects on the structure and stability of the protein. PMID:27941691

  13. Glucose 6 phosphatase dehydrogenase (G6PD and neurodegenerative disorders: Mapping diagnostic and therapeutic opportunities

    Directory of Open Access Journals (Sweden)

    Manju Tiwari

    2017-12-01

    Full Text Available Glucose 6 phosphate dehydrogenase (G6PD is a key and rate limiting enzyme in the pentose phosphate pathway (PPP. The physiological significance of enzyme is providing reduced energy to specific cells like erythrocyte by maintaining co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH. There are preponderance research findings that demonstrate the enzyme (G6PD role in the energy balance, and it is associated with blood-related diseases and disorders, primarily the anemia resulted from G6PD deficiency. The X-linked genetic deficiency of G6PD and associated non-immune hemolytic anemia have been studied widely across the globe. Recent advancement in biology, more precisely neuroscience has revealed that G6PD is centrally involved in many neurological and neurodegenerative disorders. The neuroprotective role of the enzyme (G6PD has also been established, as well as the potential of G6PD in oxidative damage and the Reactive Oxygen Species (ROS produced in cerebral ischemia. Though G6PD deficiency remains a global health issue, however, a paradigm shift in research focusing the potential of the enzyme in neurological and neurodegenerative disorders will surely open a new avenue in diagnostics and enzyme therapeutics. Here, in this study, more emphasis was made on exploring the role of G6PD in neurological and inflammatory disorders as well as non-immune hemolytic anemia, thus providing diagnostic and therapeutic opportunities.

  14. Loss of peroxisomes causes oxygen insensitivity of the histochemical assay of glucose-6-phosphate dehydrogenase activity to detect cancer cells

    NARCIS (Netherlands)

    Frederiks, Wilma M.; Vreeling-Sindelárová, Heleen; van Noorden, Cornelis J. F.

    2007-01-01

    Oxygen insensitivity of carcinoma cells and oxygen sensitivity of non-cancer cells in the histochemical assay of glucose-6-phosphate dehydrogenase (G6PD) enables detection of carcinoma cells in unfixed cell smears or cryostat sections of biopsies. The metabolic background of oxygen insensitivity is

  15. Screening of Glucose-6-Phosphate Dehydrogenase Deficiency in Cord Blood

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    Can Acipayam

    2014-02-01

    Aim: Glucose-6-phosphate dehydrogenase deficiency is an important factor in etiology of pathologic neonatal jaundice. The aim of this study was to indicate the significance of screening glucose-6-phosphate dehydrogenase deficiency in the cord blood of neonates and the frequency of this deficiency in the etiology of neonatal hyperbilirubinemia. Material and Method: The study was performed consecutive 1015 neonates were included. Five hundred fifty six (54.8% of them were male and 459 (45.2% were female. The following parameters were recorded: Gender, birth weight, birth height, head circumference and gestational age. The glucose-6-phosphate dehydrogenase level of neonates were measured with quantitative method in cord blood. Also, hemoglobine, hematocrite, red blood cell count and blood group were measured. The following parameters were recorded in cases with jaundice: exchange transfusion, phototherapy, physiologic and pathologic jaundice, peak bilirubin day, maximum bilirubin level, total bilirubin level at the first day of jaundice, beginning time of jaundice. Results: Enzyme deficiency was detected in 133 (13.1% of neonates and 76 (57% of them were male, 57 (43% were female. Significant difference was detected in low glucose-6-phosphate dehydrogenase enzyme level with jaundice group for total bilirubin level at the first day of jaundice, maximum total bilirubin level and pathologic jaundice (p<0.05. Discussion: The ratio of glucose-6-phosphate dehydrogenase deficiency was found in Edirne in this study and this ratio was higher than other studies conducted in our country. For this reason, glucose-6-phosphate dehydrogenase enzyme level in cord blood of neonates should be measured routinely and high risk neonates should be followed up for hyperbilirubinemia and parents should be informed in our region.

  16. Glucose-6-phosphate dehydrogenase deficiency: an unusual cause of acute jaundice after paracetamol overdose.

    Science.gov (United States)

    Phillpotts, Simon; Tash, Elliot; Sen, Sambit

    2014-11-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest human enzyme defect causing haemolytic anaemia after exposure to specific triggers. Paracetamol-induced haemolysis in G6PD deficiency is a rare complication and mostly reported in children. We report the first case (to the best of our knowledge) of acute jaundice without overt clinical features of a haemolytic crisis, in an otherwise healthy adult female following paracetamol overdose, due to previously undiagnosed G6PD deficiency. It is important that clinicians consider this condition when a patient presents following a paracetamol overdose with significant and disproportionate jaundice, without transaminitis or coagulopathy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Demonstration of glucose-6-phosphate dehydrogenase in rat Kupffer cells by a newly-developed ultrastructural enzyme-cytochemistry

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    S Matsubara

    2009-06-01

    Full Text Available Although various tissue macrophages possess high glucose- 6-phosphate dehydrogenase (G6PD activity, which is reported to be closely associated with their phagocytotic/bactericidal function, the fine subcellular localization of this enzyme in liver resident macrophages (Kupffer cells has not been determined.We have investigated the subcellular localization of G6PD in Kupffer cells in rat liver, using a newly developed enzyme-cytochemical (copper-ferrocyanide method. Electron-dense precipitates indicating G6PD activity were clearly visible in the cytoplasm and on the cytosolic side of the endoplasmic reticulum of Kupffer cells. Cytochemical controls ensured specific detection of the enzymatic activity. Rat Kupffer cells abundantly possessed enzyme-cytochemically detectable G6PD activity. Kupffer cell G6PD may play a role in liver defense by delivering NADPH to NADPH-dependent enzymes. G6PD enzyme-cytochemistry may be a useful tool for the study of Kupffer cell functions.

  18. Cytophotometry of glucose-6-phosphate dehydrogenase activity in individual cells

    NARCIS (Netherlands)

    van Noorden, C. J.; Tas, J.; Vogels, I. M.

    1983-01-01

    With the aid of thin films of polyacrylamide gel containing purified glucose-6-phosphate dehydrogenase subjected to cytochemical procedures for the enzyme using tetranitro blue tetrazolium, arbitrary units of integrated absorbance obtained with a Barr & Stroud GN5 cytophotometer were converted into

  19. Molecular Characterization of Cosenza Mutation among Patients with Glucose-6-Phosphate Dehydrogenase Deficiency in huzestan Province, Southwest Iran

    Science.gov (United States)

    Kazemi Nezhad, Seyed Reza; Fahmi, Fatemeh; Khatami, Saeid Reza; Musaviun, Mohsen

    2011-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common hereditary enzymatic disorders in human, increases the vulnerability of erythrocytes to oxidative stress. It is also characterized by remarkable molecular and biochemical heterogeneity. According to previous investigations, G6PD Cosenza (G1376C) is a common G6PD mutation in some parts of . Therefore in the present study we have characterized mutation among G6PD deficient individuals in Khuzestan province. In order to identify G6PD Cosenza, we analyzed the G6PD gene in 64 samples out of 231 deficient individuals who had not G6PD Mediterranean mutation, using PCR- restriction fragment length polymorphism (RFLP) method. G6PD Cosenza mutation was found in 6 males of 231 samples, resulting in the relative rate of 2.6% and allele frequency of 0.023 among Khuzestanian G6PD deficient subjects. A comparison of these results with previous findings in some parts of suggests that G6PD Cosenza is a common mutation in Khuzestanian G6PD deficient individuals. PMID:23365477

  20. Molecular Characterization of Cosenza Mutation among Patients with Glucose-6-Phosphate Dehydrogenase Deficiency in Khuzestan Province, Southwest Iran

    Directory of Open Access Journals (Sweden)

    Seyed Reza Kazemi Nezhad

    2011-03-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is one of the most common hereditary enzymatic disorders in human, increases the vulnerability of erythrocytes to oxidative stress. It is also characterized by remarkable molecular and biochemical heterogeneity. According to previous investigations, G6PD Cosenza (G1376C is a common G6PD mutation in some parts of Iran. Therefore in the present study we have characterized Cosenza mutation among G6PD deficient individuals in Khuzestan province. In order to identify G6PD Cosenza, we analyzed the G6PD gene in 64 samples out of 231 deficient individuals who had not G6PD Mediterranean mutation, using PCR- restriction fragment length polymorphism (RFLP method. G6PD Cosenza mutation was found in 6 males of 231 samples, resulting in the relative rate of 2.6% and allele frequency of 0.023 among Khuzestanian G6PD deficient subjects. A comparison of these results with previous findings in some parts of Iran suggests that G6PD Cosenza is a common mutation in Khuzestanian G6PD deficient individuals

  1. Five novel glucose-6-phosphate dehydrogenase deficiency haplotypes correlating with disease severity

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    Dallol Ashraf

    2012-09-01

    Full Text Available Abstract Background Glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49 deficiency is caused by one or more mutations in the G6PD gene on chromosome X. An association between enzyme levels and gene haplotypes remains to be established. Methods In this study, we determined G6PD enzyme levels and sequenced the coding region, including the intron-exon boundaries, in a group of individuals (163 males and 86 females who were referred to the clinic with suspected G6PD deficiency. The sequence data were analysed by physical linkage analysis and PHASE haplotype reconstruction. Results All previously reported G6PD missense changes, including the AURES, MEDITERRANEAN, A-, SIBARI, VIANGCHAN and ANANT, were identified in our cohort. The AURES mutation (p.Ile48Thr was the most common variant in the cohort (30% in males patients followed by the Mediterranean variant (p.Ser188Phe detectable in 17.79% in male patients. Variant forms of the A- mutation (p.Val68Met, p.Asn126Asp or a combination of both were detectable in 15.33% of the male patients. However, unique to this study, several of such mutations co-existed in the same patient as shown by physical linkage in males or PHASE haplotype reconstruction in females. Based on 6 non-synonymous variants of G6PD, 13 different haplotypes (13 in males, 8 in females were identified. Five of these were previously unreported (Jeddah A, B, C, D and E and were defined by previously unreported combinations of extant mutations where patients harbouring these haplotypes exhibited severe G6PD deficiency. Conclusions Our findings will help design a focused population screening approach and provide better management for G6PD deficiency patients.

  2. Glucose-6-phosphate dehydrogenase in rat lung alveolar epithelial cells. An ultrastructural enzyme-cytochemical study

    Directory of Open Access Journals (Sweden)

    S Matsubara

    2010-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is the key enzyme of the pentose phosphate pathway in carbohydrate metabolism, and it plays an important role in cell proliferation and antioxidant regulation within cells in various organs. Although marked cell proliferation and oxidant/antioxidant metabolism occur in lung alveolar epithelial cells, definite data has been lacking as to whether cytochemically detectable G6PD is present in alveolar epithelial cells. The distribution pattern of G6PD within these cells, if it is present, is also unknown. The purpose of the present study was to investigate the subcellular localization of G6PD in alveolar cells in the rat lung using a newly- developed enzyme-cytochemistry (copper-ferrocyanide method. Type I cells and stromal endothelia and fibroblasts showed no activities. Electron-dense precipitates indicating G6PD activity were clearly visible in the cytoplasm and on the cytosolic side of the endoplasmic reticulum of type II alveolar epithelial cells. The cytochemical controls ensured specific detection of enzyme activity. This enzyme may play a role in airway defense by delivering substances for cell proliferation and antioxidant forces, thus maintaining the airway architecture.

  3. Reduced glutathione and glutathione disulfide in the blood of glucose-6-phosphate dehydrogenase-deficient newborns.

    Science.gov (United States)

    Gong, Zhen-Hua; Tian, Guo-Li; Huang, Qi-Wei; Wang, Yan-Min; Xu, Hong-Ping

    2017-07-20

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly detected during mass screening for neonatal disease. We developed a method to measure reduced glutathione (GSH) and glutathione disulfide (GSSG) using tandem mass spectrometry (MS/MS) for detecting G6PD deficiency. The concentration of GSH and the GSH/GSSG ratio in newborn dry-blood-spot (DBS) screening and in blood plus sodium citrate for test confirmation were examined by MS/MS using labeled glycine as an internal standard. G6PD-deficient newborns had a lower GSH content (242.9 ± 15.9 μmol/L)and GSH/GSSG ratio (14.9 ± 7.2) than neonatal controls (370.0 ± 53.2 μmol/L and 46.7 ± 19.6, respectively). Although the results showed a significance of P blood measured using MS/MS on the first day of sample preparation are consistent with G6PD activity and are helpful for diagnosing G6PD deficiency.

  4. Evaluation of Glucose-6-Phosphate Dehydrogenase stability in stored blood samples.

    Science.gov (United States)

    Jalil, Norunaluwar; Azma, Raja Zahratul; Mohamed, Emida; Ithnin, Azlin; Alauddin, Hafiza; Baya, Siti Noor; Othman, Ainoon

    2016-01-01

    Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is the commonest cause of neonatal jaundice in Malaysia. Recently, OSMMR2000-D G6PD Assay Kit has been introduced to quantitate the level of G6PD activity in newborns delivered in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). As duration of sample storage prior to analysis is one of the matters of concern, this study was conducted to identify the stability of G6PD enzyme during storage. A total of 188 cord blood samples from normal term newborns delivered at UKMMC were selected for this study. The cord bloods samples were collected in ethylene-diamine-tetra-acetic acid (EDTA) tubes and refrigerated at 2-8 °C. In addition, 32 out of 188 cord blood samples were spotted on chromatography paper, air-dried and stored at room temperature. G6PD enzyme activities were measured daily for 7 days using the OSMMR2000-D G6PD Assay Kit on both the EDTA blood and dried blood samples. The mean value for G6PD activity was compared between days of analysis using Student Paired T-Test. In this study, 172 out of 188 cord blood samples showed normal enzyme levels while 16 had levels corresponding to severe enzyme deficiency. The daily mean G6PD activity for EDTA blood samples of newborns with normal G6PD activity showed a significant drop on the fourth day of storage (p samples with severely deficient G6PD activity, significant drop was seen on third day of storage (p = 0.002). Analysis of dried cord blood showed a significant reduction in enzyme activity as early as the second day of storage (p = 0.001). It was also noted that mean G6PD activity for spotted blood samples were lower compared to those in EDTA tubes for all days (p = 0.001). Thus, EDTA blood samples stored at 2-8 °C appeared to have better stability in terms of their G6PD enzyme level as compared to dried blood samples on filter paper, giving a storage time of up to 3 days.

  5. Prevalence of glucose-6-phosphate dehydrogenase deficiency and sickle cell trait among blood donors in Riyadh

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    Alabdulaali Mohammed

    2010-01-01

    Full Text Available Background and Aims: Blood donation from glucose-6-phosphate dehydrogenase (G6PD-deficient and sickle cell trait (SCT donors might alter the quality of the donated blood during processing, storage or in the recipient′s circulatory system. The aim of this study was to determine the prevalence of G6PD deficiency and SCT among blood donors coming to King Khalid University Hospital (KKUH in Riyadh. It was also reviewed the benefits and risks of transfusing blood from these blood donors. Materials and Methods: This cross-sectional study was conducted on 1150 blood samples obtained from blood donors that presented to KKUH blood bank during the period April 2006 to May 2006. All samples were tested for Hb-S by solubility test, alkaline gel electrophoresis; and for G6PD deficiency, by fluorescent spot test. Results: Out of the 1150 donors, 23 (2% were diagnosed for SCT, 9 (0.78% for G6PD deficiency and 4 (0.35% for both conditions. Our prevalence of SCT and G6PD deficiency is higher than that of the general population of Riyadh. Conclusion: We recommend to screen all units for G6PD deficiency and sickle cell trait and to defer donations from donors with either of these conditions, unless if needed for special blood group compatibility, platelet apheresis or if these are likely to affect the blood bank inventory. If such blood is to be used, special precautions need to be undertaken to avoid complications in high-risk recipients.

  6. Effect of thoracic x-irradiation on glucose-6-phosphate dehydrogenase activity of the pectoral muscle of guinea pig

    International Nuclear Information System (INIS)

    Bhatavdekar, J.M.; Shah, V.C.

    1981-01-01

    The histochemical distribution of glucose-6-phosphate dehydrogenase (G6PD) was observed in the major pectoral muscle of a guinea pig that had received 240 R thoracic X-irradiation. The irradiation effects were studied at 24, 48 and 72 hrs after X-irradiation. Type I fibres of the pectoral muscle were deeply stained showing high activity whereas type II fibres demonstrated minimum enzyme activity. The intermediate fibres had medium levels of G6PD activity. Type II fibres showed more staining at 24 and 48 hrs as compared with control muscle. However, at 72 hrs all three fibre types showed a marked inhibition of G6PD activity. The significance of these changes suggests that muscle G6PD metabolism generally altered after irradiation, but the specific nature of these changes and their causes still remain unclear. (author)

  7. Functional and Biochemical Characterization of Three Recombinant Human Glucose-6-Phosphate Dehydrogenase Mutants: Zacatecas, Vanua-Lava and Viangchan

    Science.gov (United States)

    Gómez-Manzo, Saúl; Marcial-Quino, Jaime; Vanoye-Carlo, America; Serrano-Posada, Hugo; González-Valdez, Abigail; Martínez-Rosas, Víctor; Hernández-Ochoa, Beatriz; Sierra-Palacios, Edgar; Castillo-Rodríguez, Rosa Angélica; Cuevas-Cruz, Miguel; Rodríguez-Bustamante, Eduardo; Arreguin-Espinosa, Roberto

    2016-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency in humans causes severe disease, varying from mostly asymptomatic individuals to patients showing neonatal jaundice, acute hemolysis episodes or chronic nonspherocytic hemolytic anemia. In order to understand the effect of the mutations in G6PD gene function and its relation with G6PD deficiency severity, we report the construction, cloning and expression as well as the detailed kinetic and stability characterization of three purified clinical variants of G6PD that present in the Mexican population: G6PD Zacatecas (Class I), Vanua-Lava (Class II) and Viangchan (Class II). For all the G6PD mutants, we obtained low purification yield and altered kinetic parameters compared with Wild Type (WT). Our results show that the mutations, regardless of the distance from the active site where they are located, affect the catalytic properties and structural parameters and that these changes could be associated with the clinical presentation of the deficiency. Specifically, the structural characterization of the G6PD Zacatecas mutant suggests that the R257L mutation have a strong effect on the global stability of G6PD favoring an unstable active site. Using computational analysis, we offer a molecular explanation of the effects of these mutations on the active site. PMID:27213370

  8. Screening for glucose-6-phosphate dehydrogenase deficiency in neonates: a comparison between cord and peripheral blood samples.

    Science.gov (United States)

    AlSaif, Saif; Ponferrada, Ma Bella; AlKhairy, Khalid; AlTawil, Khalil; Sallam, Adel; Ahmed, Ibrahim; Khawaji, Mohammed; AlHathlol, Khalid; Baylon, Beverly; AlSuhaibani, Ahmed; AlBalwi, Mohammed

    2017-07-11

    The use of cord blood in the neonatal screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency is being done with increasing frequency but has yet to be adequately evaluated against the use of peripheral blood sample which is usually employed for confirmation. We sought to determine the incidence and gender distribution of G6PD deficiency, and compare the results of cord against peripheral blood in identifying G6PD DEFICIENCY neonates using quantitative enzyme activity assay. We carried out a retrospective and cross-sectional study employing review of primary hospital data of neonates born in a tertiary care center from January to December 2008. Among the 8139 neonates with cord blood G6PD assays, an overall incidence of 2% for G6PD deficiency was computed. 79% of these were males and 21% were females with significantly more deficient males (p blood samples (n = 1253) showed a significantly higher mean G6PD value for peripheral than cord blood (15.12 ± 4.52 U/g and 14.52 ± 4.43 U/g, respectively, p = 0.0008). However, the proportion of G6PD deficient neonates did not significantly differ in the two groups (p = 0.79). Sensitivity of cord blood in screening for G6PD deficiency, using peripheral G6PD assay as a gold standard was 98.6% with a NPV of 99.5%. There was no difference between cord and peripheral blood samples in discriminating between G6PD deficient and non-deficient neonates. A significantly higher mean peripheral G6PD assay reinforces the use of cord blood for neonatal screening since it has substantially low false negative results.

  9. [Evaluations of newborn screening program performance and enzymatic diagnosis of glucose-6-phosphate dehydrogenase deficiency in Guangzhou].

    Science.gov (United States)

    Tang, F; Huang, Y L; Jiang, X; Jia, X F; Li, B; Feng, Y; Chen, Q Y; Tang, C F

    2018-05-02

    Objective: To reveal the molecular epidemiologic characteristics of glucose-6-phosphate dehydrogenase (G6PD) gene and to evaluate based on the genetic analysis the newborn screening program performance and enzymatic diagnosis of G6PD deficiency in Guangzhou. Methods: G6PD enzyme activities were measured by quantitative fluorescence assay in dry blood spots of 16 319 newborns(8 725 males, 7 594 females) 3-7 days after birth in Guangzhou Newborn Center. They were born in Guangzhou form Oct. 1 to 20, 2016. The cutoff value of G6PD was less than 2.6 U/g Hb in dry blood spots. G6PD deficiency was diagnosed when G6PDblood cells. Genetic analysis of G6PD gene was performed on the dry blood spot samples of 823 newborns (including positive 346, negative 477)with various levels of G6PD enzyme activities through fluorescence PCR melting curve analysis(FMCA) to detect 15 kinds of mutations reported to be common among Chinese.G6PD gene Sanger sequency was performed in seven highly suspicious patients with negative results by FMCA. Results: (1) Using the cutoff value of G6PDT, c.551C>T, c.835A>T hemizygote were found in 3 male's samples, respectively. (3) The estimated prevalence of harboring mutation was 6.0% in males and 13.5% in females according to rates of mutation in samples with various levels of G6PD enzyme activities. Six common mutations were c.1388G>A、c.1376G>T, c.95A> G, c.871G>A, c.1024C>T, c.392G>T, accounting for 95.5% of detected alleles .(4) based on results of G6PD gene analysis, the newborn scereening of G6PD deficiency with cutoff value G6PDblood cells were 95.5%, 97.2%, respectively. Conclusions: The prevalence of G6PD deficiency in males was 6.0% in Guangzhou. Six mutations c.1388G>A, c.1376G>T, c.95A>G, c.871G>A, c.1024C>T, c.392G>T accounted for 95.5%. The cutoff value of G6PD<2.6 U/g Hb innewborn screening program and the criteria of biochemical diagnosis could accurately identify G6PD deficiency . Combined with biochemical and molecular analysis will

  10. (G6PD) in stored blood

    African Journals Online (AJOL)

    Red blood cell viability in stored blood determines successful transfusion. Glucose-6-phosphate dehydrogenase (G6PD) activity has been shown to maintain red blood cell membrane integrity. This study was, therefore, aimed at estimating the G6PD activity in stored blood bags at the blood bank of the University of Nigeria ...

  11. Effect of High-Dose Vitamin C Infusion in a Glucose-6-Phosphate Dehydrogenase-Deficient Patient

    Science.gov (United States)

    Gerber, Bryan; Kenyon, Katharine; Muthukanagaraj, Purushothaman

    2017-01-01

    Vitamin C supplementation is generally regarded as benign. There has been a resurgence of interest in the general medical community regarding the use of vitamin C most notably in the care of sepsis. Nonetheless, caution must be taken if supraphysiologic vitamin C supplementation is being administered as it should be considered a medication just like any other. We present a case of hemolysis in a glucose-6-phosphate dehydrogenase- (G6PD-) deficient patient receiving high-dose vitamin C infusions for his rheumatoid arthritis. PMID:29317868

  12. Immune Thrombocytopenia Resolved by Eltrombopag in a Carrier of Glucose-6-Phosphate Dehydrogenase Deficiency

    Directory of Open Access Journals (Sweden)

    Laura Scaramucci

    2016-03-01

    Full Text Available Eltrombopag, a thrombopoietin mimetic peptide, may provide excellent clinical efficacy in steroid-refractory patients with immune thrombocytopenic purpura (ITP [1,2]. Eltrombopag is generally well tolerated. However, its use in the particular setting of glucose-6-phosphate dehydrogenase (G6PD and history of acute hemolytic anemia (AHA has not been reported so far. A 51-year-old female was diagnosed as having ITP in September 2014. She was not taking any medication and her past history was negative, apart from having been diagnosed a carrier (heterozygous of G6PD deficiency (Mediterranean variant after a familial screening by molecular and biochemical methods. She presented with only slightly reduced (about 50% enzyme level, belonging to World Health Organization-defined class 3 [3,4]. In the following years, the patient experienced some episodes of AHA, which were managed at outside institutions; in particular, a severe episode of AHA, probably triggered by urinary infection and antibiotics [5], had complicated her second and last delivery. The hemolytic episodes were selflimiting and resolved without sequelae. No other causes of hemolysis were documented. When the case came to our attention, a diagnosis of ITP was made; hemolytic parameters were normal, although the G6PD enzyme concentration was not measured. Oral prednisone (1 mg/kg was given with only a transient benefit. The patient was then a candidate for elective splenectomy. However, given her extremely low platelet count, she was started in October 2014 on eltrombopag at 50 mg/day as a bridge to splenectomy. Given that, to the best of our knowledge, the use of this drug has never been reported in the particular setting of G6PD deficiency, the patient was constantly monitored. A prompt platelet increase (178x109/L was observed 1 week after the start of treatment. After she achieved the target platelet count, the dose of eltrombopag was tapered to the lowest effective dose. The patient

  13. Glucose 6-phosphate dehydrogenase deficiency and cystic fibrosis

    OpenAIRE

    Congdon, P. J.; Aggarwal, R. K.; Littlewood, J. M.; Shapiro, H.

    1981-01-01

    A child born to Pakistani parents is described. He had both cystic fibrosis and G-6PD-deficiency. So far as can be ascertained, the occurrence of both these conditions in the same individual has not previously been reported.

  14. Prevalence of glucose-6-phosphate dehydrogenase deficiency and ...

    African Journals Online (AJOL)

    . ... while statistical analysis was done using STATA soft- ware version 8 (STATA Corp., College station, TX). Prevalence of G6PD and HbAS in bivariate variables ... Multivariate logis- .... technique (Enevold et al., 2007) found prevalence of.

  15. Prevalence of glucose-6-phosphate dehydrogenase deficiency in ...

    African Journals Online (AJOL)

    Pradeep Kumar

    2016-02-06

    Feb 6, 2016 ... Hemolytic anemia; ... G6PD deficiency is the commonest hemolytic X-linked genetic disease, which affects .... tain drugs or infection, can elicit acute hemolysis. ..... down syndrome risk: a meta-analysis from 34 studies.

  16. Clonal evolution following chemotherapy-induced stem cell depletion in cats heterozygous for glucose-6-phosphate dehydrogenase

    International Nuclear Information System (INIS)

    Abkowitz, J.L.; Ott, R.M.; Holly, R.D.; Adamson, J.W.

    1988-01-01

    The number of hematopoietic stem cells necessary to support normal hematopoiesis is not known but may be small. If so, the depletion or damage of such cells could result in apparent clonal dominance. To test this hypothesis, dimethylbusulfan [2 to 4 mg/kg intravenously (IV) x 3] was given to cats heterozygous for the X-linked enzyme glucose-6-phosphate dehydrogenase (G-6-PD). These cats were the daughters of domestic X Geoffroy parents. After the initial drug-induced cytopenias (2 to 4 weeks), peripheral blood counts and the numbers of marrow progenitors detected in culture remained normal, although the percentages of erythroid burst-forming cells (BFU-E) and granulocyte/macrophage colony-forming cells (CFU-GM) in DNA synthesis increased, as determined by the tritiated thymidine suicide technique. In three of six cats treated, a dominance of Geoffroy-type G-6-PD emerged among the progenitor cells, granulocytes, and RBCs. These skewed ratios of domestic to Geoffroy-type G-6-PD have persisted greater than 3 years. No changes in cell cycle kinetics or G-6-PD phenotypes were noted in similar studies in six control cats. These data suggest that clonal evolution may reflect the depletion or damage of normal stem cells and not only the preferential growth and dominance of neoplastic cells

  17. Kernicterus by glucose-6-phosphate dehydrogenase deficiency: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Cossio de Gurrola Gladys

    2008-05-01

    Full Text Available Abstract Introduction Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive disease that causes acute or chronic hemolytic anemia and potentially leads to severe jaundice in response to oxidative agents. This deficiency is the most common human innate error of metabolism, affecting more than 400 million people worldwide. Case presentation Here, we present the first documented case of kernicterus in Panama, in a glucose-6-phosphate dehydrogenase-deficient newborn clothed in naphthalene-impregnated garments, resulting in reduced psychomotor development, neurosensory hypoacousia, absence of speech and poor reflex of the pupil to light. Conclusion Mutational analysis revealed the glucose-6-phosphate dehydrogenase Mediterranean polymorphic variant, which explained the development of kernicterus after exposition of naphthalene. As the use of naphthalene in stored clothes is a common practice, glucose-6-phosphate dehydrogenase testing in neonatal screening could prevent severe clinical consequences.

  18. Glucose-6-phosphate dehydrogenase deficiency in northern Mexico ...

    Indian Academy of Sciences (India)

    screening, in which the haplotype analysis was performed. Group B .... Thr65 in the native structure of human G6PD, the same protein .... this mutation has a very low frequency in the Mexican popu- lation, we can predict a significant health impact in the males .... genase deficiency: a systematic review and meta-analysis.

  19. Glucose-6-Phosphate Dehydrogenase Deficiency A− Variant in Febrile Patients in Haiti

    Science.gov (United States)

    Carter, Tamar E.; Maloy, Halley; von Fricken, Michael; St. Victor, Yves; Romain, Jean R.; Okech, Bernard A.; Mulligan, Connie J.

    2014-01-01

    Haiti is one of two remaining malaria-endemic countries in the Caribbean. To decrease malaria transmission in Haiti, primaquine was recently added to the malaria treatment public health policy. One limitation of primaquine is that, at certain doses, primaquine can cause hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd). In this study, we genotyped two mutations (A376G and G202A), which confer the most common G6PDd variant in West African populations, G6PDd A−. We estimated the frequency of G6PDd A− in a sample of febrile patients enrolled in an on-going malaria study who represent a potential target population for a primaquine mass drug administration. We found that 33 of 168 individuals carried the G6PDd A− allele (includes A− hemizygous males, A− homozygous or heterozygous females) and could experience toxicity if treated with primaquine. These data inform discussions on safe and effective primaquine dosing and future malaria elimination strategies for Haiti. PMID:24891465

  20. Glucose-6-phosphate dehydrogenase Lodi844C: a study on its expression in blood cells and muscle.

    Science.gov (United States)

    Ninfali, P; Bresolin, N; Baronciani, L; Fortunato, F; Comi, G; Magnani, M; Scarlato, G

    1991-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency was found in erythrocytes, lymphocytes and muscle of an Italian male, whose family has lived for at least three generations in Lodi (Lombardy, northern Italy). The subject was hospitalized for myalgia and dark urine after intense physical exercise, but no sign of anemia and chronic hemolysis were present at rest. Family studies revealed that the mother and the maternal aunt had the same enzymopathy. The enzyme-specific activity in red blood cells was 15% of control and the kinetic properties were the following: slower electrophoretic mobility; biphasic pH activity curve; slightly reduced thermal stability, and increased utilization of the substrate analogs. The analysis of our patient's DNA showed a G----C mutation at nucleotide 844 which causes an Asp----His amino acid change in position 282. This is the same mutation found by De Vita et al. in the G6PD Seattle-like variant. However, by following a new convention, we labelled our variant as G6PD Lodi844C. As far as the muscle is concerned, we found that the enzyme-specific activity in this tissue was 14% of control values, but cultured myotubes and myoblasts revealed a normal level of G6PD as well as skin fibroblasts. On the contrary in the same type of cultured cells obtained from G6PD Mediterranean subjects, the G6PD activity was about 20% of normal. Our results complete the characterization of this mutant enzyme, demonstrate the expression of the deficit in muscle and describe the enzyme behaviour in cultured cells.

  1. The effects of chemical and radioactive properties of Tl-201 on human erythrocyte glucose 6-phosphate dehydrogenase activity

    International Nuclear Information System (INIS)

    Sahin, Ali; Senturk, Murat; Ciftci, Mehmet; Varoglu, Erhan; Kufrevioglu, Omer Irfan

    2010-01-01

    Aim: The inhibitory effects of thallium-201 ( 201 Tl) solution on human erythrocyte glucose 6-phosphate dehydrogenase (G6PD) activity were investigated. Methods: For this purpose, erythrocyte G6PD was initially purified 835-fold at a yield of 41.7% using 2',5'-Adenosine diphosphate sepharose 4B affinity gel chromatography. The purification was monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which showed a single band for the final enzyme preparation. The in vitro and in vivo effects of the 201 Tl solution including Tl + , Fe +3 and Cu +2 metals and the in vitro effects of the radiation effect of the 201 Tl solution and non-radioactive Tl + , Fe +3 and Cu +2 metals on human erythrocyte G6PD enzyme were studied. Enzyme activity was determined with the Beutler method at 340 nm using a spectrophotometer. All purification procedures were carried out at +4 deg. C. Results: 201 Tl solution and radiation exposure had inhibitory effects on the enzyme activity. IC 50 value of 201 Tl solution was 36.86 μl ([Tl + ]: 0.0036 μM, [Cu +2 ]: 0.0116 μM, [Fe +3 ]: 0.0132 μM), of human erythrocytes G6PD. Seven human patients were also used for in vivo studies of 201 Tl solution. Furthermore, non-radioactive Tl + , Fe +3 and Cu +2 were found not to have influenced the enzyme in vitro. Conclusion: Human erythrocyte G6PD activity was inhibited by exposure for up to 10 minutes to 0.057 mCi/kg 201 Tl solution. It was detected in in vitro and in vivo studies that the human erythrocyte G6PD enzyme is inhibited due to the radiation effect of 201 Tl solution.

  2. Simultaneous demonstration of acid phosphatase and glucose-6-phosphate dehydrogenase in mouse hepatocytes. A novel electron-microscopic dual staining enzyme-cytochemistry

    Directory of Open Access Journals (Sweden)

    S Matsubara

    2010-01-01

    Full Text Available Acid phosphatase (ACPase and glucose-6-phosphate dehydrogenase (G6PD play important roles in cell biology/disease pathophysiology in various organs including the liver. The purpose of the present report is to introduce a new enzymecytochemical method to simultaneously demonstrate the subcellular localization of ACPase and G6PD within the same hepatocyte in the mouse liver. The ultrastructural localization of ACPase and G6PD were demonstrated, with concomitant use of the cerium method and the copper-ferrocyanide method, respectively. ACPase labelings were localized in the lysosomes, and G6PD labelings were visible in the cytoplasm and on the cytosolic side of the endoplasmic reticulum of the hepatocyte. This novel double staining procedure may be a useful histochemical tool for the study of liver functions in both physiological and pathological conditions.

  3. Prevalence of Sickle Cell Trait and Glucose 6 Phosphate ...

    African Journals Online (AJOL)

    Blood donation from sickle cell trait (SCT) and glucose-6-phosphate dehydrogenase (G6PD)-deficient donors might alter the quality of the donated blood during processing, storage or in the recipients' circulatory system. The aim of this study was to determine the prevalence of SCT and G6PD deficiency among blood ...

  4. Hypoxia-induced glucose-6-phosphate dehydrogenase overexpression and -activation in pulmonary artery smooth muscle cells: implication in pulmonary hypertension

    Science.gov (United States)

    Chettimada, Sukrutha; Gupte, Rakhee; Rawat, Dhwajbahadur; Gebb, Sarah A.; McMurtry, Ivan F.

    2014-01-01

    Severe pulmonary hypertension is a debilitating disease with an alarmingly low 5-yr life expectancy. Hypoxia, one of the causes of pulmonary hypertension, elicits constriction and remodeling of the pulmonary arteries. We now know that pulmonary arterial remodeling is a consequence of hyperplasia and hypertrophy of pulmonary artery smooth muscle (PASM), endothelial, myofibroblast, and stem cells. However, our knowledge about the mechanisms that cause these cells to proliferate and hypertrophy in response to hypoxic stimuli is still incomplete, and, hence, the treatment for severe pulmonary arterial hypertension is inadequate. Here we demonstrate that the activity and expression of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, are increased in hypoxic PASM cells and in lungs of chronic hypoxic rats. G6PD overexpression and -activation is stimulated by H2O2. Increased G6PD activity contributes to PASM cell proliferation by increasing Sp1 and hypoxia-inducible factor 1α (HIF-1α), which directs the cells to synthesize less contractile (myocardin and SM22α) and more proliferative (cyclin A and phospho-histone H3) proteins. G6PD inhibition with dehydroepiandrosterone increased myocardin expression in remodeled pulmonary arteries of moderate and severe pulmonary hypertensive rats. These observations suggest that altered glucose metabolism and G6PD overactivation play a key role in switching the PASM cells from the contractile to synthetic phenotype by increasing Sp1 and HIF-1α, which suppresses myocardin, a key cofactor that maintains smooth muscle cell in contractile state, and increasing hypoxia-induced PASM cell growth, and hence contribute to pulmonary arterial remodeling and pathogenesis of pulmonary hypertension. PMID:25480333

  5. Comparison of Spectrophotometry, Chromate Inhibition, and Cytofluorometry Versus Gene Sequencing for Detection of Heterozygously Glucose-6-Phosphate Dehydrogenase-Deficient Females.

    Science.gov (United States)

    Peters, Anna L; Veldthuis, Martijn; van Leeuwen, Karin; Bossuyt, Patrick M M; Vlaar, Alexander P J; van Bruggen, Robin; de Korte, Dirk; Van Noorden, Cornelis J F; van Zwieten, Rob

    2017-11-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency worldwide. Detection of heterozygously deficient females can be difficult as residual activity in G6PD-sufficient red blood cells (RBCs) can mask deficiency. In this study, we compared accuracy of 4 methods for detection of G6PD deficiency in females. Blood samples from females more than 3 months of age were used for spectrophotometric measurement of G6PD activity and for determination of the percentage G6PD-negative RBCs by cytofluorometry. An additional sample from females suspected to have G6PD deficiency based on the spectrophotometric G6PD activity was used for measuring chromate inhibition and sequencing of the G6PD gene. Of 165 included females, 114 were suspected to have heterozygous deficiency. From 75 females, an extra sample was obtained. In this group, mutation analysis detected 27 heterozygously deficient females. The sensitivity of spectrophotometry, cytofluorometry, and chromate inhibition was calculated to be 0.52 (confidence interval [CI]: 0.32-0.71), 0.85 (CI: 0.66-0.96), and 0.96 (CI: 0.71-1.00, respectively, and the specificity was 1.00 (CI: 0.93-1.00), 0.88 (CI: 0.75-0.95), and 0.98 (CI: 0.89-1.00), respectively. Heterozygously G6PD-deficient females with a larger percentage of G6PD-sufficient RBCs are missed by routine methods measuring total G6PD activity. However, the majority of these females can be detected with both chromate inhibition and cytofluorometry.

  6. Kinetic and thermodynamic study of the reaction catalyzed by glucose-6-phosphate dehydrogenase with nicotinamide adenine dinucleotide

    International Nuclear Information System (INIS)

    Martin del Campo, Julia S.; Patino, Rodrigo

    2011-01-01

    Research highlights: → The reaction catalyzed by one enzyme of the pentose phosphate pathway was studied. → A spectrophotometric method is proposed for kinetic and thermodynamic analysis. → The pH and the temperature influences are reported on physical chemical properties. → Relative concentrations of substrates are also important in the catalytic process. - Abstract: The enzyme glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) from Leuconostoc mesenteroides has a dual coenzyme specificity with oxidized nicotinamide adenine dinucleotide (NAD ox ) and oxidized nicotinamide adenine dinucleotide phosphate as electron acceptors. The G6PD coenzyme selection is determined by the metabolic cellular prevailing conditions. In this study a kinetic and thermodynamic analysis is presented for the reaction catalyzed by G6PD from L. mesenteroides with NAD ox as coenzyme in phosphate buffer. For this work, an in situ spectrophotometric technique was employed based on the detection of one product of the reaction. Substrate and coenzyme concentrations as well as temperature and pH effects were evaluated. The apparent equilibrium constant, the Michaelis constant, and the turnover number were determined as a function of each experimental condition. The standard transformed Gibbs energy of reaction was determined from equilibrium constants at different initial conditions. For the product 6-phospho-D-glucono-1,5-lactone, a value of the standard Gibbs energy of formation is proposed, Δ f G o = -1784 ± 5 kJ mol -1 .

  7. Kinetic and thermodynamic study of the reaction catalyzed by glucose-6-phosphate dehydrogenase with nicotinamide adenine dinucleotide

    Energy Technology Data Exchange (ETDEWEB)

    Martin del Campo, Julia S. [Departamento de Fisica Aplicada, Centro de Investigacion y de Estudios Avanzados - Unidad Merida, Carretera antigua a Progreso Km. 6, A.P. 73 Cordemex, 97310, Merida, Yucatan (Mexico); Patino, Rodrigo, E-mail: rtarkus@mda.cinvestav.mx [Departamento de Fisica Aplicada, Centro de Investigacion y de Estudios Avanzados - Unidad Merida, Carretera antigua a Progreso Km. 6, A.P. 73 Cordemex, 97310, Merida, Yucatan (Mexico)

    2011-04-20

    Research highlights: {yields} The reaction catalyzed by one enzyme of the pentose phosphate pathway was studied. {yields} A spectrophotometric method is proposed for kinetic and thermodynamic analysis. {yields} The pH and the temperature influences are reported on physical chemical properties. {yields} Relative concentrations of substrates are also important in the catalytic process. - Abstract: The enzyme glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) from Leuconostoc mesenteroides has a dual coenzyme specificity with oxidized nicotinamide adenine dinucleotide (NAD{sub ox}) and oxidized nicotinamide adenine dinucleotide phosphate as electron acceptors. The G6PD coenzyme selection is determined by the metabolic cellular prevailing conditions. In this study a kinetic and thermodynamic analysis is presented for the reaction catalyzed by G6PD from L. mesenteroides with NAD{sub ox} as coenzyme in phosphate buffer. For this work, an in situ spectrophotometric technique was employed based on the detection of one product of the reaction. Substrate and coenzyme concentrations as well as temperature and pH effects were evaluated. The apparent equilibrium constant, the Michaelis constant, and the turnover number were determined as a function of each experimental condition. The standard transformed Gibbs energy of reaction was determined from equilibrium constants at different initial conditions. For the product 6-phospho-D-glucono-1,5-lactone, a value of the standard Gibbs energy of formation is proposed, {Delta}{sub f}G{sup o} = -1784 {+-} 5 kJ mol{sup -1}.

  8. Glucose-6-phosphate dehydrogenase deficiency in neonatal hyperbilirubinaemia: Hacettepe experıence.

    Science.gov (United States)

    Celik, H Tolga; Günbey, Ceren; Unal, Sule; Gümrük, Fatma; Yurdakök, Murat

    2013-05-01

    The aim of this study was to investigate the prevalence of glucose-6-phospate dehydrogenase (G6PD) deficiency in newborn infants with neonatal hyperbilirubinaemia and to compare the clinical features of G6PD-deficient and G6PD-normal newborn infants. A total of 4906 term and preterm neonates with indirect hyperbilirubinaemia were retrospectively evaluated according to demographic, neonatal features, bilirubin levels, erythrocyte G6PD levels, other risk factors and treatments. Among 4906 newborn infants with indirect hyperbilirubinaemia, 55 (1.12%) neonates were G6PD-deficient. In our study, no statistically significant difference was detected between G6PD-deficient and G6PD-normal infants in relation to the time of onset of jaundice, bilirubin levels and duration of phototherapy. However, the incidence of exchange transfusion in G6PD-deficient infants was 16.4% while it was only 3.3% in G6PD normal infants (P G6PD must be ordered to all newborns who are receiving phototherapy and especially to those who are coming from the high incident geographical regions and less responsive to phototherapy. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  9. Mutations of Glucose-6-Phosphate Dehydrogenase Durham, Santa-Maria and A+ Variants Are Associated with Loss Functional and Structural Stability of the Protein

    Science.gov (United States)

    Gómez-Manzo, Saúl; Marcial-Quino, Jaime; Vanoye-Carlo, America; Enríquez-Flores, Sergio; De la Mora-De la Mora, Ignacio; González-Valdez, Abigail; García-Torres, Itzhel; Martínez-Rosas, Víctor; Sierra-Palacios, Edgar; Lazcano-Pérez, Fernando; Rodríguez-Bustamante, Eduardo; Arreguin-Espinosa, Roberto

    2015-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in the world. More than 160 mutations causing the disease have been identified, but only 10% of these variants have been studied at biochemical and biophysical levels. In this study we report on the functional and structural characterization of three naturally occurring variants corresponding to different classes of disease severity: Class I G6PD Durham, Class II G6PD Santa Maria, and Class III G6PD A+. The results showed that the G6PD Durham (severe deficiency), and the G6PD Santa Maria and A+ (less severe deficiency) (Class I, II and III, respectively) affect the catalytic efficiency of these enzymes, are more sensitive to temperature denaturing, and affect the stability of the overall protein when compared to the wild type WT-G6PD. In the variants, the exposure of more and buried hydrophobic pockets was induced and monitored with 8-Anilinonaphthalene-1-sulfonic acid (ANS) fluorescence, directly affecting the compaction of structure at different levels and probably reducing the stability of the protein. The degree of functional and structural perturbation by each variant correlates with the clinical severity reported in different patients. PMID:26633385

  10. Mutations of Glucose-6-Phosphate Dehydrogenase Durham, Santa-Maria and A+ Variants Are Associated with Loss Functional and Structural Stability of the Protein

    Directory of Open Access Journals (Sweden)

    Saúl Gómez-Manzo

    2015-12-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common enzymopathy in the world. More than 160 mutations causing the disease have been identified, but only 10% of these variants have been studied at biochemical and biophysical levels. In this study we report on the functional and structural characterization of three naturally occurring variants corresponding to different classes of disease severity: Class I G6PD Durham, Class II G6PD Santa Maria, and Class III G6PD A+. The results showed that the G6PD Durham (severe deficiency, and the G6PD Santa Maria and A+ (less severe deficiency (Class I, II and III, respectively affect the catalytic efficiency of these enzymes, are more sensitive to temperature denaturing, and affect the stability of the overall protein when compared to the wild type WT-G6PD. In the variants, the exposure of more and buried hydrophobic pockets was induced and monitored with 8-Anilinonaphthalene-1-sulfonic acid (ANS fluorescence, directly affecting the compaction of structure at different levels and probably reducing the stability of the protein. The degree of functional and structural perturbation by each variant correlates with the clinical severity reported in different patients.

  11. Data on how several physiological parameters of stored red blood cells are similar in glucose 6-phosphate dehydrogenase deficient and sufficient donors

    Directory of Open Access Journals (Sweden)

    Vassilis L. Tzounakas

    2016-09-01

    Full Text Available This article contains data on the variation in several physiological parameters of red blood cells (RBCs donated by eligible glucose-6-phosphate dehydrogenase (G6PD deficient donors during storage in standard blood bank conditions compared to control, G6PD sufficient (G6PD+ cells. Intracellular reactive oxygen species (ROS generation, cell fragility and membrane exovesiculation were measured in RBCs throughout the storage period, with or without stimulation by oxidants, supplementation of N-acetylcysteine and energy depletion, following incubation of stored cells for 24 h at 37 °C. Apart from cell characteristics, the total or uric acid-dependent antioxidant capacity of the supernatant in addition to extracellular potassium concentration was determined in RBC units. Finally, procoagulant activity and protein carbonylation levels were measured in the microparticles population. Further information can be found in “Glucose 6-phosphate dehydrogenase deficient subjects may be better “storers” than donors of red blood cells” [1]. Keywords: G6PD deficiency, Red blood cell storage lesion, Oxidative stress, Cell fragility, Microparticles

  12. Kinetic Behaviour of Glucose 6-Phosphate Dehydrogenase and 6-Phosphogluconate Dehydrogenase in Different Tissues of Rainbow Trout (Oncorhynchus mykiss Exposed to Non-Lethal Concentrations of Cadmium

    Directory of Open Access Journals (Sweden)

    Olcay Hisar

    2009-01-01

    Full Text Available The effects of cadmium (Cd on the enzymatic activities of glucose 6-phosphate dehydrogenase (G6PD and 6-phosphogluconate dehydrogenase (6PGD were investigated in the gill, liver and kidney tissues of rainbow trout (Oncorhynchus mykiss. Three test groups of fish were subjected to increasing concentrations (1, 3 and 5 mg/l of cadmium (Cd in vivo, respectively. The G6PD and 6PGD activities in the gill, liver, and kidney tissues of each group of fish were measured on days 1, 3, 5 and 7. G6PD and 6PGD enzyme activities, measured in gill, liver and kidney homogenates, were stimulated by various concentrations (1, 3, and 5 mg/l of cadmium. Although the dose-response pattern of G6PD enzyme activities in liver and kidney tissue was very similar, that in gill was different from both other tissues. The enzyme activity of G6PD enzyme was significantly stimulated after three days (Day 3 in liver and kidney tissues at a dose of 1 mg/l Cd (p p p p p p < 0.05 in liver and kidney tissues at the doses of 3 and 1 mg/l Cd. The stimulation effect of cadmium on the three tissues studied was also calculated; for both of the enzymes (G6PD and 6PGD, the enzyme activity levels were stimulated by approximately 60% and 38% in gills, 68% and 44% in liver, and 67% and 41% in kidneys, respectively, over the base-line enzyme activity of the control groups during the sevenday experimental period. These findings indicate that tissue G6PD and 6PGD enzymes function to protect against cadmium toxicity.

  13. Purification and investigation of some kinetic properties of glucose-6-phosphate dehydrogenase from parsley (Petroselinum hortense) leaves.

    Science.gov (United States)

    Coban, T Abdül Kadir; Ciftçi, Mehmet; Küfrevioğlu, O Irfan

    2002-05-01

    In this study, glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP+ oxidoreductase, EC 1.1.1.49; G6PD) was purified from parsley (Petroselinum hortense) leaves, and analysis of the kinetic behavior and some properties of the enzyme were investigated. The purification consisted of three steps: preparation of homogenate, ammonium sulfate fractionation, and DEAE-Sephadex A50 ion exchange chromatography. The enzyme was obtained with a yield of 8.79% and had a specific activity of 2.146 U (mg protein)(-1). The overall purification was about 58-fold. Temperature of +4 degrees C was maintained during the purification process. Enzyme activity was spectrophotometrically measured according to the Beutler method, at 340 nm. In order to control the purification of enzyme, SDS-polyacrylamide gel electrophoresis was carried out in 4% and 10% acrylamide for stacking and running gel, respectively. SDS-polyacrylamide gel electrophoresis showed a single band for enzyme. The molecular weight was found to be 77.6 kDa by Sephadex G-150 gel filtration chromatography. A protein band corresponding to a molecular weight of 79.3 kDa was obtained on SDS-polyacrylamide gel electrophoresis. For the enzymes, the stable pH, optimum pH, and optimum temperature were found to be 6.0, 8.0, and 60 degrees C, respectively. Moreover, KM and Vmax values for NADP+ and G6-P at optimum pH and 25 degrees C were determined by means of Lineweaver-Burk graphs. Additionally, effects of streptomycin sulfate and tetracycline antibiotics were investigated for the enzyme activity of glucose-6-phosphate dehydrogenase in vitro.

  14. Glucose-6-phosphate dehydrogenase and glutathione reductase activity in methemoglobin reduction by methylene blue and cyst amine: study on glucose-6-phosphate dehydrogenase-deficient individuals, on normal subjects and on riboflavin-treated subjects

    Directory of Open Access Journals (Sweden)

    Benedito Barraviera

    1988-10-01

    Full Text Available The authors have standardized methods for evaluation of the activity of the glucose-6-phosphate dehydrogenase and of glutathione reductase. The general principle of the first method was based on methemoglobin formation by sodium nitrite followed by stimulation of the glucose-6-phosphate dehydrogenase with methylene blue. Forty six adults (23 males and 23 females were studied. Subjects were not G6PD deficient and were aged 20 to 30 years. The results showed that methemoglobin reduction by methylene blue was 154.40 and 139.90 mg/min (p<0.05 for males and females, respectively, in whole blood, and 221.10 and 207.85 mg/min (n.s., respectively, in washed red cells. These data showed that using washed red cells and 0.7g% sodium nitrite concentration produced no differences between sexes and also shortened reading time for the residual amount of methemoglobin to 90 minutes. Glutathione reductase activity was evaluated on the basis of the fact that cystamine (a thiol agent binds to the SH groups of hemoglobin, forming complexes. These complexes are reversed by the action of glutathione reductase, with methemoglobin reduction occurring simultaneously with this reaction. Thirty two adults (16 males and 16 females were studied. Subjects were not G6PD deficient and were aged 20 to 30 years. Methemoglobin reduction by cystamine was 81.27 and 91.13 mg/min (p<0.01 for males and females, respectively. These data showed that using washed red cells and 0.1 M cystamine concentration permits a reading of the residual amount of methemoglobin at 180 minutes of incubation. Glutathione reductase activity was evaluated by methemoglobin reduction by cystamine in 14 females before and after treatment with 10 mg riboflavin per day for 8 days. The results were 73.69 and 94.26 jug/min (p<0.01 before and after treatment, showing that riboflavin treatment increase glutathione reductase activity even in normal individuals. Three Black G6PD-deficient individuals (2 males and 1

  15. The Effects of Fenarimol and Methyl Parathion on Glucose 6-Phosphate Dehydrogenase Enzyme Activity in Rats

    Directory of Open Access Journals (Sweden)

    Ferda ARI

    2017-10-01

    Full Text Available Fenarimol and methyl parathion are pesticides that have been used in agriculture for several years. These pesticides have significant effects on environmental and human health. Therefore, we investigated the effects of methyl parathion and fenarimol on glucose 6-phosphate dehydrogenase (EC 1.1.1.49 enzyme activity in rats. The glucose 6- phosphate dehydrogenase is the first enzyme of the pentose phosphate pathway and it is important in detoxifying reactions by NADPH generated. In this study, wistar albino rats administrated with methyl parathion (7 mg kg–1 and fenarimol (200 mg kg−1 by intraperitoneally for different periods (2, 4, 8, 16, 32, 64, and 72 h. The glucose 6-phosphate dehydrogenase enzyme activity was assayed in liver, kidney, brain, and small intestine in male and female rats. The exposure of fenarimol and methyl parathion caused increase of glucose 6-phosphate dehydrogenase enzyme activity in rat tissues, especially at last periods. We suggest that this increment of enzyme activity may be the reason of toxic effects of fenarimol and methyl parathion.

  16. 21 CFR 864.7360 - Erythrocytic glucose-6-phosphate dehydrogenase assay.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Erythrocytic glucose-6-phosphate dehydrogenase assay. 864.7360 Section 864.7360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages...

  17. Correlation of viral RNA biosynthesis with glucose-6-phosphate dehydrogenase activity and host resistance

    Czech Academy of Sciences Publication Activity Database

    Šindelář, Luděk; Šindelářová, Milada

    2002-01-01

    Roč. 215, - (2002), s. 862-869 ISSN 0032-0935 R&D Projects: GA ČR GA522/99/1264 Institutional research plan: CEZ:AV0Z5038910 Keywords : Glucose 6 phosphate dehydrogenase * Nicotiana (viral infection) * Plant viruses Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.960, year: 2002

  18. Glucose-6-phosphate dehydrogenase deficiency in people living in malaria endemic districts of Nepal.

    Science.gov (United States)

    Ghimire, Prakash; Singh, Nihal; Ortega, Leonard; Rijal, Komal Raj; Adhikari, Bipin; Thakur, Garib Das; Marasini, Baburam

    2017-05-23

    Glucose-6-phosphate dehydrogenase (G6PD) is a rate limiting enzyme of the pentose phosphate pathway and is closely associated with the haemolytic disorders among patients receiving anti-malarial drugs, such as primaquine. G6PD deficiency (G6PDd) is an impending factor for radical treatment of malaria which affects the clearance of gametocytes from the blood and subsequent delay in the achievement of malaria elimination. The main objective of this study was to assess the prevalence of G6PD deficiency in six malaria endemic districts in Southern Nepal. A cross-sectional population based prevalence survey was conducted in six malaria endemic districts of Nepal, during April-Dec 2013. A total of 1341 blood samples were tested for G6PDd using two different rapid diagnostic test kits (Binax-Now ® and Care Start™). Equal proportions of participants from each district (n ≥ 200) were enrolled considering ethnic and demographic representation of the population groups. Out of total 1341 blood specimens collected from six districts, the overall prevalence of G6PDd was 97/1341; 7.23% on Binax Now and 81/1341; 6.0% on Care Start test. Higher prevalence was observed in male than females [Binax Now: male 10.2%; 53/521 versus female 5.4%; 44/820 (p = 0.003) and Care Start: male 8.4%; 44/521 versus female 4.5%; 37/820 (p = 0.003)]. G6PDd was higher in ethnic groups Rajbanshi (11.7%; 19/162) and Tharu (5.6%; 56/1005) (p = 0.006), major inhabitant of the endemic districts. Higher prevalence of G6PDd was found in Jhapa (22/224; 9.8%) and Morang districts (18/225; 8%) (p = 0.031). In a multivariate analysis, male were found at more risk for G6PDd than females, on Binax test (aOR = 1.97; CI 1.28-3.03; p = 0.002) and Care Start test (aOR = 1.86; CI 1.16-2.97; p = 0.009). The higher prevalence of G6PDd in certain ethnic group, gender and geographical region clearly demonstrates clustering of the cases and ascertained the risk groups within the population. This is the

  19. Intravenous immunoglobulin to treat hyperbilirubinemia in neonates with isolated Glucose-6-Phosphate dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    Wadah Khriesat

    2017-04-01

    Full Text Available Background Glucose-6-phosphate dehydrogenase deficiency alone or concomitant with ABO isoimmunisation is a widespread indication for neonatal exchange transfusion. Aims To evaluate the effectiveness of Intravenous Immunoglobulin in the treatment of neonatal hyperbilirubinemia due to glucose-6-phosphate dehydrogenase deficiency. Methods A retrospective cohort study was conducted between 2006 and 2014 at the Jordan University of Science and technology. The medical records of 43 infants admitted to the neonatal intensive care unit for isolated glucose-6- phosphate dehydrogenase deficiency hemolytic disease of the newborns were reviewed. Patients were divided into two groups. Group I, a historical cohort, included newborns born between 2006 and 2010, Treatment included phototherapy and exchange transfusion. Group II included newborns born between 2011 and 2014, where, in addition to phototherapy, intravenous immunoglobulin was administered. The duration of phototherapy and number of exchange transfusions were evaluated. Results Of 412 newborns that were admitted with neonatal hyperbilirubinemia, Glucose-6-phosphate dehydrogenase deficiency was present in 43. Of these, 22, did not receive intravenous immunoglobulin and served as a control group. The other 21 newborns received intravenous immunoglobulin. There was no difference in the demographic characteristics between the two groups. Infants in the control group were significantly more likely to receive exchange blood transfusion than infants in the immunoglobulin treatment group, but were significantly less likely to need phototherapy. Conclusion Intravenous immunoglobulin is an effective alternative to exchange transfusion in infants with glucose-6-phosphate dehydrogenase deficiency hemolytic disease of the newborn. It is suggested that intravenous immunoglobulin may be beneficial as a prophylaxis for infants with hyperbilirubinemia.

  20. In Vitro Effects of Imidacloprid and Lambda-cyhalothrin on Capoeta capoeta umbla Kidney Glucose 6-Phosphate Dehydrogenase Enzyme

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    Mahinur KIRICI

    2015-03-01

    Full Text Available Pesticide toxicity causes oxidative damage such as DNA damage, enhanced lipid peroxidation, the oxidation of protein sulfydryl groups and enzyme inactivation in the metabolism. In this study, we investigated the in vitro effects on glucose 6-phosphate dehydrogenase (E.C.1.1.49; G6PD from Capoeta capoeta umbla kidney of imidacloprid and lambda-cyhalothrin. For this purpose, the enzymewas purified from kidney of C. c. umbla with a specific activity of 11.26 EU mg-1 proteins and 22.7% yield using hemolysate preparation, ammonium sulfate precipitation and 2',5'-ADP Sepharose 4B affinity gel chromatography methods. In order to control the enzyme purification sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE was done. SDS-PAGE showed a single band for the enzyme. The results of this study suggested that imidacloprid and lambda-cyhalothrin have significant inhibition effect on the activity of G6PD in in vitro. In conclusion, lambda-cyhalothrin inhibits the enzyme activity more than imidacloprid.

  1. Molecular Identification of G6PD Chatham (G1003A) in Khuzestan ...

    Indian Academy of Sciences (India)

    Glucose-6-phosphate dehydrogenase (G6PD) is the first enzyme in pentose phosphate pathway and the main intracel- lular source of NADPH. Since G6PD is the only source of. NADPH in red blood cells, defense against oxidative damage strongly depends on its activity (Mehta et al. 2000). Defi- ciency of G6PD enzyme in ...

  2. Review of key knowledge gaps in glucose-6-phosphate dehydrogenase deficiency detection with regard to the safe clinical deployment of 8-aminoquinoline treatment regimens: a workshop report.

    Science.gov (United States)

    von Seidlein, Lorenz; Auburn, Sarah; Espino, Fe; Shanks, Dennis; Cheng, Qin; McCarthy, James; Baird, Kevin; Moyes, Catherine; Howes, Rosalind; Ménard, Didier; Bancone, Germana; Winasti-Satyahraha, Ari; Vestergaard, Lasse S; Green, Justin; Domingo, Gonzalo; Yeung, Shunmay; Price, Ric

    2013-03-27

    The diagnosis and management of glucose-6-phosphate dehydrogenase (G6PD) deficiency is a crucial aspect in the current phases of malaria control and elimination, which will require the wider use of 8-aminoquinolines for both reducing Plasmodium falciparum transmission and achieving the radical cure of Plasmodium vivax. 8-aminoquinolines, such as primaquine, can induce severe haemolysis in G6PD-deficient individuals, potentially creating significant morbidity and undermining confidence in 8-aminoquinoline prescription. On the other hand, erring on the side of safety and excluding large numbers of people with unconfirmed G6PD deficiency from treatment with 8-aminoquinolines will diminish the impact of these drugs. Estimating the remaining G6PD enzyme activity is the most direct, accessible, and reliable assessment of the phenotype and remains the gold standard for the diagnosis of patients who could be harmed by the administration of primaquine. Genotyping seems an unambiguous technique, but its use is limited by cost and the large range of recognized G6PD genotypes. A number of enzyme activity assays diagnose G6PD deficiency, but they require a cold chain, specialized equipment, and laboratory skills. These assays are impractical for care delivery where most patients with malaria live. Improvements to the diagnosis of G6PD deficiency are required for the broader and safer use of 8-aminoquinolines to kill hypnozoites, while lower doses of primaquine may be safely used to kill gametocytes without testing. The discussions and conclusions of a workshop conducted in Incheon, Korea in May 2012 to review key knowledge gaps in G6PD deficiency are reported here.

  3. What is the role of the second "structural" NADP+-binding site in human glucose 6-phosphate dehydrogenase?

    Science.gov (United States)

    Wang, Xiao-Tao; Chan, Ting Fai; Lam, Veronica M S; Engel, Paul C

    2008-08-01

    Human glucose 6-phosphate dehydrogenase, purified after overexpression in E. coli, was shown to contain one molecule/subunit of acid-extractable "structural" NADP+ and no NADPH. This tightly bound NADP+ was reduced by G6P, presumably following migration to the catalytic site. Gel-filtration yielded apoenzyme, devoid of bound NADP+ but, surprisingly, still fully active. Mr of the main component of "stripped" enzyme by gel filtration was approximately 100,000, suggesting a dimeric apoenzyme (subunit Mr = 59,000). Holoenzyme also contained tetramer molecules and, at high protein concentration, a dynamic equilibrium gave an apparent intermediate Mr of 150 kDa. Fluorescence titration of the stripped enzyme gave the K d for structural NADP+ as 37 nM, 200-fold lower than for "catalytic" NADP+. Structural NADP+ quenches 91% of protein fluorescence. At 37 degrees C, stripped enzyme, much less stable than holoenzyme, inactivated irreversibly within 2 d. Inactivation at 4 degrees C was partially reversed at room temperature, especially with added NADP+. Apoenzyme was immediately active, without any visible lag, in rapid-reaction studies. Human G6PD thus forms active dimer without structural NADP+. Apparently, the true role of the second, tightly bound NADP+ is to secure long-term stability. This fits the clinical pattern, G6PD deficiency affecting the long-lived non-nucleate erythrocyte. The Kd values for two class I mutants, G488S and G488V, were 273 nM and 480 nM, respectively (seven- and 13-fold elevated), matching the structural prediction of weakened structural NADP+ binding, which would explain decreased stability and consequent disease. Preparation of native apoenzyme and measurement of Kd constant for structural NADP+ will now allow quantitative assessment of this defect in clinical G6PD mutations.

  4. Post-irradiation repairing processes of glucose-6-phosphate dehydrogenase and catalase from Hansenula Polymorpha yeast

    International Nuclear Information System (INIS)

    Postolache, Carmen; Postolache, Cristian; Dinu, Diana; Dinischiotu, Anca; Sahini, Victor Emanuel

    2002-01-01

    The post-irradiation repairing mechanisms of two Hansenula Polymorpha yeast enzymes, glucose-6-phosphate dehydrogenase and catalase, were studied. The kinetic parameters of the selected enzymes were investigated over one month since the moment of γ-irradiation with different doses in the presence of oxygen. Dose dependent decrease of initial reaction rates was noticed for both enzymes. Small variation of initial reaction rate was recorded for glucose-6-phosphate dehydrogenase over one month, with a decreasing tendency. No significant electrophoretic changes of molecular forms of this enzyme were observed after irradiation. Continuous strong decrease of catalase activity was evident for the first 20 days after irradiation. Partial recovery process of the catalytic activity was revealed by this study. (authors)

  5. Prevalence of thalassaemia, iron-deficiency anaemia and glucose-6-phosphate dehydrogenase deficiency among Arab migrating nomad children, southern Islamic Republic of Iran.

    Science.gov (United States)

    Pasalar, M; Mehrabani, D; Afrasiabi, A; Mehravar, Z; Reyhani, I; Hamidi, R; Karimi, M

    2014-12-17

    This study investigated the prevalence of iron-deficiency anaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency and β-thalassaemia trait among Arab migrating nomad children in southern Islamic Republic of Iran. Blood samples were analysed from 134 schoolchildren aged child had G6PD deficiency. A total of 9.7% of children had HbA2 ≥ 3.5 g/dL, indicating β-thalassaemia trait (10.8% in females and 7.8% in males). Mean serum iron, serum ferritin and total iron binding capacity were similar in males and females. Serum ferritin index was as accurate as Hb index in the diagnosis of iron-deficiency anaemia. A high prevalence of β-thalassaemia trait was the major potential risk factor in this population.

  6. Prevalence of anemia, iron deficiency, thalassemia and glucose-6-phosphate dehydrogenase deficiency among hill-tribe school children in Omkoi District, Chiang Mai Province, Thailand.

    Science.gov (United States)

    Yanola, Jintana; Kongpan, Chatpat; Pornprasert, Sakorn

    2014-07-01

    The prevalaence of anemia, iron deficiency, thalassemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency were examined among 265 hill-tribe school children, 8-14 years of age, from Omkoi District, Chiang Mai Province, Thailand. Anemia was observed in 20 school children, of whom 3 had iron deficiency anemia. The prevalence of G-6-PD deficiency and β-thalassemia trait [codon 17 (A>T), IVSI-nt1 (G>T) and codons 71/72 (+A) mutations] was 4% and 8%, respectively. There was one Hb E trait, and no α-thalassemia-1 SEA or Thai type deletion. Furthermore, anemia was found to be associated with β-thalassemia trait in 11 children. These data can be useful for providing appropriate prevention and control of anemia in this region of Thailand.

  7. Glucose-6-phosphate dehydrogenase deficiency does not increase the susceptibility of sperm to oxidative stress induced by H2O2.

    Science.gov (United States)

    Roshankhah, Shiva; Rostami-Far, Zahra; Shaveisi-Zadeh, Farhad; Movafagh, Abolfazl; Bakhtiari, Mitra; Shaveisi-Zadeh, Jila

    2016-12-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect. G6PD plays a key role in the pentose phosphate pathway, which is a major source of nicotinamide adenine dinucleotide phosphate (NADPH). NADPH provides the reducing equivalents for oxidation-reduction reductions involved in protecting against the toxicity of reactive oxygen species such as H 2 O 2 . We hypothesized that G6PD deficiency may reduce the amount of NADPH in sperms, thereby inhibiting the detoxification of H 2 O 2 , which could potentially affect their motility and viability, resulting in an increased susceptibility to infertility. Semen samples were obtained from four males with G6PD deficiency and eight healthy males as a control. In both groups, motile sperms were isolated from the seminal fluid and incubated with 0, 10, 20, 40, 60, 80, and 120 µM concentrations of H 2 O 2 . After 1 hour incubation at 37℃, sperms were evaluated for motility and viability. Incubation of sperms with 10 and 20 µM H 2 O 2 led to very little decrease in motility and viability, but motility decreased notably in both groups in 40, 60, and 80 µM H 2 O 2 , and viability decreased in both groups in 40, 60, 80, and 120 µM H 2 O 2 . However, no statistically significant differences were found between the G6PD-deficient group and controls. G6PD deficiency does not increase the susceptibility of sperm to oxidative stress induced by H 2 O 2 , and the reducing equivalents necessary for protection against H 2 O 2 are most likely produced by other pathways. Therefore, G6PD deficiency cannot be considered as major risk factor for male infertility.

  8. Glucose-6-Phosphate Dehydrogenase Enhances Antiviral Response through Downregulation of NADPH Sensor HSCARG and Upregulation of NF-κB Signaling

    Directory of Open Access Journals (Sweden)

    Yi-Hsuan Wu

    2015-12-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD-deficient cells are highly susceptible to viral infection. This study examined the mechanism underlying this phenomenon by measuring the expression of antiviral genes—tumor necrosis factor alpha (TNF-α and GTPase myxovirus resistance 1 (MX1—in G6PD-knockdown cells upon human coronavirus 229E (HCoV-229E and enterovirus 71 (EV71 infection. Molecular analysis revealed that the promoter activities of TNF-α and MX1 were downregulated in G6PD-knockdown cells, and that the IκB degradation and DNA binding activity of NF-κB were decreased. The HSCARG protein, a nicotinamide adenine dinucleotide phosphate (NADPH sensor and negative regulator of NF-κB, was upregulated in G6PD-knockdown cells with decreased NADPH/NADP+ ratio. Treatment of G6PD-knockdown cells with siRNA against HSCARG enhanced the DNA binding activity of NF-κB and the expression of TNF-α and MX1, but suppressed the expression of viral genes; however, the overexpression of HSCARG inhibited the antiviral response. Exogenous G6PD or IDH1 expression inhibited the expression of HSCARG, resulting in increased expression of TNF-α and MX1 and reduced viral gene expression upon virus infection. Our findings suggest that the increased susceptibility of the G6PD-knockdown cells to viral infection was due to impaired NF-κB signaling and antiviral response mediated by HSCARG.

  9. Population screening for glucose-6-phosphate dehydrogenase deficiencies in Isabel Province, Solomon Islands, using a modified enzyme assay on filter paper dried bloodspots

    Directory of Open Access Journals (Sweden)

    Landry Losi

    2010-08-01

    Full Text Available Abstract Background Glucose-6-phosphate dehydrogenase deficiency poses a significant impediment to primaquine use for the elimination of liver stage infection with Plasmodium vivax and for gametocyte clearance, because of the risk of life-threatening haemolytic anaemia that can occur in G6PD deficient patients. Although a range of methods for screening G6PD deficiency have been described, almost all require skilled personnel, expensive laboratory equipment, freshly collected blood, and are time consuming; factors that render them unsuitable for mass-screening purposes. Methods A published WST8/1-methoxy PMS method was adapted to assay G6PD activity in a 96-well format using dried blood spots, and used it to undertake population screening within a malaria survey undertaken in Isabel Province, Solomon Islands. The assay results were compared to a biochemical test and a recently marketed rapid diagnostic test. Results Comparative testing with biochemical and rapid diagnostic test indicated that results obtained by filter paper assay were accurate providing that blood spots were assayed within 5 days when stored at ambient temperature and 10 days when stored at 4 degrees. Screening of 8541 people from 41 villages in Isabel Province, Solomon Islands revealed the prevalence of G6PD deficiency as defined by enzyme activity Conclusions The assay enabled simple and quick semi-quantitative population screening in a malaria-endemic region. The study indicated a high prevalence of G6PD deficiency in Isabel Province and highlights the critical need to consider G6PD deficiency in the context of P. vivax malaria elimination strategies in Solomon Islands, particularly in light of the potential role of primaquine mass drug administration.

  10. D-glucose-6-phosphate dehydrogenase (Entner-Doudoroff enzyme) from Pseudomonas fluorescens

    International Nuclear Information System (INIS)

    Lessmann, D.; Schimz, K.L.; Kurz, G.

    1975-01-01

    The existence of two different D-glucose-6-phosphate dehydrogenases in Pseudomonas fluorescens has been demonstrated. Based on their different specificity and their different metabolic regulation one enzyme is appointed to the Entner-Doudoroff pathway and the other to the hexose monophosphate pathway. A procedure is described for the isolation of that D-glucose-6-phosphate dehydrogenase which forms part of the Entner-Doudoroff pathway (Entner-Doudoroff enzyme). A 950-fold purification was achieved with an overall yield of 44%. The final preparation, having a specific activity of about 300μmol NADH formed per min per mg protein, was shown to be homogeneous. The molecular weight of the Entner-Doudoroff enzyme has been determined to be 220,000 by gel permeation chromatography, and that of the other enzyme (Zwischenferment) has been shown to be 265,000. The pI of the Entner-Doudoroff enzyme has been shown to be 5.24 and that of the Zwischenferment 4.27. The Entner-Doudoroff enzyme is stable in the range of pH 6 to 10.5 and shows its maximal acivity at pH 8.9. The Entner-Doudoroff enzyme showed specificity for NAD + as well as for NADP + and exhibited homotropic effects for D-glucose 6-phosphate. It is inhibited by ATP which acts as a negative allosteric effector. Other nucleoside triphosphates as well as ADP are also inhibitory. The enzyme catalyzes the transfer of the axial hydrogen at carbon-1 of β-D-glucopyranose 6-phosphate to the si face of carbon-4 of the nicotinamide ring and must be classified as B-side stereospecific dehydrogenase. (orig.) [de

  11. Glucose-6-phosphate dehydrogenase deficiency and Alzheimer's disease: Partners in crime? The hypothesis.

    Science.gov (United States)

    Ulusu, N Nuray

    2015-08-01

    Alzheimer's disease is a multifaceted brain disorder which involves various coupled irreversible, progressive biochemical reactions that significantly reduce quality of life as well as the actual life expectancy. Aging, genetic predispositions, head trauma, diabetes, cardiovascular disease, deficiencies in insulin signaling, dysfunction of mitochondria-associated membranes, cerebrovascular changes, high cholesterol level, increased oxidative stress and free radical formation, DNA damage, disturbed energy metabolism, and synaptic dysfunction, high blood pressure, obesity, dietary habits, exercise, social engagement, and mental stress are noted among the risk factors of this disease. In this hypothesis review I would like to draw the attention on glucose-6-phosphate dehydrogenase deficiency and its relationship with Alzheimer's disease. This enzymopathy is the most common human congenital defect of metabolism and defined by decrease in NADPH+H(+) and reduced form of glutathione concentration and that might in turn, amplify oxidative stress due to essentiality of the enzyme. This most common enzymopathy may manifest itself in severe forms, however most of the individuals with this deficiency are not essentially symptomatic. To understand the sporadic Alzheimer's disease, the writer of this paper thinks that, looking into a crystal ball might not yield much of a benefit but glucose-6-phosphate dehydrogenase deficiency could effortlessly give some clues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Glucose-6-phosphate dehydrogenase protects Escherichia coli from tellurite-mediated oxidative stress.

    Directory of Open Access Journals (Sweden)

    Juan M Sandoval

    Full Text Available The tellurium oxyanion tellurite induces oxidative stress in most microorganisms. In Escherichia coli, tellurite exposure results in high levels of oxidized proteins and membrane lipid peroxides, inactivation of oxidation-sensitive enzymes and reduced glutathione content. In this work, we show that tellurite-exposed E. coli exhibits transcriptional activation of the zwf gene, encoding glucose 6-phosphate dehydrogenase (G6PDH, which in turn results in augmented synthesis of reduced nicotinamide adenine dinucleotide phosphate (NADPH. Increased zwf transcription under tellurite stress results mainly from reactive oxygen species (ROS generation and not from a depletion of cellular glutathione. In addition, the observed increase of G6PDH activity was paralleled by accumulation of glucose-6-phosphate (G6P, suggesting a metabolic flux shift toward the pentose phosphate shunt. Upon zwf overexpression, bacterial cells also show increased levels of antioxidant molecules (NADPH, GSH, better-protected oxidation-sensitive enzymes and decreased amounts of oxidized proteins and membrane lipids. These results suggest that by increasing NADPH content, G6PDH plays an important role in E. coli survival under tellurite stress.

  13. Noninferiority of glucose-6-phosphate dehydrogenase deficiency diagnosis by a point-of-care rapid test vs the laboratory fluorescent spot test demonstrated by copper inhibition in normal human red blood cells.

    Science.gov (United States)

    Baird, J Kevin; Dewi, Mewahyu; Subekti, Decy; Elyazar, Iqbal; Satyagraha, Ari W

    2015-06-01

    Tens of millions of patients diagnosed with vivax malaria cannot safely receive primaquine therapy against repeated attacks caused by activation of dormant liver stages called hypnozoites. Most of these patients lack access to screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency, a highly prevalent disorder causing serious acute hemolytic anemia with primaquine therapy. We optimized CuCl inhibition of G6PD in normal red blood cells (RBCs) to assess G6PD diagnostic technologies suited to point of care in the impoverished rural tropics. The most widely applied technology for G6PD screening-the fluorescent spot test (FST)-is impractical in that setting. We evaluated a new point-of-care G6PD screening kit (CareStart G6PD, CSG) against FST using graded CuCl treatments to simulate variable hemizygous states, and varying proportions of CuCl-treated RBC suspensions to simulate variable heterozygous states of G6PD deficiency. In experiments double-blinded to CuCl treatment, technicians reading FST and CSG test (n = 269) classified results as positive or negative for deficiency. At G6PD activity ≤40% of normal (n = 112), CSG test was not inferior to FST in detecting G6PD deficiency (P = 0.003), with 96% vs 90% (P = 0.19) sensitivity and 75% and 87% (P = 0.01) specificity, respectively. The CSG test costs less, requires no specialized equipment, laboratory skills, or cold chain for successful application, and performs as well as the FST standard of care for G6PD screening. Such a device may vastly expand access to primaquine therapy and aid in mitigating the very substantial burden of morbidity and mortality imposed by the hypnozoite reservoir of vivax malaria. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Reaction rate studies of glucose-6-phosphate dehydrogenase activity in sections of rat liver using four tetrazolium salts

    NARCIS (Netherlands)

    Butcher, R. G.; van Noorden, C. J.

    1985-01-01

    The reaction rate of glucose-6-phosphate dehydrogenase activity in liver sections from fed and starved rats has been monitored by the continuous measurement at 37 degrees C of the reaction product as it is formed using scanning and integrating microdensitometry. Control media lacked either substrate

  15. Glucose-6-phosphate dehydrogenase: the key to sex-related xenobiotic toxicity in hepatocytes of European flounder (Platichthys flesus L.)?

    NARCIS (Netherlands)

    Winzer, Katja; van Noorden, Cornelis J. F.; Köhler, Angela

    2002-01-01

    The role of glucose-6-phosphate dehydrogenase (G6PDH) in oxidative stress responses was investigated in isolated intact living hepatocytes of immature female and male European flounder (Platichthys flesus L.) because it is the major provider of NADPH needed as reducing power for various

  16. Physiological role of glucose-6-phosphate dehydrogenase in cold acclimation of strawberry (Fragaria × ananassa)

    Science.gov (United States)

    Zhang, Yong; Yu, Dingqun; Luo, Ya; Wang, Xiaorong; Chen, Qing; Sun, Bo; Wang, Yan; Liu, Zejing; Tang, Haoru

    2018-04-01

    In recent years, there has been an increasing interest in study of new resistance mechanism in fruit trees. All these regard the climate change and subsequent fruit production. Glucose-6-phosphate dehydrogenase (G6PDH) catalyzes the first and rate-limiting step of the oxidative pentose phosphate pathway (OPPP), and the expression of this enzyme is related to different biotic and abiotic stresses. Under accumulation of low temperature stress, the significant increase in G6PDH activity was found to be closely correlated to the levels of antioxidant enzymes, malondialdehyde (MDA) contents, sugar contents as well as changes of superoxide (O2•-). It is suggested that the enhancement of cold resistance of strawberry, which induced by cold acclimation, related to the significant increase in G6PDH activity. On one hand, G6PDH activates NADPH oxidase to generate reactive oxygen species (ROS); on the other hand, it may be involved in the activation of antioxidant enzymes, and accelerates many other important NADPH-dependent enzymatic reactions. Then further result in the elevation of membrane stability and cold resistance of strawberry. Interestingly, even though the plants were placed again under a temperature of 25°C for 1 d, the higher cold resistance, enzyme activities and soluble sugar content acquired.

  17. Radiation target analyses of free and immobilized glucose 6-phosphate dehydrogenase

    International Nuclear Information System (INIS)

    Kempner, E.S.; Miller, J.H.

    2010-01-01

    The sensitivity of the enzyme glucose 6-phosphate dehydrogenase to ionizing radiation was examined under several conditions, including the presence of several free-radical scavengers. The enzyme was also irradiated when covalently bound to polyacrylamide beads whose structure is very similar to the polypeptide backbone of proteins. All the enzyme forms were irradiated in the frozen state with high-energy electrons from a linear accelerator. Surviving enzyme activity and surviving monomers were determined; the data were analyzed by target theory. Free-radical scavengers reduced the radiation target size of both the activity and monomers of the free enzyme, but not that of the immobilized enzyme activity. The target size of the activity of the free enzyme was that of a dimer mass, but in the case of the immobilized enzyme it was equal to the smaller mass of the monomer. Free-radical scavengers reduce the target size by modifying radiation energy transfer. The target size of the polyacrylamide-bound enzyme activity was expected to be very large since the connection between polyacrylamide and protein is a peptide bond which permits transfer of radiation-deposited energy. Several explanations concerning energy transfer are suggested for this result.

  18. Diurnal fluctuation of leukocyte G6PD activity. A possible explanation for the normal neutrophil bactericidal activity and the low incidence of pyogenic infections in patients with severe G6PD deficiency in Israel

    NARCIS (Netherlands)

    Wolach, Baruch; Ashkenazi, Meir; Grossmann, Rami; Gavrieli, Ronit; Friedman, Ziva; Bashan, Nava; Roos, Dirk

    2004-01-01

    Acute hemolytic anemia associated with red blood cell (RBC) glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly encountered in the Mediterranean basin. Nevertheless, concomitant clinical evidence of white blood cell G6PD deficiency is extremely rare in Israel. This study sought to assess

  19. Reduced prevalence of Plasmodium falciparum infection and of concomitant anaemia in pregnant women with heterozygous G6PD deficiency

    NARCIS (Netherlands)

    Mockenhaupt, Frank P.; Mandelkow, Jantina; Till, Holger; Ehrhardt, Stephan; Eggelte, Teunis A.; Bienzle, Ulrich

    2003-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency confers protection against malaria in children, yet its role in malaria in pregnancy is unknown. In a cross-sectional study among 529 pregnant Ghanaian women, Plasmodium falciparum infection, anaemia and G6PD genotypes were assessed. Of these,

  20. Importance of glucose-6-phosphate dehydrogenase (G6PDH) for vanillin tolerance in Saccharomyces cerevisiae.

    Science.gov (United States)

    Nguyen, Trinh Thi My; Kitajima, Sakihito; Izawa, Shingo

    2014-09-01

    Vanillin is derived from lignocellulosic biomass and, as one of the major biomass conversion inhibitors, inhibits yeast growth and fermentation. Vanillin was recently shown to induce the mitochondrial fragmentation and formation of mRNP granules such as processing bodies and stress granules in Saccharomyces cerevisiae. Furfural, another major biomass conversion inhibitor, also induces oxidative stress and is reduced in an NAD(P)H-dependent manner to its less toxic alcohol derivative. Therefore, the pentose phosphate pathway (PPP), through which most NADPH is generated, plays a role in tolerance to furfural. Although vanillin also induces oxidative stress and is reduced to vanillyl alcohol in a NADPH-dependent manner, the relationship between vanillin and PPP has not yet been investigated. In the present study, we examined the importance of glucose-6-phosphate dehydrogenase (G6PDH), which catalyzes the rate-limiting NADPH-producing step in PPP, for yeast tolerance to vanillin. The growth of the null mutant of G6PDH gene (zwf1Δ) was delayed in the presence of vanillin, and vanillin was efficiently reduced in the culture of wild-type cells but not in the culture of zwf1Δ cells. Furthermore, zwf1Δ cells easily induced the activation of Yap1, an oxidative stress responsive transcription factor, mitochondrial fragmentation, and P-body formation with the vanillin treatment, which indicated that zwf1Δ cells were more susceptible to vanillin than wild type cells. These findings suggest the importance of G6PDH and PPP in the response of yeast to vanillin. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  1. Subcellular Characterization of Porcine Oocytes with Different Glucose-6-phosphate Dehydrogenase Activities

    Directory of Open Access Journals (Sweden)

    Bo Fu

    2015-12-01

    Full Text Available The in vitro maturation (IVM efficiency of porcine embryos is still low because of poor oocyte quality. Although brilliant cresyl blue positive (BCB+ oocytes with low glucose-6-phosphate dehydrogenase (G6PDH activity have shown superior quality than BCB negative (− oocytes with high G6PDH activity, the use of a BCB staining test before IVM is still controversial. This study aimed to shed more light on the subcellular characteristics of porcine oocytes after selection using BCB staining. We assessed germinal vesicle chromatin configuration, cortical granule (CG migration, mitochondrial distribution, the levels of acetylated lysine 9 of histone H3 (AcH3K9 and nuclear apoptosis features to investigate the correlation between G6PDH activity and these developmentally related features. A pattern of chromatin surrounding the nucleoli was seen in 53.0% of BCB+ oocytes and 77.6% of BCB+ oocytes showed peripherally distributed CGs. After IVM, 48.7% of BCB+ oocytes had a diffused mitochondrial distribution pattern. However, there were no significant differences in the levels of AcH3K9 in the nuclei of blastocysts derived from BCB+ and BCB− oocytes; at the same time, we observed a similar incidence of apoptosis in the BCB+ and control groups. Although this study indicated that G6PDH activity in porcine oocytes was correlated with several subcellular characteristics such as germinal vesicle chromatin configuration, CG migration and mitochondrial distribution, other features such as AcH3K9 level and nuclear apoptotic features were not associated with G6PDH activity and did not validate the BCB staining test. In using this test for selecting porcine oocytes, subcellular characteristics such as the AcH3K9 level and apoptotic nuclear features should also be considered. Adding histone deacetylase inhibitors or apoptosis inhibitors into the culture medium used might improve the efficiency of IVM of BCB+ oocytes.

  2. Neonatal screening for sickle cell disease, Glucose-6-PhosphateDehydrogenase deficiency and Alpha-Thalassemia in Qatif and Al-Hasa

    International Nuclear Information System (INIS)

    Nasserullah, Z.; Srair, Hussain Abu; Al-Jame, A.; Mokhtar, M.; Al-Qatari, G.; Al-Naim, S.; Al-Aqib, A.

    1998-01-01

    Screening programs to determine the frequency of sickle cell,glucose-6-phosphate dehydrogenase deficiency and alpha-thalassemia gene areavailable in Saudi Arabia, although not used frequently. Greater use of theseprograms will decrease the morbidity and mortality of Saudi children affectedby these disorders. Neonatal hemoglobin electrophoresis andglucose-6-dehydrogenase fluorescent spot tests were performed on new bornbabies delivered between December 1992 and December 1993 at the Qatif CentralHospital and at the King Fahd Hospital in Al-Hasa. Cord blood samples werecollected from babies born in these two hospitals. Babies born in otherhospitals had blood collected in their first visit to Qatif primary carecenters at the time of vaccination. All specimens were sent to Dammam CentralLaboratory. The diagnosis of sickle cell and alpha-thalassemia was based oncellulose acetate electrophoresis and confirmed by agar gel electrophoresisand glucose-6-phosphate dehydrgenase was confirmed by fluorescent spot test.A total of 12,220 infants, including 11,313 Saudis (92.6%), were screenedover a 12-month period. The common phenotype detected in these infantsincluded AF, SFA, SFA Bart's, FS and FS Bart's. In Saudi infants, homozygoussickle cell disease was detected in 2.35% and 1.08% in Qatif and Al-Hasa,respectively. The frequencies of sickle cell gene were 0.1545% and 0.1109% inQatif and Al-Hasa. Alpha-thalassemia genes based on an elevated level of HbBart's were 28% and 16.3% in Qatif and Al-Hasa. The screening for G6PDdeficiency revealed a high prevalence of 30.6% and 14.7% in Qatif andAl-Hasa. In the non-Saudi infants the frequencies were low. The outcome ofthis study indicates that the Saudi populations in Qatif and Al-Hasa are atrisk for hemoglobinopathies and G6PD. Neonatal screening programs areessential and cost effective and should be maintained as a routine practice.(author)

  3. Effect of Punica granatum fruit peel on glucose-6-phosphate dehydrogenase and malate dehydrogenase in amphistome Gastrothylax indicus.

    Science.gov (United States)

    Aggarwal, Rama; Bagai, Upma

    2017-03-01

    Increasing anthelmintic resistance and the impact of conventional anthelmintics on the environment, it is important to look for alternative strategies against helminth parasite in sheep. Important lipogenic enzymes like glucose-6-phosphate dehydrogenase (G-6-PDH) and malate dehydrogenase (MDH) show subcellular distribution pattern. Activity of G-6-PDH was largely restricted to cytosolic fraction while MDH was found in both cytosolic and mitochondrial fraction in Gastrothylax indicus. Following in vitro treatment with ethanolic and aqueous extracts of Punica granatum fruit peel and commercial anthelmintic, albendazole G-6-PDH activity was decreased by 19-32 %, whereas MDH was suppressed by 24-41 %, compared to the respective control. Albendazole was quite effective when compared with negative control and both the extracts. The results indicate that phytochemicals of plant may act as potential vermifuge or vermicide.

  4. Isoniazid acetylating phenotype in patients with paracoccidioidomycosis and its relationship with serum sulfadoxin levels, glucose-6-phosphate dehydrogenase and glutathione reductase activities

    Directory of Open Access Journals (Sweden)

    Benedito Barraviera

    1991-06-01

    Full Text Available The authors evaluated the isoniazid acetylating phenotype and measured hematocrit, hemoglobin, glucose-6-phosphate dehydrogenase and glutathione reductase activities plus serum sulfadoxin levels in 39 patients with paracoccidioidomycosis (33 males and 6 females aged 17 to 58 years. Twenty one (53.84% of the patients presented a slow acetylatingphenotype and 18(46.16% a fast acetylating phenotype. Glucose-6-phosphate- dehydrogenase (G6PD acti vity was decreased in 5(23.80% slow acetylators and in 4(22.22% fast acetylators. Glutathione reductase activity was decreased in 14 (66.66% slow acetylators and in 12 (66.66% fast acetylators. Serum levels of free and total sulfadoxin Were higher in slow acetylator (p Os autores avaliaram o fenótipo acetilador da isoniazida, hematócrito, hemoglobina, atividade da glicose-6- fosfato desidrogenase, glutationa redutase e os níveis séricos de sulfadoxina de 39 doentes com paracoccidíoidomicose, senão 33 do sexo masculino e 6 do feminino, com idades compreendidas entre 17 e 58 anos. Vinte e um (53,84% doentes apresentaram fenótipo acetilador lento e 18 (46,16% rápido. A atividade da glicose-6-fosfato desidrogenase (G6PD esteve diminuída em 5 (23,80% acetiladores lentos e 4 (22,22% rápidos. A atividade da glutationa redutase esteve diminuída em 14 (66,66% acetiladores lentos e 12 (66,66% rápidos. Os níveis séricos de sulfadoxina livre e total foram maiores nos acetiladores lentos (p < 0,02. A análise dos resultados permite concluir que os níveis séricos de sulfadoxina relaciona-se com o fenótipo acetilador. Além disso, os níveis estiveram sempre acima de 50 µg/ml, níveis estes considerados terapêuticos. Por outro lado, a deficiência de glutationa redutase pode estar relacionada com a má absorção intestinal de nutrientes, entre eles riboflavina, vitamina precursora de FAD.

  5. A role for AMPK in the inhibition of glucose-6-phosphate dehydrogenase by polyunsaturated fatty acids

    Energy Technology Data Exchange (ETDEWEB)

    Kohan, Alison B.; Talukdar, Indrani; Walsh, Callee M. [Department of Biochemistry, West Virginia University, Morgantown, WV (United States); Salati, Lisa M., E-mail: lsalati@hsc.wvu.edu [Department of Biochemistry, West Virginia University, Morgantown, WV (United States)

    2009-10-09

    Both polyunsaturated fatty acids and AMPK promote energy partitioning away from energy consuming processes, such as fatty acid synthesis, towards energy generating processes, such as {beta}-oxidation. In this report, we demonstrate that arachidonic acid activates AMPK in primary rat hepatocytes, and that this effect is p38 MAPK-dependent. Activation of AMPK mimics the inhibition by arachidonic acid of the insulin-mediated induction of G6PD. Similar to intracellular signaling by arachidonic acid, AMPK decreases insulin signal transduction, increasing Ser{sup 307} phosphorylation of IRS-1 and a subsequent decrease in AKT phosphorylation. Overexpression of dominant-negative AMPK abolishes the effect of arachidonic acid on G6PD expression. These data suggest a role for AMPK in the inhibition of G6PD by polyunsaturated fatty acids.

  6. Two new glucose 6-phosphate dehydrogenase variants associated with congenital nonspherocytic hemolytic anemia found in Japan: GD(-) Tokushima and GD(-) Tokyo.

    Science.gov (United States)

    Miwa, S; Ono, J; Nakashima, K; Abe, S; Kageoka, T

    1976-01-01

    Two new variants of glucose 6-phosphate dehydrogenase (G6PD) deficiency associated with chronic nonspherocytic hemolytic anemia were discovered in Japan. Gd(-) Tokushima was found in a 17-years-old male whose erythrocytes contained 4.4% of normal enzyme activity. Partially purified enzyme revealed a main band of normal electrophoretic mobility with additional two minor bands of different mobility; normal Km G6P, and Km NADP five-to sixfold higher than normal; normal utilization of 2-deoxy-G6P, galactose-6P, and deamino-NADP; marked thermal instability; a normal pH curve; and normal Ki NADPH. The hemolytic anemia was moderate to severe. Gd(-) Tokyo was characterized from a 15-year-old male who had chronic nonspherocytic hemolytic anemia of mild degree. The erythrocytes contained 3% of normal enzyme activity, and partially purified enzyme revealed slow electrophoretic mobility (90% of normal for both a tris-hydrochloride buffer system and a tris-EDTA-borate buffer system, and 70% of normal for a phosphate buffer system); normal Km G6P and Km NADP; normal utilization of 2-deoxy-G6P, galactose-6P, and deamino-NADP; greatly increased thermal instability; a normal pH curve; and normal Ki NADPH. These two variants are clearly different from hitherto described G6PD variants, including the Japanese variants Gd(-) Heian and Gd(-) Kyoto. The mothers of both Gd(-) Tokushima and Gd(-) Tokoyo were found to be heterozygote by an ascorbate-cyanide test.

  7. Process Integration for the Disruption of Candida guilliermondii Cultivated in Rice Straw Hydrolysate and Recovery of Glucose-6-Phosphate Dehydrogenase by Aqueous Two-Phase Systems.

    Science.gov (United States)

    Gurpilhares, Daniela B; Pessoa, Adalberto; Roberto, Inês C

    2015-07-01

    Remaining cells of Candida guilliermondii cultivated in hemicellulose-based fermentation medium were used as intracellular protein source. Recovery of glucose-6-phosphate dehydrogenase (G6PD) was attained in conventional aqueous two-phase systems (ATPS) was compared with integrated process involving mechanical disruption of cells followed by ATPS. Influences of polyethylene glycol molar mass (M PEG) and tie line lengths (TLL) on purification factor (PF), yields in top (Y T ) and bottom (Y B ) phases and partition coefficient (K) were evaluated. First scheme resulted in 65.9 % enzyme yield and PF of 2.16 in salt-enriched phase with clarified homogenate (M PEG 1500 g mol(-1), TLL 40 %); Y B of 75.2 % and PF B of 2.9 with unclarified homogenate (M PEG 1000 g mol(-1), TLL 35 %). The highest PF value of integrated process was 2.26 in bottom phase (M PEG 1500 g mol(-1), TLL 40 %). In order to optimize this response, a quadratic model was predicted for the response PFB for process integration. Maximum response achieved was PFB = 3.3 (M PEG 1500 g mol(-1), TLL 40 %). Enzyme characterization showed G6P Michaelis-Menten constant (K M ) equal 0.07-0.05, NADP(+) K M 0.02-1.98 and optimum temperature 70 °C, before and after recovery. Overall, our data confirmed feasibility of disruption/extraction integration for single-step purification of intracellular proteins from remaining yeast cells.

  8. Hyperbilirubinaemia and erythrocytic glucose 6 phosphate dehydrogenase deficiency in Malaysian children.

    Science.gov (United States)

    Hon, A T; Balakrishnan, S; Ahmad, Z

    1989-03-01

    Cord blood from 8,975 babies delivered in Hospital Sultanah Aminah Johor Bahru over a period of eight months (1st August 1985 to 31st March 1986) were screened for G6PD deficiency. The overall incidence was 4.5% in Chinese, 3.5% in Malays and 1.5% in Indian babies. One hundred of these babies were observed in the nursery for seven days and their daily serum bilirubin recorded. The serum bilirubin peaked at 96 hours to a value of 12mg%. None of the babies in the nursery developed a serum bilirubin level of more than 15mg%. Six of the babies with G6PD deficiency that were sent home were readmitted with hyperbilirubinaemia that needed exchange transfusion.

  9. Deficiencia de glucosa 6-fostato deshidrogenasa en hombres sanos y en pacientes maláricos; Turbo (Antioquia, Colombia Deficiency of glucose-6-phosphate dehydrogenase in healthy men and malaria patients; Turbo (Antioquia, Colombia

    Directory of Open Access Journals (Sweden)

    Jaime Carmona-Fonseca

    2008-06-01

    Full Text Available INTRODUCCIÓN: En América Latina la deficiencia de glucosa 6-fosfato deshidrogenasa (d-G6PD ha sido poco estudiada y en Colombia solo conocemos tres publicaciones antiguas. Urge conocer más la prevalencia de d-G6PD, sobre todo ahora que el tratamiento de la malaria vivax plantea aumentar la dosis diaria o total de primaquina. OBJETIVO: Medir la prevalencia de d-G6PD en poblaciones masculina sana y de enfermos con malaria por Plasmodium vivax, en Turbo (Urabá, departamento de Antioquia, Colombia. METODOLOGÍA: Encuestas de prevalencia, para evaluar la G6PD en dos poblaciones de Turbo (Antioquia: hombres sanos; hombres y mujeres con malaria vivax. Se trabajó con muestras diseñadas con criterios estadístico-epidemiológicos. La actividad enzimática se midió con el método normalizado de Beutler para valorar la G6PD en hemolizados. RESULTADOS: Entre los hombres sanos (n = 508, el intervalo de confianza 95% para el promedio (IC95% estuvo entre 4,15 y 4,51 UI/g hemoglobina y 14,8% presentaron valores por debajo del "límite normal" de INTRODUCTION: Glucose-6-phosphate dehydrogenase (G6PD deficiency in Latin America has not been fully studied and in Colombia only three outdated publications are known. Recent information on the prevalence of G6PD deficiency is required now, because the recommended treatment of vivax malaria requires higher daily or total doses of primaquine. OBJECTIVE: To measure the prevalence of G6PD in a healthy male population and in a Plasmodium vivax infected population in Turbo (Urabá, Antioquia Department, Colombia. METHOD: Prevalence survey to evaluate G6PD in two populations of Turbo (Antioquia: healthy male; male and female with vivax malaria. The work was carried out on population samples selected using statistical and epidemiological criteria. Enzyme activity was measured using Beutler's normalized method to evaluate G6PD after hemolysis. RESULTS: For the healthy male group (n = 508, and with a 95% confidence

  10. Inhibition of catalase by aminotriazole in vivo results in reduction of glucose-6-phosphate dehydrogenase activity in Saccharomyces cerevisiae cells.

    Science.gov (United States)

    Bayliak, M; Gospodaryov, D; Semchyshyn, H; Lushchak, V

    2008-04-01

    The inhibitor of catalase 3-amino-1,2,4-triazole (AMT) was used to study the physiological role of catalase in the yeast Saccharomyces cerevisiae under starvation. It was shown that AMT at the concentration of 10 mM did not affect the growth of the yeast. In vivo and in vitro the degree of catalase inhibition by AMT was concentration- and time-dependent. Peroxisomal catalase in bakers' yeast was more sensitive to AMT than the cytosolic one. In vivo inhibition of catalase by AMT in S. cerevisiae caused a simultaneous decrease in glucose-6-phosphate dehydrogenase activity and an increase in glutathione reductase activity. At the same time, the level of protein carbonyls, a marker of oxidative modification, was not affected. Possible mechanisms compensating the negative effects caused by AMT inhibition of catalase are discussed.

  11. Incorporation of 14C glucose into glycogen and glucose-6-phosphate dehydrogenase activity in rat brain following carbon monoxide intoxication

    International Nuclear Information System (INIS)

    Sikorska, M.; Gorzkowski, B.; Szumanska, G.; Smialek, M.

    1975-01-01

    Incorporation of 14 C glucose into glycogen and glucose-6-phosphate dehydrogenase activity in rat brain following carbon monoxide intoxication was studied. In brains of rats tested on the 20, 30 and 60th minute of exposure to CO and immediately after removal from the chamber the enzyme activity showed no essential deviation from the control level. In the group of rats tested 1 hour after taking them out from the chamber increase of the enzyme activity was noticed, amounting to about 33% of the control value. The brains tested 24 hours after exposure showed the largest increase of the enzyme activity by about 94%. In the next time periods, 48 and 72 hours after intoxication, the enzyme activity was decreasing. The glycogen content in brains of control animals increased 3 hours after CO intoxication by about 69%. The increase of glycogen synthesis was expressed by increase of the total radioactivity, which amounted to 160% of the control value. (Z.M.)

  12. Recombinant human G6PD for quality control and quality assurance of novel point-of-care diagnostics for G6PD deficiency.

    Directory of Open Access Journals (Sweden)

    Maria Kahn

    Full Text Available A large gap for the support of point-of-care testing is the availability of reagents to support quality control (QC of diagnostic assays along the supply chain from the manufacturer to the end user. While reagents and systems exist to support QC of laboratory screening tests for glucose-6-phosphate dehydrogenase (G6PD deficiency, they are not configured appropriately to support point-of-care testing. The feasibility of using lyophilized recombinant human G6PD as a QC reagent in novel point-of-care tests for G6PD deficiency is demonstrated.Human recombinant G6PD (r-G6PD was expressed in Escherichia coli and purified. Aliquots were stored at -80°C. Prior to lyophilization, aliquots were thawed, and three concentrations of r-G6PD (representing normal, intermediate, and deficient clinical G6PD levels were prepared and mixed with a protective formulation, which protects the enzyme activity against degradation from denaturation during the lyophilization process. Following lyophilization, individual single-use tubes of lyophilized r-G6PD were placed in individual packs with desiccants and stored at five temperatures for one year. An enzyme assay for G6PD activity was used to ascertain the stability of r-G6PD activity while stored at different temperatures.Lyophilized r-G6PD is stable and can be used as a control indicator. Results presented here show that G6PD activity is stable for at least 365 days when stored at -80°C, 4°C, 30°C, and 45°C. When stored at 55°C, enzyme activity was found to be stable only through day 28.Lyophilized r-G6PD enzyme is stable and can be used as a control for point-of-care tests for G6PD deficiency.

  13. Peroxyl radical- and photo-oxidation of glucose 6- phosphate dehydrogenase generates cross-links and functional changes via oxidation of tyrosine and tryptophan residues

    DEFF Research Database (Denmark)

    Leinisch, Fabian; Mariotti, Michele; Rykær, Martin

    2017-01-01

    indicate that pathophysiological processes and multiple human diseases are associated with the accumulation of damaged proteins. In this study we investigated the mechanisms and consequences of exposure of the key metabolic enzyme glucose-6-phosphate dehydrogenase (G6PDH) to peroxyl radicals (ROO...

  14. Quantitative aspects of the cytochemical demonstration of glucose-6-phosphate dehydrogenase with tetranitro BT studied in a model system of polyacrylamide films

    NARCIS (Netherlands)

    van Noorden, C. J.; Tas, J.

    1980-01-01

    The cytochemical determination of the activity of glucose-6-phosphate dehydrogenase (G6PDH) with tetranitro blue tetrazolium (TNBT) was studied with model films of polyacrylamide gel incorporating purified enzyme. This model system enabled a quantitative study to be made of different parameters

  15. Quantitative aspects of the cytochemical demonstration of glucose-6-phosphate dehydrogenase with tetrazolium salts studied in a model system of polyacrylamide films

    NARCIS (Netherlands)

    van Noorden, C. J.; Tas, J.; Sanders, J. A.

    1981-01-01

    The enzyme cytochemical demonstration of glucose-6-phosphate dehydrogenase (G6PDH) with several tetrazolium salts has been studied with an artificial model of polyacrylamide films in corporated with the enzyme, which enabled teh correlation of cytochemical and biochemical data. In the model films no

  16. Quantitative cytochemical analysis of glucose-6-phosphate dehydrogenase activity in living isolated hepatocytes of European flounder for rapid analysis of xenobiotic effects

    NARCIS (Netherlands)

    Winzer, K.; van Noorden, C. J.; Köhler, A.

    2001-01-01

    There is a great need for rapid but reliable assays to determine quantitatively effects of xenobiotics on biological systems in environmental research. Hepatocytes of European flounder are sensitive to low-dose toxic stress. Glucose-6-phosphate dehydrogenase (G6PDH) is the major source of NADPH in

  17. Triiodothyronine (T3)-associated upregulation and downregulation of nuclear T3 binding in the human fibroblast cell (MRC-5)--stimulation of malic enzyme, glucose-6-phosphate-dehydrogenase, and 6-phosphogluconate-dehydrogenase by insulin, but not by T3

    DEFF Research Database (Denmark)

    Matzen, L E; Kristensen, S R; Kvetny, J

    1991-01-01

    The specific nuclear binding of triiodothyronine (T3) (NBT3) and the activity of malic enzyme (ME), glucose-6-phosphate-dehydrogenase (G6PD), and 6-phosphogluconate-dehydrogenase (6PGD) were studied in the human fibroblast cell (MRC-5). The overall apparent binding affinity (Ka) was 2.7 x 10(9) L.......mol-1 estimated from kinetic studies of nuclear T3 binding, and 2.5 x 10(9) L.mol-1 estimated from equilibrium studies. The scatchard plots were curvilinear and composed of a high-affinity binding site with Ka1 3.4 +/- 0.7 x 10(9) L.mol-1 and maximal binding capacity (MBC) MBC1 57.0 +/- 11.9 fmol/mg DNA...... and a low-affinity binding site with Ka2 2.9 +/- 1.1 x 10(8) L.mol-1 and MBC2 124.7 +/- 22.1 fmol/mg DNA (n = 6). Incubation of cells with 6 nmol/L T3 for 20 hours reduced NBT3 to 62.2% +/- 15.7% (P less than .01, n = 11). The Ka estimated from kinetic studies was reduced to 6.7 x 10(7) L.mol-1...

  18. High prevalence of Dapsone-induced oxidant hemolysis in North American SCT recipients without glucose-6-phosphate-dehydrogenase deficiency.

    Science.gov (United States)

    Olteanu, H; Harrington, A M; George, B; Hari, P N; Bredeson, C; Kroft, S H

    2012-03-01

    Dapsone (4-4'-diaminodiphenylsulfone) is commonly used for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in immunocompromised patients. Oxidant hemolysis is a known complication of dapsone, but its frequency in adult patients who have undergone a SCT for hematological malignancies is not well established. We studied the presence of oxidant hemolysis, by combining examination of RBC morphology and laboratory data, in 30 patients who underwent a SCT and received dapsone for PCP prophylaxis, and compared this group with 26 patients who underwent a SCT and received trimethoprim-sulfamethoxazole (TMP-SMX) for PCP prophylaxis. All patients had normal glucose-6-phosphate dehydrogenase (G6PDH) enzymatic activity. In SCT patients, dapsone compared with TMP-SMX for PCP prophylaxis was associated with a high incidence of oxidant hemolysis (87 vs 0%, PSCT patients is 20-fold higher than the reported rate in the population of HIV-infected patients, and thus much higher than the prevalence of G6PDH variants in the general population. In our patients, it manifested clinically as a lower Hb that was not significant enough to result in increased packed RBC transfusions.

  19. Biochemical Analysis of Two Single Mutants that Give Rise to a Polymorphic G6PD A-Double Mutant

    Directory of Open Access Journals (Sweden)

    Edson Jiovany Ramírez-Nava

    2017-10-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is a key regulatory enzyme that plays a crucial role in the regulation of cellular energy and redox balance. Mutations in the gene encoding G6PD cause the most common enzymopathy that drives hereditary nonspherocytic hemolytic anemia. To gain insights into the effects of mutations in G6PD enzyme efficiency, we have investigated the biochemical, kinetic, and structural changes of three clinical G6PD variants, the single mutations G6PD A+ (Asn126AspD and G6PD Nefza (Leu323Pro, and the double mutant G6PD A− (Asn126Asp + Leu323Pro. The mutants showed lower residual activity (≤50% of WT G6PD and displayed important kinetic changes. Although all Class III mutants were located in different regions of the three-dimensional structure of the enzyme and were not close to the active site, these mutants had a deleterious effect over catalytic activity and structural stability. The results indicated that the G6PD Nefza mutation was mainly responsible for the functional and structural alterations observed in the double mutant G6PD A−. Moreover, our study suggests that the G6PD Nefza and G6PD A− mutations affect enzyme functions in a similar fashion to those reported for Class I mutations.

  20. X-Linked G6PD Deficiency Protects Hemizygous Males but Not Heterozygous Females against Severe Malaria

    OpenAIRE

    Guindo, Aldiouma; Fairhurst, Rick M; Doumbo, Ogobara K; Wellems, Thomas E; Diallo, Dapa A

    2007-01-01

    Editors' Summary Background. “Favism” is a condition that results from a deficiency in an enzyme called glucose-6-phosphate dehydrogenase (G6PD), and this disorder is thought to be the commonest enzyme-deficiency disease worldwide. The disease is named favism after the Italian word for broad beans (fava), which cause a classic reaction when eaten by people with G6PD deficiency. The G6PD enzyme is particularly important in red blood cells, where it protects against damage that can be caused by...

  1. Icterícia neonatal e deficiência de glicose-6-fosfato desidrogenase Neonatal jaundice and glucose-6-phosphate dehydrogenase

    Directory of Open Access Journals (Sweden)

    Amauri Antiquera Leite

    2010-01-01

    Full Text Available A deficiência de glicose-6-fosfato desidrogenase em neonatos pode ser a responsável pela icterícia neonatal. Este comentário científico é decorrente do relato sobre o tema publicado neste fascículo e que preocupa diversos autores de outros países em relação às complicações em neonatos de hiperbilirrubinemia, existindo inclusive proposições de alguns autores em incluir o teste para identificar a deficiência de glicose-6-fosfato desidrogenase nos recém-nascidos.Glucose-6-phosphate dehydrogenase in newborn babies may be responsible for neonatal jaundice. There is a concern of many authors from other countries in respect to complications in neonates with hyperbilirubinemia; some authors even propose screening for glucose-6-phosphate dehydrogenase deficiency in newborn babies. A scientific report on this subject is published in this issue.

  2. Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria: A meta-analysis and trial sequential analysis

    Science.gov (United States)

    Sun, Fengmei; Zhang, Juan; Pu, Yuepu

    2017-10-01

    This study is designed to perform a meta-analysis and trial sequential analysis (TSA) to investigate whether people with G6PD deficiency suffered less malarial infection. We searched from PubMed, Science Direct, Springer Link, CNKI, and Wan Fang databases for case-control study, cohort study or cross section study until April 2017. TSA was used to determine the state of evidence and calculate the required sample size. Eight case-control studies and five cross-sectional studies (30,683participants) were included in this meta-analysis. Compared with normal control group, we found significant protection from severe malaria (OR 0.644, 95% CI [0.493-0.842]; P=0.001) among people with decreasing G6PD activity. People with variations of G6PD gene at nucleotide 202(G6PD A-) were also found to be associated with resistance on severe malaria pooled (OR 0.851, 95% CI [0.779-0.930]; P =0.0001). Sex-stratified test suggested that protection of severe malaria is conferred to both G6PD A-males and heterozygous females (with a single copy of the variant). In conclusion, our study found a significant protection from severe malaria among G6PD deficient people compared to the

  3. Protective effects of glucose-6-phosphate dehydrogenase on neurotoxicity of aluminium applied into the CA1 sector of rat hippocampus

    Directory of Open Access Journals (Sweden)

    Marina D Jovanovic

    2014-01-01

    Full Text Available Background & objectives: Aluminum (Al toxicity is closely linked to the pathogenesis of Alzheimer′s disease (AD. This experimental study was aimed to investigate the active avoidance behaviour of rats after intrahippocampal injection of Al, and biochemical and immunohistochemical changes in three bilateral brain structures namely, forebrain cortex (FBCx, hippocampus and basal forebrain (BF. Methods: Seven days after intra-hippocampal (CA1 sector injection of AlCl 3 into adult male Wistar rats they were subjected to two-way active avoidance (AA tests over five consecutive days. Control rats were treated with 0.9% w/v saline. The animals were decapitated on the day 12 post-injection. The activities of acetylcholinesterase (AChE and glucose-6-phosphate dehydrogenase (G6PDH were measured in the FBCx, hippocampus and BF. Immunohistochemical staining was performed for transferrin receptors, amyloid β and tau protein. Results: The activities of both AChE and G6PDH were found to be decreased bilaterally in the FBCx, hippocampus and basal forebrain compared to those of control rats. The number of correct AA responses was reduced by AlCl 3 treatment. G6PDH administered prior to AlCl 3 resulted in a reversal of the effects of AlCl 3 on both biochemical and behavioural parameters. Strong immunohistochemical staining of transferrin receptors was found bilaterally in the FBCx and the hippocampus in all three study groups. In addition, very strong amyloid β staining was detected bilaterally in all structures in AlCl 3 -treated rats but was moderate in G6PDH/AlCl 3 -treated rats. Strong tau staining was noted bilaterally in AlCl 3 -treated rats. In contrast, tau staining was only moderate in G6PDH/AlCl 3 -treated rats. Interpretation & conclusions: Our findings indicated that the G6PDH alleviated the signs of behavioural and biochemical effects of AlCl 3 -treatment suggesting its involvement in the pathogenesis of Al neurotoxicity and its potential

  4. Molecular association of glucose-6-phosphate isomerase and pyruvate kinase M2 with glyceraldehyde-3-phosphate dehydrogenase in cancer cells

    International Nuclear Information System (INIS)

    Das, Mahua R.; Bag, Arup K.; Saha, Shekhar; Ghosh, Alok; Dey, Sumit K.; Das, Provas; Mandal, Chitra; Ray, Subhankar; Chakrabarti, Saikat; Ray, Manju; Jana, Siddhartha S.

    2016-01-01

    For a long time cancer cells are known for increased uptake of glucose and its metabolization through glycolysis. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key regulatory enzyme of this pathway and can produce ATP through oxidative level of phosphorylation. Previously, we reported that GAPDH purified from a variety of malignant tissues, but not from normal tissues, was strongly inactivated by a normal metabolite, methylglyoxal (MG). Molecular mechanism behind MG mediated GAPDH inhibition in cancer cells is not well understood. GAPDH was purified from Ehrlich ascites carcinoma (EAC) cells based on its enzymatic activity. GAPDH associated proteins in EAC cells and 3-methylcholanthrene (3MC) induced mouse tumor tissue were detected by mass spectrometry analysis and immunoprecipitation (IP) experiment, respectively. Interacting domains of GAPDH and its associated proteins were assessed by in silico molecular docking analysis. Mechanism of MG mediated GAPDH inactivation in cancer cells was evaluated by measuring enzyme activity, Circular dichroism (CD) spectroscopy, IP and mass spectrometry analyses. Here, we report that GAPDH is associated with glucose-6-phosphate isomerase (GPI) and pyruvate kinase M2 (PKM2) in Ehrlich ascites carcinoma (EAC) cells and also in 3-methylcholanthrene (3MC) induced mouse tumor tissue. Molecular docking analyses suggest C-terminal domain preference for the interaction between GAPDH and GPI. However, both C and N termini of PKM2 might be interacting with the C terminal domain of GAPDH. Expression of both PKM2 and GPI is increased in 3MC induced tumor compared with the normal tissue. In presence of 1 mM MG, association of GAPDH with PKM2 or GPI is not perturbed, but the enzymatic activity of GAPDH is reduced to 26.8 ± 5 % in 3MC induced tumor and 57.8 ± 2.3 % in EAC cells. Treatment of MG to purified GAPDH complex leads to glycation at R399 residue of PKM2 only, and changes the secondary structure of the protein complex. PKM2

  5. Combined Effect of L-Cysteine and Vitamin E Injected Pre-Irradiation on Glucose-6-Phosphate Dehydrogenase Activity and Certain products of Glycolysis in Blood of Female Rats

    International Nuclear Information System (INIS)

    Abdel-Fattah, K.I.; Abou-Safi, H.M.; Kafafy, Y.A.; Ashry, O.M.

    1999-01-01

    The present work aims to evaluate the protective limits of L-cysteine and vitamin E combination against deleterious effects of gamma radiation on glucose-6-phosphate dehydrogenase activity, liver glycogen, blood glucose, pyruvic and lactic acids and their correlations in adult female rats. Mature female white rats were divided into four groups: 1- Control group. 2- Whole body gamma irradiated group at a dose level two Gy. 3-Group injected with 120 mg/100 g b.wt. L-cysteine+10 mg/100 g b.wt. vitamin E. 4- Group injected with cysteine+ vitamin E one hour before irradiation at 2 Gy dose level. Results revealed that combined administration of cysteine and vitamin E before gamma-irradiation have accelerated the radiation injury on liver glycogen, plasma glucose and G 6 Pd activity, while they showed a protective effect on lactic and pyruvic acids. This could be due to different mechanisms or a biphasic mechanism related to hormonal (like E 2 , T 3 and insulin), enzymatic or metabolic (e.g. oxidation/reduction, catabolic, anabolic factors) control

  6. Autoinflammatory Reaction in Dogs Treated for Cancer via G6PD Inhibition

    Directory of Open Access Journals (Sweden)

    Jonathan W. Nyce

    2017-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is an oncoprotein that is overexpressed in cancer cells to provide the NADPH required for their increased anabolism. NADPH, sourced from G6PD fuels nucleotide biosynthesis, maintains redox potential of thioredoxin and glutathione and drives the mevalonate pathway that powers many of the basic mechanisms by which cancer cells escape host control. G6PD is thus a target for cancer treatment being addressed by many groups around the world. We have discovered that systemic inhibition of G6PD by high dose dehydroepiandrosterone (DHEA causes a severe autoinflammatory response in dogs, which does not occur in mice or rats. Since dogs more closely model the human adrenal androgen system than do common laboratory animals, this finding is relevant to the design of G6PD-inhibiting drugs for humans. The autoinflammatory reaction observed closely resembles mevalonate kinase deficiency (MKD, a rare autosomal recessive disease in humans characterized by recurrent febrile attacks, arthralgia, skin rash, and aphthous ulcers of mucocutaneous tissues. In a manner comparable to animal models of MKD, the reconstitution of protein geranylgeranylation blocked the autoinflammatory reaction caused by systemic G6PD inhibition. This autoinflammatory response to systemic G6PD inhibition represents an unexpected result that must be taken into consideration when targeting this oncoprotein.

  7. G6PD Deficiency in an HIV Clinic Setting in the Dominican Republic

    Science.gov (United States)

    Xu, Julia Z.; Francis, Richard O.; Lerebours Nadal, Leonel E.; Shirazi, Maryam; Jobanputra, Vaidehi; Hod, Eldad A.; Jhang, Jeffrey S.; Stotler, Brie A.; Spitalnik, Steven L.; Nicholas, Stephen W.

    2015-01-01

    Because human immunodeficiency virus (HIV)-infected patients receive prophylaxis with oxidative drugs, those with glucose-6-phosphate dehydrogenase (G6PD) deficiency may experience hemolysis. However, G6PD deficiency has not been studied in the Dominican Republic, where many individuals have African ancestry. Our objective was to determine the prevalence of G6PD deficiency in Dominican HIV-infected patients and to attempt to develop a cost-effective algorithm for identifying such individuals. To this end, histories, chart reviews, and G6PD testing were performed for 238 consecutive HIV-infected adult clinic patients. The overall prevalence of G6PD deficiency (8.8%) was similar in males (9.3%) and females (8.5%), and higher in Haitians (18%) than Dominicans (6.4%; P = 0.01). By logistic regression, three clinical variables predicted G6PD status: maternal country of birth (P = 0.01) and a history of hemolysis (P = 0.01) or severe anemia (P = 0.03). Using these criteria, an algorithm was developed, in which a patient subset was identified that would benefit most from G6PD screening, yielding a sensitivity of 94.7% and a specificity of 97.2%, increasing the pretest probability (8.8–15.1%), and halving the number of patients needing testing. This algorithm may provide a cost-effective strategy for improving care in resource-limited settings. PMID:26240158

  8. Mediterranean glucose-6-phosphate dehydrogenase (G6PDC563T) mutation among jordanian females with acute hemolytic crisis

    International Nuclear Information System (INIS)

    Jabbar, A.A.; Kanakiri, N.; Kamil, M.; Rimawi, H.S.A.

    2010-01-01

    To evaluate the G6PDC563T Mediterranean mutation among Jordanian females who were admitted to Princess Rahma Teaching Hospital (PRTH) with/or previous history of favism. Study Design: A descriptive study. Place and Duration of Study: Jordanian University of Science and Technology and PRTH, from October 2003 to October 2004. Methodology: After obtaining approval from the Ethics Committee of Jordanian University of Science and Technology, a total of 32 females were included in this study. Samples from 15 healthy individual females were used as a negative control. Blood samples from these patients were collected and analyzed by allele-specific polymerase chain reaction (AS-PCR) to determine the G6PDC563T mutation. Results: Twenty one out of 32 patients were found to be G6PDC563T Mediterranean mutation (65.6%) positive. Three out of 21 patients were homozygous and remaining 18 were heterozygous for G6PDC563T Mediterranean mutation. Eleven (34.4%) out of 32 patients were found to be negative for G6PDC563T mutation indicating the presence of other G6PD mutations in the study sample. Conclusion: G6PDC563T Mediterranean mutation accounted for 65.6% of the study sample with favism in the North of Jordan. There is likely to be another G6PD deficiency variant implicated in acute hemolytic crisis (favism). (author)

  9. Characterization of G6PD genotypes and phenotypes on the northwestern Thailand-Myanmar border.

    Directory of Open Access Journals (Sweden)

    Germana Bancone

    Full Text Available Mutations in the glucose-6-phosphate dehydrogenase (G6PD gene result in red blood cells with increased susceptibility to oxidative damage. Significant haemolysis can be caused by primaquine and other 8-aminoquinoline antimalarials used for the radical treatment of Plasmodium vivax malaria. The distribution and phenotypes of mutations causing G6PD deficiency in the male population of migrants and refugees in a malaria endemic region on the Thailand-Myanmar border were characterized. Blood samples for G6PD fluorescent spot test (FST, G6PD genotyping, and malaria testing were taken from 504 unrelated males of Karen and Burman ethnicities presenting to the outpatient clinics. The overall frequency of G6PD deficiency by the FST was 13.7%. Among the deficient subjects, almost 90% had the Mahidol variant (487G>A genotype. The remaining subjects had Chinese-4 (392G>T, Viangchan (871G>A, Açores (595A>G, Seattle (844G>C and Mediterranean (563C>T variants. Quantification of G6PD activity was performed using a modification of the standard spectrophotometric assay on a subset of 24 samples with Mahidol, Viangchan, Seattle and Chinese-4 mutations; all samples showed a residual enzymatic activity below 10% of normal and were diagnosed correctly by the FST. Further studies are needed to characterise the haemolytic risk of using 8-aminoquinolines in patients with these genotypes.

  10. Incorporation of /sup 14/C glucose into glycogen and glucose-6-phosphate dehydrogenase activity in rat brain following carbon monoxide intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Sikorska, M; Gorzkowski, B; Szumanska, G; Smialek, M [Polska Akademia Nauk, Warsaw. Centrum Medycyny Doswiadczalnej i Klinicznej; Panstwowy Zaklad Higieny, Warsaw (Poland))

    1975-01-01

    Incorporation of /sup 14/C glucose into glycogen and glucose-6-phosphate dehydrogenase activity in rat brain following carbon monoxide intoxication was studied. In brains of rats tested on the 20, 30 and 60th minute of exposure to CO and immediately after removal from the chamber the enzyme activity showed no essential deviation from the control level. In the group of rats tested 1 hour after taking them out from the chamber increase of the enzyme activity was noticed, amounting to about 33% of the control value. The brains tested 24 hours after exposure showed the largest increase of the enzyme activity by about 94%. In the next time periods, 48 and 72 hours after intoxication, the enzyme activity was decreasing. The glycogen content in brains of control animals increased 3 hours after CO intoxication by about 69%. The increase of glycogen synthesis was expressed by increase of the total radioactivity, which amounted to 160% of the control value.

  11. EFFECTS OF PARTIAL HEPATECTOMY, PHENOBARBITAL AND 3-METHYLCHOLANTHRENE ON KINETIC-PARAMETERS OF GLUCOSE-6-PHOSPHATE AND PHOSPHOGLUCONATE DEHYDROGENASE IN-SITU IN PERIPORTAL, INTERMEDIATE AND PERICENTRAL ZONES OF RAT-LIVER LOBULES

    NARCIS (Netherlands)

    Jonges, G. N.; Vogels, I. M. C.; van Noorden, C. J. F.

    1995-01-01

    Glucose-6-phosphate dehydrogenase (G6PDH) and phosphogluconate dehydrogenase (PGDH) are heterogeneously distributed in liver lobules of female rats. The maximum activity of both enzymes is approximately twice higher in intermediate and pericentral zones than in periportal zones. Enzyme activities

  12. Erythrocyte glucose-6-phosphate dehydrogenase deficiency in male newborn babies and its relationship with neonatal jaundice Deficiência de glicose-6-fosfato desidrogenase eritrocitária em recém-nascidos do sexo masculino e sua relação com a icterícia neonatal

    Directory of Open Access Journals (Sweden)

    Marli Auxiliadora C. Iglessias

    2010-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency, the commonest red cell enzymopathy in humans, has an X-linked inheritance. The major clinical manifestations are drug induced hemolytic anemia, neonatal jaundice and chronic nonspherocytic hemolytic anemia. The incidence of neonatal hyperbilirubinemia is much greater in G6PD-deficient neonates than babies without this deficiency. The aim of this study was to ascertain the presence of neonatal jaundice in erythrocyte G6PD-deficient male newborns. Samples of umbilical cord blood from a total of 204 male newborns of the Januário Cicco School Maternity located in Natal, Rio Grande do Norte, Brazil were analyzed. The G6PD deficiency was identified by the methemoglobin reduction test (Brewer's test. The deficiency was confirmed by quantitative spectrophotometric assay for enzyme activity and cellulose acetate electrophoresis was used to identify the G6PD variant. Eight newborns were found to be G6PD deficient with four of them exhibiting jaundice during the first 48 hours after birth with bilirubin levels higher than 10 mg/dL. All deficient individuals presented the G6PD A- variant at electrophoresis. Our findings confirmed the association between G6PD deficiency and neonatal jaundice. Hence, early diagnosis of the deficiency at birth is essential to control the appearance of jaundice and to prevent the exposure of these newborns to known hemolytic agents.A deficiência de glicose-6-fosfato desidrogenase (G6PD é a anormalidade enzimática hereditária mais frequente. É transmitida como caráter recessivo ligado ao cromossomo X e as principais manifestações clínicas são hemólise induzida por fármacos, icterícia neonatal e anemia hemolítica não esferocítica. O objetivo do estudo foi determinar a presença de icterícia neonatal em recém-nascidos do sexo masculino deficientes de glicose-6-fosfato desidrogenase. Foram analisadas 204 amostras de sangue umbilical de recém-nascidos do sexo

  13. Severe acute haemolytic anaemia associated with severe methaemoglobinaemia in a G6PD-deficient man.

    Science.gov (United States)

    Rehman, Abdul; Shehadeh, Mohanad; Khirfan, Diala; Jones, Akhnuwhkh

    2018-03-28

    Methaemoglobin is a form of haemoglobin in which the ferrous (Fe 2+ ) ion contained in the iron-porphyrin complex of haem is oxidised to its ferric (Fe 3+ ) state. Methaemoglobinaemia, the presence of methaemoglobin in the blood, is most commonly treated with methylene blue. However, methylene blue cannot be used in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency as it is ineffective in such patients and it can worsen G6PD deficiency haemolysis. We report the case of a 30-year-old man who presented with clinical features of G6PD deficiency-associated haemolysis and was found to have severe methaemoglobinaemia (35%). He was administered blood transfusions and intravenous ascorbic acid. His methaemoglobinaemia resolved within 24 hours. This case demonstrates the successful management of a patient with severe methaemoglobinaemia in the setting of G6PD deficiency haemolysis. Emergency physicians should be aware of the possible co-occurrence of severe methaemoglobinaemia in a patient with G6PD deficiency haemolysis. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model

    International Nuclear Information System (INIS)

    Hu, Tao; Zhang, Chunhua; Tang, Qiongling; Su, Yanan; Li, Bo; Chen, Long; Zhang, Zheng; Cai, Tianchi; Zhu, Yuechun

    2013-01-01

    Glucose-6-phosphate dehydrogenase (G6PD), elevated in tumor cells, catalyzes the first reaction in the pentose-phosphate pathway. The regulation mechanism of G6PD and pathological change in human melanoma growth remains unknown. HEM (human epidermal melanocyte) cells and human melanoma cells with the wild-type G6PD gene (A375-WT), G6PD deficiency (A375-G6PD∆), G6PD cDNA overexpression (A375-G6PD∆-G6PD-WT), and mutant G6PD cDNA (A375-G6PD∆-G6PD-G487A) were subcutaneously injected into 5 groups of nude mice. Expressions of G6PD, STAT3, STAT5, cell cycle-related proteins, and apoptotic proteins as well as mechanistic exploration of STAT3/STAT5 were determined by quantitative real-time PCR (qRT-PCR), immunohistochemistry and western blot. Delayed formation and slowed growth were apparent in A375-G6PD∆ cells, compared to A375-WT cells. Significantly decreased G6PD expression and activity were observed in tumor tissues induced by A375-G6PD∆, along with down-regulated cell cycle proteins cyclin D1, cyclin E, p53, and S100A4. Apoptosis-inhibited factors Bcl-2 and Bcl-xl were up-regulated; however, apoptosis factor Fas was down-regulated, compared to A375-WT cells. Moderate protein expressions were observed in A375-G6PD∆-G6PD-WT and A375-G6PD∆-G6PD-G487A cells. G6PD may regulate apoptosis and expression of cell cycle-related proteins through phosphorylation of transcription factors STAT3 and STAT5, thus mediating formation and growth of human melanoma cells. Further study will, however, be required to determine potential clinical applications

  15. Deletion of the Glucose-6-Phosphate Dehydrogenase Gene KlZWF1 Affects both Fermentative and Respiratory Metabolism in Kluyveromyces lactis▿

    Science.gov (United States)

    Saliola, Michele; Scappucci, Gina; De Maria, Ilaria; Lodi, Tiziana; Mancini, Patrizia; Falcone, Claudio

    2007-01-01

    In Kluyveromyces lactis, the pentose phosphate pathway is an alternative route for the dissimilation of glucose. The first enzyme of the pathway is the glucose-6-phosphate dehydrogenase (G6PDH), encoded by KlZWF1. We isolated this gene and examined its role. Like ZWF1 of Saccharomyces cerevisiae, KlZWF1 was constitutively expressed, and its deletion led to increased sensitivity to hydrogen peroxide on glucose, but unlike the case for S. cerevisiae, the Klzwf1Δ strain had a reduced biomass yield on fermentative carbon sources as well as on lactate and glycerol. In addition, the reduced yield on glucose was associated with low ethanol production and decreased oxygen consumption, indicating that this gene is required for both fermentation and respiration. On ethanol, however, the mutant showed an increased biomass yield. Moreover, on this substrate, wild-type cells showed an additional band of activity that might correspond to a dimeric form of G6PDH. The partial dimerization of the G6PDH tetramer on ethanol suggested the production of an NADPH excess that was negative for biomass yield. PMID:17085636

  16. Glucose-6-phosphate dehydrogenase is required for hpa1xoo (harpin protein fragment)-mediated salt stress tolerance in transgenic arabidopsis thaliana

    International Nuclear Information System (INIS)

    Sang, S.L.; Xie, L.L.; Cui, X.W.; Wang, Z.Y.

    2018-01-01

    Harpin induces salicylic acid and abscisic acid signaling in plants under biotic and abiotic stress, respectively. Our previous report showed that the effective harpin fragment Hpa1xoo enhanced H2O2 production and pathogen resistance in a transgenic Arabidopsis mutant. In this study, we examined contents of thiobarbituric acid reactive substance (TBARS), H2O2 and glutathione, and glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR) and glutathione peroxidase (GPX) enzyme activity in Hpa1xoo-expressing Arabidopsis under salt stress. The results revealed increased amounts of TBARS and H2O2 in wild-type (WT) compared to mutant plants under salt stress conditions. In contrast, increased levels were observed in the mutant under stress-free conditions. Moreover, a higher reduced glutathione (GSH) content and ratio of GSH/oxidized glutathione (GSSG) was observed in mutant compared to WT plants under both stress-free and salt stress conditions. In addition, mutant plants exhibited significantly higher G6PDH, GR and GPX activity than WT plants under salt stress. Suppression of G6PDH activity via 6-aminonicotinamide (6-AN, a specific inhibitor of G6PDH) was partly reversed by L-buthionine-sulfoximine (BSO, a specific inhibitor of GSH regeneration) and aggravated by GSH. Combined with previous reports, these findings suggest that the G6PDH enzyme plays a key role in harpin fragment (Hpa1xoo)-mediated salt stress tolerance in transgenic Arabidopsis. (author)

  17. Co-immobilization of cyclohexanone monooxygenase and glucose-6-phosphate dehydrogenase onto polyethylenimine-porous agarose polymeric composite using γ irradiation to use in biotechnological processes

    International Nuclear Information System (INIS)

    Atia, K.S.

    2005-01-01

    The co-immobilization of cyclohexanone monooxygenase (CHMO) and glucose-6-phosphate dehydrogenase (G6PDH) was optimized by completely coating, via covalent immobilization, the surface aldehyde groups of porous agarose (glyoxyl-agarose) with amine groups of polyethylenimine (PEI). The highest immobilization efficiency (∼87%) (activity of enzyme per amount of immobilized enzyme) was obtained with a CHMO/G6PDH ratio 2:1. The effects of different ratios of the support to the amount of enzymes (CHMO:G6PDH=2:1), the optimum incubation pH and the incubation time on the enzymatic activity of the enzymes were determined and found to be 5:1, 8.5 and 30 min, respectively. Subjecting the co-immobilized enzymes to doses of γ-radiation (5-100 kGy) resulted in complete loss in the activity of the free enzymes at a dose of 40 kGy, while the co-immobilized ones showed relatively high resistance to γ-radiation up to a dose of 50 kGy

  18. The transcriptional regulator NtrC controls glucose-6-phosphate dehydrogenase expression and polyhydroxybutyrate synthesis through NADPH availability in Herbaspirillum seropedicae.

    Science.gov (United States)

    Sacomboio, Euclides Nenga Manuel; Kim, Edson Yu Sin; Correa, Henrique Leonardo Ruchaud; Bonato, Paloma; Pedrosa, Fabio de Oliveira; de Souza, Emanuel Maltempi; Chubatsu, Leda Satie; Müller-Santos, Marcelo

    2017-10-19

    The NTR system is the major regulator of nitrogen metabolism in Bacteria. Despite its broad and well-known role in the assimilation, biosynthesis and recycling of nitrogenous molecules, little is known about its role in carbon metabolism. In this work, we present a new facet of the NTR system in the control of NADPH concentration and the biosynthesis of molecules dependent on reduced coenzyme in Herbaspirillum seropedicae SmR1. We demonstrated that a ntrC mutant strain accumulated high levels of polyhydroxybutyrate (PHB), reaching levels up to 2-fold higher than the parental strain. In the absence of NtrC, the activity of glucose-6-phosphate dehydrogenase (encoded by zwf) increased by 2.8-fold, consequently leading to a 2.1-fold increase in the NADPH/NADP + ratio. A GFP fusion showed that expression of zwf is likewise controlled by NtrC. The increase in NADPH availability stimulated the production of polyhydroxybutyrate regardless the C/N ratio in the medium. The mutant ntrC was more resistant to H 2 O 2 exposure and controlled the propagation of ROS when facing the oxidative condition, a phenotype associated with the increase in PHB content.

  19. Kawasaki disease with G6PD deficiency--report of one case and literature review.

    Science.gov (United States)

    Chen, Chia-Hao; Lin, Li-Yan; Yang, Kuender D; Hsieh, Kai-Sheng; Kuo, Ho-Chang

    2014-06-01

    Kawasaki disease (KD) is a systemic vasculitis primarily affecting children who are younger than 5 years. The most serious complications are coronary artery aneurysms and sequelae of vasculitis with the subsequent development of coronary artery aneurysm. According to the literature, intravenous immunoglobulin (IVIG) plus high-dose aspirin (acetylsalicylic acid) were standard treatment for KD, whereas low-dose aspirin (3-5 mg/kg/day) was used for thrombocytosis in KD via antiplatelet effect. However, aspirin has been reported to have hemolytic potential in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report a child with G6PD-deficiency who has KD, and review the literature. Copyright © 2012. Published by Elsevier B.V.

  20. Association of glucose-6-phosphate dehydrogenase deficiency and X-linked chronic granulomatous disease in a child with anemia and recurrent infections

    OpenAIRE

    Agudelo-Florez, P.; Costa-Carvalho, Beatriz Tavares [UNIFESP; Lopez, J. A.; Redher, J.; Newburger, P. E.; Alla-Saad, S. T.; Condino-Neto, A.

    2004-01-01

    Patients with severe leukocyte G6PD deficiency may present with impairment of NADPH oxidase activity and a history of recurrent infections, mimicking the phenotype of chronic granulomatous disease. We report herein a child with recurrent infections who initially received the diagnosis of G6PD deficiency. His erythrocyte G6PD activity was reduced: 1.8 U/g Hb (normal: 12.1 +/- 2.1 U/g Hb). Further studies revealed that G6PD activity in neutrophils, mononuclear leukocytes, and Epstein-Barr virus...

  1. THE ASSOCIATION BETWEEN G6PD DEFICIENCY AND TOTAL SERUM BILIRUBIN LEVEL IN ICTERIC NEONATES

    Directory of Open Access Journals (Sweden)

    S. Behjati-Ardakani

    2007-07-01

    Full Text Available "nGlucose-6-phosphate dehydrogenase (G6PD deficiency is the most important disease of the hexose monophosphate pathway. Deficiency of this enzym can lead to hemolysis of red blood cells. Our aim was to study the prevalence of G6PD deficiency in relation to neonatal jaundice. We studied 456 clinically icteric neonates Laboratory investigations included determination of direct and indirect serum bilirubin concentrations, blood group typing, direct coomb's test, hemoglobin, blood smear, reticulocyte count and G6PD level. We divided these neonates to 3 groups based on total serum bilirubin level (TSB: TSB< 20 mg%, TSB=20-25 mg%, and TSB>25 mg%. In only 35 (7.6% of cases G6PD deficiency was diagnosed. All of these babies were male. From 456 icteric neonates, 213 cases belong to group 1 (TSB<20 mg%, 158 cases belong to group 2 (TSB=20-25 mg% and 85 cases belong to group 3 (TSB>25 mg%. 16 neonates from 213 neonates of group 1, 6 neonates from 158 neonates of group 2 and 13 neonates from 85 neonates of group 3 had G6PD deficiency. There was statistically significant difference of prevalence of G6PD deficiency between group 2 and 3 ( 15.3% vs 3.8%( P = 0.001. Between groups 1 vs 2 and 1 vs 3 no statistically significant difference was found. Early detection of this enzymopathy regardless of sex and close surveillance of the affected newborns may be important in reducing the risk of severe hyperbilirubinemia. This emphasizes the necessity of neonatal screening on cord blood samples for G6PD deficiency.

  2. Atividade da 6-fosfogliconato desidrogenase em deficientes de glicose-6-fosfato desidrogenase Activity of 6-phosphogluconate dehydrogenase in glucose-6-phosphate dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    Daniela B. Nicolielo

    2006-06-01

    Full Text Available As enzimas G6PD e 6PGD são responsáveis pela geração do aporte de NADPH, necessário para a detoxificação dos agentes oxidantes produzidos pelo estresse oxidativo metabólico nos eritrócitos. Devido à alta prevalência de deficiência de G6PD na população mundial, principalmente de origem negróide africana, muitos estudos têm sido realizados na tentativa de conhecer melhor a atuação destas enzimas. O objetivo deste estudo foi avaliar a atividade enzimática da 6PGD, nos deficientes de G6PD, para verificar a existência de aumento da atividade desta enzima, correlacionando com um possível aumento do número de reticulócitos ou presença de alterações da série vermelha. A pesquisa em 2.657 indivíduos do sexo masculino resultou em 97 deficientes de G6PD, determinando uma prevalência de 3,65% para a região de Bauru (SP, com atividade enzimática média de G6PD de 1,74 UI.g Hb-1. min-1 a 37ºC, 14,4% da atividade da G6PD normal. A atividade enzimática média da 6PGD foi de 9,5 UI.g Hb-1. min-1 a 37ºC, estando aumentada em 47,4% dos deficientes de G6PD. Os resultados não confirmaram que a hipótese do aumento da atividade enzimática da 6PGD, em deficientes de G6PD, seja decorrente da presença de um número aumentado de reticulócitos na corrente circulatória, faixa etária ou alterações eritrocitométricas que denotem anemia. O mais provável é que a hemólise autolimitada, imposta pelos processos oxidativos, preserve os eritrócitos mais jovens, que possuem atividade enzimática mais elevada, uma vez que naturalmente ocorre diminuição da atividade destas enzimas com o envelhecimento celular.The G6PD and 6PGD enzymes are responsible for the generation of NADPH supply necessary for the detoxification of the oxidant agents produced during the oxidative metabolic stress on erythrocytes. Due to the high prevalence of the deficiency of G6PD on world population, especially on Afro descents, many studies have been done trying

  3. Possible association of 3' UTR +357 A>G, IVS11-nt 93 T>C, c.1311 C>T polymorphism with G6PD deficiency.

    Science.gov (United States)

    Sirdah, Mahmoud M; Shubair, Mohammad E; Al-Kahlout, Mustafa S; Al-Tayeb, Jamal M; Prchal, Josef T; Reading, N Scott

    2017-07-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked inherited enzymopathic disorder affecting more than 500 million people worldwide. It has so far been linked to 217 distinct genetic variants in the exons and exon-intron boundaries of the G6PD gene, giving rise to a wide range of biochemical heterogeneity and clinical manifestations. Reports from different settings suggested the association of intronic and other mutations outside the reading frame of the G6PD gene with reduced enzyme activity and presenting clinical symptoms. The present study aimed to investigate any association of other variations apart of the exonic or exonic intronic boundaries in the development of G6PD deficiency. Sixty-seven unrelated Palestinian children admitted to the pediatric hospital with hemolytic crises due to G6PD deficiency were studied. In our Palestinian cohort of 67 [59 males (M) and 8 females (F)] G6PD-deficient children, previously hospitalized for acute hemolytic anemia due to favism, molecular sequencing of the G6PD gene revealed four cases (3M and 1F) that did not have any of the variants known to cause G6PD deficiency, but the 3' UTR c.*+357A>G (rs1050757) polymorphism in association with IVS 11 (c.1365-13T>C; rs2071429), and c.1311C>T (rs2230037). We now provide an additional evidence form Palestinian G6PD-deficient subjects for a possible role of 3' UTR c.*+357 A>G, c.1365-13T>C, and/or c.1311C>T polymorphism for G6PD deficiency, suggesting that not only a single variation in the exonic or exonic intronic boundaries, but also a haplotype of G6PD should considered as a cause for G6PD deficiency.

  4. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype.

    Science.gov (United States)

    Relling, M V; McDonagh, E M; Chang, T; Caudle, K E; McLeod, H L; Haidar, C E; Klein, T; Luzzatto, L

    2014-08-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia (AHA) induced by a number of drugs. We provide guidance as to which G6PD genotypes are associated with G6PD deficiency in males and females. Rasburicase is contraindicated in G6PD-deficient patients due to the risk of AHA and possibly methemoglobinemia. Unless preemptive genotyping has established a positive diagnosis of G6PD deficiency, quantitative enzyme assay remains the mainstay of screening prior to rasburicase use. The purpose of this article is to help interpret the results of clinical G6PD genotype tests so that they can guide the use of rasburicase. Detailed guidelines on other aspects of the use of rasburicase, including analyses of cost-effectiveness, are beyond the scope of this document. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are published and updated periodically on https://www.pharmgkb.org/page/cpic to reflect new developments in the field.

  5. L-Cysteine in vitro can restore cellular glutathione and inhibits the expression of cell adhesion molecules in G6PD-deficient monocytes.

    Science.gov (United States)

    Parsanathan, Rajesh; Jain, Sushil K

    2018-04-06

    L-Cysteine is a precursor of glutathione (GSH), a potent physiological antioxidant. Excess glucose-6-phosphate dehydrogenase (G6PD) deficiency in African Americans and low levels of L-cysteine diet in Hispanics can contributes to GSH deficiency and oxidative stress. Oxidative stress and monocyte adhesion was considered to be an initial event in the progression of vascular dysfunction and atherosclerosis. However, no previous study has investigated the contribution of GSH/G6PD deficiency to the expression of monocyte adhesion molecules. Using human U937 monocytes, this study examined the effect of GSH/G6PD deficiency and L-cysteine supplementation on monocyte adhesion molecules. G6PD/GSH deficiency induced by either siRNA or inhibitors (6AN/BSO, respectively) significantly (p adhesion molecules (ICAM-1, VCAM-1, SELL, ITGB1 and 2); NADPH oxidase (NOX), reactive oxygen species (ROS) and MCP-1 were upregulated, and decreases in levels of GSH, and nitric oxide were observed. The expression of ICAM-1 and VCAM-1 mRNA levels increased in high glucose, MCP-1 or TNF-α-treated G6PD-deficient compared to G6PD-normal cells. L-Cysteine treatment significantly (p adhesion molecules. Thus, GSH/G6PD deficiency increases susceptibility to monocyte adhesion processes, whereas L-cysteine supplementation can restore cellular GSH/G6PD and attenuates NOX activity and expression of cell adhesion molecules.

  6. Glucose-6-phosphate dehydrogenase plays a pivotal role in nitric oxide-involved defense against oxidative stress under salt stress in red kidney bean roots.

    Science.gov (United States)

    Liu, Yinggao; Wu, Ruru; Wan, Qi; Xie, Gengqiang; Bi, Yurong

    2007-03-01

    The pivotal role of glucose-6-phosphate dehydrogenase (G-6-PDH)-mediated nitric oxide (NO) production in the tolerance to oxidative stress induced by 100 mM NaCl in red kidney bean (Phaseolus vulgaris) roots was investigated. The results show that the G-6-PDH activity was enhanced rapidly in the presence of NaCl and reached a maximum at 100 mM. Western blot analysis indicated that the increase of G-6-PDH activity in the red kidney bean roots under 100 mM NaCl was mainly due to the increased content of the G-6-PDH protein. NO production and nitrate reductase (NR) activity were also induced by 100 mM NaCl. The NO production was reduced by NaN(3) (an NR inhibitor), but not affected by N(omega)-nitro-L-arginine (L-NNA) (an NOS inhibitor). Application of 2.5 mM Na(3)PO(4), an inhibitor of G-6-PDH, blocked the increase of G-6-PDH and NR activity, as well as NO production in red kidney bean roots under 100 mM NaCl. The activities of antioxidant enzymes in red kidney bean roots increased in the presence of 100 mM NaCl or sodium nitroprusside (SNP), an NO donor. The increased activities of all antioxidant enzymes tested at 100 mM NaCl were completely inhibited by 2.5 mM Na(3)PO(4). Based on these results, we conclude that G-6-PDH plays a pivotal role in NR-dependent NO production, and in establishing tolerance of red kidney bean roots to salt stress.

  7. INFLUENCE OF pH, TEMPERATURE AND DISSOLVED OXYGEN CONCENTRATION ON THE PRODUCTION OF GLUCOSE 6-PHOSPHATE DEHYDROGENASE AND INVERTASE BY Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    J. Abrahão-Neto

    1997-03-01

    Full Text Available The effect of pH (from 4.0 to 5.0, temperature (T (from 30 oC to 40 oC and dissolved oxygen concentration (DO (from 0.2 to 6.0 mg O2/L on glucose 6-phosphate dehydrogenase (G6PDH (EC 1.1.1.49 and Invertase (EC 3.2.1.26 formation by S. cerevisiae were studied. The best culture conditions for G6PDH and Invertase formation were: 2.55 L culture medium (yeast extract, 3.0 g/L; 5peptone, 5.0 g/L; glucose, 2.0 g/L; sucrose, 15.0 g/L; Na2HPO4.12 H2O, 2.4 g/L; (NH42SO4, 5.1 g/L and MgSO4. 7H2O, 0.075 g/L; 0.45 L inoculum (0.70 g dry cell/L; pH = 4.5; T = 35 oC and DO = 4.0 mg/L. G6PDH was highly sensitive to pH, T and DO variation. The increase in G6PDH production was about three times when the DO ranged from 0.2 to 4.0 mg O2/L. Moreover, by shifting pH from 5.0 to 4.5 and temperature from 30 oC to 35 oC, G6PDH formation increased by 57% and 70%, respectively. Invertase activity (IA of whole cells decreased at least 50% at extremes values of DO (2.0 and 6.0 mg O2/L and pH (4.0 and 5.0. Furthermore, IA oscillated during the fermentation due to the glucose repression/derepression mechanism

  8. BAG3 elevation inhibits cell proliferation via direct interaction with G6PD in hepatocellular carcinomas.

    Science.gov (United States)

    Kong, De-Hui; Li, Si; Du, Zhen-Xian; Liu, Chuan; Liu, Bao-Qin; Li, Chao; Zong, Zhi-Hong; Wang, Hua-Qin

    2016-01-05

    Bcl-2 associated athanogene 3 (BAG3) contains multiple protein-binding motifs to mediate potential interactions with chaperons and/or other proteins, which is possibly ascribed to the multifaceted functions assigned to BAG3. The current study demonstrated that BAG3 directly interacted with glucose 6 phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway (PPP). BAG3 suppressed the PPP flux, de novo DNA synthesis and cell growth in hepatocellular carcinomas (HCCs). The growth defect of HCCs with forced BAG3 expression can be rescued by enforced G6PD expression. However, BAG3 elevation did not cause a reduction in cellular NADPH concentrations, another main product of G6PD. In addition, supplement of nucleosides alone was sufficient to recover the growth defect mediated by BAG3 elevation. Collectively, the current study established a tumor suppressor-like function of BAG3 via direct interaction with G6PD in HCCs at the cellular level.

  9. Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana - A Cohort Study.

    Directory of Open Access Journals (Sweden)

    Ruth Owusu

    Full Text Available Sulphadoxine-Pyrimethamine (SP is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp.Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women.The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia.There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin drop post SP-IPTp but a larger

  10. Methods for the field evaluation of quantitative G6PD diagnostics: a review.

    Science.gov (United States)

    Ley, Benedikt; Bancone, Germana; von Seidlein, Lorenz; Thriemer, Kamala; Richards, Jack S; Domingo, Gonzalo J; Price, Ric N

    2017-09-11

    Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk of severe haemolysis following the administration of 8-aminoquinoline compounds. Primaquine is the only widely available 8-aminoquinoline for the radical cure of Plasmodium vivax. Tafenoquine is under development with the potential to simplify treatment regimens, but point-of-care (PoC) tests will be needed to provide quantitative measurement of G6PD activity prior to its administration. There is currently a lack of appropriate G6PD PoC tests, but a number of new tests are in development and are likely to enter the market in the coming years. As these are implemented, they will need to be validated in field studies. This article outlines the technical details for the field evaluation of novel quantitative G6PD diagnostics such as sample handling, reference testing and statistical analysis. Field evaluation is based on the comparison of paired samples, including one sample tested by the new assay at point of care and one sample tested by the gold-standard reference method, UV spectrophotometry in an established laboratory. Samples can be collected as capillary or venous blood; the existing literature suggests that potential differences in capillary or venous blood are unlikely to affect results substantially. The collection and storage of samples is critical to ensure preservation of enzyme activity, it is recommended that samples are stored at 4 °C and testing occurs within 4 days of collection. Test results can be visually presented as scatter plot, Bland-Altman plot, and a histogram of the G6PD activity distribution of the study population. Calculating the adjusted male median allows categorizing results according to G6PD activity to calculate standard performance indicators and to perform receiver operating characteristic (ROC) analysis.

  11. Modulation of nuclear T3 binding by T3 in a human hepatocyte cell-line (Chang-liver) - T3 stimulation of cell growth but not of malic enzyme, glucose-6-phosphatdehydrogenase or 6-phosphogluconate-dehydrogenase

    DEFF Research Database (Denmark)

    Matzen, L E; Kristensen, S R; Kvetny, J

    1991-01-01

    The T3 modulation of nuclear T3 binding (NBT3), the T3 effect on cell growth, and the T3 and insulin effects on malic enzyme (ME), glucose-6-phosphat-dehydrogenase (G6PD) and 6-phosphogluconat-dehydrogenase (G6PD) were studied in a human hepatocyte cell-line (Chang-liver). T3 was bound to a high ...

  12. Rapid screening for glucose-6-phosphate dehydrogenase deficiency and haemoglobin polymorphisms in Africa by a simple high-throughput SSOP-ELISA method

    DEFF Research Database (Denmark)

    Enevold, Anders; Vestergaard, Lasse S; Lusingu, John

    2005-01-01

    was available. METHODS: A simple and rapid technique was developed to detect the most prominent single nucleotide polymorphisms (SNPs) in the HbB and G6PD genes. The method is able to detect the different haemoglobin polymorphisms A, S, C and E, as well as G6PD polymorphisms B, A and A- based on PCR......-amplification followed by a hybridization step using sequence-specific oligonucleotide probes (SSOPs) specific for the SNP variants and quantified by ELISA. RESULTS: The SSOP-ELISA method was found to be specific, and compared well to the commonly used PCR-RFLP technique. Identical results were obtained in 98......% (haemoglobin) and 95% (G6PD) of the tested 90 field samples from a high-transmission area in Tanzania, which were used to validate the new technique. CONCLUSION: The simplicity and accuracy of the new methodology makes it suitable for application in settings where resources are limited. It would serve...

  13. Neonatal Hyperbilirubinemia in infants with G6PD c.563C > TVariant

    Directory of Open Access Journals (Sweden)

    Moiz Bushra

    2012-08-01

    Full Text Available Abstract Background There is a strong correlation between glucose-6-phosphate dehydrogenase (G6PD deficiency and neonatal hyperbilirubinemia with a rare but potential threat of devastating acute bilirubin encephalopathy. G6PD deficiency was observed in 4–14% of hospitalized icteric neonates in Pakistan. G6PD c.563C > T is the most frequently reported variant in this population. The present study was aimed at evaluating the time to onset of hyperbilirubinemia and the postnatal bilirubin trajectory in infants having G6PD c.563C > T. Methods This was a case–control study conducted at The Aga Khan University, Pakistan during the year 2008. We studied 216 icteric male neonates who were re-admitted for phototherapy during the study period. No selection was exercised. Medical records showed that 32 were G6PD deficient while 184 were G6PD normal. Each infant was studied for birth weight, gestational age, age at the time of presentation, presence of cephalhematoma, sepsis and neurological signs, peak bilirubin level, age at peak bilirubin level, days of hospitalization, whether phototherapy or exchange blood transfusion was initiated, and the outcome. During hospital stay, each baby was tested for complete blood count, reticulocyte count, ABO and Rh blood type, direct antiglobulin test and quantitative G6PD estimation [by kinetic determination of G6PDH]. G6PDgenotype was analyzed in 32 deficient infants through PCR-RFLP analysis and gene sequencing. Results G6PD variants c.563C > T and c.131 C > G were observed in 21 (65% and three (9% of the 32 G6PD deficient infants, respectively. DNA of eight (25% newborns remained uncharacterized. In contrast to G6PD normal neonates, infants with c.563C > T variant had significantly lower enzyme activity (mean ± 1SD; 0.3 ± 0.2 U/gHb vs. 14.0 ± 4.5 U/gHb, p p = 0.008 which peaked earlier after birth (mean ± 1SD 2.9 ± 1.6 vs. 4.3 ± 2.3 days, p = 0.007. No statistically significant

  14. Prevalence of G6PD deficiency in selected populations from two previously high malaria endemic areas of Sri Lanka.

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    Sharmini Gunawardena

    Full Text Available Glucose-6-Phosphate Dehydrogenase (G6PD enzyme deficiency is known to offer protection against malaria and an increased selection of mutant genes in malaria endemic regions is expected. However, anti-malarial drugs such as primaquine can cause haemolytic anaemia in persons with G6PD deficiency. We studied the extent of G6PD deficiency in selected persons attending Teaching Hospitals of Anuradhapura and Kurunegala, two previously high malaria endemic districts in Sri Lanka. A total of 2059 filter-paper blood spots collected between November 2013 and June 2014 were analysed for phenotypic G6PD deficiency using the modified WST-8/1-methoxy PMS method. Each assay was conducted with a set of controls and the colour development assessed visually as well as with a microplate reader at OD450-630nm. Overall, 142/1018 (13.95% and 83/1041 (7.97% were G6PD deficient in Anuradhapura and Kurunegala districts respectively. The G6PD prevalence was significantly greater in Anuradhapura when compared to Kurunegala (P0.05. Severe deficiency (<10% normal was seen among 28/1018 (2.75% in Anuradhapura (7 males; 21 females and 17/1041 (1.63% in Kurunegala (7 males; 10 females. Enzyme activity between 10-30% was observed among 114/1018 (11.20%; 28 males; 86 females in Anuradhapura while it was 66/1041 (6.34%; 18 males; 48 females in Kurunegala. Screening and educational programmes for G6PD deficiency are warranted in these high risk areas irrespective of gender for the prevention of disease states related to this condition.

  15. Glucose-6-phosphate mediates activation of the carbohydrate responsive binding protein (ChREBP)

    International Nuclear Information System (INIS)

    Li, Ming V.; Chen, Weiqin; Harmancey, Romain N.; Nuotio-Antar, Alli M.; Imamura, Minako; Saha, Pradip; Taegtmeyer, Heinrich; Chan, Lawrence

    2010-01-01

    Carbohydrate response element binding protein (ChREBP) is a Mondo family transcription factor that activates a number of glycolytic and lipogenic genes in response to glucose stimulation. We have previously reported that high glucose can activate the transcriptional activity of ChREBP independent of the protein phosphatase 2A (PP2A)-mediated increase in nuclear entry and DNA binding. Here, we found that formation of glucose-6-phosphate (G-6-P) is essential for glucose activation of ChREBP. The glucose response of GAL4-ChREBP is attenuated by D-mannoheptulose, a potent hexokinase inhibitor, as well as over-expression of glucose-6-phosphatase (G6Pase); kinetics of activation of GAL4-ChREBP can be modified by exogenously expressed GCK. Further metabolism of G-6-P through the two major glucose metabolic pathways, glycolysis and pentose-phosphate pathway, is not required for activation of ChREBP; over-expression of glucose-6-phosphate dehydrogenase (G6PD) diminishes, whereas RNAi knockdown of the enzyme enhances, the glucose response of GAL4-ChREBP, respectively. Moreover, the glucose analogue 2-deoxyglucose (2-DG), which is phosphorylated by hexokinase, but not further metabolized, effectively upregulates the transcription activity of ChREBP. In addition, over-expression of phosphofructokinase (PFK) 1 and 2, synergistically diminishes the glucose response of GAL4-ChREBP. These multiple lines of evidence support the conclusion that G-6-P mediates the activation of ChREBP.

  16. Biochemical characteristics of glucose-6-phosphate dehydrogenase variants among the Malays of Singapore with report of a new non-deficient (GdSingapore) and three deficient variants.

    Science.gov (United States)

    Saha, N; Hong, S H; Wong, H A; Jeyaseelan, K; Tay, J S

    1991-12-01

    Biochemical characteristics of one non-deficient fast G6PD variant (GdSingapore) and six different deficient variants (three new, two Mahidol, one each of Indonesian and Mediterranean) were studied among the Malays of Singapore. The GdSingapore variant had normal enzyme activity (82%) and fast electrophoretic mobilities (140% in TEB buffer, 160% in phosphate and 140% in Tris-HCl buffer systems respectively). This variant is further characterized by normal Km for G6P; utilization of analogues (Gal6P, 2dG6P; dAmNADP), heat stability and pH optimum. The other six deficient G6PD variants had normal electrophoretic mobility in TEB buffer with enzyme activities ranging from 1 to 12% of GdB+. The biochemical characteristics identity them to be 2 Mahidol, 1 Indonesian and 1 Mediterranean variants and three new deficient variants.

  17. Validation of the quantitative point-of-care CareStart biosensor for assessment of G6PD activity in venous blood.

    Directory of Open Access Journals (Sweden)

    Germana Bancone

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common enzymopathy in the human population affecting an estimated 8% of the world population, especially those living in areas of past and present malaria endemicity. Decreased G6PD enzymatic activity is associated with drug-induced hemolysis and increased risk of severe neonatal hyperbilirubinemia leading to brain damage. The G6PD gene is on the X chromosome therefore mutations cause enzymatic deficiency in hemizygote males and homozygote females while the majority of heterozygous females have an intermediate activity (between 30-80% of normal with a large distribution into the range of deficiency and normality. Current G6PD qualitative tests are unable to diagnose G6PD intermediate activities which could hinder wide use of 8-aminoquinolines for Plasmodium vivax elimination. The aim of the study was to assess the diagnostic performances of the new Carestart G6PD quantitative biosensor.A total of 150 samples of venous blood with G6PD deficient, intermediate and normal phenotypes were collected among healthy volunteers living along the north-western Thailand-Myanmar border. Samples were analyzed by complete blood count, by gold standard spectrophotometric assay using Trinity kits and by the latest model of Carestart G6PD biosensor which analyzes both G6PD and hemoglobin.Bland-Altman comparison of the CareStart normalized G6PD values to that of the gold standard assay showed a strong bias in values resulting in poor area under-the-curve values for both 30% and 80% thresholds. Performing a receiver operator curve identified threshold values for the CareStart product equivalent to the 30% and 80% gold standard values with good sensitivity and specificity values, 100% and 92% (for 30% G6PD activity and 92% and 94% (for 80% activity respectively.The Carestart G6PD biosensor represents a significant improvement for quantitative diagnosis of G6PD deficiency over previous versions. Further

  18. Validation of the quantitative point-of-care CareStart biosensor for assessment of G6PD activity in venous blood.

    Science.gov (United States)

    Bancone, Germana; Gornsawun, Gornpan; Chu, Cindy S; Porn, Pen; Pal, Sampa; Bansil, Pooja; Domingo, Gonzalo J; Nosten, Francois

    2018-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in the human population affecting an estimated 8% of the world population, especially those living in areas of past and present malaria endemicity. Decreased G6PD enzymatic activity is associated with drug-induced hemolysis and increased risk of severe neonatal hyperbilirubinemia leading to brain damage. The G6PD gene is on the X chromosome therefore mutations cause enzymatic deficiency in hemizygote males and homozygote females while the majority of heterozygous females have an intermediate activity (between 30-80% of normal) with a large distribution into the range of deficiency and normality. Current G6PD qualitative tests are unable to diagnose G6PD intermediate activities which could hinder wide use of 8-aminoquinolines for Plasmodium vivax elimination. The aim of the study was to assess the diagnostic performances of the new Carestart G6PD quantitative biosensor. A total of 150 samples of venous blood with G6PD deficient, intermediate and normal phenotypes were collected among healthy volunteers living along the north-western Thailand-Myanmar border. Samples were analyzed by complete blood count, by gold standard spectrophotometric assay using Trinity kits and by the latest model of Carestart G6PD biosensor which analyzes both G6PD and hemoglobin. Bland-Altman comparison of the CareStart normalized G6PD values to that of the gold standard assay showed a strong bias in values resulting in poor area under-the-curve values for both 30% and 80% thresholds. Performing a receiver operator curve identified threshold values for the CareStart product equivalent to the 30% and 80% gold standard values with good sensitivity and specificity values, 100% and 92% (for 30% G6PD activity) and 92% and 94% (for 80% activity) respectively. The Carestart G6PD biosensor represents a significant improvement for quantitative diagnosis of G6PD deficiency over previous versions. Further improvements

  19. Single Low Dose Primaquine (0.25 mg/kg Does Not Cause Clinically Significant Haemolysis in G6PD Deficient Subjects.

    Directory of Open Access Journals (Sweden)

    Germana Bancone

    Full Text Available Primaquine is the only drug consistently effective against mature gametocytes of Plasmodium falciparum. The transmission blocking dose of primaquine previously recommended was 0.75 mg/kg (adult dose 45 mg but its deployment was limited because of concerns over haemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD deficiency. G6PD deficiency is an inherited X-linked enzymatic defect that affects an estimated 400 million people around the world with high frequencies (15-20% in populations living in malarious areas. To reduce transmission in low transmission settings and facilitate elimination of P. falciparum, the World Health Organization now recommends adding a single dose of 0.25 mg/kg (adult dose 15 mg to Artemisinin-based Combination Therapies (ACTs without G6PD testing. Direct evidence of the safety of this low dose is lacking. Adverse events and haemoglobin variations after this treatment were assessed in both G6PD normal and deficient subjects in the context of targeted malaria elimination in a malaria endemic area on the North-Western Myanmar-Thailand border where prevalence of G6PD deficiency (Mahidol variant approximates 15%.The tolerability and safety of primaquine (single dose 0.25 mg base/kg combined with dihydroartemisinin-piperaquine (DHA-PPQ given three times at monthly intervals was assessed in 819 subjects. Haemoglobin concentrations were estimated over the six months preceding the ACT + primaquine rounds of mass drug administration. G6PD deficiency was assessed with a phenotypic test and genotyping was performed in male subjects with deficient phenotypes and in all females. Fractional haemoglobin changes in relation to G6PD phenotype and genotype and primaquine round were assessed using linear mixed-effects models. No adverse events related to primaquine were reported during the trial. Mean fractional haemoglobin changes after each primaquine treatment in G6PD deficient subjects (-5.0%, -4.2% and -4

  20. Molecular Characterization of Glucose-6-Phosphate ...

    African Journals Online (AJOL)

    HP

    The total prevalence of G6PD deficiency among the subjects was 4.59 % (4/87), all of whom were. Malay males. One of the deficient subjects had G6PD Viangchan, while the other three were G6PD. Mahidol ..... J Paediatr Child Health .1991 ...

  1. G6PD: The Test

    Science.gov (United States)

    ... a G6PD deficiency if a male inherits the single X chromosome with an altered gene. Since women have two X sex chromosomes, they inherit two ... deficiency. In addition, a mother may pass the single mutated gene to any male children. Rarely do women have two mutated gene copies ( homozygous ), which could ...

  2. Effects of whole body x-ray irradiation on induction by phenobarbital of rat liver glucose-6-phosphate dehydrogenase and glutathione reductase

    Energy Technology Data Exchange (ETDEWEB)

    Bitny-Szlachto, S.; Szyszko, A. (Wojskowy Inst. Higieny i Epidemiologii, Warsaw (Poland))

    1979-01-01

    In rats treated with phenobarbital (3x100 mg/kg, i.p.), liver G-6-P dehydrogenase activity increased by 70% in the cytosol and in the 9.000xg supernatant, and only by 20% in microsomes. Moreover, the phenobarbital treatment increased rat liver GSSG reductase activity by 30%. On the other hand, activity of the liver microsomal G-6-P dehydrogenase was found to increase by some 20% in whole body irradiated, both control and phenobarbital treated rats. In rats irradiated with 600 R prior to the first dose of the inducer there was not noted any increase in G-6-P dehydrogenase of the 9.000xg supernatant, and increase in the cytosol activity dropped to 38%. Thus, induction of the soluble liver G-6-P dehydrogenase by phenobarbital has turned out to be radiosensitive, whereas phenobarbital induction of GSSG reductase was unaffected by irradiation.

  3. Point-of-care G6PD diagnostics for Plasmodium vivax malaria is a clinical and public health urgency.

    Science.gov (United States)

    Baird, J Kevin

    2015-12-14

    Malaria caused by Plasmodium vivax threatens over 2 billion people globally and sickens tens of millions annually. Recent clinical evidence discredits the long-held notion of this infection as intrinsically benign revealing an often threatening course associated with mortality. Most acute attacks by this species derive from latent forms in the human liver called hypnozoites. Radical cure for P. vivax malaria includes therapy aimed both at the acute attack (blood schizontocidal) and against future attacks (hypnozoitocidal). The only hypnozoitocide available is primaquine, a drug causing life-threatening acute hemolytic anemia in patients with the inherited blood disorder glucose-6-phosphate dehydrogenase (G6PD) deficiency. This disorder affects 400 million people worldwide, at an average prevalence of 8 % in malaria-endemic nations. In the absence of certain knowledge regarding the G6PD status of patients infected by P. vivax, providers must choose between the risk of harm caused by primaquine and that caused by the parasite by withholding therapy. Resolving this dilemma requires the availability of point-of-care G6PD diagnostics practical for use in the impoverished rural tropics where the vast majority of malaria patients seek care.

  4. Prevalence and molecular characterization of G6PD deficiency in two Plasmodium vivax endemic areas in Venezuela: predominance of the African A-(202A/376G) variant.

    Science.gov (United States)

    Vizzi, Esmeralda; Bastidas, Gilberto; Hidalgo, Mariana; Colman, Laura; Pérez, Hilda A

    2016-01-11

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency causes acute haemolytic anaemia triggered by oxidative drugs such as primaquine (PQ), used for Plasmodium vivax malaria radical cure. However, in many endemic areas of vivax malaria, patients are treated with PQ without any evaluation of their G6PD status. G6PD deficiency and its genetic heterogeneity were evaluated in northeastern and southeastern areas from Venezuela, Cajigal (Sucre state) and Sifontes (Bolívar state) municipalities, respectively. Blood samples from 664 randomly recruited unrelated individuals were screened for G6PD activity by a quantitative method. Mutation analysis for exons 4-8 of G6PD gen was performed on DNA isolated from G6PD-deficient (G6PDd) subjects through PCR-RFLP and direct DNA sequencing. Quantitative biochemical characterization revealed that overall 24 (3.6%) subjects were G6PDd (average G6PD enzyme activity 4.5 ± 1.2 U/g Hb, moderately deficient, class III), while DNA analysis showed one or two mutated alleles in 19 of them (79.2%). The G6PD A-(202A/376G) variant was the only detected in 17 (70.8%) individuals, 13 of them hemizygous males and four heterozygous females. Two males carried only the 376A → G mutation. No other mutation was found in the analysed exons. The G6PDd prevalence was as low as that one shown by nearby countries. This study contributes to the knowledge of the genetic background of Venezuelan population, especially of those living in malaria-endemic areas. Despite the high degree of genetic mixing described for Venezuelan population, a net predominance of the mild African G6PD A-(202A/376G) variant was observed among G6PDd subjects, suggesting a significant flow of G6PD genes from Africa to Americas, almost certainly introduced through African and/or Spanish immigrants during and after the colonization. The data suggest that 1:27 individuals of the studied population could be G6PDd and therefore at risk of haemolysis under precipitating factors

  5. Molecular Characterization of Glucose-6-Phosphate ...

    African Journals Online (AJOL)

    G6PD) deficiency among staff and students of a university community in Malaysia as well as to identify molecular genetics by determination of G6PD mutations. Methods: Cross-sectional and experimental studies were carried out on the staff ...

  6. Diagnostic performances of the fluorescent spot test for G6PD deficiency in newborns along the Thailand-Myanmar border: A cohort study.

    Science.gov (United States)

    Thielemans, Laurence; Gornsawun, Gornpan; Hanboonkunupakarn, Borimas; Paw, Moo Kho; Porn, Pen; Moo, Paw Khu; Van Overmeire, Bart; Proux, Stephane; Nosten, François; McGready, Rose; Carrara, Verena I; Bancone, Germana

    2018-01-01

    Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited enzymatic disorder associated with severe neonatal hyperbilirubinemia and acute haemolysis after exposure to certain drugs or infections. The disorder can be diagnosed phenotypically with a fluorescent spot test (FST), which is a simple test that requires training and basic laboratory equipment. This study aimed to assess the diagnostic performances of the FST used on umbilical cord blood by locally-trained staff and to compare test results of the neonates at birth with the results after one month of age. Methods : We conducted a cohort study on newborns at the Shoklo Malaria Research Unit, along the Thai-Myanmar border between January 2015 and May 2016. The FST was performed at birth on the umbilical cord blood by locally-trained staff and quality controlled by specialised technicians at the central laboratory. The FST was repeated after one month of age. Genotyping for common local G6PD mutations was carried out for all discrepant results. Results: FST was performed on 1521 umbilical cord blood samples. Quality control and genotyping revealed 10 misdiagnoses. After quality control, 10.7% of the males (84/786) and 1.2% of the females (9/735) were phenotypically G6PD deficient at birth. The FST repeated at one month of age or later diagnosed 8 additional G6PD deficient infants who were phenotypically normal at birth. Conclusions : This study shows the short-comings of the G6PD FST in neonatal routine screening and highlights the importance of training and quality control. A more conservative interpretation of the FST in male newborns could increase the diagnostic performances. Quantitative point-of-care tests might show higher sensitivity and specificity for diagnosis of G6PD deficiency on umbilical cord blood and should be investigated.

  7. Diagnostic performances of the fluorescent spot test for G6PD deficiency in newborns along the Thailand-Myanmar border: A cohort study [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Laurence Thielemans

    2018-01-01

    Full Text Available Background: Glucose-6-phosphate dehydrogenase (G6PD deficiency is an inherited enzymatic disorder associated with severe neonatal hyperbilirubinemia and acute haemolysis after exposure to certain drugs or infections. The disorder can be diagnosed phenotypically with a fluorescent spot test (FST, which is a simple test that requires training and basic laboratory equipment. This study aimed to assess the diagnostic performances of the FST used on umbilical cord blood by locally-trained staff and to compare test results of the neonates at birth with the results after one month of age. Methods: We conducted a cohort study on newborns at the Shoklo Malaria Research Unit, along the Thai-Myanmar border between January 2015 and May 2016. The FST was performed at birth on the umbilical cord blood by locally-trained staff and quality controlled by specialised technicians at the central laboratory. The FST was repeated after one month of age. Genotyping for common local G6PD mutations was carried out for all discrepant results. Results: FST was performed on 1521 umbilical cord blood samples. Quality control and genotyping revealed 10 misdiagnoses. After quality control, 10.7% of the males (84/786 and 1.2% of the females (9/735 were phenotypically G6PD deficient at birth. The FST repeated at one month of age or later diagnosed 8 additional G6PD deficient infants who were phenotypically normal at birth. Conclusions: This study shows the short-comings of the G6PD FST in neonatal routine screening and highlights the importance of training and quality control. A more conservative interpretation of the FST in male newborns could increase the diagnostic performances. Quantitative point-of-care tests might show higher sensitivity and specificity for diagnosis of G6PD deficiency on umbilical cord blood and should be investigated.

  8. TLQP-21 protects human umbilical vein endothelial cells against high-glucose-induced apoptosis by increasing G6PD expression.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    Full Text Available Hyperglycemia causes oxidative stress that could damage vascular endothelial cells, leading to cardiovascular complications. The Vgf gene was identified as a nerve growth factor-responsive gene, and its protein product, VGF, is characterized by the presence of partially cleaved products. One of the VGF-derived peptides is TLQP-21, which is composed of 21 amino acids (residues 556-576. Past studies have reported that TLQP-21 could stimulate insulin secretion in pancreatic cells and protect these cells from apoptosis, which suggests that TLQP-21 has a potential function in diabetes therapy. Here, we explore the protective role of TLQP-21 against the high glucose-mediated injury of vascular endothelial cells. Using human umbilical vascular endothelial cells (HUVECs, we demonstrated that TLQP-21 (10 or 50 nM dose-dependently prevented apoptosis under high-glucose (30 mmol/L conditions (the normal glucose concentration is 5.6 mmol/L. TLQP-21 enhanced the expression of NAPDH, resulting in upregulation of glutathione (GSH and a reduction in the levels of reactive oxygen species (ROS. TLQP-21 also upregulated the expression of glucose-6-phosphate dehydrogenase (G6PD, which is known as the main source of NADPH. Knockdown of G6PD almost completely blocked the increase of NADPH induced by TLQP-21, indicating that TLQP-21 functions mainly through G6PD to promote NADPH generation. In conclusion, TLQP-21 could increase G6PD expression, which in turn may increase the synthesis of NADPH and GSH, thereby partially restoring the redox status of vascular endothelial cells under high glucose injury. We propose that TLQP-21 is a promising drug for diabetes therapy.

  9. A role for glucose-6-phosphate dehydrogenase

    African Journals Online (AJOL)

    STORAGESEVER

    2009-01-19

    Jan 19, 2009 ... mice caused a decrease in the nucleated cell counts in the peripheral blood, the .... Society of hematology, annual meeting abstracts; abstract 1049: p. 106. Salman 141. Leopold J ... Trans Res. Soc. London B. Biol. Sci. 354:.

  10. Use of a simplified spectrophotometric method for quantitative determination of glucose-6-phosphate dehydrogenase activity in normal children from two day-care centers of the city of São Paulo

    Directory of Open Access Journals (Sweden)

    Roberto Muller

    2003-06-01

    Full Text Available Objective: To evaluate the applicability of a simplified method forquantitative determination of glucose-6-phosphate dehydrogenaseactivity in normal children; to determine the mean, standarddeviation and threshold value under which the enzyme activity isconsidered deficient. Methods: Blood samples were collected from201 children from two day-care centers in the city of São Paulo.The subjects were considered normal based on physicalexamination and laboratory tests. The enzyme activity wasdetermined in red blood cells of normal children using the “TestCombination G-6-PDH®” kit. The following statistical analyses werecarried out: the results were submitted to Student’s t test,Kolmogorov-Smirnov test, lower confidence interval (one-tailedtest and Spearman’s correlation coefficient. Results: The meanhemoglobin value for girls was slightly higher than the mean valuefor boys, but this difference was not statistically significant. Therewas no statistical difference in mean enzyme activities for Caucasianand non-Caucasian children. There was no significant correlation amongenzyme activity levels, red blood cells, hemoglobin levels,hematocrit, reticulocytes, white blood cells and age of patients.The mean enzyme activity for boys was 4.448 U/g Hb, standarddeviation = 1.380 U/g Hb. For girls, the mean enzyme activity was4.531 U/g Hb, standard deviation = 1.386 U/g Hb, and the differencewas not statistically significant. Therefore, the two populationgroups were considered as one single population, presenting amean enzyme activity of 4.490 U/g Hb, standard deviation = 1.380 U/g Hb.Since the distribution curve of enzyme activity values was normal,a lower confidence interval was determined (one-tailed test, witha cutoff point of 2.227 U/g Hb. Conclusion: The method used bySolem proved to be simple, fast, very accurate and useful to detectglucose-6-phosphate dehydrogenase activity and to identifychildren with enzyme deficiency.

  11. Is GERD a Factor in Osteonecrosis of the Jaw? Evidence of Pathology Linked to G6PD Deficiency and Sulfomucins

    Directory of Open Access Journals (Sweden)

    Stephanie Seneff

    2016-01-01

    Full Text Available Osteonecrosis of the jaw (ONJ, a rare side effect of bisphosphonate therapy, is a debilitating disorder with a poorly understood etiology. FDA’s Adverse Event Reporting System (FAERS provides the opportunity to investigate this disease. Our goals were to analyze FAERS data to discover possible relationships between ONJ and specific conditions and drugs and then to consult the scientific literature to deduce biological explanations. Our methodology revealed a very strong association between gastroesophageal reflux and bisphosphonate-induced ONJ, suggesting acidosis as a key factor. Overgrowth of acidophilic species, particularly Streptococcus mutans, in the oral microbiome in the context of insufficient acid buffering due to impaired salivary glands maintains the low pH that sustains damage to the mucosa. Significant associations between ONJ and adrenal insufficiency, vitamin C deficiency, and Sjögren’s syndrome were found. Glucose 6 phosphate dehydrogenase (G6PD deficiency can explain much of the pathology. An inability to maintain vitamin C and other antioxidants in the reduced form leads to vascular oxidative damage and impaired adrenal function. Thus, pathogen-induced acidosis, hypoxia, and insufficient antioxidant defenses together induce ONJ. G6PD deficiency and adrenal insufficiency are underlying factors. Impaired supply of adrenal-derived sulfated sterols such as DHEA sulfate may drive the disease process.

  12. [Neonatal screening of hemoglobinopathies and G6PD deficiency in Catalonia (Spain). Molecular study of sickle cell disease associated with alpha thalassemia and G6PD deficiency].

    Science.gov (United States)

    Mañú Pereira, María Del Mar; Cabot, Anna; Martínez González, Ana; Sitjà Navarro, Eulalia; Cararach, Vicent; Sabrià, Josep; Boixaderas, Jordi; Teixidor, Roser; Bosch, Albert; López Vílchez, M Angeles; Martín Ibáñez, Itziar; Carrión, Teresa; Plaja, Pere; Sánchez, Mario; Vives Corrons, José Luis

    2007-06-30

    The prevalence of hemoglobinopathies and glucose-6-phosphate dehidrogenase (G6PD) deficiency in the Catalan neonatal population is increasing due to immigration. Coinheritance of more than a single RBC genetic defect is becoming more frequent and diagnostic pitfalls are also increasing. We intended to demonstrate the need to perform an early diagnosis of sickle cell disease (SCD) by means of neonatal screening, to establish the prevalence of SCD associated with alpha thalassemia and G6PD deficiency and to identify genotypes associated with sickle cell disease and G6PD deficiency. 4,020 blood samples from newborns were screened. For the screening of hemoglobinopathies the high performance liquid chromatography method was used and for G6PD deficiency the fluorescent spot test was employed. We studied the association between betaS gene and alpha thalassaemia del-3.7 Kb. SCD and G6PD deficiency genotypes were established. Prevalence of SCD in population at risk was 1/475 newborns. Prevalence of G6PD deficiency in population at risk was 1/43, and in autochthonous population was 1/527 newborns. In all the cases, sickle hemoglobin was confirmed by ARMS (amplification refractory mutation system). Association between betaS gene and alpha thalassaemia del-3.7 Kb was found in 32.2% of the samples, and an association between betaS gene and G6PD deficiency was observed in 7% of the samples. This study confirms the high prevalence of SCD and G6PD deficiency in population at risk as well as their genetic and clinical heterogeneity. The study of genotype/phenotype relationships allows a better knowledge of molecular mechanism and is useful to establish suitable criteria of diagnosis.

  13. G6PD deficiency in Latin America: systematic review on prevalence and variants

    Science.gov (United States)

    Monteiro, Wuelton M; Val, Fernando FA; Siqueira, André M; Franca, Gabriel P; Sampaio, Vanderson S; Melo, Gisely C; Almeida, Anne CG; Brito, Marcelo AM; Peixoto, Henry M; Fuller, Douglas; Bassat, Quique; Romero, Gustavo AS; Maria Regina F, Oliveira; Marcus Vinícius G, Lacerda

    2014-01-01

    Plasmodium vivax radical cure requires the use of primaquine (PQ), a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA) and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curaçao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10%) of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available. PMID:25141282

  14. G6PD deficiency in Latin America: systematic review on prevalence and variants

    Directory of Open Access Journals (Sweden)

    Wuelton M Monteiro

    2014-08-01

    Full Text Available Plasmodium vivax radical cure requires the use of primaquine (PQ, a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curaçao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10% of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available.

  15. G6PD deficiency in Latin America: systematic review on prevalence and variants.

    Science.gov (United States)

    Monteiro, Wuelton M; Val, Fernando F A; Siqueira, André M; Franca, Gabriel P; Sampaio, Vanderson S; Melo, Gisely C; Almeida, Anne C G; Brito, Marcelo A M; Peixoto, Henry M; Fuller, Douglas; Bassat, Quique; Romero, Gustavo A S; Maria Regina F, Oliveira; Marcus Vinícius G, Lacerda

    2014-08-01

    Plasmodium vivax radical cure requires the use of primaquine (PQ), a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA) and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curaçao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10%) of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available.

  16. Using G6PD tests to enable the safe treatment of Plasmodium vivax infections with primaquine on the Thailand-Myanmar border: A cost-effectiveness analysis.

    Directory of Open Access Journals (Sweden)

    Angela Devine

    2017-05-01

    Full Text Available Primaquine is the only licensed antimalarial for the radical cure of Plasmodium vivax infections. Many countries, however, do not administer primaquine due to fear of hemolysis in those with glucose-6-phosphate dehydrogenase (G6PD deficiency. In other settings, primaquine is given without G6PD testing, putting patients at risk of hemolysis. New rapid diagnostic tests (RDTs offer the opportunity to screen for G6PD deficiency prior to treatment with primaquine. Here we assessed the cost-effectiveness of using G6PD RDTs on the Thailand-Myanmar border and provide the model as an online tool for use in other settings.Decision tree models for the management of P. vivax malaria evaluated the costs and disability-adjusted life-years (DALYs associated with recurrences and primaquine-induced hemolysis from a health care provider perspective. Screening with G6PD RDTs before primaquine use was compared to (1 giving chloroquine alone and (2 giving primaquine without screening. Data were taken from a recent study on the impact of primaquine on P. vivax recurrences and a literature review. Compared to the use of chloroquine alone, the screening strategy had similar costs while averting 0.026 and 0.024 DALYs per primary infection in males and females respectively. Compared to primaquine administered without screening, the screening strategy provided modest cost savings while averting 0.011 and 0.004 DALYs in males and females respectively. The probabilistic sensitivity analyses resulted in a greater than 75% certainty that the screening strategy was cost-effective at a willingness to pay threshold of US$500, which is well below the common benchmark of per capita gross domestic product for Myanmar.In this setting G6PD RDTs could avert DALYs by reducing recurrences and reducing hemolytic risk in G6PD deficient patients at low costs or cost savings. The model results are limited by the paucity of data available in the literature for some parameter values

  17. Frequency of G6PD Mediterranean in individuals with and without malaria in Southern Pakistan.

    Science.gov (United States)

    Moiz, Bushra; Arshad, Haroon Muhammad; Raheem, Ahmed; Hayat, Hasan; Karim Ghanchi, Najia; Beg, M Asim

    2017-10-24

    Pakistan has an estimated annual burden of 1.5 million malaria cases. The current situation calls for an effective malaria control and eradication programme in this country. Currently, primaquine is an attractive option for eliminating reservoirs of Plasmodium vivax hypnozoites and killing gametocytes of Plasmodium falciparum. However, this drug causes haemolysis in individuals who are glucose-6-phosphate (G6PD) deficient. It is important to map G6PD deficiency and malaria distribution in Pakistan to design an effective malaria eradication regimen. Frequency of G6PD deficiency (G6PDd) in malaria patients has not been reported from Pakistan in any meaningful way. The purpose of this study was to evaluate the frequency of G6PD c.563C>T (G6PD Mediterranean) in male individuals with and without falciparum malaria. Two hundred and ten archived DNA samples from males (110 from falciparum malaria patients and 100 from healthy individuals) were utilized in this study. Healthy blood donors were selected based on stringent pre-defined criteria. Patients were confirmed for malaria parasites on microscopy and or immune chromatographic assay detecting P. falciparum histidine-rich protein 2. Parasitaemia was also computed. DNA samples were tested for G6PD c.563C>T mutation through PCR-RFLP according to the previously defined protocol and its allelic frequency was computed. G6PD c.563C>T was observed in four of 110 patients with falciparum malaria and in two of 100 healthy donors. Mean (± SD) haemoglobin, median (IQR) platelet and median (IQR) parasite count in G6PD-deficient malaria-patients were 8.9 ± 0.9 g/dL, 124 × 109/L (IQR 32, 171) and 57,920/μL of blood (IQR 12,920, 540,000) respectively. Cumulative allelic frequency for G6PD 563c.C>T was 0.0285 detected in 6 of 210 X-chromosomes in Southern Pakistan. Frequency for this G6PD allele was 0.0364 in malaria-patients and 0.0200 in healthy individuals. Large studies including females are needed to elucidate the true

  18. Effects of iron chloride/zeolıte on G6PD of rainbow trout (Oncorhynchus mykiss)'s liver tissue

    Science.gov (United States)

    Alak, Gonca; Uçar, Arzu; Parlak, Veysel; Kocaman, Esat Mahmut; Atamanalp, Muhammed

    2016-04-01

    Aquatic ecosystems have been negatively affected by the contamination of ground and surface waters as a result of various activities. Due to the ferrous chloride (FeCl2), which is used as the reducing agent for the organic synthesis reactions in the contamination of water column and sediment, iron salts may be very toxic for some aquatic organisms. In order to minimize these effects, natural products such as zeolite have been widely used in recently years. For this reason, rainbow trout were exposed to FeCl2 and/or zeolite ((FeCl2 (0.002 mg/l)(A), FeCl2+zeolite (0.002 mg/l+1 gr/l) (B), zeolite (1 gr/l) (C) and control (without FeCl2 and/or zeolite (D)). for 28 days and their oxidative stress responses were investigated. At the end of the treatment period, Glucose-6- phosphate dehydrogenase (G6PD) activity was determined in the samples taken from livers. G6PD values for liver tissues were found statistically important in the control and treatment groups (p<0.01).

  19. Quantitative comparison between the gel-film and polyvinyl alcohol methods for dehydrogenase histochemistry reveals different intercellular distribution patterns of glucose-6-phosphate and lactate dehydrogenases in mouse liver

    NARCIS (Netherlands)

    Griffini, P.; Vigorelli, E.; Bertone, V.; Freitas, I.; van Noorden, C. J.

    1994-01-01

    The precise histochemical localization and quantification of the activity of soluble dehydrogenases in unfixed cryostat sections requires the use of tissue protectants. In this study, two protectants, polyvinyl alcohol (PVA) and agarose gel, were compared for assaying the activity of lactate

  20. Cell-derived microparticles after exercise in individuals with G6PD Viangchan.

    Science.gov (United States)

    Chanda, Makamas; Nantakomol, Duangdao; Suksom, Daroonwan; Palasuwan, Attakorn

    2015-07-16

    Glucose-6-phospate dehydrogenase (G6PD) deficient cells are sensitive to oxidative damage leading to the formation of microparticles (MPs). Therefore, we examined the concentration of MPs and changes in the antioxidant balance after an acute strenuous exercise (SEx) and moderate-intensity exercise (MEx). Eighteen healthy females (18-24 years) with G6PD normal and eighteen age-matched females with G6PD Viangchan (871G>A) were tested by running on a treadmill at their maximal oxygen uptake for SEx and at 75% of their maximal heart rate for MEx. It was found that SEx triggered the release of total microparticles (TTMPs) above baseline levels and remained significantly higher 45 minutes after the exercise in G6PD normal individuals. However, SEx-induced increase in TTMPs was significantly higher in G6PD Viangchan as compared to G6PD normal. In contrast, MEx did not to alter the release of TTMPs in both G6PD normal and Viangchan. Moreover, TTMPs concentrations were inversely correlated with G6PD activity (r =-0.82, P stress compared with G6PD normal.

  1. Central Nervous System Symptoms Due to Transient Methemoglobinemia in a Child With G6PD Deficiency.

    Science.gov (United States)

    Sharma, Shreya; Srinivasaraghavan, Rangan; Krishnamurthy, Sriram

    2017-01-01

    The authors herein report a 5-year-old child who presented with massive hemolysis, irritability, and cyanosis. The final diagnosis was glucose-6-phosphate dehydrogenase deficiency with associated central nervous system symptoms probably because of concomitantly acquired methemoglobinemia following oxidant drug exposure. The associated acute-onset anemia would have contributed to the development of cerebral anoxia-related seizures and encephalopathy.

  2. Molecular Characterization of Glucose-6-Phosphate ...

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, ... United Arab Emirates (UAE), 3School of Pharmacy, Pharmacology Department, University Sains Malaysia ... International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index ..... dehydrogenase deficiency in a student population.

  3. Influence of sickle heterozygous status and glucose-6-phosphate ...

    African Journals Online (AJOL)

    Dr. J. T. Ekanem

    genes are known to offer reliable protection against falciparum malaria in malaria endemic areas ... study, we investigated the contribution of HbS and G6PD enzyme deficiency status in .... were analysed using an automated system,.

  4. assessment of the activity of glucose-6-phosphate dehydrogenase

    African Journals Online (AJOL)

    Uwaifoh

    2012-10-31

    Oct 31, 2012 ... Chemical Pathology, Irrua Specialist Teaching Hospital, Irrua, Edo ... in type 2 diabetes mellitus patients and control subjects using enzymatic ... inappropriate antioxidation process. ... without a previous diagnosis of diabetes develop a ... variants. It confers protection against malaria, which accounts for its ...

  5. Glucose-6-phosphate dehydro- genase deficiency; the single most ...

    African Journals Online (AJOL)

    2017-03-10

    Mar 10, 2017 ... possible Icterogenic agents, such as naphthalene balls, henna .... Table 4: Causes of jaundice among the 100 babies in the study n denote ... rate of 11%. Five (45.5%) of these were preterm with low weigh. The mortality rate among the G-6-PD defi- cient neonates was proportionately higher 15.2% (7 of.

  6. Neonatal nucleated red blood cells in G6PD deficiency.

    Science.gov (United States)

    Yeruchimovich, Mark; Shapira, Boris; Mimouni, Francis B; Dollberg, Shaul

    2002-05-01

    The objective of this study is to study the absolute number of nucleated red blood cells (RBC) at birth, an index of active fetal erythropoiesis, in infants with G6PD deficiency and in controls. We tested the hypothesis that hematocrit and hemoglobin would be lower, and absolute nucleated RBC counts higher, in the G6PD deficient and that these changes would be more prominent in infants exposed passively to fava bean through maternal diet. Thirty-two term infants with G6PD deficiency were compared with 30 term controls. Complete blood counts with manual differential counts were obtained within 12 hours of life. Absolute nucleated RBC and corrected leukocyte counts were computed from the Coulter results and the differential count. G6PD deficient patients did not differ from controls in terms of gestational age, birth weight, or Apgar scores or in any of the hematologic parameters studied, whether or not the mother reported fava beans consumption in the days prior to delivery. Although intrauterine hemolysis is possible in G6PD deficient fetuses exposed passively to fava beans, our study supports that such events must be very rare.

  7. Infleunce of pH on the partition of glucose-6-phosphate dehydrogenase and hexokinase in aqueous two-phase system Influência do pH na partição da glicose 6-fosfato desidrogenase e hexoquinase em sistema de duas fases aquosas

    Directory of Open Access Journals (Sweden)

    Daniel Pereira da Silva

    2002-09-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PDH and hexokinase (HK are important enzymes used in biochemical and medical studies and in several analytical methods. Aqueous two-phase system (ATPS formed by a polymer solution and an electrolyte solution provides a method for the separation and purification of enzymes with several advantages, including biocompatibility and easy scale up of the process. In this work, the effects of different pH values on the storage stability and partitioning behavior (K, partition coefficient of the enzymes G6PDH and HK from baker's yeast extract were investigated in ATPS. The results, obtained from the 17.5% PEG 400 : 15.0% phosphate system, showed that when the pH was increased from 5.0 to 8.8, the K HK increased 26-fold and the K G6PDH 2.2-fold. In the 20.0% PEG 1500 : 17.5% phosphate system, the K HK and K G6PDH increased 13 and 1.2-fold, when the pH value was increased from 3.8 to 8.8, respectively. This leads to the conclusion that the partition coefficient for both enzymes is favored by high pH values. A statistical analysis of the results was conducted to confirm this conclusion.Glicose-6-fosfato desidrogenase (G6PDH e hexoquinase (HK são importantes enzimas usadas em estudos bioquímicos e médicos e em diversos métodos analíticos. Sistema de duas fases aquosas (SDFA formado por uma solução polimérica e uma solução eletrolítica proporciona um método para separação e purificação de enzimas com diversas vantagens, incluindo biocompatibilidade, que pode ser facilmente escalonado para nível industrial. Neste trabalho, os efeitos de diferentes valores de pH na estabilidade e na partição (K, coeficiente de partição por SDFA das enzimas G6PDH e HK, obtidas através de levedura de panificação, foram investigados. Os resultados, obtidos do sistema constituído por 17,5% de PEG 400 e 15,0% de fosfato, mostraram que com a elevação do pH de 5,0 para 8,8, o K HK aumentou 26 vezes e o K G6PDH 2,2 vezes

  8. Comparison of Three Screening Test Kits for G6PD Enzyme Deficiency: Implications for Its Use in the Radical Cure of Vivax Malaria in Remote and Resource-Poor Areas in the Philippines.

    Directory of Open Access Journals (Sweden)

    Fe Esperanza Espino

    Full Text Available We evaluated a battery of Glucose-6-Phosphate Dehydrogenase diagnostic point-of-care tests (PoC to assess the most suitable product in terms of performance and operational characteristics for remote areas.Samples were collected in Puerto Princesa City, Palawan, Philippines and tested for G6PD deficiency with a fluorescent spot test (FST; Procedure 203, Trinity Biotech, Ireland, the semiquantitative WST8/1-methoxy PMS (WST; Dojindo, Japan and the Carestart G6PD Rapid Diagnostic Test (CSG; AccessBio, USA. Results were compared to spectrophotometry (Procedure 345, Trinity Biotech, Ireland. Sensitivity and specificity were calculated for each test with cut-off activities of 10%, 20%, 30% and 60% of the adjusted male median.The adjusted male median was 270.5 IU/10(12 RBC. FST and WST were tested on 621 capillary blood samples, the CSG was tested on venous and capillary blood on 302 samples. At 30% G6PD activity, sensitivity for the FST was between 87.7% (95%CI: 76.8% to 93.9% and 96.5% (95%CI: 87.9% to 99.5% depending on definition of intermediate results; the WST was 84.2% (95%CI: 72.1% to 92.5%; and the CSG was between 68.8% (95%CI: 41.3% to 89.0% and 93.8% (95%CI: 69.8% to 99.8% when the test was performed on capillary or venous blood respectively. Sensitivity of FST and CSG (tested with venous blood were comparable (p>0.05. The analysis of venous blood samples by the CSG yielded significantly higher results than FST and CSG performed on capillary blood (p<0.05. Sensitivity of the CSG varied depending on source of blood used (p<0.05.The operational characteristics of the CSG were superior to all other test formats. Performance and operational characteristics of the CSG performed on venous blood suggest the test to be a good alternative to the FST.

  9. Molecular epidemiology and activity of erythrocyte G6PD variants in ...

    African Journals Online (AJOL)

    G6PD activity decreased significantly with age among non-deficient individuals. The range of enzyme activities was wide and overlapping among the different G6PD variants. Conclusion: G6PD deficiency was very high in the population. The gene frequencies were similar to previous findings. Molecular methods of typing ...

  10. Burden of Hemoglobinopathies (Thalassemia, Sickle Cell Disorders and G6PD Deficiency) in Iran, 1990-2010: findings from the Global Burden of Disease Study 2010.

    Science.gov (United States)

    Rezaei, Nazila; Naderimagham, Shohreh; Ghasemian, Anoosheh; Saeedi Moghaddam, Sahar; Gohari, Kimia; Zareiy, Saeid; Sobhani, Sahar; Modirian, Mitra; Kompani, Farzad

    2015-08-01

    Hemoglobinopathies are known as the most common genetic disorders in Iran. The paper aims to provide global estimates of deaths and disability adjusted life years (DALYs) due to hemoglobinopathies in Iran by sex and age during 1990 to 2010 and describe the challenges due to limitations of the Global Burden of Disease Study 2010 (GBD 2010). GBD 2010 estimates of the numbers of deaths and years of life lost (YLLs) due to premature mortality were calculated using the Cause of Death Ensemble model (CODEm). Years of life lost due to disability (YLDs) were computed by multiplication of prevalence, the disability weight for occurrence of sequelae, and the duration of symptoms. Prevalence was estimated through a systematic search of published and available unpublished data sources, with a Bayesian meta-regression model developed for GBD 2010. Disability weights were produced using collected data from population-based surveys. Uncertainty from all inputs was incorporated into the computations of DALYs using simulation methods. We aim to prepare and criticize the results of GBD 2010 and provide some recommendations for reaching better conclusions about the burden of hemoglobinopathies in Iran. Between 1990 and 2010, the overall deaths attributed to hemoglobinopathies decreased from 0.51% to 0.36% of total deaths, with the corresponding burden declining from 1% to 0.82% of total DALYs. There was a reduction in deaths and DALYs rates for all ages and the rates attributed to all ages followed the same pattern in Iranian men and women. The highest DALYs for hemoglobinopathies, thalassemia, sickle cell disorder, and glucose-6-phosphate dehydrogenase deficiency (G6PD-D) were found in those aged less than 5 years. The collective burden of all of these hemoglobin disorder was lower in 2010 than in 1990. Although the screening programs in Iran have been very successful in reducing the number of thalassemia patients between 1990 to 2010, in order to provide a better estimation of the

  11. Fluorometric determination of free glucose and glucose 6-phosphate in cows' milk and other opaque matrices

    DEFF Research Database (Denmark)

    Larsen, Torben

    2015-01-01

    Analyses of free glucose and glucose 6-phosphate in milk have until now been dependent upon several time consuming and troublesome procedures. This has limited investigations in the area. The present article presents a new, reliable, analytical procedure, based on enzymatic degradation and fluoro......Analyses of free glucose and glucose 6-phosphate in milk have until now been dependent upon several time consuming and troublesome procedures. This has limited investigations in the area. The present article presents a new, reliable, analytical procedure, based on enzymatic degradation...... and fluorometric detection. Standards and control materials were based on milk that was stripped of intrinsic glucose and glucose 6-phosphate in order to obtain standards and samples based on the same matrix. The analysis works without pre-treatment of the samples, e.g. without centrifugation and precipitation...

  12. Present status of understanding on the G6PD deficiency and natural selection

    Directory of Open Access Journals (Sweden)

    Tripathy V

    2007-01-01

    Full Text Available G6PD deficiency is a common hemolytic genetic disorder, particularly in the areas endemic to malaria. Individuals are generally asymptomatic and hemolytic anemia occurs when some anti-malarial drugs or other oxidizing chemicals are administered. It has been proposed that G6PD deficiency provides protection against malaria. Maintaining of G6PD deficient alleles at polymorphic proportions is complicated because of the X-linked nature of G6PD deficiency. A comprehensive review of the literature on the hypothesis of malarial protection and the nature of the selection is being presented. Most of the epidemiological, in vitro and in vivo studies report selection for G6PD deficiency. Analysis of the G6PD gene also reveals that G6PD-deficient alleles show some signatures of selection. However, the question of how this polymorphism is being maintained remains unresolved because the selection/fitness coefficients for the different genotypes in the two sexes have not been established. Prevalence of G6PD deficiency in Indian caste and tribal populations and the different variants reported has also been reviewed.

  13. Parental discussion of G6PD deficiency and child health: implications for clinical practice.

    Science.gov (United States)

    Guan, Yue; Roter, Debra L; Huang, Aichu; Erby, Lori A H; Chien, Yin-Hsiu; Hwu, Wuh-Liang

    2014-03-01

    Parents are encouraged to discuss self-care with children affected by G6PD deficiency; however, little is known about the extent or impact of these discussions on the physical and psychosocial health of these children. The purpose of this study was to examine the nature of parental-child discussions of G6PD deficiency self-care and their relationship to child health. A quantitative cross-sectional survey of 178 Taiwanese parents of children with G6PD deficiency was conducted. The extent of parental-child self-care discussions was assessed in regards to coverage of nine key topics. Parent's G6PD deficiency status, knowledge of haemolytic anaemia symptoms and reported G6PD deficiency education from providers were examined as correlates of parental discussion. Child health was assessed with the child health questionnaire-parent form (Chinese version) and a 13-item haemolytic anaemia symptom list. Self-care discussions were positively correlated with parental G6PD deficiency status (β=2.08, p=0.03), accurate identification of haemolytic anaemia symptoms (β=0.18, p=0.01), the thoroughness and clarity of patient education (β=0.14, pchild age (β=1.04, pchild health (β=1.18, pchild G6PD deficiency self-care discussions are associated with better child health, and parental involvement in these discussions is facilitated by the thoroughness and clarity of patient education received from providers.

  14. Polimorfisme Enzim Glucose-6-Phosphate Isomerase pada Tiga Populasi Tuna Sirip Kuning (Thunnus albacares)

    OpenAIRE

    Permana, Gusti Ngurah; Hutapea, Jhon H.; Moria, Sari Budi; Haryanti, Haryanti

    2006-01-01

    Samples of yellowfin tuna (Thunnus albacares) were taken from three locations Bali, North Sulawesi and North Maluku. The glucose-6-phosphate isomerase (GPI) was analyzed from liver using allozyme electrophoresis method. Polymorphism of GPI enzyme was observed and four alleles (A, B ,C, D) were found in Bali population, three alleles (A,B,C) were found in North Maluku and North Sulawesi populations. Heterozygosity values, from Bali, North Maluku and North Sulawesi were 0.419; 0.417; 0.143 resp...

  15. Metabolic impact of an NADH-producing glucose-6-phosphate dehydrogenase in Escherichia coli

    DEFF Research Database (Denmark)

    Olavarria, K.; De Ingeniis, J.; Zielinski, D. C.

    2014-01-01

    In Escherichia coli, the oxidative branch of the pentose phosphate pathway (oxPPP) is one of the major sources of NADPH when glucose is the sole carbon nutrient. However, unbalanced NADPH production causes growth impairment as observed in a strain lacking phosphoglucoisomerase (Δpgi). In this work......PDH(R46E,Q47E). Through homologous recombination, the zwf loci (encoding G6PDH) in the chromosomes of WT and Δpgi E. coli strains were replaced by DNA encoding LmG6PDH(R46E,Q47E). Contrary to some predictions performed with flux balance analysis, the replacements caused a substantial effect...

  16. G6PD Deficiency and Antimalarial Efficacy for Uncomplicated Malaria in Bangladesh: A Prospective Observational Study.

    Directory of Open Access Journals (Sweden)

    Benedikt Ley

    Full Text Available The Bangladeshi national treatment guidelines for uncomplicated malaria follow WHO recommendations but without G6PD testing prior to primaquine administration. A prospective observational study was conducted to assess the efficacy of the current antimalarial policy.Patients with uncomplicated malaria, confirmed by microscopy, attending a health care facility in the Chittagong Hill Tracts, Bangladesh, were treated with artemether-lumefantrine (days 0-2 plus single dose primaquine (0.75mg/kg on day2 for P. falciparum infections, or with chloroquine (days 0-2 plus 14 days primaquine (3.5mg/kg total over 14 days for P. vivax infections. Hb was measured on days 0, 2 and 9 in all patients and also on days 16 and 30 in patients with P. vivax infection. Participants were followed for 30 days. The study was registered with the clinical trials website (NCT02389374.Between September 2014 and February 2015 a total of 181 patients were enrolled (64% P. falciparum, 30% P. vivax and 6% mixed infections. Median parasite clearance times were 22.0 (Interquartile Range, IQR: 15.2-27.3 hours for P. falciparum, 20.0 (IQR: 9.5-22.7 hours for P. vivax and 16.6 (IQR: 10.0-46.0 hours for mixed infections. All participants were afebrile within 48 hours, two patients with P. falciparum infection remained parasitemic at 48 hours. No patient had recurrent parasitaemia within 30 days. Adjusted male median G6PD activity was 7.82U/gHb. One male participant (1/174 had severe G6PD deficiency (<10% activity, five participants (5/174 had mild G6PD deficiency (10-60% activity. The Hb nadir occurred on day 2 prior to primaquine treatment in P. falciparum and P. vivax infected patients; mean fractional fall in Hb was -8.8% (95%CI -6.7% to -11.0% and -7.4% (95%CI: -4.5 to -10.4% respectively.The current antimalarial policy remains effective. The prevalence of G6PD deficiency was low. Main contribution to haemolysis in G6PD normal individuals was attributable to acute malaria rather

  17. Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum

    Directory of Open Access Journals (Sweden)

    Jeffrey Thomas Cole

    2012-04-01

    Full Text Available Brain cells expend large amounts of energy sequestering calcium (Ca2+, while loss of Ca2+ compartmentalization leads to cell damage or death. Upon cell entry, glucose is converted to glucose-6-phosphate (G6P, a parent substrate to several metabolic major pathways, including glycolysis. In several tissues, G6P alters the ability of the endoplasmic reticulum to sequester Ca2+. This led to the hypothesis that G6P regulates Ca2+ accumulation by acting as an endogenous ligand for sarco-endoplasmic reticulum calcium ATPase (SERCA. Whole brain ER microsomes were pooled from adult male Sprague-Dawley rats. Using radio-isotopic assays, 45Ca2+ accumulation was quantified following incubation with increasing amounts of G6P, in the presence or absence of thapsigargin, a potent SERCA inhibitor. To qualitatively assess SERCA activity, the simultaneous release of inorganic phosphate (Pi coupled with Ca2+ accumulation was quantified. Addition of G6P significantly and decreased Ca2+ accumulation in a dose-dependent fashion (1-10 mM. The reduction in Ca2+ accumulation was not significantly different that seen with addition of thapsigargin. Addition of glucose-1-phosphate or fructose-6-phosphate, or other glucose metabolic pathway intermediates, had no effect on Ca2+ accumulation. Further, the release of Pi was markedly decreased, indicating G6P-mediated SERCA inhibition as the responsible mechanism for reduced Ca2+ uptake. Simultaneous addition of thapsigargin and G6P did decrease inorganic phosphate in comparison to either treatment alone, which suggests that the two treatments have different mechanisms of action. Therefore, G6P may be a novel, endogenous regulator of SERCA activity. Additionally, pathological conditions observed during disease states that disrupt glucose homeostasis, may be attributable to Ca2+ dystasis caused by altered G6P regulation of SERCA activity

  18. Final Report for research on The Glucose 6-Phosphate Shunt Around the Calvin-Benson Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Sharkey, Thomas D. [Michigan State Univ., East Lansing, MI (United States)

    2017-10-30

    In this research, photosynthetic carbon metabolism was studied to identify mechanisms by which plants store energy from sunlight as carbon compounds, especially sugars. Conditions were identified in which carbon appeared to flow backwards from outside the photosynthetic compartment (chloroplast) back into it. A specific gene product was manipulated to make the flow bigger or smaller. Preventing the flow (by eliminating the gene) had little effect on plant growth but increasing the flow, by overexpressing the gene, caused the plants to become extremely sensitive to changes in light. Plants with the gene overexpressed had high rates of cyclic electron flow, the photosynthetic electron transport pathway that occurs when plants need more of the energy molecule ATP. These and other observations led us to conclude that a metabolic pathway that is normally turned off because it is counter-productive during photosynthesis, in fact occurs at about 10% of the rate of normal photosynthesis. This creates an inefficiency but may stabilize photosynthesis allowing it to cope with the very large and rapid changes that leaves experience such as the hundred-fold changes in light intensity that can occur in seconds on a partly cloudy day. We also concluded that the back flow of carbon into chloroplasts could be important at high rates of photosynthesis allowing increased rates of starch synthesis. Starch synthesis allows plants to store sugars during the day for use at night. At high rates of photosynthesis starch synthesis becomes very important to protect against end-product inhibition of photosynthesis. This research identified two metabolic pathways that extend the primary carbon fixation pathway called the Calvin-Benson cycle. These pathway extensions are now called the cytosolic bypass and the glucose 6-phosphate shunt. This improvement in our understanding of carbon metabolism of photosynthesis will guide efforts to increase photosynthesis to increase production of food, fuel

  19. Fatal Chromobacterium violaceum septicaemia in northern Laos, a modified oxidase test and post-mortem forensic family G6PD analysis

    Directory of Open Access Journals (Sweden)

    Mayxay Mayfong

    2009-07-01

    Full Text Available Abstract Background Chromobacterium violaceum is a Gram negative facultative anaerobic bacillus, found in soil and stagnant water, that usually has a violet pigmented appearance on agar culture. It is rarely described as a human pathogen, mostly from tropical and subtropical areas. Case presentation A 53 year-old farmer died with Chromobacterium violaceum septicemia in Laos. A modified oxidase method was used to demonstrate that this violacious organism was oxidase positive. Forensic analysis of the glucose-6-phosphate dehydrogenase genotypes of his family suggest that the deceased patient did not have this possible predisposing condition. Conclusion C. violaceum infection should be included in the differential diagnosis in patients presenting with community-acquired septicaemia in tropical and subtropical areas. The apparently neglected but simple modified oxidase test may be useful in the oxidase assessment of other violet-pigmented organisms or of those growing on violet coloured agar.

  20. Fatal Chromobacterium violaceum septicaemia in northern Laos, a modified oxidase test and post-mortem forensic family G6PD analysis.

    Science.gov (United States)

    Slesak, Günther; Douangdala, Phouvieng; Inthalad, Saythong; Silisouk, Joy; Vongsouvath, Manivanh; Sengduangphachanh, Amphonesavanh; Moore, Catrin E; Mayxay, Mayfong; Matsuoka, Hiroyuki; Newton, Paul N

    2009-07-29

    Chromobacterium violaceum is a Gram negative facultative anaerobic bacillus, found in soil and stagnant water, that usually has a violet pigmented appearance on agar culture. It is rarely described as a human pathogen, mostly from tropical and subtropical areas. A 53 year-old farmer died with Chromobacterium violaceum septicemia in Laos. A modified oxidase method was used to demonstrate that this violacious organism was oxidase positive. Forensic analysis of the glucose-6-phosphate dehydrogenase genotypes of his family suggest that the deceased patient did not have this possible predisposing condition. C. violaceum infection should be included in the differential diagnosis in patients presenting with community-acquired septicaemia in tropical and subtropical areas. The apparently neglected but simple modified oxidase test may be useful in the oxidase assessment of other violet-pigmented organisms or of those growing on violet coloured agar.

  1. Interesting case of G6PD deficiency anemia with severe hemolysis

    Directory of Open Access Journals (Sweden)

    Anupam Chhabra

    2013-01-01

    Full Text Available Severe hemolysis was observed in a critically ill patient with G6Pd deficiency where the causative trigger could not be identified. We describe one young patient with severe hemolysis treated with two cycles of plasmapheresis which proved to be an effective tool in the treatment. The patient presented with diffuse pain abdomen, vomiting, yellowish discoloration of sclera and skin and acute breathlessness. Hemoglobin 5.4 mg/dl and total (T serum bilirubin 17.08 mg/dl: Direct (D 4.10 mg/dl and Indirect (I 12.98 mg/dl. Subsequently patient started passing black color urine. As the patient developed severe hemolysis and the trigger agent of hemolysis was unknown, two cycles of plasmapheresis were performed with the aim to remove unknown causative agent. Consequently no trace of hemolysis was found and patient stabilized. Plasmapheresis can be used to treat G6PD deficient patients with severe hemolysis due to unidentified trigger agent.

  2. The level of glucose-6-phosphate dehydrogenase activity strongly influences xylose fermentation and inhibitor sensitivity in recombinant Saccharomyces cerevisiae strains

    DEFF Research Database (Denmark)

    Jeppsson, M.; Johansson, B.; Jensen, Peter Ruhdal

    2003-01-01

    production levels of G6PDH on xylose fermentation. We used a synthetic promoter library and the copper-regulated CUP1 promoter to generate G6PDH-activities between 0% and 179% of the wildtype level. G6PDH-activities of 1% and 6% of the wild-type level resulted in 2.8- and 5.1-fold increase in specific xylose...

  3. Oral supplementation of vitamin E reduces osmotic fragility of RBC in hemolytic anemic patients with G6PD deficiency

    International Nuclear Information System (INIS)

    Sultana, N.; Begum, S.; Begum, N.; Ali, T.

    2009-01-01

    Vitamin E has role in maintaining the integrity of red cell member by preventing oxidation of polyunsaturated fatty acids, thus protects cells from oxidative stress-induced lysis in G6PD deficiency. Changes in osmotic fragility of RBC and some absolute values like MCV, MCH and MCHC may occur in haemolytic anaemic patients with G6PD deficiency. To observe the effects of vitamin E supplementation on these changes in order to evaluate the role of this anti-oxidant vitamin in reducing chronic haemolysis in G6PD deficient patients. A total number of 102 subjects with age ranged of 5 to 40 years of both sexes were included in the study. Among them 68 were G6PD enzyme deficient patients, of whom 34 were in supplemented group (experimental group) and 34 were in non-supplemented group (control group). The supplemented group received vitamin E supplementation for 60 consecutive days at a dose of 800 IU/day for adult and 400 IU/day for children ?12 years (in a divided dose, i.e., 4 times daily). Age and sex matched 34 apparently healthy subjects with normal blood G6PD level were taken to observe the base line data (healthy control) and also for comparison. All the G6PD deficient patients were selected from Out Patient Department (OPD) of Haematology, Banglabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2005 to June 2006 and all healthy subjects were selected from personal contact. Blood G6PD level, osmotic fragility of RBC were measured by standard techniques and MCV, MCH, and MCHC were obtained by calculation. All the parameters were measured on day 1 of their first visit and also were on day 60 in deficient group. Data were compared among the deficient groups, also in supplemented group just before and after supplementation. Analysis of data was done by appropriate statistical method. Mean starting and completing points of osmotic fragility of RBC were significantly higher but MCV. MCH, MCHC were significantly lower in patients suffering from

  4. Efficient regeneration of NADPH in a 3-enzyme cascade reaction by in situ generation of glucose 6-phosphate from glucose and pyrophosphate

    NARCIS (Netherlands)

    Hartog, A.F.; van Herk, T.; Wever, R.

    2011-01-01

    We report here a promising method to regenerate NADPH (nicotinamide adenine dinucleotide phosphate) using the intermediate formation of glucose 6-phosphate (G6P) from glucose and pyrophosphate (PPi) catalyzed by the acid phosphatase from Shigella flexneri (PhoN-Sf). The G6P formed is used in turn by

  5. Cytosolic NADP(+)-dependent isocitrate dehydrogenase status modulates oxidative damage to cells.

    Science.gov (United States)

    Lee, Su Min; Koh, Ho-Jin; Park, Dong-Chan; Song, Byoung J; Huh, Tae-Lin; Park, Jeen-Woo

    2002-06-01

    NADPH is an important cofactor in many biosynthesis pathways and the regeneration of reduced glutathione, critically important in cellular defense against oxidative damage. It is mainly produced by glucose 6-phosphate dehydrogenase (G6PD), malic enzyme, and the cytosolic form of NADP(+)-dependent isocitrate dehydrogenase (IDPc). Little information is available about the role of IDPc in antioxidant defense. In this study we investigated the role of IDPc against cytotoxicity induced by oxidative stress by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 3-4-fold higher and 35% lower, respectively, than that in the parental cells carrying the vector alone. Although the activities of other antioxidant enzymes, such as superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and G6PD, were comparable in all transformed cells, the ratio of GSSG to total glutathione was significantly higher in the cells expressing the lower level of IDPc. This finding indicates that IDPc is essential for the efficient glutathione recycling. Upon transient exposure to increasing concentrations of H(2)O(2) or menadione, an intracellular source of free radicals and reactive oxygen species, the cells with low levels of IDPc became more sensitive to oxidative damage by H(2)O(2) or menadione. Lipid peroxidation, oxidative DNA damage, and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly over-expressed IDPc exhibited enhanced resistance against oxidative stress, compared to the control cells. This study provides direct evidence correlating the activities of IDPc and the maintenance of the cellular redox state, suggesting that IDPc plays an important role in cellular defense against oxidative stress.

  6. SLC37A1 and SLC37A2 are phosphate-linked, glucose-6-phosphate antiporters.

    Directory of Open Access Journals (Sweden)

    Chi-Jiunn Pan

    Full Text Available Blood glucose homeostasis between meals depends upon production of glucose within the endoplasmic reticulum (ER of the liver and kidney by hydrolysis of glucose-6-phosphate (G6P into glucose and phosphate (P(i. This reaction depends on coupling the G6P transporter (G6PT with glucose-6-phosphatase-α (G6Pase-α. Only one G6PT, also known as SLC37A4, has been characterized, and it acts as a P(i-linked G6P antiporter. The other three SLC37 family members, predicted to be sugar-phosphate:P(i exchangers, have not been characterized functionally. Using reconstituted proteoliposomes, we examine the antiporter activity of the other SLC37 members along with their ability to couple with G6Pase-α. G6PT- and mock-proteoliposomes are used as positive and negative controls, respectively. We show that SLC37A1 and SLC37A2 are ER-associated, P(i-linked antiporters, that can transport G6P. Unlike G6PT, neither is sensitive to chlorogenic acid, a competitive inhibitor of physiological ER G6P transport, and neither couples to G6Pase-α. We conclude that three of the four SLC37 family members are functional sugar-phosphate antiporters. However, only G6PT/SLC37A4 matches the characteristics of the physiological ER G6P transporter, suggesting the other SLC37 proteins have roles independent of blood glucose homeostasis.

  7. Time course of radiolabeled 2-deoxy-D-glucose 6-phosphate turnover in cerebral cortex of goats

    International Nuclear Information System (INIS)

    Pelligrino, D.A.; Miletich, D.J.; Albrecht, R.F.

    1987-01-01

    The vivo dephosphorylation rate of 2-deoxy-D-glucose 6-phosphate (DGP) in the cerebral cortex of goats injected intravenously with radiolabeled 2-deoxy-D-glucose (DG) was investigated. Serial rapidly frozen samples of parietal cortical gray tissue were obtained at regular intervals over time periods from 45 min to 3 h in awake goats or in paralyzed and artificially ventilated goats maintained under 70% N 2 O or pentobarbital sodium anesthesia. The samples were analyzed for glucose content and separate DG and DGP activities. The rate parameters for phosphorylation (k/sup */ 4 ) and dephosphorylation (k/sup */ 4 ) were estimated in each animal. The glucose phosphorylation rate (PR) was calculated over the intervals 3-5 (or 6), 3-10, 3-20, 3-30, and 3-45 min, assuming k/sup */ 4 = O. As the evaluation period was extended beyond 10 min, the calculated PR became increasingly less when compared with that calculated over the 3- to 5- (or 6) min interval (PR/sub i/). Furthermore, as metabolic activity decreased, the magnitude of the error increased such that at 45 min pentobarbital-anesthetize goats underestimated the PR/sub i/ by 46.5% compared with only 23.1 in N 2 O-anesthetized goats. This was also reflected in the >twofold higher k/sup */ 4 /k/sup */ 3 ratio in the pentobarbital vs. N 2 O-anesthetized group. It is concluded that when using the DG method in the goat, DGP dephosphorylation cannot be ignored when employing >10-min evaluation periods

  8. Benfotiamine improves functional recovery of the infarcted heart via activation of pro-survival G6PD/Akt signaling pathway and modulation of neurohormonal response.

    Science.gov (United States)

    Katare, Rajesh; Caporali, Andrea; Emanueli, Costanza; Madeddu, Paolo

    2010-10-01

    Benfotiamine (BFT) is a transketolase activator that directs glucose to the pentose phosphate pathway. The present study investigated whether BFT improves the recovery after myocardial infarction (MI) and explored underlying mechanisms of protection. Non-diabetic and streptozotocin-induced type 1 diabetic mice were supplemented with BFT (70 mg/kg/day in drinking water) for 4 weeks and then subjected to MI or sham operation. Cardiac function was monitored by echocardiography. At two weeks post-MI, intra-ventricular pressure was measured by Millar tip-catheter and hearts were collected for biochemical, immunohistochemical and expressional analyses. No treatment effect was observed in sham-operated mice. Post-MI mortality was higher in diabetic mice and hemodynamic studies confirmed the worsening effect of diabetes on functional recovery. Furthermore, diabetic mice demonstrated increased cardiomyocyte apoptosis, reduced reparative angiogenesis, larger scars, enhanced oxidative stress, and blunted activation of the pro-survival VEGF receptor-2/Akt/Pim-1 signaling pathway. BFT improved post-MI survival, functional recovery and neovascularization and reduced cardiomyocyte apoptosis and neurohormonal activation in diabetic as well as in non-diabetic mice. In addition, BFT stimulated the activity of pentose phosphate pathway enzymes, leading to reduction of oxidative stress, phosphorylation/activation of VEGF receptor-2 and Akt and increased Pim-1, pBad and Bcl-2 levels. These effects were contrasted on silencing glucose-6-phosphate dehydrogenase, the key enzyme in pentose phosphate pathway, or inhibiting Akt. BFT benefits post-MI recovery through stimulation of pro-survival mechanisms and containment of neurohormonal response. These results may have implications for the treatment of myocardial ischemia. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Primaquine

    Science.gov (United States)

    ... deficiency (a genetic condition), glucose-6-phosphate dehydrogenase (G6PD) deficiency (a genetic condition), or if you or someone ... eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. ...

  10. Dabrafenib

    Science.gov (United States)

    ... have ever had diabetes; glucose-6-phosphate dehydrogenase (G6PD) deficiency (a genetic condition); bleeding problems; eye problems; heart, ... pregnant, or if you plan to father a child. You or your partner should not become pregnant ...

  11. Sulfamethoxazole/Trimethoprim (Bactrim or Septra) and Pregnancy

    Science.gov (United States)

    ... condition known as glucose-6- phosphate dehydrogenase deficiency (G6PD deficiency). However, it is not always necessary to stop ... may affect a man’s ability to father a child. There are no studies looking at risk for ...

  12. Differences in associations between markers of antioxidative defense and asthma are sex specific

    DEFF Research Database (Denmark)

    Malling, Tine Halsen; Sigsgaard, Torben; Andersen, Helle R

    2010-01-01

    on a screening questionnaire, random sampling, or both. Serum selenium concentrations and antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase [GPX], glutathione reductase [GR], and glucose-6-phosphate dehydrogenase [G6PD]) in erythrocytes were measured. Asthma was defined as either...

  13. Synthesis and modifications of heterocyclic derivatives of D-arabinose: potential inhibitors of glucose-6-phosphate isomerase and glucosamine-6-phosphate synthase

    International Nuclear Information System (INIS)

    Viana, Renato Marcio Ribeiro; Prado, Maria Auxiliadora Fontes; Alves, Ricardo Jose

    2008-01-01

    The synthesis of -5-(D-arabino-1,2,3,4-tetrahydroxybutyl)tetrazole and -2-(d-arabino-1,2,3,4-tetra-acetoxybutyl)-5-methyl-1,3,4-oxadiazole from d-arabinose is described. Attempts at removing the protecting groups of the oxadiazole derivative were unsuccessful, leading to products resulting from the opening of the oxadiazole ring. The unprotected tetrazole derivative was selectively phosphorylated at the primary hydroxyl group with diethyl phosphoryl chloride. The resulting 5-[d-arabino-4-(diethylphosphoryloxy)-1,2,3-trihydroxybutyl]tetrazole is a protected form of a potential inhibitor of the enzymes glucose-6-phosphate isomerase and glucosamine synthase. (author)

  14. Distinguishing two types of gray mullet, Mugil cephalus L. (Mugiliformes: Mugilidae), by using glucose-6-phosphate isomerase (GPI) allozymes with special reference to enzyme activities.

    Science.gov (United States)

    Huang, C S; Weng, C F; Lee, S C

    2001-06-01

    The resident and migratory types of gray mullet, Mugil cephalus, on the coast of Taiwan can not be separated morphologically. Allozyme analysis was applied to estimate genetic variation between the two types of gray mullet and to test whether they belong to different populations. After starch gel electrophoresis, different allelic frequency spectra of glucose-6-phosphate isomerase-A (GPI-A) between stocks was observed. The resident stock contained Gpi-A(135) and Gpi-A(100), whereas the migratory type contained Gpi-A(100) only. In addition, GPI activities of locus A showed two distinct profiles between the two alleles. The results broadly revealed that Gpi-A allelic frequency was not regulated by temperature changes even after 6 months of thermal acclimation. This suggests that natural selection may play a role in shaping the allelic frequency change during the migratory journey. These findings suggest that the Gpi-A allelic difference can be used for population discrimination.

  15. Discovery of ebselen as an inhibitor of Cryptosporidium parvum glucose-6-phosphate isomerase (CpGPI by high-throughput screening of existing drugs

    Directory of Open Access Journals (Sweden)

    Rana Eltahan

    2018-04-01

    Full Text Available Cryptosporidium parvum is a water-borne and food-borne apicomplexan pathogen. It is one of the top four diarrheal-causing pathogens in children under the age of five in developing countries, and an opportunistic pathogen in immunocompromised individuals. Unlike other apicomplexans, C. parvum lacks Kreb's cycle and cytochrome-based respiration, thus relying mainly on glycolysis to produce ATP. In this study, we characterized the primary biochemical features of the C. parvum glucose-6-phosphate isomerase (CpGPI and determined its Michaelis constant towards fructose-6-phosphate (Km = 0.309 mM, Vmax = 31.72 nmol/μg/min. We also discovered that ebselen, an organoselenium drug, was a selective inhibitor of CpGPI by high-throughput screening of 1200 known drugs. Ebselen acted on CpGPI as an allosteric noncompetitive inhibitor (IC50 = 8.33 μM; Ki = 36.33 μM, while complete inhibition of CpGPI activity was not achieved. Ebselen could also inhibit the growth of C. parvum in vitro (EC50 = 165 μM at concentrations nontoxic to host cells, albeit with a relatively small in vitro safety window of 4.2 (cytotoxicity TC50 on HCT-8 cells = 700 μM. Additionally, ebselen might also target other enzymes in the parasite, leading to the parasite growth reduction. Therefore, although ebselen is useful in studying the inhibition of CpGPI enzyme activity, further proof is needed to chemically and/or genetically validate CpGPI as a drug target. Keywords: Apicomplexan, Cryptosporidium parvum, Glucose-6-phosphate isomerase (GPI, Ebselen

  16. Rapid diagnostic test for G6PD deficiency in Plasmodium vivax-infected men: a budget impact analysis based in Brazilian Amazon.

    Science.gov (United States)

    Peixoto, Henry Maia; Brito, Marcelo Augusto Mota; Romero, Gustavo Adolfo Sierra; Monteiro, Wuelton Marcelo; de Lacerda, Marcus Vinícius Guimarães; de Oliveira, Maria Regina Fernandes

    2017-01-01

    The aim of this study was to estimate the incremental budget impact (IBI) of a rapid diagnostic test to detect G6PDd in male patients infected with Plasmodium vivax in the Brazilian Amazon, as compared with the routine protocol recommended in Brazil which does not include G6PDd testing. The budget impact analysis was performed from the perspective of the Brazilian health system, in the Brazilian Amazon for the years 2013, 2014 and 2015. The analysis used a decision model to compare two scenarios: the first consisting of the routine recommended in Brazil which does not include prior diagnosis of dG6PD, and the second based on the use of RDT CareStart™ G6PD (CS-G6PD) in all male subjects diagnosed with vivax malaria. The expected implementation of the diagnostic test was 30% in the first year, 70% the second year and 100% in the third year. The analysis identified negative IBIs which were progressively smaller in the 3 years evaluated. The sensitivity analysis showed that the uncertainties associated with the analytical model did not significantly affect the results. A strategy based on the use of CS-G6PD would result in better use of public resources in the Brazilian Amazon. © 2016 John Wiley & Sons Ltd.

  17. Predicting the Kinetic Properties Associated with Redox Imbalance after Oxidative Crisis in G6PD-Deficient Erythrocytes: A Simulation Study

    Directory of Open Access Journals (Sweden)

    Hanae Shimo

    2011-01-01

    Full Text Available It is well known that G6PD-deficient individuals are highly susceptible to oxidative stress. However, the differences in the degree of metabolic alterations among patients during an oxidative crisis have not been extensively studied. In this study, we applied mathematical modeling to assess the metabolic changes in erythrocytes of various G6PD-deficient patients during hydrogen peroxide- (H2O2- induced perturbation and predict the kinetic properties that elicit redox imbalance after exposure to an oxidative agent. Simulation results showed a discrepancy in the ability to restore regular metabolite levels and redox homeostasis among patients. Two trends were observed in the response of redox status (GSH/GSSG to oxidative stress, a mild decrease associated with slow recovery and a drastic decline associated with rapid recovery. The former was concluded to apply to patients with severe clinical symptoms. Low max and high mG6P of G6PD were shown to be kinetic properties that enhance consequent redox imbalance.

  18. The chemopreventive properties of chlorogenic acid reveal a potential new role for the microsomal glucose-6-phosphate translocase in brain tumor progression

    Directory of Open Access Journals (Sweden)

    Desgagnés Julie

    2006-03-01

    Full Text Available Abstract Background Chlorogenic acid (CHL, the most potent functional inhibitor of the microsomal glucose-6-phosphate translocase (G6PT, is thought to possess cancer chemopreventive properties. It is not known, however, whether any G6PT functions are involved in tumorigenesis. We investigated the effects of CHL and the potential role of G6PT in regulating the invasive phenotype of brain tumor-derived glioma cells. Results RT-PCR was used to show that, among the adult and pediatric brain tumor-derived cells tested, U-87 glioma cells expressed the highest levels of G6PT mRNA. U-87 cells lacked the microsomal catalytic subunit glucose-6-phosphatase (G6Pase-α but expressed G6Pase-β which, when coupled to G6PT, allows G6P hydrolysis into glucose to occur in non-glyconeogenic tissues such as brain. CHL inhibited U-87 cell migration and matrix metalloproteinase (MMP-2 secretion, two prerequisites for tumor cell invasion. Moreover, CHL also inhibited cell migration induced by sphingosine-1-phosphate (S1P, a potent mitogen for glioblastoma multiform cells, as well as the rapid, S1P-induced extracellular signal-regulated protein kinase phosphorylation potentially mediated through intracellular calcium mobilization, suggesting that G6PT may also perform crucial functions in regulating intracellular signalling. Overexpression of the recombinant G6PT protein induced U-87 glioma cell migration that was, in turn, antagonized by CHL. MMP-2 secretion was also inhibited by the adenosine triphosphate (ATP-depleting agents 2-deoxyglucose and 5-thioglucose, a mechanism that may inhibit ATP-mediated calcium sequestration by G6PT. Conclusion We illustrate a new G6PT function in glioma cells that could regulate the intracellular signalling and invasive phenotype of brain tumor cells, and that can be targeted by the anticancer properties of CHL.

  19. Discovery of ebselen as an inhibitor of Cryptosporidium parvum glucose-6-phosphate isomerase (CpGPI) by high-throughput screening of existing drugs.

    Science.gov (United States)

    Eltahan, Rana; Guo, Fengguang; Zhang, Haili; Xiang, Lixin; Zhu, Guan

    2018-04-01

    Cryptosporidium parvum is a water-borne and food-borne apicomplexan pathogen. It is one of the top four diarrheal-causing pathogens in children under the age of five in developing countries, and an opportunistic pathogen in immunocompromised individuals. Unlike other apicomplexans, C. parvum lacks Kreb's cycle and cytochrome-based respiration, thus relying mainly on glycolysis to produce ATP. In this study, we characterized the primary biochemical features of the C. parvum glucose-6-phosphate isomerase (CpGPI) and determined its Michaelis constant towards fructose-6-phosphate (K m  = 0.309 mM, V max  = 31.72 nmol/μg/min). We also discovered that ebselen, an organoselenium drug, was a selective inhibitor of CpGPI by high-throughput screening of 1200 known drugs. Ebselen acted on CpGPI as an allosteric noncompetitive inhibitor (IC 50  = 8.33 μM; K i  = 36.33 μM), while complete inhibition of CpGPI activity was not achieved. Ebselen could also inhibit the growth of C. parvum in vitro (EC 50  = 165 μM) at concentrations nontoxic to host cells, albeit with a relatively small in vitro safety window of 4.2 (cytotoxicity TC 50 on HCT-8 cells = 700 μM). Additionally, ebselen might also target other enzymes in the parasite, leading to the parasite growth reduction. Therefore, although ebselen is useful in studying the inhibition of CpGPI enzyme activity, further proof is needed to chemically and/or genetically validate CpGPI as a drug target. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. G6PD deficiency and absence of α-thalassemia increase the risk for cerebral vasculopathy in children with sickle cell anemia.

    Science.gov (United States)

    Joly, Philippe; Garnier, Nathalie; Kebaili, Kamila; Renoux, Céline; Dony, Arthur; Cheikh, Nathalie; Renard, Cécile; Ceraulo, Antony; Cuzzubbo, Daniela; Pondarré, Corinne; Martin, Cyril; Pialoux, Vincent; Francina, Alain; Bertrand, Yves; Connes, Philippe

    2016-04-01

    The aim of this study was to test the association between hematological/genetic factors and cerebral vasculopathy in children with sickle cell anemia (SCA). A group with cerebral vasculopathy (VASC) was composed of children who had stroke (n = 6), silent infarct (n = 11), or an abnormal transcranial Doppler (n = 5). Eighty-four patients had neither positive history of stroke or silent infarct, nor abnormal transcranial Doppler (NORM group). An intermediate group (COND; n = 15) was composed of SCA children with a conditional transcranial Doppler. Biological analyses were performed on samples obtained at steady state and before the beginning of any chronic treatment. The comparisons of the three groups demonstrated a protective effect of α-thalassemia against cerebral vasculopathy through its effects on hemoglobin and reticulocyte levels. Moreover, we observed higher frequency of G6PD deficiency in the VASC group compared with the other groups. Our study confirms the key role of α-thalassemia and G6PD status in the pathophysiology of cerebral vasculopathy in SCA children. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Sequence analysis and molecular characterization of Clonorchis sinensis hexokinase, an unusual trimeric 50-kDa glucose-6-phosphate-sensitive allosteric enzyme.

    Directory of Open Access Journals (Sweden)

    Tingjin Chen

    Full Text Available Clonorchiasis, which is induced by the infection of Clonorchis sinensis (C. sinensis, is highly associated with cholangiocarcinoma. Because the available examination, treatment and interrupting transmission provide limited opportunities to prevent infection, it is urgent to develop integrated strategies to prevent and control clonorchiasis. Glycolytic enzymes are crucial molecules for trematode survival and have been targeted for drug development. Hexokinase of C. sinensis (CsHK, the first key regulatory enzyme of the glycolytic pathway, was characterized in this study. The calculated molecular mass (Mr of CsHK was 50.0 kDa. The obtained recombinant CsHK (rCsHK was a homotrimer with an Mr of approximately 164 kDa, as determined using native PAGE and gel filtration. The highest activity was obtained with 50 mM glycine-NaOH at pH 10 and 100 mM Tris-HCl at pH 8.5 and 10. The kinetics of rCsHK has a moderate thermal stability. Compared to that of the corresponding negative control, the enzymatic activity was significantly inhibited by praziquantel (PZQ and anti-rCsHK serum. rCsHK was homotropically and allosterically activated by its substrates, including glucose, mannose, fructose, and ATP. ADP exhibited mixed allosteric effect on rCsHK with respect to ATP, while inorganic pyrophosphate (PPi displayed net allosteric activation with various allosteric systems. Fructose behaved as a dose-dependent V activator with the substrate glucose. Glucose-6-phosphate (G6P displayed net allosteric inhibition on rCsHK with respect to ATP or glucose with various allosteric systems in a dose-independent manner. There were differences in both mRNA and protein levels of CsHK among the life stages of adult worm, metacercaria, excysted metacercaria and egg of C. sinensis, suggesting different energy requirements during different development stages. Our study furthers the understanding of the biological functions of CsHK and supports the need to screen for small

  2. Sequence Analysis and Molecular Characterization of Clonorchis sinensis Hexokinase, an Unusual Trimeric 50-kDa Glucose-6-Phosphate-Sensitive Allosteric Enzyme

    Science.gov (United States)

    Chen, Tingjin; Ning, Dan; Sun, Hengchang; Li, Ran; Shang, Mei; Li, Xuerong; Wang, Xiaoyun; Chen, Wenjun; Liang, Chi; Li, Wenfang; Mao, Qiang; Li, Ye; Deng, Chuanhuan; Wang, Lexun; Wu, Zhongdao; Huang, Yan; Xu, Jin; Yu, Xinbing

    2014-01-01

    Clonorchiasis, which is induced by the infection of Clonorchis sinensis (C. sinensis), is highly associated with cholangiocarcinoma. Because the available examination, treatment and interrupting transmission provide limited opportunities to prevent infection, it is urgent to develop integrated strategies to prevent and control clonorchiasis. Glycolytic enzymes are crucial molecules for trematode survival and have been targeted for drug development. Hexokinase of C. sinensis (CsHK), the first key regulatory enzyme of the glycolytic pathway, was characterized in this study. The calculated molecular mass (Mr) of CsHK was 50.0 kDa. The obtained recombinant CsHK (rCsHK) was a homotrimer with an Mr of approximately 164 kDa, as determined using native PAGE and gel filtration. The highest activity was obtained with 50 mM glycine-NaOH at pH 10 and 100 mM Tris-HCl at pH 8.5 and 10. The kinetics of rCsHK has a moderate thermal stability. Compared to that of the corresponding negative control, the enzymatic activity was significantly inhibited by praziquantel (PZQ) and anti-rCsHK serum. rCsHK was homotropically and allosterically activated by its substrates, including glucose, mannose, fructose, and ATP. ADP exhibited mixed allosteric effect on rCsHK with respect to ATP, while inorganic pyrophosphate (PPi) displayed net allosteric activation with various allosteric systems. Fructose behaved as a dose-dependent V activator with the substrate glucose. Glucose-6-phosphate (G6P) displayed net allosteric inhibition on rCsHK with respect to ATP or glucose with various allosteric systems in a dose-independent manner. There were differences in both mRNA and protein levels of CsHK among the life stages of adult worm, metacercaria, excysted metacercaria and egg of C. sinensis, suggesting different energy requirements during different development stages. Our study furthers the understanding of the biological functions of CsHK and supports the need to screen for small molecule inhibitors

  3. High glucose impairs superoxide production from isolated blood neutrophils

    DEFF Research Database (Denmark)

    Perner, A; Nielsen, S E; Rask-Madsen, J

    2003-01-01

    Superoxide (O(2)(-)), a key antimicrobial agent in phagocytes, is produced by the activity of NADPH oxidase. High glucose concentrations may, however, impair the production of O(2)(-) through inhibition of glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the formation of NADPH. This study...... measured the acute effects of high glucose or the G6PD inhibitor dehydroepiandrosterone (DHEA) on the production of O(2)(-) from isolated human neutrophils....

  4. Triagem neonatal de deficiência de glicose-6-fosfato desidrogenase e prevalência das mutações G202A (G6PD A-) e C563T (G6PD Mediterrâneo) em Mato Grosso/Brasil

    OpenAIRE

    Maria de Fatima de Carvalho Ferreira

    2014-01-01

    Objetivos: A deficiência de glicose-6-fosfato desidrogenase (G6PD) está associada a um maior risco de encefalopatia bilirrubínica e de crise hemolítica aguda grave desencadeada por drogas como a primaquina e a dapsona. Conhecer a prevalência dessa deficiência enzimática em área onde a malária e a hanseníase ainda estão presentes e conhecer a prevalência das principais mutações traz subsídios para planejamento de estratégias com vistas à redução de riscos associados a esta deficiência enzimáti...

  5. Prevalence and risk factors of anaemia in paediatric patients in ...

    African Journals Online (AJOL)

    South African Journal of Child Health ... deficiency 42.3% (p=0.001), glucose-6 phosphate dehydrogenase (G6PD) deficiency 24.8% (p=0.02), ... Malaria and iron deficiency remain common among ill children <5 years old who are anaemic.

  6. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 100 of 150 ... HU Nwanjo, G Oze. Vol 14, No 2 (2005), Incidence of Glucose-6-Phosphate Dehydrogenase (G-6-PD) Deficiency in Apparently Healthy Individuals in Some Parts of North Central Nigeria, Abstract. A Abubakar, A Musa, B Lliyasu, J Adetunji, O Olaniru, T Akande, A T Mokogwu. Vol 14, No 1 (2005) ...

  7. Birth control necessary to limit family size in tribal couples with aberrant heterosis of G-6-PD deficiency and sickle cell disorders in India: an urgency of creating awareness and imparting genetic counseling.

    Science.gov (United States)

    Balgir, R S

    2010-06-01

    (i) To study the outcome of ignorance and lack of awareness about sickle cell disease and G-6-PD deficiency among Dhelki Kharia tribal families of Orissa, and (ii) to study the reproductive output in relation to clinical genetics and patho-physiological implications. A random genetic study of screening for hemoglobinopathies and G-6-PD deficiency among Dhelki Kharia tribal community in Sundargarh district of Orissa was carried out for intervention during the year 2000-2004. A total of 81 Dhelki Kharia families were screened and six families with double heterozygosity for above genetic anomalies were encountered. About 2-3 ml. intravenous blood samples were collected in EDTA by disposable syringes and needles after taking informed consent from each individual in the presence of a doctor and community leaders and sent to laboratory at Bhubaneswar for hematological investigations. Analysis was carried out following the standard procedures after cross checking for quality control. There were 12 (about 52%) children out of 23 who were either suffering from sickle cell trait or disease in concurrence with G-6-PD deficiency in hemizygous/heterozygous/homozygous condition in Dhelki Kharia tribal community of Orissa. There were on an average 3.83 number of surviving (range 2-6) children per mother in families of G-6-PD deficiency and sickle cell disorders. The average number of children (3.83) born (range 2-6 children) per mother to carrier/affected mother was much higher than the average for India (2.73). It is very difficult to maintain the normal health of an affected child with aberrant anomalies due to exorbitant cost of treatment, frequent transfusions and huge involvement of economy. One of the implications of aberrant heterosis is its adverse affects on routine individual physiology and hard activities. It is suggested to limit the family size in carrier couples to avoid aberrant heterosis of hereditary hemolytic disorders in their offsprings.

  8. High-Throughput, Multiplex Genotyping Directly from Blood or Dried Blood Spot without DNA Extraction for the Screening of Multiple G6PD Gene Variants at Risk for Drug-Induced Hemolysis.

    Science.gov (United States)

    Tian, Xiaoyi; Zhou, Jun; Zhao, Ye; Cheng, Zhibin; Song, Wenqi; Sun, Yu; Sun, Xiaodong; Zheng, Zhi

    2017-09-01

    Clinical or epidemiologic screening of single-nucleotide polymorphism markers requires large-scale multiplexed genotyping. Available genotyping tools require DNA extraction and multiplex PCR, which may limit throughput and suffer amplification bias. Herein, a novel genotyping approach has been developed, multiplex extension and ligation-based probe amplification (MELPA), which eliminates DNA extraction and achieves uniform PCR amplification. MELPA lyses blood or dried blood spot and directly captures specific target DNA to 96-well plates using tailed probes. Subsequent enzymatic extension and ligation form target single-nucleotide polymorphism-spanning single-stranded templates, which are PCR-amplified using universal primers. Multiplexed genotyping by single-base primer extension is analyzed by mass spectrometry, with a call rate >97%. MELPA was compared with a commercial assay (iPLEX) for detecting 24 G6PD variants known to be at risk for primaquine-induced hemolysis. MELPA provided results that were more reliable than iPLEX, with higher throughput and lower cost. Genotyping archival blood from 106 malaria patients taking primaquine found 10 G6PD-deficient variants, including 1 patient with a hemizygous Mahidol mutation who had hemolysis. Preemptive G6PD genotyping of 438 dried blood spots from a malaria-endemic area identified three variants. MELPA also enabled pooled genotyping without diluting rare alleles, in which undesired common-allele background increased by sample pooling can be repressed by adding specific common allele blockers. Thus, MELPA represents a high-throughput, cost-effective approach to targeted genotyping at the population level. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  9. Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells

    Directory of Open Access Journals (Sweden)

    Müller Sylke

    2009-05-01

    Full Text Available Abstract Background Plasmodium falciparum-parasitized red blood cells (RBCs are equipped with protective antioxidant enzymes and heat shock proteins (HSPs. The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense. Those issues are interesting as several antimalarials increase the oxidative stress or block antioxidant defense in the parasitized RBC. In addition, numerous inhibitors of HSPs are currently developed for cancer therapy and might be tested as anti-malarials. Thus, the joint disruption of the parasite antioxidant enzymes/HSP system would interfere with parasite growth and open new perspectives for anti-malaria therapy. Methods Stage-dependent mRNA expression of ten representative P. falciparum antioxidant enzymes and hsp60/70–2/70–3/75/90 was studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, in RBCs oxidatively-stressed by moderate H2O2 generation and in G6PD-deficient RBCs. Protein expression of antioxidant enzymes was assayed by Western blotting. The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane. Results In parasites growing in normal RBCs, mRNA expression of antioxidant enzymes and HSPs displayed co-ordinated stage-dependent modulation, being low at ring, highest at early trophozoite and again very low at schizont stage. Additional exogenous oxidative stress or growth in antioxidant blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of

  10. Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells.

    Science.gov (United States)

    Akide-Ndunge, Oscar Bate; Tambini, Elisa; Giribaldi, Giuliana; McMillan, Paul J; Müller, Sylke; Arese, Paolo; Turrini, Francesco

    2009-05-29

    Plasmodium falciparum-parasitized red blood cells (RBCs) are equipped with protective antioxidant enzymes and heat shock proteins (HSPs). The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense. Those issues are interesting as several antimalarials increase the oxidative stress or block antioxidant defense in the parasitized RBC. In addition, numerous inhibitors of HSPs are currently developed for cancer therapy and might be tested as anti-malarials. Thus, the joint disruption of the parasite antioxidant enzymes/HSP system would interfere with parasite growth and open new perspectives for anti-malaria therapy. Stage-dependent mRNA expression of ten representative P. falciparum antioxidant enzymes and hsp60/70-2/70-3/75/90 was studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, in RBCs oxidatively-stressed by moderate H2O2 generation and in G6PD-deficient RBCs. Protein expression of antioxidant enzymes was assayed by Western blotting. The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane. In parasites growing in normal RBCs, mRNA expression of antioxidant enzymes and HSPs displayed co-ordinated stage-dependent modulation, being low at ring, highest at early trophozoite and again very low at schizont stage. Additional exogenous oxidative stress or growth in antioxidant blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of antioxidant enzymes and HSPs. Protein expression of

  11. Gaped deficiency distribution and variants in Saudi Arabia: An overview

    International Nuclear Information System (INIS)

    El-Hazmi, Mohsen A.F.; Warsy, Arjumand S.

    2001-01-01

    The first report of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Saudi population of the Eastern Province paved the way for extensive investigations to determine the distribution and molecular pathogenesis of G6PD deficiency in Saudis in different parts of the country. During a national study lasting from 1980 to 1993, 24,407 Saudi in 31 different areas of Saudi Arabia screened for G6PD deficiency using spectrophoretic estimation of enzyme activity and electrophoretic separation of the phenotypes. The results in the males and females were separately analyzed and showed a statistically significant difference in the frequency in the male (0.0905) and female (0.041) population (P<0.05). The frequency in the male varied from 0 to 0.398 and in the female from 0 to 0.214. The phenotypes identified included G6PD-A, G6PD-Mediterranean and G6PD-Med-Like with G6PD-B as the normal phenotype in all areas. This study shows that G6PD deficiency is a frequently identified single-gene disorder in Saudi Arabia and G6PD-Mediterranean is the major variant producing the severe deficiency state in this population. (author)

  12. Remote Sensing and Geographic Information Systems as Decision Support Tools for Malaria Control in the Republic of Korea

    Science.gov (United States)

    2001-05-30

    remote sensing and GIS techniques to monitor vectors and vector-borne disease in Mexico, Belize and, more recently, Peru (Roberts et al. 1999...parasite is severe hemolytic anemia in persons who are deficient in glucose-6- phosphate dehydrogenase (G-6-PD). Primaquine is the only drug currently...the denaturation of hemoglobin, resulting in hemoglobinuria, kidney damage and anemia . Erythrocytes are protected from oxidation by the hexose

  13. Probable clonal origin of acute myeloblastic leukemia following radiation and chemotherapy of colon cancer

    International Nuclear Information System (INIS)

    Wiggans, R.G.; Jacobson, R.J.; Fialkow, P.J.; Woolley, P.V. III; Macdonald, J.S.; Schein, P.S.

    1978-01-01

    A 64-yr-old female developed acute myeloblastic leukemia following radiation and drug therapy for colon carcinoma. The patient was heterozygous for glucose-6-phosphate dehydrogenase [G-6-PD) and displayed types A and B isoenzymes in nonhematopoietic tissue. In contrast, only type B G-6-PD was observed in peripheral blood white cells. In addition, a karyotypic abnormality was found in peripheral blood and marrow cells but not in skin fibroblasts. The data are consistent with a clonal origin of this leukemia

  14. Prevalence of sickle cell, malaria and glucose-6-phosphate ...

    African Journals Online (AJOL)

    PD) deficiency are relatively common genetic disorders in population exposed to malaria in sub-Saharan Africa. The prevalence of these two genetic disorders differs between different malaria transmission areas. Objectives: This cross ...

  15. Glucose 6-phosphate compartmentation and the control of glycogen synthesis

    NARCIS (Netherlands)

    Meijer, Alfred

    2002-01-01

    Using adenovirus-mediated gene transfer into FTO-2B cells, a rat hepatoma cell line, we have overexpressed hexokinase I, (HK I), glucokinase (GK), liver glycogen synthase (LGS), muscle glycogen synthase (MGS), and combinations of each of the two glucose phosphorylating enzymes with each one of the

  16. New onset diabetes complicated by haemolysis and rhabdomyolysis: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Galtrey Clare M

    2008-05-01

    Full Text Available Abstract Introduction Previously undiagnosed glucose-6-phosphate dehydrogenase (G6PD deficiency can be unmasked by a diabetic crisis and both can be associated with rhabdomyolysis. The relationship between diabetes and G6PD deficiency is discussed and the possible triggers for haemolysis as outlined in this case report. The incidence of G6PD deficiency is 10% in African-American males and up to 35% in parts of Africa so an increased awareness of G6PD deficiency is important when treating diabetes in these populations. Case presentation A 54-year-old Kenyan man presented with a 3-day history of reduced appetite, weakness and reduced level of consciousness as a result of a hyperglycaemic diabetic crisis with both hyperosmolarity and ketoacidosis. The patient then developed haemolysis and a raised creatine kinase level. A diagnosis of G6PD deficiency and rhabdomyolysis was made. Conclusion This case highlights the importance of simple laboratory investigations in the early identification of the rarer complications of diabetic crisis such as haemolysis secondary to G6PD deficiency and rhabdomyolysis.

  17. Metabolism of excised embryos of Lupinus luteus L. VI. An electrophoretic analysis of some dehydrogenases in cultured embryos as compared with the normal seedling axes

    Directory of Open Access Journals (Sweden)

    J. Czosnowski

    2015-01-01

    Full Text Available The electrophoretic patterns (disc electrophoresis of the studied dehydrogenases: glucose-6-phosphate - (A, malate - (B, glutamate - (C, alcohol - (D and lactate dehydrogenase (E, in the axial organs of isolated Lupinus luteus embryos and seedlings cultivated over 12 days are characterized by great similarities. With time, after the third day of cultivation the patterns begin to become less deyeloped. Analyses performed during the first 10 hours of imbibition of seed parts indicate that the maximal development of isozyme patterns occurs during the third hour after which the patterns become poorer. The most uniform type of pattern. and the lowest number of isozymes was shown by glutamate dehydrogenase, the richest pattern was shown by malate dehydrogenase. No band common for a 11 the 27 experimental elements was found.

  18. Deficiencia de glucosa-6-fosfato deshidrogenasa en un paciente con síndrome de Down

    Directory of Open Access Journals (Sweden)

    Francisco R. Cammarata Scalisi

    2012-07-01

    Full Text Available El síndrome de Down, es una alteración genética que ocurre cuando un individuo exhibe todo o una parte específica adicional del cromosoma 21 y es la entidad más frecuentemente asociada a retardo mental. La deficiencia de glucosa-6-fosfato deshidrogenasa, es el defecto enzimático más común en humanos y presenta patrón de herencia ligado al cromosoma X recesivo. Se debe a la mutación del gen G6PD, el cual causa diversos fenotipos bioquímicos y clínicos. Reportamos un caso de lactante menor masculino, evaluado en la Unidad de Genética Médica de la Universidad de Los Andes, con el diagnóstico de deficiencia de glucosa-6-fosfato deshidrogenasa con doble mutación A376G y G202A y síndrome de Down con estudio citogenético 47, XY, +21. Palabras clave:Síndrome de Down; deficiencia de glucosa-6-fosfato deshidrogenasa; G6PD; A37G6; G202A. Glucose-6-phosphate dehydrogenase deficiency in a patient with Down syndrome Abstract Down syndrome, is a genetic disorder that occurring when an individual exhibits all or part of an extra copy of chromosome 21 and the most common entity associated mental retardation. Glucose-6-phosphate dehydrogenase deficiency, is the most common human enzyme defect and has a X-linked recessive inheritance. Due to mutations in the G6PD gene, which cause many biochemical and clinical phenotypes. We reported a case of child male, evaluated in the Unit of Medical Genetics of the University of The Andes, with diagnosis of glucose-6-phosphate dehydrogenase deficiency with double mutation A376G and G202A and Down syndrome with cytogenetic study 47, XY, + 21.

  19. InterProScan Result: FS765596 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available 001282 Glucose-6-phosphate dehydrogenase Molecular Function: glucose-6-phosphate dehydrogenase activity (GO:0004345)|Biological... Process: glucose metabolic process (GO:0006006)|Biological Process: oxidation reduction (GO:0055114) ...

  20. Modulation of NADP(+)-dependent isocitrate dehydrogenase in aging.

    Science.gov (United States)

    Kil, In Sup; Lee, Young Sup; Bae, Young Seuk; Huh, Tae Lin; Park, Jeen-Woo

    2004-01-01

    NADPH is an important cofactor in many biosynthesis pathways and the regeneration of reduced glutathione, critically important in cellular defense against oxidative damage. It is mainly produced by glucose-6-phosphate dehydrogenase, malic enzyme, and NADP(+)-specific isocitrate dehydrogenases (ICDHs). Here, we investigated age-related changes in ICDH activity and protein expression in IMR-90 human diploid fibroblast cells and tissues from Fischer 344 rats. We found that in IMR-90 cells the activity of cytosolic ICDH (IDPc) gradually increased with age up to the 46-48 population doubling level (PDL) and then gradually decreased at later PDL. 2',7'-Dichloro-fluorescein fluorescence which reflects intracellular ROS generation was increased with aging in IMR-90 cells. In ad libitum-fed rats, we noted age-related, tissue-specific modulations of IDPc and mitochondrial ICDH (IDPm) activities and protein expression in the liver, kidney and testes. In contrast, ICDH activities and protein expression were not significantly modulated in diet-restricted rats. These data suggest that modulation of ICDH is an age-dependent and a tissue-specific phenomenon.

  1. Inhibition of the pentose phosphate shunt by 2,3-diphosphoglycerate in erythrocyte pyruvate kinase deficiency.

    Science.gov (United States)

    Tomoda, A; Lachant, N A; Noble, N A; Tanaka, K R

    1983-07-01

    Pentose phosphate shunt activity was studied by the release of 14CO2 from 14C-1-glucose and 14C-2-glucose in the red cells of five patients with pyruvate kinase deficiency and found to be significantly decreased after new methylene blue stimulation when compared to high reticulocyte controls. Incubated Heinz body formation was increased and the ascorbate cyanide test was positive in blood from these patients. The activity of glucose-6-phosphate dehydrogenase (G6PD) as well as that of 6-phosphogluconate dehydrogenase (6PGD) was inhibited to 20% of baseline in normal red cell haemolysate by 4 mM 2,3-diphosphoglycerate at pH 7.1. 2,3-Diphosphoglycerate was a competitive inhibitor with 6-phosphogluconate (Ki=1.05 mM) and a noncompetitive inhibitor with NADP (Ki=3.3 mM) for 6PGD. Since the intracellular concentrations of glucose-6-phosphate, 6-phosphogluconate and NADP are below their Kms for G6PD and 6PGD, the kinetic data suggest that increased concentrations of 2,3-diphosphoglycerate in pyruvate kinase deficient red cells are sufficiently high to suppress pentose phosphate shunt activity. This suppression may be an additional factor contributing to the haemolytic anaemia of pyruvate kinase deficiency, particularly during periods of infection or metabolic stress.

  2. Prophylactic Role of Spermine in Rats Intoxicated With Lead and/or Gamma Irradiation

    International Nuclear Information System (INIS)

    Habieb, M.E.; Mohamed, M.A.; Hawas, A.M.; Abu-Khudir, R.; Mohamed, T.M.

    2017-01-01

    The current study was conducted to investigate the protective effect of spermine, a natural polyamine against toxicity of lead and /or gamma irradiation in male rats. Eight groups of rats were used in this study (control, irradiated group (6 GY), lead (40 mg/kg bw), spermine (10 mg/kg bw), lead plus irradiation, irradiation plus spermine, lead plus spermine, irradiation plus lead co-treated with spermine) for consecutive 14 days. Blood samples were used for complete blood count (CBC) and glucose 6-phosphate-dehydrogenase (G6PD) levels. Moreover, malondialdhyde (MDA), glutathione (GSH), metallothionein (MT) levels and catalase (CAT) activity were investigated in liver, kidney and brain. G6PD activity significantly decreased post exposure to lead and /or gamma irradiation. Hepatic, renal and brain MDA, GSH, MT and CAT were significantly increased in lead intoxicated group, while GSH, MT and CAT activity were significantly decreased in gamma-irradiated group. Spermine administration alleviated changes in CBC, G6PD, MDA, MT and CAT to normal control levels, but with significant increase in G6PD activity and platelets count. In conclusion, spermine acts as an antioxidant and plays a prophylactic role against intoxication with lead and/or gamma irradiation exposure.

  3. Morphologic, biometric, and isoenzyme characterization of Trichuris suis.

    Science.gov (United States)

    Oliveros, R; Cutillas, C; Arias, P; Guevara, D

    1998-06-01

    Trichuris suis isolates were collected from the cecum of Sus scrofa domestica (pig) and S. s. scrofa (wild boar). Morphology and biometry studies were carried out. Morphology studies showed the existence of typical caudal papillae in males of T. suis from wild boars, but no other difference was observed in the biometric parameters (total length, esophageal length, posterior-portion body length, and spicular length) of T. suis isolated from either host. Individual extracts were subjected to malate dehydrogenase (MDH), malic enzyme (ME), glucose 6-phosphate dehydrogenase (G6PD), lactate dehydrogenase (LDH), and superoxide dismutase (SOD) isoenzyme analysis following starch-gel electrophoresis, and the isoenzyme patterns were compared with those obtained from other species of trichurids. MDH, ME, G6PD, LDH, and SOD isoenzyme patterns were identical for T. suis from both hosts. MDH isoenzyme patterns were characterized by the presence of one cathodic isoenzyme. ME, G6PD, and LDH isoenzyme patterns indicated the presence of three phenotypes, whereas the SOD isoenzyme pattern showed only one phenotype characterized by the existence of two (anodic and cathodic) bands. Different LDH and SOD isoenzyme patterns observed for T. suis, T. ovis, and T. skrjabini confirm once more that isoenzyme patterns have potential as a diagnostic tool for differentiation of different species of Trichuris.

  4. Hexose-6-phosphate dehydrogenase contributes to skeletal muscle homeostasis independent of 11β-hydroxysteroid dehydrogenase type 1.

    LENUS (Irish Health Repository)

    Semjonous, Nina M

    2011-01-01

    Glucose-6-phosphate (G6P) metabolism by the enzyme hexose-6-phosphate dehydrogenase (H6PDH) within the sarcoplasmic reticulum lumen generates nicotinamide adenine dinucleotide phosphate (reduced) to provide the redox potential for the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) to activate glucocorticoid (GC). H6PDH knockout (KO) mice have a switch in 11β-HSD1 activity, resulting in GC inactivation and hypothalamic-pituitary-adrenal axis activation. Importantly, H6PDHKO mice develop a type II fiber myopathy with abnormalities in glucose metabolism and activation of the unfolded protein response (UPR). GCs play important roles in muscle physiology, and therefore, we have examined the importance of 11β-HSD1 and GC metabolism in mediating aspects of the H6PDHKO myopathy. To achieve this, we examined 11β-HSD1\\/H6PDH double-KO (DKO) mice, in which 11β-HSD1 mediated GC inactivation is negated. In contrast to H6PDHKO mice, DKO mice GC metabolism and hypothalamic-pituitary-adrenal axis set point is similar to that observed in 11β-HSD1KO mice. Critically, in contrast to 11β-HSD1KO mice, DKO mice phenocopy the salient features of the H6PDHKO, displaying reduced body mass, muscle atrophy, and vacuolation of type II fiber-rich muscle, fasting hypoglycemia, increased muscle glycogen deposition, and elevated expression of UPR genes. We propose that muscle G6P metabolism through H6PDH may be as important as changes in the redox environment when considering the mechanism underlying the activation of the UPR and the ensuing myopathy in H6PDHKO and DKO mice. These data are consistent with an 11β-HSD1-independent function for H6PDH in which sarcoplasmic reticulum G6P metabolism and nicotinamide adenine dinucleotide phosphate-(oxidized)\\/nicotinamide adenine dinucleotide phosphate (reduced) redox status are important for maintaining muscle homeostasis.

  5. [Intensity of pentose phosphate metabolism of carbohydrates in various brain areas in normal and starved animals].

    Science.gov (United States)

    Kerimov, B F

    2002-01-01

    The activities of key enzymes of pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G-6 PD) and 6-phosphogluconate dehydrogenase (6-PGD), were studied in cytoplasmatic fractions of brain cortical (limbic, orbital, sensorimotor cortex) and subcortical (myelencefalon, mesencefalon, hypothalamus) structures of rats subjected to starvation for 1, 2, 3, 5 and 7 days. Short-term starvation (1-3 days) caused activation of 6-GPD and 6-PGD both in cortical and subcortical structures. Long-term starvation for 5-7 days caused a decrease of activities of the pentose phosphate pathway enzymes in all studied structures. It is suggested that enzymes of pentose phosphate pathway in nervous tissues are functionally and metabolically related to glutathione system and during starvation they indirectly participate in the regulation lipid peroxidation processes.

  6. Nutritional history does not modulate hepatic oxidative status of European sea bass (Dicentrarchus labrax) submitted to handling stress.

    Science.gov (United States)

    Castro, Carolina; Peréz-Jiménez, Amalia; Coutinho, Filipe; Corraze, Geneviève; Panserat, Stéphane; Peres, Helena; Teles, Aires Oliva; Enes, Paula

    2018-02-19

    The aim of the present study was to assess the impact of an acute handling stress on hepatic oxidative status of European sea bass (Dicentrarchus labrax) juveniles fed diets differing in lipid so urce and carbohydrate content. For that purpose, four diets were formulated with fish oil (FO) and vegetable oils (VO) as lipid source and with 20 or 0% gelatinized starch as carbohydrate source. Triplicate groups of fish with 74 g were fed each diet during 13 weeks and then subjected to an acute handling stress. Stress exposure decreased hematocrit (Ht) and hemoglobin (Hb) levels. Independent of dietary treatment, stress exposure increased hepatic lipid peroxidation (LPO). Stressed fish exhibited lower glucose 6-phosphate dehydrogenase (G6PD), catalase (CAT), and superoxide dismutase (SOD) activities, independent of previous nutritional history. In the VO groups, stress exposure increased glutathione peroxidase (GPX) activity. Diet composition had no effect on Ht and Hb levels. In contrast, dietary carbohydrate decreased hepatic LPO and CAT activity and increased glutathione reductase (GR) and G6PD activities. Dietary lipids had no effect on LPO. Fish fed the VO diets exhibited higher G6PD activity than fish fed the FO diets. In conclusion, dietary carbohydrates contributed to the reduction of oxidative stress in fish. However, under the imposed handling stress conditions, liver enzymatic antioxidant mechanisms were not enhanced, which may explain the overall increased oxidative stress.

  7. X-linked gene expression in the Virginia opossum: differences between the paternally derived Gpd and Pgk-A loci

    Energy Technology Data Exchange (ETDEWEB)

    Samollow, P.B.; Ford, A.L.; VandeBerg, J.L.

    1987-01-01

    Expression of X-linked glucose-6-phosphate dehydrogenase (G6PD) and phosphoglycerate kinase-A (PGK-A) in the Virginia opossum (Didelphis virginiana) was studied electrophoretically in animals from natural populations and those produced through controlled laboratory crosses. Blood from most of the wild animals exhibited a common single-banded phenotype for both enzymes. Rare variant animals, regardless of sex, exhibited single-banded phenotypes different in mobility from the common mobility class of the respective enzyme. The laboratory crosses confirmed the allelic basis for the common and rare phenotypes. Transmission of PGK-A phenotypes followed the pattern of determinate (nonrandom) inactivation of the paternally derived Pgk-A allele, and transmission of G6PD also was consistent with this pattern. A survey of tissue-specific expression of G6PD phenotypes of heterozygous females revealed, in almost all tissues, three-banded patterns skewed in favor of the allele that was expressed in blood cells. Three-banded patterns were never observed in males or in putatively homozygous females. These patterns suggest simultaneous, but unequal, expression of the maternally and paternally derived Gpd alleles within individual cells. The absence of such partial expression was noted in a parallel survey of females heterozygous at the Pgd-A locus. Thus, it appears that Gpd and Pgk-A are X-linked in D. virginiana and subject to preferential paternal allele inactivation, but that dosage compensation may not be complete for all paternally derived X-linked genes.

  8. Estrogen supplementation failed to attenuate biochemical indices of neutrophil infiltration or damage in rat skeletal muscles following ischemia.

    Science.gov (United States)

    Tiidus, Peter M; Deller, Mirada; Bombardier, Eric; Gül, Mustafa; Liu, X Linda

    2005-01-01

    This study examined the effects of estrogen supplementation on markers of neutrophil infiltration and damage in skeletal muscle of rats following ischemia. Male and female gonad-intact rats, with or without 14 days of estrogen supplementation were subjected to two hours of hind-limb ischemia and sacrificed at 24, 48 or 72 hours post-ischemia. Control animals were sacrificed without ischemia. Plantaris and red and white gastrocneimus muscles were removed and assayed for myeloperoxidase (MPO), a marker of neutrophil infiltration, and glucose-6-phosphate dehydrogenase (G6PD) and beta-glucuronidase (betaGLU), as markers of muscle damage. Significant elevations of MPO, G6PD and betaGLU activities were observed at various time points post-ischemia. No systematic differences between genders were noted in any of the measures. Estrogen supplementation in both male and female animals failed to significantly attenuate post-ischemia increases in MPO, G6PD and betaGLU activities in any of the muscles studied and in some cases accentuated activities of some of these measures. Unlike previous findings following exercise in skeletal muscle, this study failed to demonstrate estrogen-induced attenuation of indices of neutrophil infiltration or damage in skeletal muscles of rats up to 72 hours following ischemia. This demonstrates that estrogen may not consistently attenuate neutrophil infiltration and that a number of variables including damage modality, tissue or estrogen level may influence this.

  9. Estrogen supplementation failed to attenuate biochemical indices of neutrophil infiltration or damage in rat skeletal muscles following ischemia

    Directory of Open Access Journals (Sweden)

    PETER M TIIDUS

    2005-01-01

    Full Text Available This study examined the effects of estrogen supplementation on markers of neutrophil infiltration and damage in skeletal muscle of rats following ischemia. Male and female gonad-intact rats, with or without 14 days of estrogen supplementation were subjected to two hours of hind-limb ischemia and sacrificed at 24, 48 or 72 hours post-ischemia. Control animals were sacrificed without ischemia. Plantaris and red and white gastrocneimus muscles were removed and assayed for myeloperoxidase (MPO, a marker of neutrophil infiltration, and glucose-6-phosphate dehydrogenase (G6PD and ß-glucuronidase (GLU, as markers of muscle damage. Significant elevations of MPO, G6PD and GLU activities were observed at various time points post-ischemia. No systematic differences between genders were noted in any of the measures. Estrogen supplementation in both male and female animals failed to significantly attenuate post-ischemia increases in MPO, G6PD and GLU activities in any of the muscles studied and in some cases accentuated activities of some of these measures. Unlike previous findings following exercise in skeletal muscle, this study failed to demonstrate estrogen-induced attenuation of indices of neutrophil infiltration or damage in skeletal muscles of rats up to 72 hours following ischemia. This demonstrates that estrogen may not consistently attenuate neutrophil infiltration and that a number of variables including damage modality, tissue or estrogen level may influence this.

  10. Two-phase aqueous micellar systems: an alternative method for protein purification

    Directory of Open Access Journals (Sweden)

    Rangel-Yagui C. O.

    2004-01-01

    Full Text Available Two-phase aqueous micellar systems can be exploited in separation science for the extraction/purification of desired biomolecules. This article reviews recent experimental and theoretical work by Blankschtein and co-workers on the use of two-phase aqueous micellar systems for the separation of hydrophilic proteins. The experimental partitioning behavior of the enzyme glucose-6-phosphate dehydrogenase (G6PD in two-phase aqueous micellar systems is also reviewed and new results are presented. Specifically, we discuss very recent work on the purification of G6PD using: i a two-phase aqueous micellar system composed of the nonionic surfactant n-decyl tetra(ethylene oxide (C10E4, and (ii a two-phase aqueous mixed micellar system composed of C10E4 and the cationic surfactant decyltrimethylammonium bromide (C10TAB. Our results indicate that the two-phase aqueous mixed (C10E4/C10TAB micellar system can improve significantly the partitioning behavior of G6PD relative to that observed in the two-phase aqueous C10E4 micellar system.

  11. Labelling of the pineal gland with 99mTc-glucose-6-phosphate

    International Nuclear Information System (INIS)

    Ribeiro, M.J.; Santos, A.C.; De Lima, J.J.P.

    1998-01-01

    Lately, the pineal body has been the subject of a large variety of studies. Only recently it has been understood the role played by this endocrine gland to maintain the balance of the human body and also in animal models. Although small in dimensions, the pineal body is a very active organ, able to transmit precise temporal information. It probably participates in the synchronization of several organic functions. The present work aims to study a possible use of 99m Tc-glucose-6-P as a tracer for the pineal gland. Histoautoradiographic studies have been performed in Wistar rats. Tomoscintigraphic studies were acquired in patients and in albine rabbits (oryctolagus cuniculus hyplus). The labelling efficiency and the radiochemical purity of the labelled products have always been tested. Animal and human SPECT exams, show an activity focus projected over the area corresponding to the pineal body localization. Autoradiographic studies using [1- 14 C]-glucose-6-P did not reveal a more relevant activity at the pineal level, probably due to its hepatic conversion to 14 C-glucose. (author)

  12. Toxicological effects of thiomersal and ethylmercury: Inhibition of the thioredoxin system and NADP+-dependent dehydrogenases of the pentose phosphate pathway

    International Nuclear Information System (INIS)

    Rodrigues, Juan; Branco, Vasco; Lu, Jun; Holmgren, Arne; Carvalho, Cristina

    2015-01-01

    Mercury (Hg) is a strong toxicant affecting mainly the central nervous, renal, cardiovascular and immune systems. Thiomersal (TM) is still in use in medical practice as a topical antiseptic and as a preservative in multiple dose vaccines, routinely given to young children in some developing countries, while other forms of mercury such as methylmercury represent an environmental and food hazard. The aim of the present study was to determine the effects of thiomersal (TM) and its breakdown product ethylmercury (EtHg) on the thioredoxin system and NADP + -dependent dehydrogenases of the pentose phosphate pathway. Results show that TM and EtHg inhibited the thioredoxin system enzymes in purified suspensions, being EtHg comparable to methylmercury (MeHg). Also, treatment of neuroblastoma and liver cells with TM or EtHg decreased cell viability (GI 50 : 1.5 to 20 μM) and caused a significant (p < 0.05) decrease in the overall activities of thioredoxin (Trx) and thioredoxin reductase (TrxR) in a concentration- and time-dependent manner in cell lysates. Compared to control, the activities of Trx and TrxR in neuroblastoma cells after EtHg incubation were reduced up to 60% and 80% respectively, whereas in hepatoma cells the reduction was almost 100%. In addition, the activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were also significantly inhibited by all mercurials, with inhibition intensity of Hg 2+ > MeHg ≈ EtHg > TM (p < 0.05). Cell incubation with sodium selenite alleviated the inhibitory effects on TrxR and glucose-6-phosphate dehydrogenase. Thus, the molecular mechanism of toxicity of TM and especially of its metabolite EtHg encompasses the blockage of the electrons from NADPH via the thioredoxin system. - Highlights: • TM and EtHg inhibit Trx and TrxR both in purified suspensions and cell lysates. • TM and EtHg also inhibit the activities of G6PDH and 6PGDH in cell lysates, • Co-exposure to selenite alleviates the

  13. Toxicological effects of thiomersal and ethylmercury: Inhibition of the thioredoxin system and NADP{sup +}-dependent dehydrogenases of the pentose phosphate pathway

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Juan, E-mail: juanricardorodrigues@gmail.com [Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa (Portugal); Laboratory of Biochemistry, Faculty of Pharmacy, Central University of Venezuela (Venezuela, Bolivarian Republic of); Branco, Vasco [Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa (Portugal); Lu, Jun; Holmgren, Arne [Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet (Sweden); Carvalho, Cristina, E-mail: cristina.carvalho@ff.ulisboa.pt [Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa (Portugal)

    2015-08-01

    Mercury (Hg) is a strong toxicant affecting mainly the central nervous, renal, cardiovascular and immune systems. Thiomersal (TM) is still in use in medical practice as a topical antiseptic and as a preservative in multiple dose vaccines, routinely given to young children in some developing countries, while other forms of mercury such as methylmercury represent an environmental and food hazard. The aim of the present study was to determine the effects of thiomersal (TM) and its breakdown product ethylmercury (EtHg) on the thioredoxin system and NADP{sup +}-dependent dehydrogenases of the pentose phosphate pathway. Results show that TM and EtHg inhibited the thioredoxin system enzymes in purified suspensions, being EtHg comparable to methylmercury (MeHg). Also, treatment of neuroblastoma and liver cells with TM or EtHg decreased cell viability (GI{sub 50}: 1.5 to 20 μM) and caused a significant (p < 0.05) decrease in the overall activities of thioredoxin (Trx) and thioredoxin reductase (TrxR) in a concentration- and time-dependent manner in cell lysates. Compared to control, the activities of Trx and TrxR in neuroblastoma cells after EtHg incubation were reduced up to 60% and 80% respectively, whereas in hepatoma cells the reduction was almost 100%. In addition, the activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were also significantly inhibited by all mercurials, with inhibition intensity of Hg{sup 2+} > MeHg ≈ EtHg > TM (p < 0.05). Cell incubation with sodium selenite alleviated the inhibitory effects on TrxR and glucose-6-phosphate dehydrogenase. Thus, the molecular mechanism of toxicity of TM and especially of its metabolite EtHg encompasses the blockage of the electrons from NADPH via the thioredoxin system. - Highlights: • TM and EtHg inhibit Trx and TrxR both in purified suspensions and cell lysates. • TM and EtHg also inhibit the activities of G6PDH and 6PGDH in cell lysates, • Co-exposure to selenite alleviates

  14. Adaptation of red cell enzymes and intermediates in metabolic disorders.

    Science.gov (United States)

    Goebel, K M; Goebel, F D; Neitzert, A; Hausmann, L; Schneider, J

    1975-01-01

    The metabolic activity of the red cell glycolytic pathway hexose monophosphate shunt (HMP) with dependent glutathione system was studied in patients with hyperthyroidism (n = 10), hyperlipoproteinemia (n = 16), hypoglycemia (n = 25) and hyperglycemia (n = 23). In uncontrolled diabetics and patients with hyperthyroidism the mean value of glucose phosphate isomerase (GPI), glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GR) was increased, whereas these enzyme activities were reduced in patients with hypoglycemia. Apart from a few values of hexokinase (HK) which were lower than normal the results in hyperlipoproteinemia patients remained essentially unchanged, including the intermediates such as 2,3-diphosphoglycerate (2,3-DPG), adenosine triphosphate (ATP) and reduced glutathione (GSH). While increased rates of 2,3-DPG and ATP in hypoglycemia patients were obtained, these substrates were markedly reduced in diabetics.

  15. Enhanced neuronal glucose transporter expression reveals metabolic choice in a HD Drosophila model.

    Science.gov (United States)

    Besson, Marie Thérèse; Alegría, Karin; Garrido-Gerter, Pamela; Barros, Luis Felipe; Liévens, Jean-Charles

    2015-01-01

    Huntington's disease is a neurodegenerative disorder caused by toxic insertions of polyglutamine residues in the Huntingtin protein and characterized by progressive deterioration of cognitive and motor functions. Altered brain glucose metabolism has long been suggested and a possible link has been proposed in HD. However, the precise function of glucose transporters was not yet determined. Here, we report the effects of the specifically-neuronal human glucose transporter expression in neurons of a Drosophila model carrying the exon 1 of the human huntingtin gene with 93 glutamine repeats (HQ93). We demonstrated that overexpression of the human glucose transporter in neurons ameliorated significantly the status of HD flies by increasing their lifespan, reducing their locomotor deficits and rescuing eye neurodegeneration. Then, we investigated whether increasing the major pathways of glucose catabolism, glycolysis and pentose-phosphate pathway (PPP) impacts HD. To mimic increased glycolytic flux, we overexpressed phosphofructokinase (PFK) which catalyzes an irreversible step in glycolysis. Overexpression of PFK did not affect HQ93 fly survival, but protected from photoreceptor loss. Overexpression of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the PPP, extended significantly the lifespan of HD flies and rescued eye neurodegeneration. Since G6PD is able to synthesize NADPH involved in cell survival by maintenance of the redox state, we showed that tolerance to experimental oxidative stress was enhanced in flies co-expressing HQ93 and G6PD. Additionally overexpressions of hGluT3, G6PD or PFK were able to circumvent mitochondrial deficits induced by specific silencing of genes necessary for mitochondrial homeostasis. Our study confirms the involvement of bioenergetic deficits in HD course; they can be rescued by specific expression of a glucose transporter in neurons. Finally, the PPP and, to a lesser extent, the glycolysis seem to mediate the hGluT3

  16. Enhanced neuronal glucose transporter expression reveals metabolic choice in a HD Drosophila model.

    Directory of Open Access Journals (Sweden)

    Marie Thérèse Besson

    Full Text Available Huntington's disease is a neurodegenerative disorder caused by toxic insertions of polyglutamine residues in the Huntingtin protein and characterized by progressive deterioration of cognitive and motor functions. Altered brain glucose metabolism has long been suggested and a possible link has been proposed in HD. However, the precise function of glucose transporters was not yet determined. Here, we report the effects of the specifically-neuronal human glucose transporter expression in neurons of a Drosophila model carrying the exon 1 of the human huntingtin gene with 93 glutamine repeats (HQ93. We demonstrated that overexpression of the human glucose transporter in neurons ameliorated significantly the status of HD flies by increasing their lifespan, reducing their locomotor deficits and rescuing eye neurodegeneration. Then, we investigated whether increasing the major pathways of glucose catabolism, glycolysis and pentose-phosphate pathway (PPP impacts HD. To mimic increased glycolytic flux, we overexpressed phosphofructokinase (PFK which catalyzes an irreversible step in glycolysis. Overexpression of PFK did not affect HQ93 fly survival, but protected from photoreceptor loss. Overexpression of glucose-6-phosphate dehydrogenase (G6PD, the key enzyme of the PPP, extended significantly the lifespan of HD flies and rescued eye neurodegeneration. Since G6PD is able to synthesize NADPH involved in cell survival by maintenance of the redox state, we showed that tolerance to experimental oxidative stress was enhanced in flies co-expressing HQ93 and G6PD. Additionally overexpressions of hGluT3, G6PD or PFK were able to circumvent mitochondrial deficits induced by specific silencing of genes necessary for mitochondrial homeostasis. Our study confirms the involvement of bioenergetic deficits in HD course; they can be rescued by specific expression of a glucose transporter in neurons. Finally, the PPP and, to a lesser extent, the glycolysis seem to

  17. Identification and functional evaluation of the reductases and dehydrogenases from Saccharomyces cerevisiae involved in vanillin resistance.

    Science.gov (United States)

    Wang, Xinning; Liang, Zhenzhen; Hou, Jin; Bao, Xiaoming; Shen, Yu

    2016-04-01

    Vanillin, a type of phenolic released during the pre-treatment of lignocellulosic materials, is toxic to microorganisms and therefore its presence inhibits the fermentation. The vanillin can be reduced to vanillyl alcohol, which is much less toxic, by the ethanol producer Saccharomyces cerevisiae. The reducing capacity of S. cerevisiae and its vanillin resistance are strongly correlated. However, the specific enzymes and their contribution to the vanillin reduction are not extensively studied. In our previous work, an evolved vanillin-resistant strain showed an increased vanillin reduction capacity compared with its parent strain. The transcriptome analysis suggested the reductases and dehydrogenases of this vanillin resistant strain were up-regulated. Using this as a starting point, 11 significantly regulated reductases and dehydrogenases were selected in the present work for further study. The roles of these reductases and dehydrogenases in the vanillin tolerance and detoxification abilities of S. cerevisiae are described. Among the candidate genes, the overexpression of the alcohol dehydrogenase gene ADH6, acetaldehyde dehydrogenase gene ALD6, glucose-6-phosphate 1-dehydrogenase gene ZWF1, NADH-dependent aldehyde reductase gene YNL134C, and aldo-keto reductase gene YJR096W increased 177, 25, 6, 15, and 18 % of the strain μmax in the medium containing 1 g L(-1) vanillin. The in vitro detected vanillin reductase activities of strain overexpressing ADH6, YNL134C and YJR096W were notably higher than control. The vanillin specific reduction rate increased by 8 times in ADH6 overexpressed strain but not in YNL134C and YJR096W overexpressed strain. This suggested that the enzymes encoded by YNL134C and YJR096W might prefer other substrate and/or could not show their effects on vanillin on the high background of Adh6p in vivo. Overexpressing ALD6 and ZWF1 mainly increased the [NADPH]/[NADP(+)] and [GSH]/[GSSG] ratios but not the vanillin reductase activities. Their

  18. Role of cytosolic NADP+-dependent isocitrate dehydrogenase in ischemia-reperfusion injury in mouse kidney.

    Science.gov (United States)

    Kim, Jinu; Kim, Ki Young; Jang, Hee-Seong; Yoshida, Takumi; Tsuchiya, Ken; Nitta, Kosaku; Park, Jeen-Woo; Bonventre, Joseph V; Park, Kwon Moo

    2009-03-01

    Cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) synthesizes reduced NADP (NADPH), which is an essential cofactor for the generation of reduced glutathione (GSH), the most abundant and important antioxidant in mammalian cells. We investigated the role of IDPc in kidney ischemia-reperfusion (I/R) in mice. The activity and expression of IDPc were highest in the cortex, modest in the outer medulla, and lowest in the inner medulla. NADPH levels were greatest in the cortex. IDPc expression in the S1 and S2 segments of proximal tubules was higher than in the S3 segment, which is much more susceptible to I/R. IDPc protein was also highly expressed in the mitochondrion-rich intercalated cells of the collecting duct. IDPc activity was 10- to 30-fold higher than the activity of glucose-6-phosphate dehydrogenase, another producer of cytosolic NADPH, in various kidney regions. This study identifies that IDPc may be the primary source of NADPH in the kidney. I/R significantly reduced IDPc expression and activity and NADPH production and increased the ratio of oxidized glutathione to total glutathione [GSSG/(GSH+GSSG)], resulting in kidney dysfunction, tubular cell damage, and lipid peroxidation. In LLC-PK(1) cells, upregulation of IDPc by IDPc gene transfer protected the cells against hydrogen peroxide, enhancing NADPH production, inhibiting the increase of GSSG/(GSH+GSSG), and reducing lipid peroxidation. IDPc downregulation by small interference RNA treatment presented results contrasting with the upregulation. In conclusion, these results demonstrate that IDPc is expressed differentially along tubules in patterns that may contribute to differences in susceptibility to injury, is a major enzyme in cytosolic NADPH generation in kidney, and is downregulated with I/R.

  19. Methaemoglobinaemia in a G6PD-deficient child treated with rasburicase

    OpenAIRE

    Bontant, Thomas; Le Garrec, Sophie; Avran, David; Dauger, Stephane

    2014-01-01

    A 5-year-old boy from the Congo, was admitted for hyperleucocytic acute lymphoblastic leukaemia, with a high risk of tumour lysis syndrome (TLS). He had splenomegaly and mediastinal lymphadenopathy on chest X-ray. We started steroids and hyperhydration with rasburicase to prevent TLS. Respiratory failure with mediastinal enlargement developed rapidly. A few hours after intensive care unit (ICU) admission, he was started on mechanical ventilation. Chemotherapy was started immediately given the...

  20. Common mutations in G6PD of Vietnamese-Kinh deficient patients

    African Journals Online (AJOL)

    DANG THI LAN ANH

    2013-03-20

    Mar 20, 2013 ... (2009) found out six mutations in Kinh and Stieng's ethnics population by ... 6. P. D e n z y m e a c tiv ity. (IU. /g. Hb. ) Figure 1. Distribution of patients within the enzyme activity level. step lysis method. This method was improved from method of. Chaimosit ... sent to Sigma Aldrich- Singapore for synthesis.

  1. Oxidative Stress in Patients With Nongenital Warts

    Directory of Open Access Journals (Sweden)

    Sezai Sasmaz

    2005-01-01

    Full Text Available Comparison of oxidative stress status between subjects with or without warts is absent in the literature. In this study, we evaluated 31 consecutive patients with warts (15 female, 16 male and 36 control cases with no evidence of disease to determine the effects of oxidative stress in patients with warts. The patients were classified according to the wart type, duration, number, and location of lesions. We measured the indicators of oxidative stress such as catalase (CAT, glucose-6-phosphate dehydrogenase (G6PD, superoxide dismutase (SOD, and malondialdehyde (MDA in the venous blood by spectrophotometry. There was a statistically significant increase in levels of CAT, G6PD, SOD activities and MDA in the patients with warts compared to the control group (P<.05. However, we could not define a statistically significant correlation between these increased enzyme activities and MDA levels and the type, the duration, the number, and the location of lesions. We determined possible suppression of T cells during oxidative stress that might have a negative effect on the prognosis of the disease. Therefore, we propose an argument for the appropriateness to give priority to immunomodulatory treatment alternatives instead of destructive methods in patients with demonstrated oxidative stress.

  2. Altered oxidative stress and carbohydrate metabolism in canine mammary tumors

    Directory of Open Access Journals (Sweden)

    K. Jayasri

    2016-12-01

    Full Text Available Aim: Mammary tumors are the most prevalent type of neoplasms in canines. Even though cancer induced metabolic alterations are well established, the clinical data describing the metabolic profiles of animal tumors is not available. Hence, our present investigation was carried out with the aim of studying changes in carbohydrate metabolism along with the level of oxidative stress in canine mammary tumors. Materials and Methods: Fresh mammary tumor tissues along with the adjacent healthy tissues were collected from the college surgical ward. The levels of thiobarbituric acid reactive substances (TBARS, glutathione, protein, hexose, hexokinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, and glucose-6-phosphate dehydrogenase (G6PD were analyzed in all the tissues. The results were analyzed statistically. Results: More than two-fold increase in TBARS and three-fold increase in glutathione levels were observed in neoplastic tissues. Hexokinase activity and hexose concentration (175% was found to be increased, whereas glucose-6-phosphatase (33%, fructose-1, 6-bisphosphatase (42%, and G6PD (5 fold activities were reduced in tumor mass compared to control. Conclusion: Finally, it was revealed that lipid peroxidation was increased with differentially altered carbohydrate metabolism in canine mammary tumors.

  3. Delayed effects of radiation on enzymes in erythrocytes

    International Nuclear Information System (INIS)

    Li Jinying; Zhang Weiping; Liu Benti

    1998-01-01

    Objective: To study the delayed effects of radiation on the enzymes in erythrocytes. Methods: The activity of 8 enzymes, related glycolysis, hexose monophosphate shunt, nucleotide metabolism, redox reaction and esterase in erythrocytes of five patients with bone marrow form of acute radiation sickness (ARS) were assayed at 1,2,3 and 6 years after exposure to 60 Co radiation. Results: The decreased activities of glucose-6-phosphate dehydrogenase (G6PD), pyruvate kinase (PK), NADH-methemoglobin reductase (MR) during the stage of crisis and of acetylcholinesterase (ACE) during the stage of convalescence were recovered to varying extent, whereas the lowered activities of the first three enzymes in some cases remained unchanged. There was no correlation between the enzyme activity and the radiation dose as well as the age of the patients. Conclusion: It is demonstrated that the delayed effects of radiation damage to erythrocyte enzymes are most significant in PK of glycolysis, G6PD of hexose monophosphate shunt and MR of redox reaction. It is suggested that the genes related to the synthesis of erythrocyte enzymes may be damaged by radiation

  4. Effects of dehydroepiandrosterone (DHEA) on glucose metabolism in isolated hepatocytes from Zucker rats

    International Nuclear Information System (INIS)

    Finan, A.; Cleary, M.P.

    1986-01-01

    DHEA has been shown to competitively inhibit the pentose phosphate shunt (PPS) enzyme glucose-6-phosphate dehydrogenase (G6PD) when added in vitro to supernatants or homogenates prepared from mammalian tissues. However, no consistent effect on G6PD activity has been determined in tissue removed from DHEA-treated rats. To explore the effects of DHEA on PPS, glucose utilization was measured in hepatocytes from lean and obese male Zucker rats (8 wks of age) following 1 wk of DHEA treatment (0.6% in diet). Incubation of isolated hepatocytes from treated lean Zucker rats with either [1- 14 C] glucose or [6- 14 C] glucose resulted in significant decreases in CO 2 production and total glucose utilization. DHEA-lean rats also had lowered fat pad weights. In obese rats, there was no effect of 1 wk of treatment on either glucose metabolism or fat pad weight. The calculated percent contribution of the PPS to glucose metabolism in hepatocytes was not changed for either DHEA-lean or obese rats when compared to control rats. In conclusion, 1 wk of DHEA treatment lowered overall glucose metabolism in hepatocytes of lean Zucker rats, but did not selectively affect the PPS. The lack of an effect of short-term treatment in obese rats may be due to differences in their metabolism or storage/release of DHEA in tissues in comparison to lean rats

  5. Hemoglobin H disease in the Al-Qatif region of Saudi Arabia

    International Nuclear Information System (INIS)

    Ankra-Badu, George A.; Al-Jama, A.; Al-Kadim, Y.

    2001-01-01

    The Al-Qatif region in the Eastern Province of Saudi Arabia has thehighest prevalence of alpha-thalassemia genes in the Kingdom. Hemoglobin H(Hb H) disease, however, has been rarely reported. We decided therefore toverify the rarity of disease and characterize the presenting features incases identified. All patients seen in Qatif Central Hospital betweenSeptember 1988 and November 1990 with low red cell indices were screened forHb H disease and those found positive had clinical data compiled from theirhospital records and analyzed. Thirty-nine cases of Hb H were diagnosed. Themean age of patients was 18 years. The mean hemoglobin was 13.5 g/dL forneonates and 7.6 g/dL for others. The mean Hb Bart's level was 27.5% inneonates and the mean Hb H level in others was 11.1%. In addition to low redcell indices, all patients had a high red cell distribution width (RDW) meanof 25.6%. The main clinical signs were jaundice and hepatosplenomegaly.Concurrent glucose-6-phosphate Dehydrogenase (G6PD) deficiency was seen in28.2% of patients. Hemoglobin H disease is not uncommon in the Al-Qatifregion of Saudi Arabia. The red cell indices may mimic iron deficiency, whichshould be excluded by the presence of jaundice and organomegaly. Thecondition often co-exists with G6PD deficiency. (author)

  6. Expression stability and selection of optimal reference genes for gene expression normalization in early life stage rainbow trout exposed to cadmium and copper.

    Science.gov (United States)

    Shekh, Kamran; Tang, Song; Niyogi, Som; Hecker, Markus

    2017-09-01

    Gene expression analysis represents a powerful approach to characterize the specific mechanisms by which contaminants interact with organisms. One of the key considerations when conducting gene expression analyses using quantitative real-time reverse transcription-polymerase chain reaction (qPCR) is the selection of appropriate reference genes, which is often overlooked. Specifically, to reach meaningful conclusions when using relative quantification approaches, expression levels of reference genes must be highly stable and cannot vary as a function of experimental conditions. However, to date, information on the stability of commonly used reference genes across developmental stages, tissues and after exposure to contaminants such as metals is lacking for many vertebrate species including teleost fish. Therefore, in this study, we assessed the stability of expression of 8 reference gene candidates in the gills and skin of three different early life-stages of rainbow trout after acute exposure (24h) to two metals, cadmium (Cd) and copper (Cu) using qPCR. Candidate housekeeping genes were: beta actin (b-actin), DNA directed RNA polymerase II subunit I (DRP2), elongation factor-1 alpha (EF1a), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), glucose-6-phosphate dehydrogenase (G6PD), hypoxanthine phosphoribosyltransferase (HPRT), ribosomal protein L8 (RPL8), and 18S ribosomal RNA (18S). Four algorithms, geNorm, NormFinder, BestKeeper, and the comparative ΔCt method were employed to systematically evaluate the expression stability of these candidate genes under control and exposed conditions as well as across three different life-stages. Finally, stability of genes was ranked by taking geometric means of the ranks established by the different methods. Stability of reference genes was ranked in the following order (from lower to higher stability): HPRTG6PDG6PD

  7. High-sugar intake does not exacerbate metabolic abnormalities or cardiac dysfunction in genetic cardiomyopathy.

    Science.gov (United States)

    Hecker, Peter A; Galvao, Tatiana F; O'Shea, Karen M; Brown, Bethany H; Henderson, Reney; Riggle, Heather; Gupte, Sachin A; Stanley, William C

    2012-05-01

    A high-sugar intake increases heart disease risk in humans. In animals, sugar intake accelerates heart failure development by increased reactive oxygen species (ROS). Glucose-6-phosphate dehydrogenase (G6PD) can fuel ROS production by providing reduced nicotinamide adenine dinucleotide phosphate (NADPH) for superoxide generation by NADPH oxidase. Conversely, G6PD also facilitates ROS scavenging using the glutathione pathway. We hypothesized that a high-sugar intake would increase flux through G6PD to increase myocardial NADPH and ROS and accelerate cardiac dysfunction and death. Six-week-old TO-2 hamsters, a non-hypertensive model of genetic cardiomyopathy caused by a δ-sarcoglycan mutation, were fed a long-term diet of high starch or high sugar (57% of energy from sucrose plus fructose). After 24 wk, the δ-sarcoglycan-deficient animals displayed expected decreases in survival and cardiac function associated with cardiomyopathy (ejection fraction: control 68.7 ± 4.5%, TO-2 starch 46.1 ± 3.7%, P sugar 58.0 ± 4.2%, NS, versus TO-2 starch or control; median survival: TO-2 starch 278 d, TO-2 sugar 318 d, P = 0.133). Although the high-sugar intake was expected to exacerbate cardiomyopathy, surprisingly, there was no further decrease in ejection fraction or survival with high sugar compared with starch in cardiomyopathic animals. Cardiomyopathic animals had systemic and cardiac metabolic abnormalities (increased serum lipids and glucose and decreased myocardial oxidative enzymes) that were unaffected by diet. The high-sugar intake increased myocardial superoxide, but NADPH and lipid peroxidation were unaffected. A sugar-enriched diet did not exacerbate ventricular function, metabolic abnormalities, or survival in heart failure despite an increase in superoxide production. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Effects of x-irradiation on lens reducing systems

    International Nuclear Information System (INIS)

    Giblin, F.J.; Chakrapani, B.; Reddy, V.N.

    1978-01-01

    Studies have been made of the effects of x ray on various lens reducing systems including the levels of NADPH and glutathione (GSH), the activity of the hexose monophosphate shunt (HMS), and the activities of certain enzymes including glutathion reductase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase (G-6-PD). It was found that during several weeks following x irradiation but prior to cataract formation there was very little change in the number of reduced -SH groups per unit weight of lens protein but that, with the appearance of cataract, there was a sudden loss of protein -SH groups. In contrast, the concentration of GSH in the x-rayed lens decreased throughout the experimental period. Similarly, the concentration of NADPH in the x-rayed lens was found to decrease significantly relative to controls one week prior to cataract formation and the ratio of NADPH to NADP + in the lens shifted at this time period from a value greater than 1.0 in the control lens to less than 1.0 in the x-rayed lens. A corresponding decrease occurred in the activity of the HMS in x-rayed lenses as measured by culture in the presence of 1- 14 C-labelled glucose. G-6-PD was partially inactivated in the x-rayed lens. Of the eight enzymes studied, G-6-PD appeared to be the most sensitive to x-irradiation. The data indicate that x-irradiation results in a steady decrease in the effectiveness of lens reducing systems and that, when these systems reach a critically low point, sudden oxidation of protein -SH groups and formation of high molecular weight protein aggregates may be initiated

  9. Effects of x-irradiation on lens reducing systems. [Rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Giblin, F.J.; Chakrapani, B.; Reddy, V.N.

    1978-01-01

    Studies have been made of the effects of x ray on various lens reducing systems including the levels of NADPH and glutathione (GSH), the activity of the hexose monophosphate shunt (HMS), and the activities of certain enzymes including glutathion reductase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase (G-6-PD). It was found that during several weeks following x irradiation but prior to cataract formation there was very little change in the number of reduced -SH groups per unit weight of lens protein but that, with the appearance of cataract, there was a sudden loss of protein -SH groups. In contrast, the concentration of GSH in the x-rayed lens decreased throughout the experimental period. Similarly, the concentration of NADPH in the x-rayed lens was found to decrease significantly relative to controls one week prior to cataract formation and the ratio of NADPH to NADP/sup +/ in the lens shifted at this time period from a value greater than 1.0 in the control lens to less than 1.0 in the x-rayed lens. A corresponding decrease occurred in the activity of the HMS in x-rayed lenses as measured by culture in the presence of 1-/sup 14/C-labelled glucose. G-6-PD was partially inactivated in the x-rayed lens. Of the eight enzymes studied, G-6-PD appeared to be the most sensitive to x-irradiation. The data indicate that x-irradiation results in a steady decrease in the effectiveness of lens reducing systems and that, when these systems reach a critically low point, sudden oxidation of protein -SH groups and formation of high molecular weight protein aggregates may be initiated.

  10. Machine learning prioritizes synthesis of primaquine ureidoamides with high antimalarial activity and attenuated cytotoxicity.

    Science.gov (United States)

    Levatić, Jurica; Pavić, Kristina; Perković, Ivana; Uzelac, Lidija; Ester, Katja; Kralj, Marijeta; Kaiser, Marcel; Rottmann, Matthias; Supek, Fran; Zorc, Branka

    2018-02-25

    Primaquine (PQ) is a commonly used drug that can prevent the transmission of Plasmodium falciparum malaria, however toxicity limits its use. We prepared five groups of PQ derivatives: amides 1a-k, ureas 2a-k, semicarbazides 3a,b, acylsemicarbazides 4a-k and bis-ureas 5a-v, and evaluated them for antimalarial activity in vitro against the erythrocytic stage of P. falciparum NF54. Particular substituents, such as trityl (in 2j and 5r) and methoxybenzhydryl (in 3b and 5v) were associated with a favorable cytotoxicity-to-activity ratio. To systematically link structural features of PQ derivatives to antiplasmodial activity, we performed a quantitative structure-activity relationship (QSAR) study using the Support Vector Machines machine learning method. This yielded a highly accurate statistical model (R 2  = 0.776 in cross-validation), which was used to prioritize novel candidate compounds. Seven novel PQ-ureidoamides 10a-g were synthesized and evaluated for activity, highlighting the benzhydryl ureidoamides 10e and 10f derived from p-chlorophenylglycine. Further experiments on human cell lines revealed that 10e and 10f are an order of magnitude less toxic than PQ in vitro while having antimalarial activity indistinguishable from PQ. The toxicity profile of novel compounds 10 toward human cells was particularly favorable when the glucose-6-phosphate dehydrogenase (G6PD) was inhibited, while toxicity of PQ was exacerbated by G6PD inhibition. Our work therefore highlights promising lead compounds for the development of effective antimalarial drugs that may also be safer for G6PD-deficient patients. In addition, we provide computational inferences of antimalarial activity and cytotoxicity for thousands of PQ-like molecular structures. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. Oral lipid-based nanoformulation of tafenoquine enhanced bioavailability and blood stage antimalarial efficacy and led to a reduction in human red blood cell loss in mice

    Directory of Open Access Journals (Sweden)

    Melariri P

    2015-02-01

    Full Text Available Paula Melariri,1 Lonji Kalombo,2 Patric Nkuna,2 Admire Dube,2,3 Rose Hayeshi,2 Benhards Ogutu,4,5 Liezl Gibhard,6 Carmen deKock,6 Peter Smith,6 Lubbe Wiesner,6 Hulda Swai2 1Polymers and Composites, Material Science and Manufacturing, Council for Scientific and Industrial Research, Port Elizabeth, South Africa; 2Polymer and Composites, Material Science and Manufacturing, Council for Scientific and Industrial Research, Pretoria, South Africa; 3School of Pharmacy, University of the Western Cape, Bellville, South Africa; 4Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya; 5Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya; 6Division of Pharmacology, University of Cape Town Medical School, Groote Schuur Hospital, Cape Town, South Africa Abstract: Tafenoquine (TQ, a new synthetic analog of primaquine, has relatively poor bioavailability and associated toxicity in glucose-6-phosphate dehydrogenase (G6PD-deficient individuals. A microemulsion formulation of TQ (MTQ with sizes <20 nm improved the solubility of TQ and enhanced the oral bioavailability from 55% to 99% in healthy mice (area under the curve 0 to infinity: 11,368±1,232 and 23,842±872 min·µmol/L for reference TQ and MTQ, respectively. Average parasitemia in Plasmodium berghei-infected mice was four- to tenfold lower in the MTQ-treated group. In vitro antiplasmodial activities against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum indicated no change in half maximal inhibitory concentration, suggesting that the microemulsion did not affect the inherent activity of TQ. In a humanized mouse model of G6PD deficiency, we observed reduction in toxicity of TQ as delivered by MTQ at low but efficacious concentrations of TQ. We hereby report an enhancement in the solubility, bioavailibility, and efficacy of TQ against blood stages of Plasmodium parasites without a corresponding increase in toxicity

  12. Influence of salts on the coexistence curve and protein partitioning in nonionic aqueous two-phase micellar systems

    Directory of Open Access Journals (Sweden)

    A. M. Lopes

    2014-12-01

    Full Text Available Aqueous two-phase micellar systems (ATPMS can be exploited in separation science for the extraction/purification of desired biomolecules. Prior to phase separation the surfactant solution reaches a cloud point temperature, which is influenced by the presence of electrolytes. In this work, we provide an investigation on the cloud point behavior of the nonionic surfactant C10E4 in the presence of NaCl, Li2SO4 and KI. We also investigated the salts' influence on a model protein partitioning. NaCl and Li2SO4 promoted a depression of the cloud point. The order of salts and the concentration that decreased the cloud point was: Li2SO4 0.5 M > NaCl 0.5 M ≈ Li2SO4 0.2 M. On the other hand, 0.5 M KI dislocated the curve to higher cloud point values. For our model protein, glucose-6-phosphate dehydrogenase (G6PD, partitioning experiments with 0.5 M NaCl or 0.2 M Li2SO4 at 13.85 ºC showed similar results, with K G6PD ~ 0.46. The lowest partition coefficient was obtained in the presence of 0.5 M KI (K G6PD = 0.12, with major recovery of the enzyme in the micelle-dilute phase (%Recovery = 90%. Our results show that choosing the correct salt to add to ATPMS may be useful to attain the desired partitioning conditions at more extreme temperatures. Furthermore, this system can be effective to separate a target biomolecule from fermented broth contaminants.

  13. Rheological properties of erythrocytes in patients infected with Clostridium difficile.

    Science.gov (United States)

    Czepiel, Jacek; Jurczyszyn, Artur; Biesiada, Grażyna; Sobczyk-Krupiarz, Iwona; Jałowiecka, Izabela; Świstek, Magdalena; Perucki, William; Teległów, Aneta; Marchewka, Jakub; Dąbrowski, Zbigniew; Mach, Tomasz; Garlicki, Aleksander

    2014-12-04

    Clostridium difficile infection (CDI) is a bacterial infection of the digestive tract. Acute infections are accompanied by increased risk for venous thromboembolism (VTE). To date, there have been no studies of the rheological properties of blood during the course of digestive tract infections. The aim of our study was to examine the effects of CDI on red blood cell (RBC) rheology, specifically RBC deformability, RBC aggregation, and plasma viscosity. In addition, the activity of glucose 6 phosphate dehydrogenase (G6PD) and acetylcholinesterase (AChE) in RBC was studied. Our study group included 20 patients with CDI, 20 healthy persons comprised the control group. We examined the effects of CDI on the rheology of RBCs, their deformability and aggregation, using a Laser-assisted Optical Rotational Cell Analyzer (LORCA). Plasma viscosity was determined using a capillary tube plasma viscosymeter. Moreover, we estimated the activity of AChE and G6PD in RBC using spectrophotometric method. A statistically significant increase was found in the aggregation index, viscosity and activity of G6PD whereas the amount of time to reach half of maximum aggregation (t½) and the amplitude of aggregation (AMP) both showed statistically significantly decreases among patients with CDI compared to the control group. We also observed that the Elongation Index (EI) was decreased when shear stress values were low, between 0.3 Pa and 0.58 Pa, whereas EI was increased for shear stress in the range of 1.13-59.97 Pa. These observations were statistically significant. We report for the first time that acute infection of the gastrointestinal tract with Clostridium difficile is associated with abnormalities in rheological properties of blood, increased serum viscosity as well as increased aggregation of RBCs, which correlated with severity of inflammation. These abnormalities may be an additional mechanism causing increased incidence of VTE in CDI.

  14. Rheological properties of erythrocytes in patients infected with Clostridium difficile

    Directory of Open Access Journals (Sweden)

    Jacek Czepiel

    2014-12-01

    Full Text Available Clostridium difficile infection (CDI is a bacterial infection of the digestive tract. Acute infections are accompanied by increased risk for venous thromboembolism (VTE. To date, there have been no studies of the rheological properties of blood during the course of digestive tract infections. The aim of our study was to examine the effects of CDI on red blood cell (RBC rheology, specifically RBC deformability, RBC aggregation, and plasma viscosity. In addition, the activity of glucose 6 phosphate dehydrogenase (G6PD and acetylcholinesterase (AChE in RBC was studied. Our study group included 20 patients with CDI, 20 healthy persons comprised the control group. We examined the effects of CDI on the rheology of RBCs, their deformability and aggregation, using a Laser–assisted Optical Rotational Cell Analyzer (LORCA. Plasma viscosity was determined using a capillary tube plasma viscosymeter. Moreover, we estimated the activity of AChE and G6PD in RBC using spectrophotometric method. A statistically significant increase was found in the aggregation index, viscosity and activity of G6PD whereas the amount of time to reach half of maximum aggregation (t½ and the amplitude of aggregation (AMP both showed statistically significantly decreases among patients with CDI compared to the control group. We also observed that the Elongation Index (EI was decreased when shear stress values were low, between 0.3 Pa and 0.58 Pa, whereas EI was increased for shear stress in the range of 1.13 - 59.97 Pa. These observations were statistically significant. We report for the first time that acute infection of the gastrointestinal tract with Clostridium difficile is associated with abnormalities in rheological properties of blood, increased serum viscosity as well as increased aggregation of RBCs, which correlated with severity of inflammation. These abnormalities may be an additional mechanism causing increased incidence of VTE in CDI.

  15. Malaria in Brazil, Colombia, Peru and Venezuela: current challenges in malaria control and elimination.

    Science.gov (United States)

    Recht, Judith; Siqueira, André M; Monteiro, Wuelton M; Herrera, Sonia M; Herrera, Sócrates; Lacerda, Marcus V G

    2017-07-04

    In spite of significant progress towards malaria control and elimination achieved in South America in the 2000s, this mosquito-transmitted tropical disease remains an important public health concern in the region. Most malaria cases in South America come from Amazon rain forest areas in northern countries, where more than half of malaria is caused by Plasmodium vivax, while Plasmodium falciparum malaria incidence has decreased in recent years. This review discusses current malaria data, policies and challenges in four South American Amazon countries: Brazil, Colombia, Peru and the Bolivarian Republic of Venezuela. Challenges to continuing efforts to further decrease malaria incidence in this region include: a significant increase in malaria cases in recent years in Venezuela, evidence of submicroscopic and asymptomatic infections, peri-urban malaria, gold mining-related malaria, malaria in pregnancy, glucose-6-phosphate dehydrogenase (G6PD) deficiency and primaquine use, and possible under-detection of Plasmodium malariae. Some of these challenges underscore the need to implement appropriate tools and procedures in specific regions, such as a field-compatible molecular malaria test, a P. malariae-specific test, malaria diagnosis and appropriate treatment as part of regular antenatal care visits, G6PD test before primaquine administration for P. vivax cases (with weekly primaquine regimen for G6PD deficient individuals), single low dose of primaquine for P. falciparum malaria in Colombia, and national and regional efforts to contain malaria spread in Venezuela urgently needed especially in mining areas. Joint efforts and commitment towards malaria control and elimination should be strategized based on examples of successful regional malaria fighting initiatives, such as PAMAFRO and RAVREDA/AMI.

  16. Next-generation sequencing-based molecular diagnosis of chronic non-spherocytic hemolysis in erythrocytic enzymopathies

    Directory of Open Access Journals (Sweden)

    Manu Jamwal

    2017-10-01

    Full Text Available Mutations in genes encoding red blood cell enzymes are often inherited in an autosomal recessive manner and can lead to chronic nonspherocytic hemolytic anemia (CNSHA in homozygotes and compound heterozygotes. Usual clinical manifestations include jaundice, cholelithiasis and splenomegaly with normocytic normochromic hemolysis. Phenotypes range from fully-compensated hemolysis (without anemia to transfusion-dependent states. Definitive diagnosis requires biochemical testing of enzyme levels, which for rarer enzymes are often difficult and not easily available. Molecular diagnosis using a gene-by-gene approach is expensive, time-consuming and cumbersome. Targeted resequencing can expedite the molecular diagnosis in cases where the hemolysis remains unexplained after routine laboratory tests. Ten patients with clinical and laboratory evidence suggestive of hemolytic anemia, but negative family history, were enrolled. Various biochemical and molecular tests were used to exclude glucose-6-phosphate dehydrogenase (G6PD deficiency, thalassemias, hemoglobinopathies, autoimmune hemolysis, hereditary spherocytosis and pyruvate kinase (PKLR deficiency. Common G6PD and PKLR variants were excluded by molecular tests. DNA Libraries were prepared using TruSight One™ panel and sequenced on MiSeq™ Sequencing System. MiSeq Reporter™ and VariantStudio™ v2.1 were used for analysis, classification, and reporting of genomic variants reporting genomic variants. All 10 patients’ diagnoses were resolved by targeted resequencing: two had G6PD deficiency, two had glucose-6-phosphate isomerase (GPI deficiency and six unexpectedly had pyruvate kinase deficiency despite pyruvate kinase enzyme activity assays previously being normal in all. All the mutations were predicted deleterious by PolyPhen, SIFT, Provean, mutpred and Mutationtaster software. The mutations were validated in parents and/or siblings (where available to establish the mode of inheritance. Our

  17. Are free glucose and glucose-6-phosphate in milk indicators of specific physiological states in the cow?

    DEFF Research Database (Denmark)

    Larsen, Torben; Moyes, Kasey M

    2015-01-01

    that they are not hydrolysis product from lactose post secretion, but rather reflecting the energy status of the mammary epithelial cells pre-secretion. Wide variation in range of these metabolites, that is, from 90 to 630 μM and 5 to 324 μM, for glucose and G6P, respectively, was observed. During the first 21 weeks in milk....... In addition, lactose, protein, fat, citrate and β-hydroxybutyrate were determined and comparisons between these variables were made. Data were analysed using GLM model for the effect of parity, breed, time from last milking and stage of lactation on variations in parameters in milk. Pearson’s correlations...

  18. Five isozymograms of Trichomonas vaginalis and Trichomonas tenax: A comparative study%阴道毛滴虫和口腔毛滴虫5种同工酶谱对比分析

    Institute of Scientific and Technical Information of China (English)

    梁裕芬; 韦俊彬; 运晨霞; 黄庶识

    2010-01-01

    目的 分析阴道毛滴虫(Trichomonas vaginalis,Tv)和口腔毛滴虫(Trichomonas tenax,TT)的同工谱特征及其亲缘关系,寻找同工酶谱鉴别指标.方法 采用聚丙烯酰胺凝胶垂直板电泳,分别进行苹果酸脱氢酶(malate dehydrogenase, MDH)、谷氨酸脱氢酶(glutamic dehydrogenase, GLDH)、6-磷酸-葡萄糖脱氧酶(glucose-6-phosphate dehydrogenase, G6PD)、乙醇脱氢酶(alcohol dehydrogenase, ADH)和过氧化氢酶(Catalase)5种同工酶染色,比较分析2种滴虫的酶谱.结果 MDH同工酶:2种滴虫只有相对迁移率(Rm) 52、85 2条区带相同,而Rm 34、42、94、100 4条区带在2种滴虫之间明显不同;GLDH同工酶:TV无显带,TT共分离出6条酶带;G6PD同工酶:TV只有Rm35、42、52 3条区带,而TT除了显示这3条区带外,还显示出其他迁移率更大的区带;ADH和Catalase均无区带显示.结论 MDH、GLDH和G6PD3种同工酶均具有鉴别意义.

  19. [Role of primaquine in malaria control and elimination in French-speaking Africa].

    Science.gov (United States)

    Briolant, S; Pradines, B; Basco, L K

    2017-08-01

    Primaquine, an 8-aminoquinoline, is a relatively unknown and underutilized drug in French-speaking African countries. It acts against the liver stage parasites of all human malaria species, asexual blood stages of Plasmodium vivax and, to a lesser degree, Plasmodium falciparum; P. falciparum mature gametocytes, and P. vivax and Plasmodium ovale hypnozoites. Gastrointestinal disturbances are its most common side effects. The clinical utility of primaquine is limited due to its hematological side effects in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency and other contraindications (pregnant woman, breastfeeding woman, infants less than 6 months old). In the light of the recent recommendations of the World Health Organization (WHO), we propose to examine how primaquine can be used in French-speaking Africa to improve malaria control and move towards malaria elimination. Two indications supported by the WHO are of relevance in Africa. First, artemisinin-based combination therapies and primaquine given as a single low dose (0.25 mg base/kg) are effective to kill asexual and sexual parasites of P. falciparum, are well-tolerated, and have very little risk even in mild to moderate G6PD-deficient patients. This strategy may be helpful to contain transmission in an area in Africa where P. falciparum malaria incidence has decreased considerably. There is an ethical concern in administering primaquine as a gametocytocide as it does not confer any direct benefit to the treated patient. However, the single low-dose primaquine is most likely associated with very low risk for adverse hematological effects, and WHO recommends its use even without prior G6PD testing. In our opinion, clinical studies including G6PD test should be conducted to assess the safety of low-dose primaquine in African patients. Second, primaquine is effective and necessary for radical treatment of P. vivax and P. ovale, but the standard 14-day treatment (0.25-0.5 mg base/kg/day) is not

  20. Effect of exposure to sublethal concentrations of sodium cyanide on the carbohydrate metabolism of the Indian Major Carp Labeo rohita (Hamilton, 1822

    Directory of Open Access Journals (Sweden)

    Praveen N. Dube

    2013-07-01

    Full Text Available Experiments were designed to study in-vivo effects of sodium cyanide on biochemical endpoints in the freshwater fish Labeo rohita. Fish were exposed to two sublethal concentrations (0.106 and 0.064mg/L for a period of 15 days. Levels of glycogen, pyruvate, lactate and the enzymatic activities of lactate dehydrogenase (LDH, succinate dehydrogenase (SDH, glucose-6-phosphate dehydrogenase (G6PDH, phosphorylase, alkaline phosphatase (ALP, acid phosphatase (AcP were assessed in different tissues (liver, muscle and gills. Result indicated a steady decrease in glycogen, pyruvate, SDH, ALP and AcP activity with a concomitant increase in the lactate, phosphorylase, LDH and G6PD activity in all selected tissues. The alterations in all the above biochemical parameters were significantly (p<0.05 time and dose dependent. In all the above parameters, liver pointing out the intensity of cyanide intoxication compare to muscle and gills. Study revealed change in the metabolic energy by means of altered metabolic profile of the fish. Further, these observations indicated that even sublethal concentrations of sodium cyanide might not be fully devoid of deleterious influence on metabolism in L. rohita.

  1. Plant Formate Dehydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    John Markwell

    2005-01-10

    The research in this study identified formate dehydrogenase, an enzyme that plays a metabolic role on the periphery of one-carbon metabolism, has an unusual localization in Arabidopsis thaliana and that the enzyme has an unusual kinetic plasticity. These properties make it possible that this enzyme could be engineered to attempt to engineer plants with an improved photosynthetic efficiency. We have produced transgenic Arabidopsis and tobacco plants with increased expression of the formate dehydrogenase enzyme to initiate further studies.

  2. Optimal response of key enzymes and uncoupling protein to cold in BAT depends on local T3 generation

    International Nuclear Information System (INIS)

    Bianco, A.C.; Silva, J.E.

    1987-01-01

    The authors have examined the activity of three lipogenic enzymes [malic enzyme (ME), glucose-6-phosphate dehydrogenase (G-6-PD), and acetyl coenzyme A (CoA) carboxylase], the activity of the mitochondrial FAD-dependent α-glycerolphosphate dehydrogenase (α-GPD), and the mitochondrial concentration of uncoupling protein (UCP) in brown adipose tissue (BAT) of euthyroid and hypothyroid rats, both at room temperature and in response to acute cold stress. These enzymes and UCP are important for the thermogenic response of BAT in adaptation to cold. The basal level of the lipogenic enzymes was normal or slightly elevated in hypothyroid rats maintained at 23 0 C, but the levels of α-GPD and UCP were markedly reduced. Forty-eight hours at 4 0 C resulted in an increase in the activity of G-6-PD, acetyl-CoA carboxylase, and α-GPD and in the concentration of UCP both in euthyroid and hypothyroid animals, but the levels reached were invariably less in hypothyroid animals, indicating that thyroid hormone is necessary for a full metabolic response of BAT under maximal demands. Of all variables measured, the most affected was UCP followed by α-GDP. Dose-response relationship analysis of the UCP response to T 3 indicated that the normalization of the response to cold requires saturation of the nuclear T 3 receptors. They concluded, therefore, that the activation of the BAT 5'-deiodinase induced by cold exposure is essential to provide the high levels of nuclear T 3 required for the full expression of BAT thermogenic potential

  3. Severe G6PD Deficiency Due to a New Missense Mutation in an Infant of Northern European Descent

    DEFF Research Database (Denmark)

    Warny, Marie; Lausen, Birgitte; Birgens, Henrik

    2015-01-01

    We report a term male infant born to parents of Danish descent, who on the second day of life developed jaundice peaking at 67 hours and decreasing on applied double-sided phototherapy. In the weeks following, the infant showed signs of ongoing hemolysis. Laboratory tests showed very low glucose-6...

  4. Point-of-care G6PD diagnostics for Plasmodium vivax malaria is a clinical and public health urgency

    OpenAIRE

    Baird, J. Kevin

    2015-01-01

    Malaria caused by Plasmodium vivax threatens over 2 billion people globally and sickens tens of millions annually. Recent clinical evidence discredits the long-held notion of this infection as intrinsically benign revealing an often threatening course associated with mortality. Most acute attacks by this species derive from latent forms in the human liver called hypnozoites. Radical cure for P. vivax malaria includes therapy aimed both at the acute attack (blood schizontocidal) and against fu...

  5. Intrauterine Growth Retardation Increases the Susceptibility of Pigs to High-Fat Diet-Induced Mitochondrial Dysfunction in Skeletal Muscle

    Science.gov (United States)

    Liu, Jingbo; Chen, Daiwen; Yao, Ying; Yu, Bing; Mao, Xiangbing; He, Jun; Huang, Zhiqing; Zheng, Ping

    2012-01-01

    It has been recognized that there is a relationship between prenatal growth restriction and the development of metabolic-related diseases in later life, a process involved in mitochondrial dysfunction. In addition, intrauterine growth retardation (IUGR) increases the susceptibility of offspring to high-fat (HF) diet-induced metabolic syndrome. Recent findings suggested that HF feeding decreased mitochondrial oxidative capacity and impaired mitochondrial function in skeletal muscle. Therefore, we hypothesized that the long-term consequences of IUGR on mitochondrial biogenesis and function make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. Normal birth weight (NBW), and IUGR pigs were allotted to control or HF diet in a completely randomized design, individually. After 4 weeks of feeding, growth performance and molecular pathways related to mitochondrial function were determined. The results showed that IUGR decreased growth performance and plasma insulin concentrations. In offspring fed a HF diet, IUGR was associated with enhanced plasma leptin levels, increased concentrations of triglyceride and malondialdehyde (MDA), and reduced glycogen and ATP contents in skeletal muscle. High fat diet-fed IUGR offspring exhibited decreased activities of lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD). These alterations in metabolic traits of IUGR pigs were accompanied by impaired mitochondrial respiration function, reduced mitochondrial DNA (mtDNA) contents, and down-regulated mRNA expression levels of genes responsible for mitochondrial biogenesis and function. In conclusion, our results suggest that IUGR make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. PMID:22523560

  6. Protective effect of Piper betle leaf extract against cadmium-induced oxidative stress and hepatic dysfunction in rats.

    Science.gov (United States)

    Milton Prabu, S; Muthumani, M; Shagirtha, K

    2012-04-01

    The present study was undertaken to examine the attenuative effect of Piper betle leaf extract (PBE) against cadmium (Cd) induced oxidative hepatic dysfunction in the liver of rats. Pre-oral supplementation of PBE (200 mg/kg BW) treated rats showed the protective efficacy against Cd induced hepatic oxidative stress. Oral administration of Cd (5 mg/kg BW) for four weeks to rats significantly (P > 0.05) elevated the level of serum hepatic markers such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), bilirubin (TBRNs), oxidative stress markers viz., thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), protein carbonyls (PC) and conjugated dienes (CD) and significantly (P > 0.05) reduced the enzymatic antioxidants viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) and non-enzymatic antioxidants Viz., reduced glutathione (GSH), total sulfhydryls (TSH), vitamin C and vitamin E in the liver. Pre-oral supplementation of PBE (200 mg/kg BW) in Cd intoxicated rats, the altered biochemical indices and pathological changes were recovered significantly (P > 0.05) which showed ameliorative effect of PBE against Cd induced hepatic oxidative stress. From the above findings, we suggested that the pre-administration of P. betle leaf extract exhibited remarkable protective effects against cadmium-induced oxidative hepatic injury in rats.

  7. Fenugreek Seed Extract Inhibit Fat Accumulation and Ameliorates Dyslipidemia in High Fat Diet-Induced Obese Rats

    Directory of Open Access Journals (Sweden)

    Parveen Kumar

    2014-01-01

    Full Text Available This study investigated the inhibitory effect of aqueous extract of Trigonella foenum-graecum seeds (AqE-TFG on fat accumulation and dyslipidemia in high fat diet- (HFD- induced obese rats. Female Wistar rats were fed with HFD ad libitum, and the rats on HFD were treated orally with AqE-TFG or orlistat ((HFD for 28 days + AqE-TFG (0.5 and 1.0 g/kg or orlistat (10 mg/kg from day 8 to 28, respectively. Treatment with AqE-TFG produced significant reduction in body weight gain, body mass index (BMI, white adipose tissue (WAT weights, blood glucose, serum insulin, lipids, leptin, lipase, and apolipoprotein-B levels and elevation in adiponectin levels. AqE-TFG improved serum aspartate amino transferase (AST, alanine amino transferase (ALT, and lactate dehydrogenase (LDH levels. AqE-TFG treatment reduced the hepatic and cardiac thiobarbituric acid reactive substances (TBARS and elevated the antioxidant enzyme (glutathione (GSH, superoxide dismutase (SOD, and catalase (CAT levels. In addition, liver and uterine WAT lipogenic enzyme (fatty acid synthetase (FAS and glucose-6-phosphate dehydrogenase (G6PD activities were restored towards normal levels. These findings demonstrated the preventive effect of AqE-TFG on fat accumulation and dyslipidemia, due to inhibition of impaired lipid digestion and absorption, in addition to improvement in glucose and lipid metabolism, enhancement of insulin sensitivity, increased antioxidant defense, and downregulation of lipogenic enzymes.

  8. Gas Chromatography/Mass Spectrometry-Based Metabolomic Profiling Reveals Alterations in Mouse Plasma and Liver in Response to Fava Beans.

    Science.gov (United States)

    Xiao, Man; Du, Guankui; Zhong, Guobing; Yan, Dongjing; Zeng, Huazong; Cai, Wangwei

    2016-01-01

    Favism is a life-threatening hemolytic anemia resulting from the intake of fava beans by susceptible individuals with low erythrocytic glucose 6-phosphate dehydrogenase (G6PD) activity. However, little is known about the metabolomic changes in plasma and liver after the intake of fava beans in G6PD normal and deficient states. In this study, gas chromatography/mass spectrometry was used to analyze the plasma and liver metabolic alterations underlying the effects of fava beans in C3H- and G6PD-deficient (G6PDx) mice, and to find potential biomarkers and metabolic changes associated with favism. Our results showed that fava beans induced oxidative stress in both C3H and G6PDx mice. Significantly, metabolomic differences were observed in plasma and liver between the control and fava bean treated groups of both C3H and G6PDx mice. The levels of 7 and 21 metabolites in plasma showed significant differences between C3H-control (C3H-C)- and C3H fava beans-treated (C3H-FB) mice, and G6PDx-control (G6PDx-C)- and G6PDx fava beans-treated (G6PDx-FB) mice, respectively. Similarly, the levels of 7 and 25 metabolites in the liver showed significant differences between C3H and C3H-FB, and G6PDx and G6PDx-FB, respectively. The levels of oleic acid, linoleic acid, and creatinine were significantly increased in the plasma of both C3H-FB and G6PDx-FB mice. In the liver, more metabolic alterations were observed in G6PDx-FB mice than in C3H-FB mice, and were involved in a sugar, fatty acids, amino acids, cholesterol biosynthesis, the urea cycle, and the nucleotide metabolic pathway. These findings suggest that oleic acid, linoleic acid, and creatinine may be potential biomarkers of the response to fava beans in C3H and G6PDx mice and therefore that oleic acid and linoleic acid may be involved in oxidative stress induced by fava beans. This study demonstrates that G6PD activity in mice can affect their metabolic pathways in response to fava beans.

  9. Gas Chromatography/Mass Spectrometry-Based Metabolomic Profiling Reveals Alterations in Mouse Plasma and Liver in Response to Fava Beans.

    Directory of Open Access Journals (Sweden)

    Man Xiao

    Full Text Available Favism is a life-threatening hemolytic anemia resulting from the intake of fava beans by susceptible individuals with low erythrocytic glucose 6-phosphate dehydrogenase (G6PD activity. However, little is known about the metabolomic changes in plasma and liver after the intake of fava beans in G6PD normal and deficient states. In this study, gas chromatography/mass spectrometry was used to analyze the plasma and liver metabolic alterations underlying the effects of fava beans in C3H- and G6PD-deficient (G6PDx mice, and to find potential biomarkers and metabolic changes associated with favism. Our results showed that fava beans induced oxidative stress in both C3H and G6PDx mice. Significantly, metabolomic differences were observed in plasma and liver between the control and fava bean treated groups of both C3H and G6PDx mice. The levels of 7 and 21 metabolites in plasma showed significant differences between C3H-control (C3H-C- and C3H fava beans-treated (C3H-FB mice, and G6PDx-control (G6PDx-C- and G6PDx fava beans-treated (G6PDx-FB mice, respectively. Similarly, the levels of 7 and 25 metabolites in the liver showed significant differences between C3H and C3H-FB, and G6PDx and G6PDx-FB, respectively. The levels of oleic acid, linoleic acid, and creatinine were significantly increased in the plasma of both C3H-FB and G6PDx-FB mice. In the liver, more metabolic alterations were observed in G6PDx-FB mice than in C3H-FB mice, and were involved in a sugar, fatty acids, amino acids, cholesterol biosynthesis, the urea cycle, and the nucleotide metabolic pathway. These findings suggest that oleic acid, linoleic acid, and creatinine may be potential biomarkers of the response to fava beans in C3H and G6PDx mice and therefore that oleic acid and linoleic acid may be involved in oxidative stress induced by fava beans. This study demonstrates that G6PD activity in mice can affect their metabolic pathways in response to fava beans.

  10. Defectos eritrocíticos y densidad de la parasitemia en pacientes con malaria por Plasmodium falciparum en Buenaventura, Colombia Erythrocyte defects and parasitemia density in patients with Plasmodium falciparum malaria in Buenaventura, Colombia

    Directory of Open Access Journals (Sweden)

    Martha Moyano

    2005-07-01

    . falciparum malaria who had gone for consultation at the Program of Tropical Diseases diagnostic center in the city of Buenaventura, Colombia. The parasitemia levels were measured, and also determined was the presence of congenital erythrocyte defects (glucose-6-phosphate dehydrogenase (G6PD deficiency, abnormal hemoglobins, and thalassemias and of other factors possibly related to parasitemia levels. RESULTS: The prevalence of erythrocyte defects was 26.4% (95% confidence interval, 21.0%-32.5%, which was similar to what had been found in previous studies in the same area of Colombia. In the multiple regression models, individuals with sickle cell anemia or a complete deficiency of G6PD had a lower density of parasitemia than did persons without any erythrocyte defect. After adjusting for other variables of interest, the risk of high parasitemias was lower in persons with sickle cell anemia (odds ratio = 0.30 and individuals with a complete deficiency of G6PD (odds ratio = 0.72. CONCLUSIONS: Our results confirm the high prevalence of erythrocyte defects in Colombia's Pacific coastal region, in a population with ethnic characteristics that are similar to those of some populations in West Africa. Our results also lend support for the existence of innate resistance to malaria among carriers of hemoglobin AS and in persons with G6PD deficiency.

  11. Differential induction of enzymes and genes involved in lipid metabolism in liver and visceral adipose tissue of juvenile yellow catfish Pelteobagrus fulvidraco exposed to copper

    International Nuclear Information System (INIS)

    Chen, Qi-Liang; Luo, Zhi; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

    2013-01-01

    Highlights: •Cu downregulates lipogenesis and reduces lipid deposition in liver and adipose tissue. •Mechanism of Cu affecting lipid metabolism is determined at the enzymatic and molecular levels. •Cu exposure differentially influences lipid metabolism between liver and adipose tissue. -- Abstract: The present study was conducted to determine the mechanism of waterborne Cu exposure influencing lipid metabolism in liver and visceral adipose tissue (VAT) of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure had a negative effect on growth and several condition indices (condition factor, viscerosomatic index, hepatosomatic index and visceral adipose index). In liver, lipid content, activities of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and fatty acid synthase (FAS)) as well as mRNA levels of 6PGD, G6PD, FAS and sterol-regulator element-binding protein-1 (SREBP-1) genes decreased with increasing Cu concentrations. However, activity and mRNA level of lipoprotein lipase (LPL) gene in liver increased. In VAT, G6PD, ME and LPL activities as well as the mRNA levels of FAS, LPL and PPARγ genes decreased in fish exposed to higher Cu concentrations. The differential Pearson correlations between transcription factors (SREBP-1 and peroxisome proliferators-activated receptor-γ (PPARγ)), and the activities and mRNA expression of lipogenic enzymes and their genes were observed between liver and VAT. Thus, our study indicated that reduced lipid contents in liver and VAT after Cu exposure were attributable to the reduced activities and mRNA expression of lipogenic enzymes and their genes in these tissues. Different response patterns of several tested enzymes and genes to waterborne Cu

  12. Differential induction of enzymes and genes involved in lipid metabolism in liver and visceral adipose tissue of juvenile yellow catfish Pelteobagrus fulvidraco exposed to copper

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qi-Liang; Luo, Zhi, E-mail: luozhi99@yahoo.com.cn; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

    2013-07-15

    Highlights: •Cu downregulates lipogenesis and reduces lipid deposition in liver and adipose tissue. •Mechanism of Cu affecting lipid metabolism is determined at the enzymatic and molecular levels. •Cu exposure differentially influences lipid metabolism between liver and adipose tissue. -- Abstract: The present study was conducted to determine the mechanism of waterborne Cu exposure influencing lipid metabolism in liver and visceral adipose tissue (VAT) of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure had a negative effect on growth and several condition indices (condition factor, viscerosomatic index, hepatosomatic index and visceral adipose index). In liver, lipid content, activities of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and fatty acid synthase (FAS)) as well as mRNA levels of 6PGD, G6PD, FAS and sterol-regulator element-binding protein-1 (SREBP-1) genes decreased with increasing Cu concentrations. However, activity and mRNA level of lipoprotein lipase (LPL) gene in liver increased. In VAT, G6PD, ME and LPL activities as well as the mRNA levels of FAS, LPL and PPARγ genes decreased in fish exposed to higher Cu concentrations. The differential Pearson correlations between transcription factors (SREBP-1 and peroxisome proliferators-activated receptor-γ (PPARγ)), and the activities and mRNA expression of lipogenic enzymes and their genes were observed between liver and VAT. Thus, our study indicated that reduced lipid contents in liver and VAT after Cu exposure were attributable to the reduced activities and mRNA expression of lipogenic enzymes and their genes in these tissues. Different response patterns of several tested enzymes and genes to waterborne Cu

  13. Cuscuta chinensis seeds water extraction protecting murine osteoblastic MC3T3-E1 cells against tertiary butyl hydroperoxide induced injury.

    Science.gov (United States)

    Gao, Jian-mei; Li, Ran; Zhang, Lei; Jia, Li-long; Ying, Xi-xiang; Dou, De-qiang; Li, Jian-chun; Li, Hai-bo

    2013-07-09

    Cuscuta chinensis (C. chinensis) is a well-known traditional Chinese herb that has been used to treat heart disease, diabetes, liver injury, cancer, and aging. Murine osteoblastic MC3T3-E1 cells were treated with various concentrations of C. chinensis water extraction at different time intervals. The antioxidant effect of C. chinensis on MC3T3-E1 cells was evaluated using MTT and TUNEL assays. The effect of C. chinensis on cell cycle was analyzed by flow cytometry with propidium iodide. Lipid peroxidation was measured by the HPLC method. The cellular redox status was determined from the reduced glutathione to oxidized glutathione ratio (GSH/GSSG) and the enzymes involved in glutathione metabolism, including glutathione reductase (GR), Glutathione S-transferase (GST), and Glucose-6-phosphate dehydrogenase (G6PD). The changes in relative mitochondrial transmembrane potential (ΔΨm) in the MC3T3-E1 cells were analyzed with rhodamine 123 staining. Western blot analysis was used to evaluate the levels of cytochrome c (cyto c), Bax, Bcl-2, caspase 3, Sirt3, and IDH2 expressions. The C. chinensis water extraction protects tertiary butyl hydroperoxide (TBHP)-treated MC3T3-E1 cells from death in a dose-dependent manner. C. chinensis treatment significantly inhibited the reactive oxygen species (ROS) generation, malondialdehyde (MDA) production, and increased the activity of superoxide dismutase (SOD), GR, GST, and G6PD. The release of cyto c from mitochondria was reduced by C. chinensis, which increased the expression of antiapoptotic IDH2, Sirt3, and Bcl-2 and decreased the expression of Bax, cyto c, and caspase 3. C. chinensis modulated the oxidative stress-induced apoptosis in MC3T3-E1 cells, probably due to its antioxidant activity and functioning via mitochondria-dependent pathways. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Growth performance and antioxidant enzyme activities in rainbow trout (Oncorhynchus mykiss) juveniles fed diets supplemented with sage, mint and thyme oils.

    Science.gov (United States)

    Sönmez, Adem Yavuz; Bilen, Soner; Alak, Gonca; Hisar, Olcay; Yanık, Talat; Biswas, Gouranga

    2015-02-01

    This study evaluated effects of dietary supplementation of sage (Salvia officinalis), mint (Mentha spicata) and thyme (Thymus vulgaris) oils on growth performance, lipid peroxidation level (melondialdehyde, MDA) and liver antioxidant enzyme activities (superoxide dismutase, SOD; catalase, CAT; glucose-6-phosphate dehydrogenase, G6PD; glutathione reductase, GR; glutathione-S-transferase, GST and glutathione peroxidase, GPx) in rainbow trout (Oncorhynchus mykiss) juveniles. For this purpose, triplicate groups of rainbow trout were fed daily ad libitum with diets containing sage, mint and thyme oils at 500, 1,000 and 1,500 mg kg(-1) for 60 days. While weight gain percentage of fish fed the diets containing sage and thyme oils was significantly higher than the control group, that of fish fed mint oil was the lowest. Similarly, specific growth rate was found to be the highest in all groups of the sage and thyme oil feeding and the lowest in the mint groups. Moreover, feed conversion ratio was significantly higher in the mint oil administered groups. Survival rate was also significantly reduced in the fish fed the diet containing mint oil. It was observed that SOD, G6PD and GPx activities were significantly increased in liver tissues of all the treated fish groups compared to that of control diet-fed group. However, CAT, GST and GR activities were significantly decreased in experimental diet-fed fish groups at the end of the experiment. On the other hand, a significant reduction was found in MDA levels in the fish fed the diets with sage and thyme oils compared to control and mint diets on the 30th and 60th days of experiment. Overall, dietary inclusion of sage and thyme oils is effective in enhancing rainbow trout growth, reduction in MDA and least changing antioxidant enzyme activities at a low level of 500 mg kg(-1) diet, and they can be used as important feed supplements for rainbow trout production.

  15. Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species

    International Nuclear Information System (INIS)

    Wells, Peter G.; Bhuller, Yadvinder; Chen, Connie S.; Jeng, Winnie; Kasapinovic, Sonja; Kennedy, Julia C.; Kim, Perry M.; Laposa, Rebecca R.; McCallum, Gordon P.; Nicol, Christopher J.; Parman, Toufan; Wiley, Michael J.; Wong, Andrea W.

    2005-01-01

    Developmental pathologies may result from endogenous or xenobiotic-enhanced formation of reactive oxygen species (ROS), which oxidatively damage cellular macromolecules and/or alter signal transduction. This minireview focuses upon several model drugs (phenytoin, thalidomide, methamphetamine), environmental chemicals (benzo[a]pyrene) and gamma irradiation to examine this hypothesis in vivo and in embryo culture using mouse, rat and rabbit models. Embryonic prostaglandin H synthases (PHSs) and lipoxygenases bioactivate xenobiotics to free radical intermediates that initiate ROS formation, resulting in oxidation of proteins, lipids and DNA. Oxidative DNA damage and embryopathies are reduced in PHS knockout mice, and in mice treated with PHS inhibitors, antioxidative enzymes, antioxidants and free radical trapping agents. Thalidomide causes embryonic DNA oxidation in susceptible (rabbit) but not resistant (mouse) species. Embryopathies are increased in mutant mice deficient in the antioxidative enzyme glucose-6-phosphate dehydrogenase (G6PD), or by glutathione (GSH) depletion, or inhibition of GSH peroxidase or GSH reductase. Inducible nitric oxide synthase knockout mice are partially protected. Inhibition of Ras or NF-kB pathways reduces embryopathies, implicating ROS-mediated signal transduction. Atm and p53 knockout mice deficient in DNA damage response/repair are more susceptible to xenobiotic or radiation embryopathies, suggesting a teratological role for DNA damage, consistent with enhanced susceptibility to methamphetamine in ogg1 knockout mice with deficient repair of oxidative DNA damage. Even endogenous embryonic oxidative stress carries a risk, since untreated G6PD- or ATM-deficient mice have increased embryopathies. Thus, embryonic processes regulating the balance of ROS formation, oxidative DNA damage and repair, and ROS-mediated signal transduction may be important determinants of teratological risk

  16. Boosting the pentose phosphate pathway restores cardiac progenitor cell availability in diabetes.

    Science.gov (United States)

    Katare, Rajesh; Oikawa, Atsuhiko; Cesselli, Daniela; Beltrami, Antonio P; Avolio, Elisa; Muthukrishnan, Deepti; Munasinghe, Pujika Emani; Angelini, Gianni; Emanueli, Costanza; Madeddu, Paolo

    2013-01-01

    Diabetes impinges upon mechanisms of cardiovascular repair. However, the biochemical adaptation of cardiac stem cells to sustained hyperglycaemia remains largely unknown. Here, we investigate the molecular targets of high glucose-induced damage in cardiac progenitor cells (CPCs) from murine and human hearts and attempt safeguarding CPC viability and function through reactivation of the pentose phosphate pathway. Type-1 diabetes was induced by streptozotocin. CPC abundance was determined by flow cytometry. Proliferating CPCs were identified in situ by immunostaining for the proliferation marker Ki67. Diabetic hearts showed marked reduction in CPC abundance and proliferation when compared with controls. Moreover, Sca-1(pos) CPCs isolated from hearts of diabetic mice displayed reduced activity of key enzymes of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD), and transketolase, increased levels of superoxide and advanced glucose end-products (AGE), and inhibition of the Akt/Pim-1/Bcl-2 signalling pathway. Similarly, culture of murine CPCs or human CD105(pos) progenitor cells in high glucose inhibits the pentose phosphate and pro-survival signalling pathways, leading to the activation of apoptosis. In vivo and in vitro supplementation with benfotiamine reactivates the pentose phosphate pathway and rescues CPC availability and function. This benefit is abrogated by either G6PD silencing by small interfering RNA (siRNA) or Akt inhibition by dominant-negative Akt. We provide new evidence of the negative impact of diabetes and high glucose on mechanisms controlling CPC redox state and survival. Boosting the pentose phosphate pathway might represent a novel mechanistic target for protection of CPC integrity.

  17. Activation of neuronal nitric oxide synthase in cerebellum of chronic hepatic encephalopathy rats is associated with up-regulation of NADPH-producing pathway.

    Science.gov (United States)

    Singh, Santosh; Trigun, Surendra K

    2010-09-01

    Cerebellum-associated functions get affected during mild hepatic encephalopathy (MHE) in patients with chronic liver failure (CLF). Involvement of nitrosative and antioxidant factors in the pathogenesis of chronic hepatic encephalopathy is an evolving concept and needs to be defined in a true CLF animal model. This article describes profiles of NADPH-dependent neuronal nitric oxide synthase (nNOS) and those of glutathione peroxidase and glutathione reductase (GR) vis-a-vis regulation of NADPH-producing pathway in the cerebellum of CLF rats induced by administration of thioacetamide (100 mg kg⁻¹ b.w., i.p.) up to 10 days and confirming MHE on Morris water maze tests. Significant increases in the expression of nNOS protein and nitric oxide (NOx) level coincided with a similar increment in NADPH-diaphorase activity in the cerebellum of CLF rats. Glutathione peroxidase and GR utilize NADPH to regenerate reduced glutathione (GSH) in the cells. Both these enzymes and GSH level were found to be static and thus suggested efficient turnover of GSH in the cerebellum of MHE rats. Relative levels of glucose-6-phosphate dehydrogenase (G6PD) vs. phosphofructokinase 2 (PFK2) determine the rate of pentose phosphate pathway (PPP) responsible to synthesize NADPH. The cerebellum of CLF rats showed overactivation of G6PD with a significant decline in the expression of PFK2 and thus suggested activation of PPP in the cerebellum during MHE. It is concluded that concordant activations of PPP and nNOS in cerebellum of MHE rats could be associated with the implication of NOx in the pathogenesis of MHE.

  18. Development and validation of PCR-based assays for diagnosis of American cutaneous leishmaniasis and identificatio nof the parasite species

    Directory of Open Access Journals (Sweden)

    Grazielle Cardoso da Graça

    2012-08-01

    Full Text Available In this study, PCR assays targeting different Leishmania heat-shock protein 70 gene (hsp70 regions, producing fragments ranging in size from 230-390 bp were developed and evaluated to determine their potential as a tool for the specific molecular diagnosis of cutaneous leishmaniasis (CL. A total of 70 Leishmania strains were analysed, including seven reference strains (RS and 63 previously typed strains. Analysis of the RS indicated a specific region of 234 bp in the hsp70 gene as a valid target that was highly sensitive for detection of Leishmania species DNA with capacity of distinguishing all analyzed species, after polymerase chain reaction-restriction fragment length polymorfism (PCR-RFLP. This PCR assay was compared with other PCR targets used for the molecular diagnosis of leishmaniasis: hsp70 (1400-bp region, internal transcribed spacer (ITS1 and glucose-6-phosphate dehydrogenase (G6pd. A good agreement among the methods was observed concerning the Leishmania species identification. Moreover, to evaluate the potential for molecular diagnosis, we compared the PCR targets hsp70-234 bp, ITS1, G6pd and mkDNA using a panel of 99 DNA samples from tissue fragments collected from patients with confirmed CL. Both PCR-hsp70-234 bp and PCR-ITS1 detected Leishmania DNA in more than 70% of the samples. However, using hsp70-234 bp PCR-RFLP, identification of all of the Leishmania species associated with CL in Brazil can be achieved employing a simpler and cheaper electrophoresis protocol.

  19. Protective effects of a wheat germ rich diet against the toxic influence of profenofos on rat tissue lipids and oxidative pentose phosphate shunt enzymes

    Directory of Open Access Journals (Sweden)

    Abdel-Rahim, G. A.

    2011-09-01

    Full Text Available The effects of technical and formulated forms of profenofos on the metabolic lipid fractions of the liver, brain and kidneys as well as the activity of glucose-6-phosphate dehydrogenase (G6PD and 6-phosphogluconate dehydrogenase (6PGD, which consider lipid related enzymes, were studied. The two forms of profenofos were given separately either orally or by dermal at doses of 1/20 LD50 for 3 months (one dose every 48 h. Total lipids and lipid fractions (cholesterol, triglycerides and phospholipid contents decreased in the three studied organ tissues either in technical or formulated profenofos-induced rats compared with normal control animals. The highest effect was observed in the case of orally formulated profenofo induction, and the lowest was detected for the dermal technical one. The same trend was found in the activities of G6PD and 6PGD associated with lipid metabolism in the liver, brain and kidney tissues under the same conditions. On other hand, the treatment of profenofos-induced animals by feeding a wheat germ rich diet (as antioxidant agent produced significant improvements in both lipid fraction content and enzyme activity. In addition, the effects of the wheat germ rich diet (α-tocopherol rich source readjusted and improved the disturbed metabolic fractions of the lipid profiles in the profenofos-induced rats as well as their related enzyme activities (G6PD and 6PGD: oxidative pentose phosphate shunt.

    El efecto de formas técnicas o formuladas de profenofós en la fracción lipídica metabólica de hígado, cerebro y riñones así como la actividad de la glucosa-6-fosfato deshidrogenasa (G6PD y 6-fosfogluconato deshidrogenasa (6PGD, que son consideradas enzimas relacionadas con los lípidos, fueron estudiadas. Ambas formas de profenofós fueron suministradas separadamente tanto por vía oral como cutánea a una dosis de 1/20 LD50 durante 3 meses (una dosis cada 48 horas. Los lípidos totales y

  20. Two-stage gene regulation of the superoxide stress response soxRS system in Escherichia coli.

    Science.gov (United States)

    Nunoshiba, T

    1996-01-01

    All organisms have adapted to environmental changes by acquiring various functions controlled by gene regulation. In bacteria, a number of specific responses have been found to confer cell survival in various nutrient-limited conditions, and under physiological stresses such as high or low temperature, extreme pH, radiation, and oxidation (for review, see Neidhardt et al., 1987). In this article, I introduce an Escherichia coli (E. coli) global response induced by superoxide stress, the soxRS regulon. The functions controlled by this system consist of a wide variety of enzymes such as manganese-containing SOD (Mn-SOD); glucose 6-phosphate dehydrogenase (G6PD), the DNA repair enzyme endonuclease IV, fumarase C, NADPH:ferredoxin oxidoreductase, and aconitase. This response is positively regulated by a two-stage control system in which SoxR iron-sulfur protein senses exposure to superoxide and nitric oxide, and then activates transcription of the soxS gene, whose product stimulates the expression of the regulon genes. Our recent finding indicates that soxS transcription is initiated in a manner dependent on the rpoS gene encoding RNA polymerase sigma factor, theta s, in response to entering the stationary phase of growth. With this information, mechanisms for prokaryotic coordinating gene expression in response to superoxide stress and in stationary phase are discussed.

  1. Lupine Alleviate Hyperglycemia in Streptozotocin Diabetic gamma- Irradiated Rats

    International Nuclear Information System (INIS)

    El-Sayed, S.M.

    2010-01-01

    This study was to examine the regulatory effect of lupine on the diabetic profile developed in Streptozotocin (STZ) induced diabetic albino rats. The effectiveness of lupine against diabetes in gamma irradiated rats was purposed in the present study. Rats were received lupine seeds powder suspension (1 g/kg body weight for 14 consecutive days) before whole body exposure to 8 Gy of gamma radiation and /or STZ (55 mg/kg body weight, single dose) injection. The results pointed out that radiation exposure sustained the diabetic profile in rats received STZ comparing with STZ diabetic not irradiated rats. The prolonged administration of lupine suspension before STZ induction of diabetic and/or irradiated rats reduced the changes in the level of blood glucose, insulin concentration, liver glycogen, and the activity of glucose-6-phosphatase associated with significant amelioration in blood antioxidant status (superoxide dismutase, SOD; catalase, CAT; glucose-6-phosphate dehydrogenase, G-6-PD activities and reduced glutathione concentration GSH). Also, the level of blood lipid peroxides (TBARS) were reduced greatly when compared with its matched value in diabetic and /or gamma irradiated rats. It could be postulated that lupine powder suspension might be attenuate the diabetic profile development throughout reducing oxidative damages and modulating the antioxidant status. In addition, lupine could be considered as one of a remarkable radio protective agent owing to its antioxidants property

  2. Investigation of Pokemon-regulated proteins in hepatocellular carcinoma using mass spectrometry-based multiplex quantitative proteomics.

    Science.gov (United States)

    Bi, Xin; Jin, Yibao; Gao, Xiang; Liu, Feng; Gao, Dan; Jiang, Yuyang; Liu, Hongxia

    2013-01-01

    Pokemon is a transcription regulator involved in embryonic development, cellular differentiation and oncogenesis. It is aberrantly overexpressed in multiple human cancers including Hepatocellular carcinoma (HCC) and is considered as a promising biomarker for HCC. In this work, the isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics strategy was used to investigate the proteomic profile associated with Pokemon in human HCC cell line QGY7703 and human hepatocyte line HL7702. Samples were labeled with four-plex iTRAQ reagents followed by two-dimensional liquid chromatography coupled with tandem mass spectrometry analysis. A total of 24 differentially expressed proteins were selected as significant. Nine proteins were potentially up-regulated by Pokemon while 15 proteins were potentially down-regulated and many proteins were previously identified as potential biomarkers for HCC. Gene ontology (GO) term enrichment revealed that the listed proteins were mainly involved in DNA metabolism and biosynthesis process. The changes of glucose-6-phosphate 1-dehydrogenase (G6PD, up-regulated) and ribonucleoside-diphosphate reductase large sub-unit (RIM1, down-regulated) were validated by Western blotting analysis and denoted as Pokemon's function of oncogenesis. We also found that Pokemon potentially repressed the expression of highly clustered proteins (MCM3, MCM5, MCM6, MCM7) which played key roles in promoting DNA replication. Altogether, our results may help better understand the role of Pokemon in HCC and promote the clinical applications.

  3. Molecular genetics in affective illness

    Energy Technology Data Exchange (ETDEWEB)

    Mendlewicz, J.; Sevy, S.; Mendelbaum, K. (Erasme Univ. Hospital, Brussels (Belgium))

    1993-01-01

    Genetic transmission in manic depressive illness (MDI) has been explored in twins, adoption, association, and linkage studies. The X-linked transmission hypothesis has been tested by using several markers on chromosome X: Xg blood group, color blindness, glucose-6-phosphate dehydrogenase (G6PD), factor IX (hemophilia B), and DNA probes such as DXS15, DXS52, F8C, ST14. The hypothesis of autosomal transmission has been tested by association studies with the O blood group located on chromosome 9, as well as linkage studies on chromosome 6 with the Human Leucocyte Antigens (HLA) haplotypes and on Chromosome 11 with DNA markers for the following genes: D2 dopamine receptor, tyrosinase, C-Harvey-Ras-A (HRAS) oncogene, insuline (ins), and tyrosine hydroxylase (TH). Although linkage studies support the hypothesis of a major locus for the transmission of MDI in the Xq27-28 region, several factors are limiting the results, and are discussed in the present review. 105 refs., 1 fig., 2 tabs.

  4. Upregulation of Oxidative Stress Related Genes in a Chronic Kidney Disease Attributed to Specific Geographical Locations of Sri Lanka.

    Science.gov (United States)

    Sayanthooran, Saravanabavan; Magana-Arachchi, Dhammika N; Gunerathne, Lishanthe; Abeysekera, Tilak D J; Sooriyapathirana, Suneth S

    2016-01-01

    Objective. To infer the influence of internal and external oxidative stress in chronic kidney disease patients of unknown etiology (CKDu) in Sri Lanka, by analyzing expression of genes related directly or indirectly to oxidative stress: glutamate-cysteine ligase catalytic subunit (GCLC), glutathione S-transferase mu 1 (GSTM1), glucose-6-phosphate dehydrogenase (G6PD), fibroblast growth factor-23 (FGF23), and NLR family pyrin domain containing 3 (NLRP3). Methods. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was carried out for the selected populations: CKDu patients ( n = 43), chronic kidney disease patients (CKD; n = 14), healthy individuals from a CKDu endemic area (GHI; n = 9), and nonendemic area (KHI; n = 16). Fold changes were quantified relative to KHI. Results. GCLC had greater than threefold upregulation in all three study groups, with a maximum of 7.27-fold upregulation in GHI ( p = 0.000). GSTM1 was not expressed in 25.6% of CKDu and 42.9% of CKD patients, but CKDu patients expressing GSTM1 showed upregulation of 2.60-fold ( p CKDu was observed ( p CKDu, possibly owing to environmental conditions.

  5. Upregulation of Oxidative Stress Related Genes in a Chronic Kidney Disease Attributed to Specific Geographical Locations of Sri Lanka

    Directory of Open Access Journals (Sweden)

    Saravanabavan Sayanthooran

    2016-01-01

    Full Text Available Objective. To infer the influence of internal and external oxidative stress in chronic kidney disease patients of unknown etiology (CKDu in Sri Lanka, by analyzing expression of genes related directly or indirectly to oxidative stress: glutamate-cysteine ligase catalytic subunit (GCLC, glutathione S-transferase mu 1 (GSTM1, glucose-6-phosphate dehydrogenase (G6PD, fibroblast growth factor-23 (FGF23, and NLR family pyrin domain containing 3 (NLRP3. Methods. Reverse transcription quantitative polymerase chain reaction (RT-qPCR was carried out for the selected populations: CKDu patients (n=43, chronic kidney disease patients (CKD; n=14, healthy individuals from a CKDu endemic area (GHI; n=9, and nonendemic area (KHI; n=16. Fold changes were quantified relative to KHI. Results. GCLC had greater than threefold upregulation in all three study groups, with a maximum of 7.27-fold upregulation in GHI (p=0.000. GSTM1 was not expressed in 25.6% of CKDu and 42.9% of CKD patients, but CKDu patients expressing GSTM1 showed upregulation of 2.60-fold (p<0.05. Upregulation of FGF23 and NLRP3 genes in CKD and CKDu was observed (p<0.01, with greater fold changes in CKD. Conclusion. Results suggest higher influence of external sources of oxidative stress in CKDu, possibly owing to environmental conditions.

  6. Sickle cell disease in tribal populations in India.

    Science.gov (United States)

    Colah, Roshan B; Mukherjee, Malay B; Martin, Snehal; Ghosh, Kanjaksha

    2015-05-01

    The sickle gene is widespread among many tribal population groups in India with prevalence of heterozygotes varying from 1-40 per cent. Co-inheritance of the sickle gene with β-thalassaemia, HbD Punjab and glucose-6-phosphate dehydrogenase (G6PD) deficiency has also been reported. Most of the screening programmes in India now use high performance liquid chromatography (HPLC) analysis although the solubility test is also sensitive and cheap. Sickle cell disease (SCD) among tribal populations is generally milder than among non-tribal groups with fewer episodes of painful crises, infections, acute chest syndrome and need for hospitalization. This has partly been attributed to the very high prevalence of α-thalassaemia among these tribes as well as higher foetal haemoglobin levels. However, the clinical presentation is variable with many cases having a severe presentation. There is not much information available on maternal and perinatal outcome in tribal women with sickle cell disease. Newborn screening programmes for SCD have recently been initiated in Maharashtra, Gujarat, Orissa and Chattisgarh and monitoring these birth cohorts will help to understand the natural history of SCD in India. Prenatal diagnosis is acceptable by tribal families in India. The Indian Council of Medical Research and the National Rural Health Mission in different States are undertaking outreach programmes for better management and control of the disease.

  7. Strengthening of antioxidant defense by Azadirachta indica in alloxan-diabetic rat tissues

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    Sweta Shailey

    2012-01-01

    Full Text Available Background: Azadirachta indica has been reported to correct altered glycaemia in diabetes. Objective: The aqueous extract of A. indica leaf and bark has been evaluated for its effect on antioxidant status of alloxan diabetic rats and compared with insulin treatment. Materials and Methods: The oral effective dose of A. indica leaf (500 mg/kg body weight and A. indica bark (100 mg/kg body weight were given once daily for 21 days to separate groups of diabetic rats. At the end of the experimental period blood glucose level and activity of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx, glutathione reductase (GR, glucose-6-phosphate dehydrogenase (G-6-PD, and membrane lipid peroxidation were determined in different fractions of liver and kidney tissues. Results: Diabetic rats showed high blood glucose (P<0.01, increased level of malondialdehyde (P<0.05 and a significant decrease in the activity of antioxidant enzymes. Treatment with insulin, A. indica leaf extract (AILE, and A. indica bark extract (AIBE restored the above altered parameters close to the control ones. Conclusions: Both AILE and AIBE were found significantly effective in reducing hyperglycemia-induced oxidative stress. The findings suggest further investigations for the possible use of A. indica as alternative medicine to prevent long-term complications of diabetes.

  8. A randomized, double-blind, placebo-controlled, dose-ranging trial of tafenoquine for weekly prophylaxis against Plasmodium falciparum.

    Science.gov (United States)

    Hale, Braden R; Owusu-Agyei, Seth; Fryauff, David J; Koram, Kwadwo A; Adjuik, Martin; Oduro, Abraham R; Prescott, W Roy; Baird, J Kevin; Nkrumah, Francis; Ritchie, Thomas L; Franke, Eileen D; Binka, Fred N; Horton, John; Hoffman, Stephen L

    2003-03-01

    Tafenoquine is a promising new 8-aminoquinoline drug that may be useful for malaria prophylaxis in nonpregnant persons with normal glucose-6-phosphate dehydrogenase (G6PD) function. A randomized, double-blind, placebo-controlled chemoprophylaxis trial was conducted with adult residents of northern Ghana to determine the minimum effective weekly dose of tafenoquine for the prevention of infection by Plasmodium falciparum. The primary end point was a positive malaria blood smear result during the 13 weeks of study drug coverage. Relative to the placebo, all 4 tafenoquine dosages demonstrated significant protection against P. falciparum infection: for 25 mg/week, protective efficacy was 32% (95% confidence interval [CI], 20%-43%); for 50 mg/week, 84% (95% CI, 75%-91%); for 100 mg/week, 87% (95% CI, 78%-93%); and for 200 mg/week, 86% (95% CI, 76%-92%). The mefloquine dosage of 250 mg/week also demonstrated significant protection against P. falciparum infection (protective efficacy, 86%; 95% CI, 72%-93%). There was little difference between study groups in the adverse events reported, and there was no evidence of a relationship between tafenoquine dosage and reports of physical complaints or the occurrence of abnormal laboratory parameters. Tafenoquine dosages of 50, 100, and 200 mg/week were safe, well tolerated, and effective against P. falciparum infection in this study population.

  9. Biochemical Studies on Rosemary Extracts as an Antioxidant in Irradiated Rats

    International Nuclear Information System (INIS)

    Abady, M.M.; Zahran, A.M.; Mansour, S.Z.; Ragab, E.A.

    2003-01-01

    The antioxidant properties of rosemary (Rosmarinus officinalis) essential oil and crude ethanolic extract, have been attributed to its phenolic diterpene, carnosol, carnosic acid, caffeic acid and its derivatives such as rosmarinic acid. These aroma compounds were identified to protect biological membranes from oxidative stress in addition to divers pharmacological and therapeutic activities. This study was undertaken to investigate the effect of natural extract derived from rosemary herb, as an antioxidant defensive element in irradiated rats. Mixture of essential oil and hydroalcoholic extract was orally administered to rats by gavage (150 mg/kg B.w.) for 35 days before exposure to the first fraction of irradiation exposure and during the whole period of irradiation treatment (12 days). Whole body irradiation was delivered as fractionated doses at 1 Gy increment every other day up to total cumulative dose of 6 Gy. Changes in the content of reduced glutathion (GSH), glutathion peroxidase (GSHPx), glucose -6- phosphate dehydrogenase (G-6-PD), superoxide dismutase (SOD) and catalase (Cat.) in blood, liver and spleen were evaluated in different rat groups. The results revealed that transient noticeable increase during the 1st hour post irradiation in the aforementioned parameters, followed by significant decrease recorded after 7 days. Rats supplemented rosemary extract before irradiation have significantly ameliorate the radiation induced depletion in the antioxidant component system

  10. Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.

    Science.gov (United States)

    Shiraki, Hiroaki; Kozar, Michael P; Melendez, Victor; Hudson, Thomas H; Ohrt, Colin; Magill, Alan J; Lin, Ai J

    2011-01-13

    In an attempt to separate the antimalarial activity of tafenoquine (3) from its hemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients, a series of 5-aryl-8-aminoquinoline derivatives was prepared and assessed for antimalarial activities. The new compounds were found metabolically stable in human and mouse microsomal preparations, with t(1/2) > 60 min, and were equal to or more potent than primaquine (2) and 3 against Plasmodium falciparum cell growth. The new agents were more active against the chloroquine (CQ) resistant clone than to the CQ-sensitive clone. Analogues with electron donating groups showed better activity than those with electron withdrawing substituents. Compounds 4bc, 4bd, and 4be showed comparable therapeutic index (TI) to that of 2 and 3, with TI ranging from 5 to 8 based on IC(50) data. The new compounds showed no significant causal prophylactic activity in mice infected with Plasmodium berghei sporozoites, but are substantially less toxic than 2 and 3 in mouse tests.

  11. Risk factors and outcome of neonatal jaundice in a tertiary hospital

    Directory of Open Access Journals (Sweden)

    Bedowra Zabeen

    2010-07-01

    Full Text Available Neonatal jaundice is a common cause of newborn hospital admission. The risk factors, the characteristics and outcomes related to neonatal jaundice in Bangladesh has not been studied so far. This study addressed the outcomes, characteristics and risks of the jaundiced newborn admitted into hospital. The babies who had significant jaundice and required phototherapy and /or exchange transfusion were investigated. A detailed history of delivery with gestational age was noted and clinical examination of the admitted newborn was done. Birth weight was recorded. The investigations included complete blood count, ABO and Rh compatibility, serum bilirubin, glucose 6 phosphate dehydrogenase (G6PD, thyroid stimulating hormone (TSH and ultrasonography (USG of brain. The newborns were closely monitored for the prognosis. The requirement of individualized phototherapy and exchange transfusion were also noted. Finally, the outcomes were recorded. Overall, 60 (m v. f = 58.3 v. 41.7% newborns were found who developed significant jaundice and were investigated. Of them, 35% had gestational age less than 32wks and only 32% had equal to or greater than 35wks. Regarding delivery, 83.3 % had the history of caesarean section. ABO- and Rh– incompatibilities were found in 13.3% and 3.3%, respectively. Septicemia was diagnosed among 26.7% though blood culture yielded growth only in 20%. Compared with the higher gestational age-group ( 35 wks the lower group (<32 wks showed significantly higher rate of septicemia (12.5 v. 68.8%, p<0.005. G6PD deficiency was found in only one (1.7% case. Birth asphyxia was found as a concomitant factor in three patients. Exchange transfusion was done only in 2 (3.3% babies. Among them one was preterm IDM with septicemia and other had G6PD deficiency. None of these babies developed kernicterus. Five (8.3% babies died, all of them had septicemia and one baby also had intraventricular hemorrhage (IVH with PDA. The study revealed that a

  12. Evaluation of the causes of neonatal jaundice, based on the infant’s age at disease onset and age at hospital admission

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    Hassan Boskabadi

    2016-01-01

    Full Text Available Background: Jaundice is the most common cause of neonatal admission within the first month after birth. Therefore, by identifying the causes of jaundice based on the infant’s age at disease onset and age at hospital admission and providing the required training, jaundice can be managed and its associated complications can be prevented. This study was performed to evaluate the causes of neonatal jaundice, based on the infant’s age at disease onset and age at hospital admission. Methods: In this cross-sectional study, out of 3,130 infants with jaundice, referring to Ghaem Hospital, Mashhad, Iran, from 2003 to 2015, 2,658 newborns were selected. Causes of jaundice are determined based on hematocrit, direct and indirect bilirubin, Coombs test, reticulocyte count, blood group and Rh of mother and neonate, thyroid tests, glucose-6-phosphate dehydrogenase (G6PD enzyme testing, urinalysis, urine culture, and If necessary, Na, blood urea nitrogen, creatinine and other tests depending on the doctor's supervision. After confirming jaundice in infants, based on the physician’s diagnosis and laboratory results, a researcher-made questionnaire including the infant’s characteristics, was completed. Results: Based on our study, 27.9% of infants had identified as causes of jaundice. Known causes of jaundice were blood group incompatibility (40%, infection (19%, G6PD enzyme deficiency (12%, endocrine disorders (8%, neonatal hypernatremic dehydration (7%, polycythemia (6%, congenital heart disease (CHD (4%, occult bleeding (3% and Crigler-Najjar syndrome (2%. The most common time of hospital admission of jaundice was 4-6 days after birth due to blood incompatibilities, occult bleeding, endocrine disorders, hypernatremic dehydration, CHD, polycythemia and G6PD enzyme deficiency. Moreover, the most common time of admission due to infection was after the first week of birth. Conclusion: The most common age of onset of jaundice was first three days of birth

  13. Cytogenetic and molecular studies on a recombinant human X chromosome: implications for the spreading of X chromosome inactivation

    International Nuclear Information System (INIS)

    Mohandas, T.; Geller, R.L.; Yen, P.H.; Rosendorff, J.; Bernstein, R.; Yoshida, A.; Shapiro, L.J.

    1987-01-01

    A pericentric inversion of human X chromosome and a recombinant X chromosome [rec(X)] derived from crossing-over within the inversion was identified in a family. The rec(X) had a duplication of the segment Xq26.3 → Xqter and a deletion of Xp22.3 → Xpter and was interpreted to be Xqter → Xq26.3::Xp22.3 → Xqter. To characterize the rec(X) chromosome, dosage blots were done on genomic DNA from carriers of this rearranged X chromosome using a number of X chromosome probes. Results showed that anonymous sequences from the distal end of the long arm to which probes 4D8, Hx120A, DX13, and St14 bind as well as the locus for glucose-6-phosphate dehydrogenase (G6PD) wee duplicated on the rec(X). Mouse-human cell hybrids were constructed that retained the rec(X) in the active or inactive state. Analyses of these hybrid clones for markers from the distal short arm of the X chromosome showed that the rec(X) retained the loci for steroid sulfatase (STS) and the cell surface antigen 12E7 (MIC2); but not the pseudoautosomal sequence 113D. These molecular studies confirm that the rec(X) is a duplication-deficiency chromosome as expected. In the inactive state in cell hybrids, STS and MIC2 (which usually escape X chromosome inactivation) were expressed from the rec(X), whereas G6PD was not. Therefore, in the rec(X) X chromosome inactivation has spread through STS and MIC2 leaving these loci unaffected and has inactivated G6PD in the absence of an inactivation center in the q26.3 → qter region of the human X chromosome. The mechanism of spreading of inactivation appears to operate in a sequence-specific fashion. Alternatively, STS and MIC2 may have undergone inactivation initially but could not be maintained in an inactive state

  14. The effects of storage on the retention of enzyme activity in cryostat sections. A quantitative histochemical study on rat liver

    NARCIS (Netherlands)

    Frederiks, W. M.; Ouwerkerk, I. J.; Bosch, K. S.; Marx, F.; Kooij, A.; van Noorden, C. J.

    1993-01-01

    The effect of storage of unfixed cryostat sections from rat liver for 4 h, 24 h, 3 days and 7 days at -25 degrees C was studied on the activities of lactate dehydrogenase, glucose-6-phosphate dehydrogenase, xanthine oxidoreductase, glutamate dehydrogenase, succinate dehydrogenase (all demonstrated

  15. Enhanced glucose cycling and suppressed de novo synthesis of glucose-6-phosphate result in a net unchanged hepatic glucose output in ob/ob mice

    NARCIS (Netherlands)

    Bandsma, RHJ; Grefhorst, A; van Dijk, TH; van der Sluijs, FH; Hammer, A; Reijngoud, DJ; Kuipers, F

    2004-01-01

    Aims/hypothesis. Leptin-deficient ob/ob mice are hyperinsulinaemic and hyperglycaemic; however, the cause of hyperglycaemia remains largely unknown. Methods. Glucose metabolism in vivo in 9-h fasted ob/ob mice and lean littermates was studied by infusing [U-C-13]-glucose, [2-C-13]-glycerol,

  16. Enzymes and membrane proteins of ADSOL-preserved red blood cells

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    Maria Sueli Soares Leonart

    2000-03-01

    Full Text Available CONTEXT: The preservative solution ADSOL (adenine, dextrose, sorbitol, sodium chloride and mannitol maintains red cell viability for blood trans-fusion for 6 weeks. It would be useful to know about its preservation qualities over longer periods. OBJECTIVE: To determine some red cell biochemical parameters for peri-ods of up to 14 weeks in order to determine whether the red cell metabo-lism integrity would justify further studies aiming at increasing red cell preservation and viability. DESIGN: Biochemical evaluation designed to study red cell preservation. SETTING: São Paulo University erythrocyte metabolism referral center. SAMPLE: Six normal blood donors from the University Hospital of the Universidade Federal do Paraná, Curitiba, Brazil. MAIN MEASUREMENTS: Weekly assay of erythrocyte adenosine-5´-triphosphate (ATP, 2,3-diphosphoglycerate (2,3DPG, hexokinase (HX, phosphofructokinase (PFK, pyruvate kinase (PK, glucose-6-phosphate dehydrogenase (G-6-PD, 6-phosphogluconic dehydrogenase (6-PGD, glyceraldehyde-3-phosphate dehydrogenase (GAPD, glutathione reduc-tase (GR, glutathione peroxidase (GSHPx, plasma sodium and potas-sium, blood pH, and membrane proteins of red cells preserved in ADSOL were studied during storage for 14 weeks storage. RESULTS: During ADSOL preservation, erythrocyte ATP concentration decreased 60% after 5 weeks, and 90% after 10 weeks; the pH fell from 6.8 to 6.4 by the 14th week. 2,3-DPG concentration was stable during the first week, but fell 90% after 3 weeks and was exhausted after 5 weeks. By the end of the 5th week, an activity decrease of 16-30% for Hx, GAPD, GR, G-6-PD and 6-PGD, 35% for PFK and GSHPx, and 45% for PK were observed. Thereafter, a uniform 10% decay was observed for all enzymes up to the 14th week. The red blood cell membrane pro-teins did not show significant alterations in polyacrylamide gel electro-phoresis (SDS-PAGE during the 14 weeks. CONCLUSION: Although the blood viability was shown to be poor

  17. Genetics Home Reference: dihydropyrimidine dehydrogenase deficiency

    Science.gov (United States)

    ... 5-fluorouracil and capecitabine. These drugs are not broken down efficiently by people with dihydropyrimidine dehydrogenase deficiency ... of this enzyme. Because fluoropyrimidine drugs are also broken down by the dihydropyrimidine dehydrogenase enzyme, deficiency of ...

  18. Intrauterine growth retardation increases the susceptibility of pigs to high-fat diet-induced mitochondrial dysfunction in skeletal muscle.

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    Jingbo Liu

    Full Text Available It has been recognized that there is a relationship between prenatal growth restriction and the development of metabolic-related diseases in later life, a process involved in mitochondrial dysfunction. In addition, intrauterine growth retardation (IUGR increases the susceptibility of offspring to high-fat (HF diet-induced metabolic syndrome. Recent findings suggested that HF feeding decreased mitochondrial oxidative capacity and impaired mitochondrial function in skeletal muscle. Therefore, we hypothesized that the long-term consequences of IUGR on mitochondrial biogenesis and function make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. Normal birth weight (NBW, and IUGR pigs were allotted to control or HF diet in a completely randomized design, individually. After 4 weeks of feeding, growth performance and molecular pathways related to mitochondrial function were determined. The results showed that IUGR decreased growth performance and plasma insulin concentrations. In offspring fed a HF diet, IUGR was associated with enhanced plasma leptin levels, increased concentrations of triglyceride and malondialdehyde (MDA, and reduced glycogen and ATP contents in skeletal muscle. High fat diet-fed IUGR offspring exhibited decreased activities of lactate dehydrogenase (LDH and glucose-6-phosphate dehydrogenase (G6PD. These alterations in metabolic traits of IUGR pigs were accompanied by impaired mitochondrial respiration function, reduced mitochondrial DNA (mtDNA contents, and down-regulated mRNA expression levels of genes responsible for mitochondrial biogenesis and function. In conclusion, our results suggest that IUGR make the offspring more susceptible to HF diet-induced mitochondrial dysfunction.

  19. Wheat Germ Oil Attenuates Gamma Radiation- Induced Skeletal Muscles Damage in Rats

    International Nuclear Information System (INIS)

    Said, U.Z.; Saada, H.N.; Shedid, Sh.M.; Mahdy, E.M.E.; Shousha, W.Gh.

    2008-01-01

    Muscular strength is important in sport as well as in daily activities. Exposure to ionizing radiation is thought to increase oxidative stress and damage muscle tissue. Wheat germ oil is a natural unrefined vegetable oil. It is an excellent source of vitamin E, octacosanol, linoleic and linolenic essential fatty acids, which may be beneficial in neutralizing the free oxygen radicals. The present study was designed to investigate the efficacy of wheat germ oil, on radiation-induced oxidative damage in rats skeletal muscle. Wheat germ oil was supplemented orally via gavages to rats at a dose of 54 mg/ kg body weight/day for 14 successive days pre- and 7 post-exposure to 5 Gy (one shot dose) of whole body gamma irradiation. Animals were sacrificed 7, 14 and 21 days post radiation exposure. The results revealed that whole body gamma-irradiation of rats induces oxidative stress in skeletal muscles obvious by significant elevation in the level of thiobarbituric acid reactive substances (TBARS) associated with significant decreases in the content of reduced glutathione (GSE1), as well as decreases in superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities. Irradiated rats showed, also, significant decreases in creatine phosphokinase (CPK), glutamate dehydrogenase (GDH) and glucose-6-phosphate dehydrogenase (G-6-PD) activities. Furthermore, total iron, total copper and total calcium levels were significantly increased in skeletal muscles of irradiated rats group compared to control group. Wheat germ oil treated-irradiated rats showed significantly less sever damage and remarkable improvement in all the measured parameters, compared to irradiated rats. It could be concluded that wheat germ oil by attenuating radiation induced oxidative stress might play a role in maintaining skeletal muscle integrity

  20. Inhibition effects of furfural on alcohol dehydrogenase, aldehyde dehydrogenase and pyruvate dehydrogenase.

    Science.gov (United States)

    Modig, Tobias; Lidén, Gunnar; Taherzadeh, Mohammad J

    2002-01-01

    The kinetics of furfural inhibition of the enzymes alcohol dehydrogenase (ADH; EC 1.1.1.1), aldehyde dehydrogenase (AlDH; EC 1.2.1.5) and the pyruvate dehydrogenase (PDH) complex were studied in vitro. At a concentration of less than 2 mM furfural was found to decrease the activity of both PDH and AlDH by more than 90%, whereas the ADH activity decreased by less than 20% at the same concentration. Furfural inhibition of ADH and AlDH activities could be described well by a competitive inhibition model, whereas the inhibition of PDH was best described as non-competitive. The estimated K(m) value of AlDH for furfural was found to be about 5 microM, which was lower than that for acetaldehyde (10 microM). For ADH, however, the estimated K(m) value for furfural (1.2 mM) was higher than that for acetaldehyde (0.4 mM). The inhibition of the three enzymes by 5-hydroxymethylfurfural (HMF) was also measured. The inhibition caused by HMF of ADH was very similar to that caused by furfural. However, HMF did not inhibit either AlDH or PDH as severely as furfural. The inhibition effects on the three enzymes could well explain previously reported in vivo effects caused by furfural and HMF on the overall metabolism of Saccharomyces cerevisiae, suggesting a critical role of these enzymes in the observed inhibition. PMID:11964178

  1. Salubrious effect of C-phycocyanin against oxalate-mediated renal cell injury.

    Science.gov (United States)

    Farooq, Shukkur Muhammed; Asokan, Devarajan; Sakthivel, Ramasamy; Kalaiselvi, Periandavan; Varalakshmi, Palaninathan

    2004-10-01

    C-phycocyanin, a biliprotein pigment found in some blue green algae (Spirulina platensis) with nutritional and medicinal properties, was investigated for its efficacy on sodium oxalate-induced nephrotoxicity in experimentally induced urolithic rats. Male Wistar rats were divided into four groups. Hyperoxaluria was induced in two of these groups by intraperitoneal infusion of sodium oxalate (70 mg/kg), and a pretreatment of phycocyanin (100 mg/kg) as a single oral dosage was given to one of these groups by 1 h prior to sodium oxalate infusion challenges. The study also encompasses an untreated control group and a phycocyanin-alone treated drug control group. The extent of lipid peroxidation (LPO) was evaluated in terms of renal concentrations of MDA, conjugated diene and hydroperoxides. The following assay was performed in the renal tissue (a) antioxidant enzymes such as superoxide dismutase (SOD) and catalase, (b) glutathione metabolizing enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and glucose 6-phosphate dehydrogenase (G6PD), (c) the low molecular weight antioxidants (GSH, vitamins E and C) and protein carbonyl content. The increased concentrations of MDA, conjugated diene and hydroperoxide (index of the lipid peroxidation) were controlled (P antioxidants were appreciably increased (P antioxidants. It was noticed that the activities of antioxidant enzymes and glutathione metabolizing enzymes were considerably stabilized in rats pretreated with phycocyanin. We suggest that phycocyanin protects the integrity of the renal cell by stabilizing the free radical mediated LPO and protein carbonyl, as well as low molecular weight antioxidants and antioxidant enzymes in renal cells. Thus, the present analysis reveals that the antioxidant nature of C-phycocyanin protects the renal cell against oxalate-induced injury and may be a nephroprotective agent.

  2. Knowledge Level and Determinants of Neonatal Jaundice: A Cross-Sectional Study in the Effutu Municipality of Ghana

    Science.gov (United States)

    Kontor, Kate Adomakowaah; Bentsil, Joseph-Josiah; Anderson, Maxwell; Nsiah, Paul

    2018-01-01

    Background Neonatal jaundice (NNJ) is a major cause of hospital admission during the neonatal period and is associated with significant mortality. This case-control study with cross-sectional design sought to identify the possible factors associated with neonatal jaundice and assess maternal knowledge level of this condition. Methods One hundred and fifty (150) neonates comprising 100 with clinically evident jaundice and 50 without jaundice were conveniently recruited from the Trauma and Specialist Hospital in the Effutu Municipality. Blood samples were collected for the determination of serum bilirubin, glucose-6-phosphate dehydrogenase (G6PD), status and blood group (ABO and Rhesus). Well-structured questionnaire was used to collect maternal and neonate sociodemographic and clinical history. Results Majority (54%) of neonates developed jaundice within 1–3 days after birth with 10% having it at birth. Duration of labour and neonatal birth weight were associated with neonatal jaundice (P jaundice and ABO incompatibility was present in 18%. Neonates delivered by mothers with formal occupation and those who had prolonged duration of labour were significantly more likely to have neonatal jaundice (OR = 4.174, P = 0.003; OR = 2.389, P = 0.025, resp.). Neonates with low birth weight were also more likely to develop neonatal jaundice (OR = 2.347, P = 0.044). Only 17.3% of mothers had heard of neonatal jaundice. School was the major source of information on neonatal jaundice (34.6%). Majority of participants (mothers) did not know that NNJ can cause damage to other organs in the body (90%). Conclusion Low neonatal birth weight and prolonged duration of labour are associated with neonatal jaundice. Mothers had inadequate knowledge of neonatal jaundice and its causes. PMID:29686715

  3. Hemato-biochemical and clinico-epidemiological aspects of parturient hemoglobinuria in Nili-Ravi buffaloes

    Directory of Open Access Journals (Sweden)

    A. Khan

    2010-02-01

    Full Text Available For this study, 60 buffaloes suffering from parturient hemoglobinuria (PHU were randomly selected from field cases occurring in three districts of Punjab, Pakistan and simultaneously, 60 clinically healthy buffaloes of similar description from the same localities were included for case control study. Clinico-epidemiological data were collected. Blood/serum samples from all buffaloes were collected and analyzed. The most prominent clinical sign was passing of red to coffee colored urine. Milk production was reduced and respiration and pulse rates were significantly accelerated. Ruminal motility was significantly weak and reduced along with characteristic straining while defecating. The case fatality was 15%. A significantly high occurrence of PHU was observed in the winter season (41.8%. Maximum number of affected buffaloes (25.0% was in 4th lactation. Twenty-seven (45.0% buffaloes developed hemoglobinuria in the post calving period and majority (59.3% of these were within 1-23 days of calving. Of the 33 (55.0% PHU affected pregnant buffaloes, 18 (54.6% were in their third trimester. The highest cases of PHU were observed in buffaloes producing 10 or more liters of milk/day (42.5%. Recurrence of PHU was observed in 18.3% buffaloes. Mean values of total erythrocyte counts, hemoglobin concentration and packed cell volume were lower (P<0.001, while erythrocyte sediment rate was higher (P<0.001 in PHU affected buffaloes as compared to the values in healthy buffaloes. Neutrophils were significantly higher, while lymphocytes and erythrocytic glucose-6-phosphate dehydrogenase (G6PD were lower, in PHU affected buffaloes than in healthy buffaloes. Serum phosphorus, copper and selenium were significantly (P<0.001 lower, whereas potassium, iron and molybdenum (P<0.001 were higher in buffaloes suffering from PHU than healthy buffaloes.

  4. Mangiferin Reduces Oxidative Stress-mediated Renal Injury in γ-radiated Mice

    International Nuclear Information System (INIS)

    El-Kabany, H.; Lotfi, S.A.

    2012-01-01

    Whole body exposure to ionizing radiation induces the formation of reactive oxygen species in different tissues provoking oxidative damage and tissue injury. Mangiferin (MGN), 1,3,6,7-tetra hydroxyxanthone-C 2 -β-D-glucoside, a naturally occurring polyphenol, present in Mangifera indica (M. indica) in large amounts in the leaves and edible mango fruits has been reported to possess antioxidant properties. The purpose of this study was to evaluate the role of MGN on radiation-induced oxidative stress and histological changes in the kidney of mice. MGN (20 mg/ kg body weight) was administrated to male albino mice via gavages during 15 successive days before whole body exposures to gamma rays (4 Gy). The animals were sacrificed 48 hours post irradiation. Biochemical analysis in the kidney of irradiated mice revealed an imbalance between oxidant and antioxidant species. A significant increase was recorded in the level of lipid peroxidation products; thiobarbituric acid reactive substances (TBARs) and lipid hydroperoxides (HDPx), in addition to a significant increase in the level of protein carbonyl content (PC) , marker of protein oxidation. The increase of oxidative markers was accompanied by a significant decrease in the contents of total sulphydryl (SH) group ,glutathione (GSH) content, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activity. Moreover, irradiation induced a significant decrease in the activity of glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD). Histological observations in the kidney of irradiated mice revealed tubular necrosis, degeneration, dilatation, desquamation, thickening of basement membrane and luminal cast formation. MGN pre-treatment has significantly improved the oxidant /antioxidant status, which was associated with significant regeneration of the kidney tissue. Based on these results, it is concluded that the natural dietary antioxidant M GN m ight

  5. Prevalence of Bilirubin Encephalopathy in Calabar, South-South Nigeria: A Five-year Review Study

    Directory of Open Access Journals (Sweden)

    Sunny Oteikwu Ochigbo

    2016-03-01

    Full Text Available Background: Bilirubin encephalopathy is a clinical syndrome, associated with bilirubin toxicity in the central nervous system, resulting in chronic and permanent sequelae. It has been estimated that approximately 60% and 80% of term and preterm newborns develop jaundice in the first week of life, respectively. In the present study, we aimed to determine the prevalence, morbidity, and mortality of bilirubin encephalopathy in the neonatal unit of the University of Calabar Teaching Hospital, Calabar, Nigeria. Methods: In this retrospective, descriptive review, medical records of all newborns, diagnosed with bilirubin encephalopathy over the past five years (from January 2010 to December 2014, were studied. Information retrieved from the medical records included age, sex, presence of fever, duration of disease, place of delivery, causes of the disease, and selected treatments. Variables such as hospital discharge, discharge against medical advice, and mortality were also evaluated. Results: Out of 2,820 newborns, 21 (0.74% cases were admitted on account of bilirubin encephalopathy. Among these affected cases, 17 (81% were male and 4 (19% were female (male-to-female ratio of 5:1. Based on the findings, 18 newborns (85.7% had pyrexia, while 8 (38.1% and 6 (28.6% cases were hypertonic and hypotonic, respectively upon admission. Only 33.3% of deliveries took place in healthcare facilities. The established factors responsible for jaundice included infection, i.e., septicemia (n=15, 71.4%, ABO incompatibility (n=4, 19.1%, and glucose-6-phosphate-dehydrogenase (G6PD deficiency (n=2, 9.5%. The mean maximum total bilirubin level in subjects was 321.3 μmol/L (range: 242.5–440.3 μmol/L. Also, mortality was reported in 4 (19% out of 21 cases. Conclusion: Based on the findings, neonatal septicemia is associated with bilirubin encephalopathy. Therefore, identification and prompt treatment are of utmost importance in preventing the associated morbidity and

  6. Potential impact of Paracentrotus lividus extract on diabetic rat models induced by high fat diet/streptozotocin

    Directory of Open Access Journals (Sweden)

    Amel M. Soliman

    2016-10-01

    Full Text Available Antioxidant therapy has been thought to be effectual for the prevention and treatment of various diseases including diabetes. Therefore, the present study was designed to investigate the potency of Paracentrotus lividus extract (PLE for alleviating the complications that resulted after induction of the diabetic rat models (T1DM and T2DM using high fat diet (HFD/streptozotocin (STZ. Thirty six male Wistar albino rats were assigned into normal control, T1DM and T2DM untreated, and PLE treated diabetic rat groups. Induction of T1DM was performed by streptozotocin injection (60 mg/kg of dissolved in sodium citrate buffer, 0.1 mol/L, i.p. T2DM induction through 4 weeks of high fat diet (HFD intervention was followed by a single low dosage of STZ (30 mg/kg dissolved in 0.1 mol/L citrate buffer at pH 4.5, i.p. Both diabetic rat models showed a significant increase in serum; levels of fasting glucose, total protein, bilirubin, activities of arginase, transaminases (AST and ALT, alkaline phosphatase (ALP, γ glutamyl transferase (GGT, lipid profile parameters, and liver malondialdehyde (MDA. However, T1DM and T2DM rats have decreased levels of serum insulin, and liver glucose 6 phosphate dehydrogenase (G6PD, glutathione reduced (GSH, nitric oxide (NO, and antioxidant enzymes. Furthermore, the present study showed the hypoglycemic, hypolipidemic, and antioxidant potency of the PLE as confirmed by its ability for ameliorating most of the alterations caused in the studied parameters of diabetic rats. In conclusion, PLE may be useful as therapy against oxidative stress and liver damage in both types of diabetes mellitus and is therefore recommended for further studies.

  7. Prevalence of peripheral blood parasitaemia, anaemia and low birthweight among pregnant women in a suburban area in coastal Ghana.

    Science.gov (United States)

    Stephens, Judith Koryo; Ofori, Michael F; Quakyi, Isabella Akyinbah; Wilson, Mark Lee; Akanmori, Bartholomew Dicky

    2014-01-01

    Malaria and anaemia have adverse effects in pregnant women and on the birth weight of infants in malaria endemic areas. P. falciparum malaria, the most virulent species continues to be a major health problem in sub-Saharan Africa. This study was carried out to establish the prevalence of pregnancy-associated malaria and its associated consequences including maternal anaemia and low birthweight (LBW) deliveries and placental malaria among pregnant women in a sub-urban area in coastal Ghana. A facility-based investigation was carried out among 320 pregnant women seeking antenatal care in a hospital in suburban coastal Ghana. Information on the use of Insecticide Treated Nets (ITNs) and Intermittent Preventive Treatment in pregnancy (IPTp) were collected using a structured questionnaire at enrollment. Venous blood was collected for microscopy and screening for Glucose 6-phosphate dehydrogenase (G6PD) deficiency. Haemoglobin concentration was obtained from an automatic blood analyzer. Placental smears and birth weight measurements were taken at delivery. The prevalence of Plasmodium falciparum parasitaemia was 5%. The mean haemoglobin (Hb) level at registration was 11.44 g/dL (95% CI 11.29 - 11.80). Placental blood parasitaemia and low birthweight were 2.5% and 3% respectively. ITN possession was 31.6% with 5.4% usage. The IPTp coverage was 55%. The prevalence of malaria and anaemia among the pregnant women were low at enrollment. Placental blood parasitaemia and LBW at delivery were also low. These are clear indications of the high coverage of the IPTp. Increase in ITN use will further improve birthweight outcomes and reduce placental malaria.

  8. Effect of the Antibiotic Neomycin on the Toxicity of the Glycoside Vicine in Rats

    Directory of Open Access Journals (Sweden)

    Mahmoud S. Arbid

    2013-01-01

    Full Text Available Vicine is hydrolyzed by microflora to highly reactive free radical generating compound divicine which causes mortality and other adverse effects. This study in the rats established the effect of a broad spectrum and poorly absorbed antibiotic, neomycin sulfate on the toxicity of vicine. The results showed extremely decrease in mortality rate in the group pretreated with neomycin. Hemoglobin (Hb concentration, hematocrit (Hct value, and red blood cells (RBCs count were significantly decreased after injection of vicine and the improvement of these values in the group pretreated with neomycin. The same results were observed in white blood cells (WBCs. The results showed a significant decrease in glucose level and returned to normal in group pretreated with neomycin. Glutathione (GSH was significantly decreased in the vicine group and returned to normal value in the group pretreated with neomycin. Lipid peroxide (TBARs was significantly increased in the group treated with vicine and neomycin pretreated group decreased to the normal level. Glucose-6-phosphate dehydrogenase (G6-PD activity was significantly decreased and returned to normal level in rats pretreated with neomycin. Serum protein and globulin were significantly decreased but serum albumin showed insignificant decrease in vicine and neomycin groups compared to control. Alanine aminotransferase (ALT and aspartate aminotransferase (AST were significantly decreased in the vicine group. The group pretreated with neomycin showed significantly increased activities of AST and ALT compared with vicine group. In conclusion, neomycin pretreatment of rats injected with glycoside vicine decreased to a great extent of its toxic and mortality effects and is useful in favism and hemolytic anemia.

  9. A Coincidental Discovery of a New Stable Variant (Hb Hachioji or HBB: c.187C>T) in a Patient with Chronic Hemolytic Anemia of Unexplained Origin.

    Science.gov (United States)

    Mella, Ferania; Yamashiro, Yasuhiro; Adhiyanto, Chris; Tanaka, Tatehiko; Nitta, Takenori; Amao, Yuki; Kimoto, Masafumi

    2018-01-01

    We report a new hemoglobin (Hb) variant, Hb Hachioji (HBB: c.187C>T), which was detected in a 32-year-old male with hemolytic anemia. The proband had undergone splenectomy in his childhood after being diagnosed with hereditary spherocytosis (HS) with no clinical improvement. A recent study showed that Heinz bodies were frequently observed in his red cells, however, no abnormal band was separated by isoelectric focusing (IEF), and the isopropanol (instability) test was negative. Direct sequencing revealed that the proband was a heterozygous carrier of a novel mutation (GCT>GTT) at codon 62 of the β-globin gene, leading to an alanine to valine substitution. This variant was named Hb Hachioji. Characterization at the mRNA level by cDNA sequencing detected β Hachioji mRNA, as well as β A mRNA. Subsequently, study of the proband's family indicated that his father was a carrier of this Hb variant, although unexpectedly, the father was asymptomatic and clinically healthy. Oxygen affinity measurement of total Hb showed no alteration in the P 50 and oxygen equilibrium curve. The presence of Hb Hachioji was confirmed by mass spectrometry (MS). Hb Hachioji comprised approximately 50.0% of the total Hb and was a stable variant. The phenotypic discrepancy between these two carriers suggests that Hb Hachioji may not be associated with the hemolytic involvement in the proband. P4.2Nippon, which is the primary cause of most cases of Japanese HS, was absent in the proband's parents. The coexistence of glucose-6-phosphate dehydrogenase (G6PD) deficiency was ruled out. Thus, the cause of hemolytic involvement in this patient remains unclear.

  10. LDH and G-6PDH activities in the ovaries of adult female Wistar rats ...

    African Journals Online (AJOL)

    The present study was designed to evaluate the effects of aqueous extracts of neem (Azadirachta Indica) leaves (which have been documented for its antifertility effect on experimental animals) on glucose-6-phosphate dehydrogenase (G-6PDH) and lactate dehydrogenase (LDH) levels in the ovaries of adult female wistar ...

  11. Effects of lead nitrate on the activity of metabolic enzymes during early developmental stages of the African catfish, Clarias gariepinus (Burchell, 1822)

    NARCIS (Netherlands)

    Osman, A.G.M.; Mekkawy, Imam A.; Verreth, J.A.J.; Kirschbaum, Frank

    2007-01-01

    Glucose-6-phosphate dehydrogenase (G6PDH), lactate dehydrogenase (LDH) and pyruvate kinase (PK) are key metabolic enzymes. G6PDH has been used as a biomarker of pollution-induced carcinogenesis in fish. LDH has been used as marker of lesions in toxicology and clinical chemistry, and PK catalyses the

  12. ENZYMOCHEMICAL AND BIOCHEMICAL CHANGES IN THE LIVER OF RATS INDUCED BY FURFURAL

    Directory of Open Access Journals (Sweden)

    Dragana Veličković

    2011-06-01

    Full Text Available In today's industrial expansion of the chemical products, the liver is becoming increasingly important. Furfural (C4C3OCHO is a colorless liquid with pleasant aroma and it is partially soluble in water (8, 3% of weight. The elimination of furfural is done slowly through the kidneys and lungs, while the liver oxidizes it into pyromucic acid (C4C3OCOOH. Glucose-6-phosphate dehydrogenase (G6PD is a multi-component system of gluconeogenesis. Biochemical parameters (AST, ALT, glucose, γ-GT and alkaline phosphatase are important markers of liver damage.The aim of our study was to analyze the function of hepatocytes using biochemical parameters and to show the dynamics and topography in the development of changes in enzyme activity.The experiment was conducted on Wistar rats aged 6 weeks. The animals were divided into three groups. The control group received pure drinking water, the second group received a 50 mg/kg body weight (BW dose of furfural for seven days and in the third group the dose was progressively increased after which the animals were sacrificed. Biochemical methods were used to determine the parameters of liver damage. Enzyme-histochemical tests were performed on 8nm WKF 1150 cryostat cross sections which were stained according to Pearse (1968. The results are presented tables and graphs.The amount of enzymes and biochemical parameters in the control group were normal. In the group treated for 7 days, the activity of the enzymes was diffusely decreased while the biochemical parameters were increased. In the group of rats treated for 90 days, the periportal G6PD was constantly preserved. Biochemical parameters were different. The differences in all parameters were statistically significant (p<0.05 both in the group treated for 7 days and the group treated for 90 days. The same goes for the control group and the group treated for 7 days.Acute treatment with furfural causes damage to liver functions. The synthetic liver function is

  13. Severe Neonatal Hyperbilirubinaemia in the First 24 Hours of Life: Tertiary Center Experience in Oman

    Directory of Open Access Journals (Sweden)

    Mujtaba Ali Al Ajmi

    2018-01-01

    Full Text Available Introduction: Neonatal jaundice is a common condition observed in approximately two-thirds of all newborns in the first postnatal week of life. In most cases it is benign and no treatment is required. However, in severe cases, pathological jaundice can lead to acute bilirubin encephalopathy and kernicterus. Aim: To characterise the main predisposing factors as well as the treatment modalities of babies with significant neonatal jaundice presenting in the first 24 hours of life. Materials and Methods: We conducted a retrospective, observational study of all babies admitted to the neonatal unit at the Royal hospital in Oman in the period between 1st January 2014 and 31st December 2014 and treated for significant hyperbilirubinaemia presenting in the first 24 hours of life. Patients were selected from the Royal Hospital neonatal admission registry. A total of 125 patients records were analysed for the sake of the study. Results: The mean gestational age was 34 weeks and the mean birth weight was 2070 grams. Male to female ratio was 1:1.2. About 30 (45% of the males and 15 (26% of the females had Glucose-6-Phosphate Dehydrogenase (G6PD deficiency. Blood group of the babies was A 42 (33.6%, B 34 (27.2%, AB 4 (3.2% and O 45 (36%. About 4.8% were Rhesus negative. In all 27 (21.6% of the babies tested positive for Direct Coombs Test. The maximum Total Serum Bilirubin (TSB in the first 24 hours of life was 130±65 µmol/L and the maximum TSB anytime during the admission was 215±80 µmol/L. About 88 (70% of the babies received standard phototherapy and 37 (30% received intensive phototherapy. Intravenous Immunoglobulin (IVIG in addition to phototherapy was administered in 21 (17% of the babies. None of the babies required exchange transfusion. Conclusion: It was observed that the most common predisposing factors for significant neonatal jaundice presenting in the first 24 hours of life were prematurity, G6PD deficiency and isoimmune hemolytic disease

  14. Efeito do uso de óleo na dieta sobre a lipogênese e o perfil lipídico de tilápias-do-nilo Effect of different oils in the diet on lipogenesis and the lipid profile of nile tilapias

    Directory of Open Access Journals (Sweden)

    Paula Adriane Perez Ribeiro

    2008-08-01

    Full Text Available Trinta e cinco machos de tilápia com peso médio de 205 g foram mantidos em caixas de 250 litros para avaliar o metabolismo lipídico de tilápias-do-nilo (Oreochromis niloticus. O experimento foi conduzido durante 30 dias, entre os meses de outubro e novembro de 2006. Foram avaliadas cinco dietas, cada uma contendo óleo de oliva, óleo de milho, óleo de soja, óleo de linhaça ou óleo de peixe. Utilizou-se delineamento inteiramente casualizado, com cinco tratamentos e sete repetições. Avaliaram-se a composição química, o perfil lipídico muscular e a atividade hepática de glicose-6-P desidrogenase (G6PD e enzima málica. Os dados foram submetidos à análise de variância com médias comparadas pelo teste de Scott-Knott (5%. Não houve diferenças significativas para os teores de umidade e cinzas, porém, foram observadas alterações nos teores de lipídios e proteína nos peixes alimentados com as rações contendo óleo de oliva, milho ou soja. O fornecimento de dietas ricas em ácidos graxos poliinsaturados aumentou a composição desses ácidos graxos nos peixes. A atividade da G6PD foi superior à da enzima málica e foi mais alta nos animais alimentados com rações contendo óleos de oliva, milho ou soja, o que evidencia maior deposição lipídica muscular nesses peixes.A total of 35 males of Nile tilapia, averaging initial weight of 205 g, were maintained in five 250 L metabolism boxes to evaluate the lipid metabolism of Nile tilapias (Oreochromis niloticus. The experiment lasted 30 days, from October to November 2006. The treatments were: control diet plus olive oil; control diet plus corn oil; control diet plus soybean oil; control diet plus linseed oil; control diet plus fish oil. The experiment was in a completely randomized design with five treatments and seven replicates. The evaluated parameters were: fatty acid profile of the muscle tissue and hepatic activity of glucose-6-phosphate dehydrogenase (G6PD and malic

  15. 21 CFR 862.1670 - Sorbitol dehydrogenase test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Sorbitol dehydrogenase test system. 862.1670... Systems § 862.1670 Sorbitol dehydrogenase test system. (a) Identification. A sorbitol dehydrogenase test system is a device intended to measure the activity of the enzyme sorbitol dehydrogenase in serum...

  16. Histochemical localization of cytokinin oxidase/dehydrogenase ...

    African Journals Online (AJOL)

    Jane

    2011-08-15

    dehydrogenase, Withania somnifera, CKX localization. INTRODUCTION. Cytokinin (Ck) is a plant hormone that plays a crucial role in many fundamental processes of plant development throughout the life cycle. These include ...

  17. Shikimate dehydrogenase from Pinu sylvestris L. needles

    International Nuclear Information System (INIS)

    Osipov, V.I.; Shein, I.V.

    1986-01-01

    Shikimate dehydrogenase was isolated by extraction from pine needles and partially purified by fractionation with ammonium sulfate. In conifers, in contrast to other plants, all three isoenzymes of shikimate dehydrogenase exhibit activity not only with NADP + , but also with NAD + . The values of K/sub m/ for shikimate, when NADP + and NAD + are used as cofactors, are 0.22 and 1.13 mM, respectively. The enzyme is maximally active at pH 10 with both cofactors. It is suggested that NAD-dependent shikimate dehydrogenase catalyzes the initial reaction of the alternative pathway of the conversion of shikimic acid to hydroxybenzoic acid. The peculiarities of the organization and regulation of the initial reactions of the shikimate pathway in conifers and in plants with shikimate dehydrogenase absolutely specific for NADP are discussed

  18. Phosphorylation site on yeast pyruvate dehydrogenase complex

    International Nuclear Information System (INIS)

    Uhlinger, D.J.

    1986-01-01

    The pyruvate dehydrogenase complex was purified to homogeneity from baker's yeast (Saccharomyces cerevisiae). Yeast cells were disrupted in a Manton-Gaulin laboratory homogenizer. The pyruvate dehydrogenase complex was purified by fractionation with polyethylene glycol, isoelectric precipitation, ultracentrifugation and chromatography on hydroxylapatite. Final purification of the yeast pyruvate dehydrogenase complex was achieved by cation-exchange high pressure liquid chromatography (HPLC). No endogenous pyruvate dehydrogenase kinase activity was detected during the purification. However, the yeast pyruvate dehydrogenase complex was phosphorylated and inactivated with purified pyruvate dehydrogenase kinase from bovine kidney. Tryptic digestion of the 32 P-labeled complex yielded a single phosphopeptide which was purified to homogeniety. The tryptic digest was subjected to chromatography on a C-18 reverse phase HPLC column with a linear gradient of acetonitrile. Radioactive fractions were pooled, concentrated, and subjected to anion-exchange HPLC. The column was developed with a linear gradient of ammonium acetate. Final purification of the phosphopeptide was achieved by chromatography on a C-18 reverse phase HPLC column developed with a linear gradient of acetonitrile. The amino acid sequence of the homogeneous peptide was determined by manual modified Edman degradation

  19. Inducible xylitol dehydrogenases in enteric bacteria.

    OpenAIRE

    Doten, R C; Mortlock, R P

    1985-01-01

    Morganella morganii ATCC 25829, Providencia stuartii ATCC 25827, Serratia marcescens ATCC 13880, and Erwinia sp. strain 4D2P were found to induce a xylitol dehydrogenase when grown on a xylitol-containing medium. The xylitol dehydrogenases were partially purified from the four strains, and those from M. morganii ATCC 25829, P. stuartii ATCC 25827, and S. marcescens ATCC 13880 were all found to oxidize xylitol to D-xylulose. These three enzymes had KmS for xylitol of 7.1 to 16.4 mM and molecul...

  20. 2-Methylbutyryl-coenzyme A dehydrogenase deficiency

    DEFF Research Database (Denmark)

    Sass, Jörn Oliver; Ensenauer, Regina; Röschinger, Wulf

    2008-01-01

    2-Methylbutyryl-CoA dehydrogenase (MBD; coded by the ACADSB gene) catalyzes the step in isoleucine metabolism that corresponds to the isovaleryl-CoA dehydrogenase reaction in the degradation of leucine. Deficiencies of both enzymes may be detected by expanded neonatal screening with tandem...... individuals showed clinical symptoms attributable to MBD deficiency although the defect in isoleucine catabolism was demonstrated both in vivo and in vitro. Several mutations in the ACADSB gene were identified, including a novel one. MBD deficiency may be a harmless metabolic variant although significant...

  1. ONLINE MONITORING OF EXTRACELLULAR BRAIN GLUCOSE USING MICRODIALYSIS AND A NADPH-LINKED ENZYMATIC ASSAY

    NARCIS (Netherlands)

    VANDERKUIL, JHF; KORF, J

    A method to monitor extracellular glucose in freely moving rats, based on intracerebral microdialysis coupled to an enzyme reactor is described. The dialysate is continuously mixed with a solution containing the enzymes hexokinase and glucose-6-phosphate dehydrogenase, and the fluorescence of NADPH

  2. Metabolic Control Analysis aimed at the ribose synthesis pathways of tumor cells: a new strategy for antitumor drug development

    NARCIS (Netherlands)

    Boren, Joan; Montoya, Antonio Ramos; de Atauri, Pedro; Comin-Anduix, Begoña; Cortes, Antonio; Centelles, Josep J.; Frederiks, Wilma M.; van Noorden, Cornelis J. F.; Cascante, Marta

    2002-01-01

    Metabolic control analysis predicts that effects on tumor growth are likely to be obtained with lower concentrations of drug, if an enzyme with a high control coefficient on tumor growth is being inhibited. Here we measure glucose-6-phosphate dehydrogenase (G6PDH) control coefficient on in vivo

  3. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 60 ... Vol 1, No 2 (2012), Assessment of the activity of glucose-6-phosphate dehydrogenase in ... Vol 5, No 3 (2016), Effect of aqueous extract of alligator pepper ... antigen sero-positivity and Hepatitis C virus among voluntary blood ...

  4. Recovery of active pathogenesis-related enzymes from the apoplast ...

    African Journals Online (AJOL)

    Overall protease activity intensity was higher in the symplast. Maximum symplast contamination of the apoplast was 2% as estimated by glucose 6-phosphate dehydrogenase activity, a biochemical marker for symplast. Accumulation of pathogenesis-related enzymatic activities in the apoplast of M. acuminata leaf tissue was ...

  5. HL-1 mouse cardiomyocyte injury and death after simulated ischemia and reperfusion: roles of pH, Ca2+-independent phospholipase A2, and Na+/H+ exchange

    DEFF Research Database (Denmark)

    Andersen, Ann-Dorit; Poulsen, Kristian Arild; Lambert, Ian H

    2009-01-01

    activation were reduced after acidic compared with neutral SI, whereas necrotic death, estimated as glucose-6-phosphate dehydrogenase release, was similar in the two conditions. Inhibition of iPLA(2)-VI activity by bromoenol lactone (BEL) elicited cardiomyocyte necrosis during normoxia and after acidic, yet...

  6. Histochemical demonstration of creatine kinase activity using polyvinyl alcohol and auxiliary enzymes

    NARCIS (Netherlands)

    Frederiks, W. M.; Marx, F.; van Noorden, C. J.

    1987-01-01

    Creatine kinase activity (EC 2.7.3.2.) has been demonstrated in myocardium and skeletal muscle from rats by a method based on the incubation of cryostat sections with a polyvinyl alcohol-containing medium and the use of auxiliary enzymes. Hexokinase and glucose-6-phosphate dehydrogenase were spread

  7. Optimization of Adsorptive Immobilization of Alcohol Dehydrogenases

    NARCIS (Netherlands)

    Trivedi, Archana; Heinemann, Matthias; Spiess, Antje C.; Daussmann, Thomas; Büchs, Jochen

    2005-01-01

    In this work, a systematic examination of various parameters of adsorptive immobilization of alcohol dehydrogenases (ADHs) on solid support is performed and the impact of these parameters on immobilization efficiency is studied. Depending on the source of the enzymes, these parameters differently

  8. O-Alkyl Hydroxamates as Metaphors of Enzyme-Bound Enolate Intermediates in Hydroxy Acid Dehydrogenases. Inhibitors of Isopropylmalate Dehydrogenase, Isocitrate Dehydrogenase, and Tartrate Dehydrogenase(1).

    Science.gov (United States)

    Pirrung, Michael C.; Han, Hyunsoo; Chen, Jrlung

    1996-07-12

    The inhibition of Thermus thermophilus isopropylmalate dehydrogenase by O-methyl oxalohydroxamate was studied for comparison to earlier results of Schloss with the Salmonella enzyme. It is a fairly potent (1.2 &mgr;M), slow-binding, uncompetitive inhibitor against isopropylmalate and is far superior to an oxamide (25 mM K(i) competitive) that is isosteric with the ketoisocaproate product of the enzyme. This improvement in inhibition was attributed to its increased NH acidity, which presumably is due to the inductive effect of the hydroxylamine oxygen. This principle was extended to the structurally homologous enzyme isocitrate dehydrogenase from E. coli, for which the compound O-(carboxymethyl) oxalohydroxamate is a 30 nM inhibitor, uncompetitive against isocitrate. The pH dependence of its inhibition supports the idea that it is bound to the enzyme in the anionic form. Another recently discovered homologous enzyme, tartrate dehydrogenase from Pseudomonas putida, was studied with oxalylhydroxamate. It has a relatively low affinity for the enzyme, though it is superior to tartrate. On the basis of these leads, squaric hydroxamates with increased acidity compared to squaric amides directed toward two of these enzymes were prepared, and they also show increased inhibitory potency, though not approaching the nanomolar levels of the oxalylhydroxamates.

  9. Differential effect of waterborne cadmium exposure on lipid metabolism in liver and muscle of yellow catfish Pelteobagrus fulvidraco

    International Nuclear Information System (INIS)

    Chen, Qi-Liang; Gong, Yuan; Luo, Zhi; Zheng, Jia-Lang; Zhu, Qing-Ling

    2013-01-01

    Highlights: •Cd triggered hepatic lipid accumulation through the improvement of lipogenesis. •Lipid homeostasis in muscle after Cd exposure derived from the down-regulation of both lipogenesis and lipolysis. •Our study determines the mechanism of waterborne Cd exposure on lipid metabolism in fish on a molecular level. •Our study indicates the tissue-specific regulatory effect of lipid metabolism under waterborne Cd exposure. -- Abstract: The present study was conducted to investigate the effect of waterborne cadmium (Cd) exposure on lipid metabolism in liver and muscle of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to 0 (control), 0.49 and 0.95 mg Cd/l, respectively, for 6 weeks, the lipid deposition, Cd accumulation, the activities and expression level of several enzymes as well as the mRNA expression of transcription factors involved in lipid metabolism in liver and muscle were determined. Waterborne Cd exposure reduced growth performance, but increased Cd accumulation in liver and muscle. In liver, lipid content, the activities and the mRNA expression of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), fatty acid synthetase (FAS)) and lipoprotein lipase (LPL) activity increased with increasing waterborne Cd concentrations. However, the mRNA expressions of LPL and peroxisome proliferators-activated receptor (PPAR) α were down-regulated by Cd exposure. Carnitine palmitoyltransferase 1 (CPT1) activity as well as the mRNA expressions of CPT1 and PPARγ showed no significant differences among the treatments. In muscle, lipid contents showed no significant differences among the treatments. The mRNA expression of 6PGD, FAS, CPT1, LPL, PPARα and PPARγ were down-regulated by Cd exposure. Thus, our study indicated that Cd triggered hepatic lipid accumulation through the improvement of lipogenesis, and that lipid homeostasis in muscle was probably conducted by the down

  10. Differential effect of waterborne cadmium exposure on lipid metabolism in liver and muscle of yellow catfish Pelteobagrus fulvidraco

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qi-Liang; Gong, Yuan [Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of P.R.C., Fishery College, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovative Centre of Hubei Province, Wuhan 430070 (China); Luo, Zhi, E-mail: luozhi99@mail.hzau.edu.cn [Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of P.R.C., Fishery College, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovative Centre of Hubei Province, Wuhan 430070 (China); Zheng, Jia-Lang; Zhu, Qing-Ling [Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of P.R.C., Fishery College, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovative Centre of Hubei Province, Wuhan 430070 (China)

    2013-10-15

    Highlights: •Cd triggered hepatic lipid accumulation through the improvement of lipogenesis. •Lipid homeostasis in muscle after Cd exposure derived from the down-regulation of both lipogenesis and lipolysis. •Our study determines the mechanism of waterborne Cd exposure on lipid metabolism in fish on a molecular level. •Our study indicates the tissue-specific regulatory effect of lipid metabolism under waterborne Cd exposure. -- Abstract: The present study was conducted to investigate the effect of waterborne cadmium (Cd) exposure on lipid metabolism in liver and muscle of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to 0 (control), 0.49 and 0.95 mg Cd/l, respectively, for 6 weeks, the lipid deposition, Cd accumulation, the activities and expression level of several enzymes as well as the mRNA expression of transcription factors involved in lipid metabolism in liver and muscle were determined. Waterborne Cd exposure reduced growth performance, but increased Cd accumulation in liver and muscle. In liver, lipid content, the activities and the mRNA expression of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), fatty acid synthetase (FAS)) and lipoprotein lipase (LPL) activity increased with increasing waterborne Cd concentrations. However, the mRNA expressions of LPL and peroxisome proliferators-activated receptor (PPAR) α were down-regulated by Cd exposure. Carnitine palmitoyltransferase 1 (CPT1) activity as well as the mRNA expressions of CPT1 and PPARγ showed no significant differences among the treatments. In muscle, lipid contents showed no significant differences among the treatments. The mRNA expression of 6PGD, FAS, CPT1, LPL, PPARα and PPARγ were down-regulated by Cd exposure. Thus, our study indicated that Cd triggered hepatic lipid accumulation through the improvement of lipogenesis, and that lipid homeostasis in muscle was probably conducted by the down

  11. Characterization of housekeeping genes in zebrafish: male-female differences and effects of tissue type, developmental stage and chemical treatment

    Directory of Open Access Journals (Sweden)

    Callard Gloria V

    2008-11-01

    Full Text Available Abstract Background Research using the zebrafish model has experienced a rapid growth in recent years. Although real-time reverse transcription PCR (QPCR, normalized to an internal reference ("housekeeping" gene, is a frequently used method for quantifying gene expression changes in zebrafish, many commonly used housekeeping genes are known to vary with experimental conditions. To identify housekeeping genes that are stably expressed under different experimental conditions, and thus suitable as normalizers for QPCR in zebrafish, the present study evaluated the expression of eight commonly used housekeeping genes as a function of stage and hormone/toxicant exposure during development, and by tissue type and sex in adult fish. Results QPCR analysis was used to quantify mRNA levels of bactin1, tubulin alpha 1(tuba1, glyceraldehyde-3-phosphate dehydrogenase (gapdh, glucose-6-phosphate dehydrogenase (g6pd, TATA-box binding protein (tbp, beta-2-microglobulin (b2m, elongation factor 1 alpha (elfa, and 18s ribosomal RNA (18s during development (2 – 120 hr postfertilization, hpf; in different tissue types (brain, eye, liver, heart, muscle, gonads of adult males and females; and after treatment of embryos/larvae (24 – 96 hpf with commonly used vehicles for administration and agents that represent known environmental endocrine disruptors. All genes were found to have some degree of variability under the conditions tested here. Rank ordering of expression stability using geNorm analysis identified 18s, b2m, and elfa as most stable during development and across tissue types, while gapdh, tuba1, and tpb were the most variable. Following chemical treatment, tuba1, bactin1, and elfa were the most stably expressed whereas tbp, 18s, and b2m were the least stable. Data also revealed sex differences that are gene- and tissue-specific, and treatment effects that are gene-, vehicle- and ligand-specific. When the accuracy of QPCR analysis was tested using

  12. Primaquine or other 8-aminoquinolines for reducing Plasmodium falciparum transmission

    Science.gov (United States)

    Graves, Patricia M; Choi, Leslie; Gelband, Hellen; Garner, Paul

    2018-01-01

    infectiousness precedes the effect of PQ on gametocyte prevalence. We do not know whether single dose PQ could reduce malaria transmission at community level. What is the aim of this review? To assess the effects of adding a single dose of primaquine (PQ) to treatment for falciparum malaria to reduce disease transmission. This Cochrane Review update includes 25 controlled trials. The date of latest search was 21 July 2017. Key messages A single low dose of PQ, at 0.25 mg/kg, which the World Health Organization (WHO) recommends adding to artemisinin-based combination therapy for malaria, reduces infectiousness (transmission from people to mosquitoes). In the trials, the percentage of people who infected mosquitoes three to four days after treatment was reduced from 14% to 2%, with a smaller effect at day 8, from 4% to 1%, with no evidence of harm. What was studied in the review PQ kills gametocytes (malaria transmission stages) of the falciparum malaria parasite. Gametocytes infect mosquitoes during a bite, thus perpetuating transmission. There is concern that PQ may cause red blood cells to burst (haemolysis) in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, a genetically-determined condition common in many malaria-endemic settings, which can lead to anaemia. Recognizing concerns about the risk of haemolysis, the WHO reduced the recommended PQ dose from 0.75 mg/kg to 0.25 mg/kg in 2012. Ideally, this approach would be tested by randomly assigning villages to standard malaria treatment, or standard treatment plus a low dose of PQ, then measuring the effect on malaria over time but this would be difficult and expensive. So, indirect indicators are used to shed light on effectiveness, including feeding studies, in which mosquitoes are allowed to feed on people (or their blood), comparing those who were assigned PQ with those who were not. Alternatively, researchers may simply monitor the presence (prevalence), number (density), and duration (time of persistence

  13. Cloning and expression analysis of alcohol dehydrogenase ( Adh ...

    African Journals Online (AJOL)

    Hybrid promoters are created by shuffling of DNA fragments while keeping intact regulatory regions crucial of promoter activity. Two fragments of alcohol dehydrogenase (Adh) promoter from Zea mays were selected to generate hybrid promoter. Sequence analysis of both alcohol dehydrogenase promoter fragments through ...

  14. Enzymatic urea adaptation: lactate and malate dehydrogenase in elasmobranchs

    Czech Academy of Sciences Publication Activity Database

    Lagana, G.; Bellocco, E.; Mannucci, C.; Leuzzi, U.; Tellone, E.; Kotyk, Arnošt; Galtieri, A.

    2006-01-01

    Roč. 55, č. 6 (2006), s. 675-688 ISSN 0862-8408 Institutional research plan: CEZ:AV0Z50110509 Keywords : elasmobranchs * lactate dehydrogenase * malate dehydrogenase Subject RIV: CE - Biochemistry Impact factor: 2.093, year: 2006

  15. Some Properties of Glutamate Dehydrogenase from the Marine Red ...

    African Journals Online (AJOL)

    Keywords: ammonia assimilation, glutamate dehydrogenase, GDH, Gracilaria sordida, red alga, enzyme activity. Glutamate dehydrogenases (GDH, EC ... Anabolic functions could be assimilation of ammonia released during photorespiration and synthesis of N-rich transport compounds. Western Indian Ocean Journal of ...

  16. Study on the triphenyl tetrazolium chloride– dehydrogenase activity ...

    African Journals Online (AJOL)

    A quick analysis of the sludge activity method based on triphenyltetrazolium chloride-dehydrogenase activity (TTC-DHA) was developed to change the rule and status of the biological activity of the activated sludge in tomato paste wastewater treatment. The results indicate that dehydrogenase activity (DHA) can effectively ...

  17. INFLUENCE OF SELECTED PHARMACEUTICALS ON ACTIVATED SLUDGE DEHYDROGENASE ACTIVITY

    Directory of Open Access Journals (Sweden)

    Agnieszka Tomska

    2016-06-01

    The aim of this work was to evaluate the effect of selected antibiotics - sulfanilamide and erythromycin on activated sludge dehydrogenase activity with use of trifenyltetrazolinum chloride (TTC test. Dehydrogenases activity is an indicator of biochemical activity of microorganisms present in activated sludge or the ability to degrade organic compounds in waste water. TTC test is particularly useful for the regularity of the course of treatment, in which the presence of inhibitors of biochemical reactions and toxic compounds are present. It was observed that the dehydrogenase activity decreases with the increase of a antibiotics concentration. The lowest value of the dehydrogenase activity equal to 32.4 μmol TF / gMLSS obtained at sulfanilamide concentration 150mg / l. For this sample, an inhibition of dehydrogenase activity was 31%.

  18. Gaseous environment of plants and activity of enzymes of carbohydrate catabolism

    International Nuclear Information System (INIS)

    Ivanov, B.F.; Zemlyanukhin, A.A.; Igamberdiev, A.U.; Salam, A.M.M.

    1989-01-01

    The authors investigated the action of hypoxia and high CO 2 concentration in the atmosphere on activity of phosphofructokinase, aldolase, glucose phosphate isomerase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase, alcohol dehydrogenase, and isocitrate lyase in pea seedlings (Pisum sativum L.), corn scutella (Zea mays L.), and hemp cotyledons (Cannabis sativa L.). The first 4-12h of hypoxia witnessed suppression of enzymes of the initial stages of glycolysis (glucose-6-phosphate isomerase, phosphofructokinase)and activation of enzymes of its final stages (alcohol dehydrogenase and lactate dehydrogenase) and enzymes linking glycolysis and the pentose phosphate pathway (aldolase and glucose-6-phosphate dehydrogenase). An excess of CO 2 in the environment accelerated and amplified this effect. At the end of a 24-h period of anaerobic incubation, deviations of enzyme activity from the control were leveled in both gaseous environments. An exception was observed in the case of phosphofructokinase, whose activity increased markedly at this time in plants exposed to CO 2 . Changes in activity of the enzymes were coupled with changes in their kinetic parameters (apparent K m and V max values). The activity of isocitrate lyase was suppressed in both variants of hypoxic gaseous environments, a finding that does not agree with the hypothesis as to participation of the glyoxylate cycle in the metabolic response of plants to oxygen stress. Thus, temporary inhibition of the system of glycolysis and activation of the pentose phosphate pathway constituted the initial response of the plants to O 2 stress, and CO 2 intensified this metabolic response

  19. Enantiocomplementary Yarrowia lipolytica Oxidoreductases: Alcohol Dehydrogenase 2 and Short Chain Dehydrogenase/Reductase

    Directory of Open Access Journals (Sweden)

    Margit Winkler

    2013-08-01

    Full Text Available Enzymes of the non-conventional yeast Yarrowia lipolytica seem to be tailor-made for the conversion of lipophilic substrates. Herein, we cloned and overexpressed the Zn-dependent alcohol dehydrogenase ADH2 from Yarrowia lipolytica in Escherichia coli. The purified enzyme was characterized in vitro. The substrate scope for YlADH2 mediated oxidation and reduction was investigated spectrophotometrically and the enzyme showed a broader substrate range than its homolog from Saccharomyces cerevisiae. A preference for secondary compared to primary alcohols in oxidation direction was observed for YlADH2. 2-Octanone was investigated in reduction mode in detail. Remarkably, YlADH2 displays perfect (S-selectivity and together with a highly (R-selective short chain dehydrogenase/ reductase from Yarrowia lipolytica it is possible to access both enantiomers of 2-octanol in >99% ee with Yarrowia lipolytica oxidoreductases.

  20. Enantiocomplementary Yarrowia lipolytica Oxidoreductases: Alcohol Dehydrogenase 2 and Short Chain Dehydrogenase/Reductase.

    Science.gov (United States)

    Napora-Wijata, Kamila; Strohmeier, Gernot A; Sonavane, Manoj N; Avi, Manuela; Robins, Karen; Winkler, Margit

    2013-08-12

    Enzymes of the non-conventional yeast Yarrowia lipolytica seem to be tailor-made for the conversion of lipophilic substrates. Herein, we cloned and overexpressed the Zn-dependent alcohol dehydrogenase ADH2 from Yarrowia lipolytica in Escherichia coli. The purified enzyme was characterized in vitro. The substrate scope for YlADH2 mediated oxidation and reduction was investigated spectrophotometrically and the enzyme showed a broader substrate range than its homolog from Saccharomyces cerevisiae. A preference for secondary compared to primary alcohols in oxidation direction was observed for YlADH2. 2-Octanone was investigated in reduction mode in detail. Remarkably, YlADH2 displays perfect (S)-selectivity and together with a highly (R)-selective short chain dehydrogenase/ reductase from Yarrowia lipolytica it is possible to access both enantiomers of 2-octanol in >99% ee with Yarrowia lipolytica oxidoreductases.

  1. Genetic characterization of a brangus-ibage cattle population: biochemical polymorphisms and reproductive efficiency Caracterização genética de uma população de bovinos brangus-ibagé: polimorfismos bioquímicos e eficiência reprodutiva

    Directory of Open Access Journals (Sweden)

    Luiz Ernani Henkes

    2000-10-01

    Full Text Available Biochemical techniques were used to investigate the genetic variability in a Brangus-Ibage population by determining allele frequencies of 18 blood protein systems: Hemogloin beta-Chain (Hb, Albumin (Alb, Amylase (Am, Transferrin (Tf, Carbonic Anhydrase (CA, Ceruloplasmin (Cp, Malic Enzyme (ME, Diaphorase I and II (Dia I and Dia II, Slow Alpha 2 Macroglobulin (Ap, Acid Phosphatase (ACP, Esterase B and D (EstB and EstD, Phosphogluconate Dehydrogenase (PGD, Glucose-6-Phosphate Dehydrogenase (G-6-PD, Glucose-Phosphate-Isomerase (GPI, Superoxide Dismutase (SOD and Glyoxalase I (GLO. The percentage of polymorphic loci were estimated at 0.27, the mean number of alleles was 1.33 and the mean heterozygosity was 0.07. There was a good agreement between expected and observed heterozygosity values. The population was in agreement with Hardy-Weinberg expectations in all systems. Reproductive records allowed to estimate three parameters of reproductive efficiency: mean age at first calving (1152.15 ± 166.60 days, mean calving interval (539.23 ± 124.10 days and mean weight at first calving (391.02 ± 37.59kg. No relationship was found between reproductive efficiency and genetic systems.Técnicas bioquímicas foram utilizadas para determinar a variabilidade genética numa população de bovinos da raça Brangus-Ibagé com relação a 18 sistemas protéicos sangüíneos: Hemoglobina - Cadeia beta (Hb, Albumina (Alb, Amilase (Am, Transferrina (Tf, Anidrase Carbônica (CA, Ceruloplasmina (Cp, Enzima Málica (ME, Diaforase I and II (Dia I and Dia II, Macroglobulina alfa2 lenta (Ap, Fosfatase Ácida (ACP, Esterase B and D (EstB and EstD, Fosfogliconato Desidrogenase (PGD, Glicose-6-Fosfato Desidrogenase (G-6-PD, Glicose-Fosfato-Isomerase (GPI, Superóxido Dismutase (SOD e Glioxalase I (GLO. O percentual de locos polimórficos foi estimado em 0,27, o número médio de alelos foi 1,33 e a heterozigosidade média foi de 0,07. Houve boa concordância entre a

  2. Action of sulphite on plant malate dehydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    Ziegler, I.

    1974-01-01

    SO/sub 3//sup 2 -/ acts on NAD- and NADP-dependent malate dehydrogenase in several ways. Firstly, SO/sub 3//sup 2 -/ favours the appearance of low MW species (65000 and 39000 daltons) in Sephadex gel chromatography. Secondly, the enzyme from which is obtained by gel chromatography with dithioerythritol plus nucleotide cofactor is changed in the presence of SO/sub 3//sup 2 -/. This is indicated by the appearance of a linear reaction (instead of curvilinear), and by the abolition of the biphasic sigmoidal kinetics on varying substrate and cofactor concentrations. Thus the inhibition of initial velocity at high substrate or cofactor concentrations is even more marked than at lower ones. Thirdly, SO/sub 3//sup 2 -/ strongly reduces the activity in substrate saturating conditions.

  3. Enantiocomplementary Yarrowia lipolytica Oxidoreductases: Alcohol Dehydrogenase 2 and Short Chain Dehydrogenase/Reductase

    OpenAIRE

    Napora-Wijata, Kamila; Strohmeier, Gernot A.; Sonavane, Manoj N.; Avi, Manuela; Robins, Karen; Winkler, Margit

    2013-01-01

    Enzymes of the non-conventional yeast Yarrowia lipolytica seem to be tailor-made for the conversion of lipophilic substrates. Herein, we cloned and overexpressed the Zn-dependent alcohol dehydrogenase ADH2 from Yarrowia lipolytica in Escherichia coli. The purified enzyme was characterized in vitro. The substrate scope for YlADH2 mediated oxidation and reduction was investigated spectrophotometrically and the enzyme showed a broader substrate range than its homolog from Saccharomyces cerevisia...

  4. Multiple alcohol dehydrogenases but no functional acetaldehyde dehydrogenase causing excessive acetaldehyde production from ethanol by oral streptococci.

    Science.gov (United States)

    Pavlova, Sylvia I; Jin, Ling; Gasparovich, Stephen R; Tao, Lin

    2013-07-01

    Ethanol consumption and poor oral hygiene are risk factors for oral and oesophageal cancers. Although oral streptococci have been found to produce excessive acetaldehyde from ethanol, little is known about the mechanism by which this carcinogen is produced. By screening 52 strains of diverse oral streptococcal species, we identified Streptococcus gordonii V2016 that produced the most acetaldehyde from ethanol. We then constructed gene deletion mutants in this strain and analysed them for alcohol and acetaldehyde dehydrogenases by zymograms. The results showed that S. gordonii V2016 expressed three primary alcohol dehydrogenases, AdhA, AdhB and AdhE, which all oxidize ethanol to acetaldehyde, but their preferred substrates were 1-propanol, 1-butanol and ethanol, respectively. Two additional dehydrogenases, S-AdhA and TdhA, were identified with specificities to the secondary alcohol 2-propanol and threonine, respectively, but not to ethanol. S. gordonii V2016 did not show a detectable acetaldehyde dehydrogenase even though its adhE gene encodes a putative bifunctional acetaldehyde/alcohol dehydrogenase. Mutants with adhE deletion showed greater tolerance to ethanol in comparison with the wild-type and mutant with adhA or adhB deletion, indicating that AdhE is the major alcohol dehydrogenase in S. gordonii. Analysis of 19 additional strains of S. gordonii, S. mitis, S. oralis, S. salivarius and S. sanguinis showed expressions of up to three alcohol dehydrogenases, but none showed detectable acetaldehyde dehydrogenase, except one strain that showed a novel ALDH. Therefore, expression of multiple alcohol dehydrogenases but no functional acetaldehyde dehydrogenase may contribute to excessive production of acetaldehyde from ethanol by certain oral streptococci.

  5. Individual-level factors associated with the risk of acquiring human Plasmodium knowlesi malaria in Malaysia: a case-control study.

    Science.gov (United States)

    Grigg, Matthew J; Cox, Jonathan; William, Timothy; Jelip, Jenarun; Fornace, Kimberly M; Brock, Patrick M; von Seidlein, Lorenz; Barber, Bridget E; Anstey, Nicholas M; Yeo, Tsin W; Drakeley, Christopher J

    2017-06-09

    The emergence of human malaria due to the monkey parasite Plasmodium knowlesi threatens elimination efforts in southeast Asia. Changes in land use are thought to be driving the rise in reported P knowlesi cases, but the role of individual-level factors is unclear. To address this knowledge gap we assessed human and environmental factors associated with zoonotic knowlesi malaria risk. We did this population-based case-control study over a 2 year period in the state of Sabah in Malaysia. We enrolled cases with microscopy-positive, PCR-confirmed malaria who presented to two primary referral hospitals serving the adjacent districts of Kudat and Kota Marudu. We randomly selected three malaria-negative community controls per case, who were matched by village within 2 weeks of case detection. We obtained questionnaire data on demographics, behaviour, and residential malaria risk factors, and we also assessed glucose-6-phosphate dehydrogenase (G6PD) enzyme activity. We used conditional logistic regression models to evaluate exposure risk between P knowlesi cases and controls, and between P knowlesi and human-only Plasmodium spp malaria cases. From Dec 5, 2012, to Jan 30, 2015, we screened 414 patients and subsequently enrolled 229 cases with P knowlesi malaria mono-infection and 91 cases with other Plasmodium spp infection. We enrolled 953 matched controls, including 683 matched to P knowlesi cases and 270 matched to non- P knowlesi cases. Age 15 years or older (adjusted odds ratio [aOR] 4·16, 95% CI 2·09-8·29, pwork (3·50, CI, 1·34-9·15, p=0·011), sleeping outside (3·61, 1·48-8·85, p=0·0049), travel (2·48, 1·45-4·23, p=0·0010), being aware of the presence of monkeys in the past 4 weeks (3·35, 1·91-5·88, pworking in agricultural areas were at highest risk of knowlesi malaria, although peri-domestic transmission also occurrs. Human behavioural factors associated with P knowlesi transmission could be targeted in future public health interventions. United

  6. Primaquine for reducing Plasmodium falciparum transmission.

    Science.gov (United States)

    Graves, Patricia M; Gelband, Hellen; Garner, Paul

    2012-09-12

    Mosquitoes become infected with malaria when they ingest gametocyte stages of the parasite from the blood of a human host. Plasmodium falciparum gametocytes are sensitive to the drug primaquine (PQ). The World Health Organization (WHO) recommends giving a single dose or short course of PQ alongside primary treatment for people ill with P. falciparum infection to reduce malaria transmission. Gametocytes themselves cause no symptoms, so this intervention does not directly benefit individuals. PQ causes haemolysis in some people with glucose-6-phosphate dehydrogenase (G6PD) deficiency so may not be safe.   To assess whether a single dose or short course of PQ added to treatments for malaria caused by P. falciparum infection reduces malaria transmission and is safe. We searched the following databases up to 10 April 2012 for studies: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; metaRegister of Controlled Trials (mRCT) and the WHO trials search portal using 'malaria*', 'falciparum', and 'primaquine' as search terms. In addition, we searched conference proceedings and reference lists of included studies, and we contacted likely researchers and organizations for relevant trials. Trials of mass treatment of whole populations (or actively detected fever or malaria cases within such populations) with antimalarial drugs, compared to treatment with the same drug plus PQ; or patients with clinical malaria being treated for malaria at health facilities randomized to short course/single dose PQ versus no PQ. Two authors (PMG and HG) independently screened all abstracts, applied inclusion criteria, and abstracted data. We sought data on the effect of PQ on malaria transmission intensity, participant infectiousness, the number of participants with gametocytes, and gametocyte density over time. We stratified results by primary treatment drug as

  7. Genetics Home Reference: 3-beta-hydroxysteroid dehydrogenase deficiency

    Science.gov (United States)

    ... for This Page Lutfallah C, Wang W, Mason JI, Chang YT, Haider A, Rich B, Castro-Magana ... A, Copeland KC, Chang YT, Lutfallah C, Mason JI. Carriers for type II 3beta-hydroxysteroid dehydrogenase (HSD3B2) ...

  8. Properties of glucoside 3-dehydrogenase and its potential applications

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... dehydrogenase has attracted considerable attention in recent years due to broad substrate specificity and excellent ... site-selective oxidation of the C-3 hydroxyl group. .... single peptide with a molecular mass of 67 kDa in.

  9. 21 CFR 862.1500 - Malic dehydrogenase test system.

    Science.gov (United States)

    2010-04-01

    ... plasma. Malic dehydrogenase measurements are used in the diagnosis and treatment of muscle and liver... marrow) leukemia. (b) Classification. Class I (general controls). The device is exempt from the premarket...

  10. Modeling of NAD+ analogues in horse liver alcohol dehydrogenase

    NARCIS (Netherlands)

    Beijer, N.A.; Buck, H.M.; Sluyterman, L.A.A.E.; Meijer, E.M.

    1990-01-01

    So far, the interactions of nicotinamide adenine dinucleotide (NAD+) derivatives with dehydrogenases are not very well understood. This hampers the introduction of NAD+ analogues with improved characteristics concerning industrial application. We have developed an AMBER molecular mechanics model in

  11. An improved method for the assay of platelet pyruvate dehydrogenase

    International Nuclear Information System (INIS)

    Schofield, P.J.; Griffiths, L.R.; Rogers, S.H.

    1980-01-01

    An improved method for the assay of human platelet pyruvate dehydrogenase is described. By generating the substrate [1- 14 C]pyruvate in situ from [1- 14 C]lactate plus L-lactate dehydrogenase, the rate of spontaneous decarboxylation is dramatically reduced, allowing far greater sensitivity in the assay of low activities of pyruvate dehydrogenase. In addition, no special precautions are required for the storage and use of [1- 14 C]lactate, in contrast to those for [1- 14 C]pyruvate. These factors allow a 5-10-fold increase in sensitivity compared with current methods. The pyruvate dehydrogenase activity of normal subjects as determined by the [1- 14 C]lactate system was 215+-55 pmol min -1 mg -1 protein (n=18). The advantages of this assay system are discussed. (Auth.)

  12. Genetics Home Reference: 17-beta hydroxysteroid dehydrogenase 3 deficiency

    Science.gov (United States)

    ... 000 newborns. It is more common in the Arab population of Gaza, where it affects 1 in ... fetus, resulting in the abnormalities in the external sex organs that occur in 17-beta hydroxysteroid dehydrogenase ...

  13. Rapid synthesis of triazine inhibitors of inosine monophosphate dehydrogenase.

    Science.gov (United States)

    Pitts, William J; Guo, Junqing; Dhar, T G Murali; Shen, Zhongqi; Gu, Henry H; Watterson, Scott H; Bednarz, Mark S; Chen, Bang Chi; Barrish, Joel C; Bassolino, Donna; Cheney, Daniel; Fleener, Catherine A; Rouleau, Katherine A; Hollenbaugh, Diane L; Iwanowicz, Edwin J

    2002-08-19

    A series of novel triazine-based small molecule inhibitors (IV) of inosine monophosphate dehydrogenase was prepared. The synthesis and the structure-activity relationships (SAR) derived from in vitro studies are described.

  14. Novel amide-based inhibitors of inosine 5'-monophosphate dehydrogenase.

    Science.gov (United States)

    Watterson, Scott H; Liu, Chunjian; Dhar, T G Murali; Gu, Henry H; Pitts, William J; Barrish, Joel C; Fleener, Catherine A; Rouleau, Katherine; Sherbina, N Z; Hollenbaugh, Diane L; Iwanowicz, Edwin J

    2002-10-21

    A series of novel amide-based small molecule inhibitors of inosine monophosphate dehydrogenase (IMPDH) was explored. The synthesis and the structure-activity relationships (SARs) derived from in vitro studies are described.

  15. Eucalypt NADP-Dependent Isocitrate Dehydrogenase1

    Science.gov (United States)

    Boiffin, Vincent; Hodges, Michael; Gálvez, Susana; Balestrini, Raffaella; Bonfante, Paola; Gadal, Pierre; Martin, Francis

    1998-01-01

    NADP-dependent isocitrate dehydrogenase (NADP-ICDH) activity is increased in roots of Eucalyptus globulus subsp. bicostata ex Maiden Kirkp. during colonization by the ectomycorrhizal fungus Pisolithus tinctorius Coker and Couch. To investigate the regulation of the enzyme expression, a cDNA (EgIcdh) encoding the NADP-ICDH was isolated from a cDNA library of E. globulus-P. tinctorius ectomycorrhizae. The putative polypeptide sequence of EgIcdh showed a high amino acid similarity with plant NADP-ICDHs. Because the deduced EgICDH protein lacks an amino-terminal targeting sequence and shows highest similarity to plant cytosolic ICDHs, it probably represents a cytoplasmic isoform. RNA analysis showed that the steady-state level of EgIcdh transcripts was enhanced nearly 2-fold in ectomycorrhizal roots compared with nonmycorrhizal roots. Increased accumulation of NADP-ICDH transcripts occurred as early as 2 d after contact and likely led to the observed increased enzyme activity. Indirect immunofluorescence microscopy indicated that NADP-ICDH was preferentially accumulated in the epidermis and stele parenchyma of nonmycorrhizal and ectomycorrhizal lateral roots. The putative role of cytosolic NADP-ICDH in ectomycorrhizae is discussed. PMID:9662536

  16. Human liver aldehyde dehydrogenase: coenzyme binding

    International Nuclear Information System (INIS)

    Kosley, L.L.; Pietruszko, R.

    1987-01-01

    The binding of [U- 14 C] NAD to mitochondrial (E2) and cytoplasmin(E1) aldehyde dehydrogenase was measured by gel filtration and sedimentation techniques. The binding data for NAD and (E1) yielded linear Scatchard plots giving a dissociation constant of 25 (+/- 8) uM and the stoichiometry of 2 mol of NAD bound per mol of E1. The binding data for NAD and (E2) gave nonlinear Scatchard plots. The binding of NADH to E2 was measured via fluorescence enhancement; this could not be done with E1 because there was no signal. The dissociation constant for E2 by this technique was 0.7 (+/- 0.4) uM and stoichiometry of 1.0 was obtained. The binding of [U- 14 C] NADH to (E1) and (E2) was also measured by the sedimentation technique. The binding data for (E1) and NADH gave linear Scatchard plots giving a dissociation constant of 13 (+/- 6) uM and the stoichiometry of 2.0. The binding data for NADH to (E2) gave nonlinear Scatchard plots. With (E1), the dissociation constants for both NAD and NADH are similar to those determined kinetically, but the stoichiometry is only half of that found by stopped flow technique. With (E2) the dissociation constant by fluorometric procedure was 2 orders of magnitude less than that from catalytic reaction

  17. Radioimmunoassay of lactate dehydrogenase, H forms

    International Nuclear Information System (INIS)

    Malvano, R.; Massaglia, A.; Zannino, M.; Palmucci, F.; Cali, V.; Zucchelli, G.C.; Consiglio Nazionale delle Ricerche, Pisa

    1979-01-01

    Antisera to H 4 -lactate dehydrogenase (LDH) were elicited in rabbits, against both human (h) and porcine (p) isoenzymes. 125 I-labelled H 4 -LDH was prepared by electrolytic iodination. A simple and fast procedure (1-h incubation for clinical assays) was set up by using polyethylene glycol for the bound-free separation. The results obtained in the antiserum characterization indicated that the heterologous homotetramer, M 4 was completely discriminated in the porcine system, while a weak cross-reaction with human antisera resulted. In both cases, for the hybrid forms, a cross-reactivity level related to the stoichiometric contents of the H-subunit in the tetramers was observed. The H 4 -LDH from other species was found to be much more effectively distinguished in the procine than in the human system. The assay for human LDH was further validated in terms of analytical suitability and clinical response. For healthy subjects the mean concentration was 0.46 +- 0.19 μg/ml (mean +- SD). Patients with acute myocardial infarction had levels ranging from 1.2 to 5.9 μg/ml. (orig.) [de

  18. Pyruvate dehydrogenase complex and lactate dehydrogenase as targets for therapy of acute liver failure.

    Science.gov (United States)

    Ferriero, Rosa; Nusco, Edoardo; De Cegli, Rossella; Carissimo, Annamaria; Manco, Giuseppe; Brunetti-Pierri, Nicola

    2018-03-23

    Acute liver failure is a rapidly progressive deterioration of hepatic function resulting in high mortality and morbidity. Metabolic enzymes can translocate in the nucleus to regulate histone acetylation and gene expression. Levels and activities of pyruvate dehydrogenase complex (PDHC) and lactate dehydrogenase (LDH) were evaluated in nuclear fractions of livers of mice exposed to various hepatotoxins including CD95-Ab, α-amanitin, and acetaminophen. Whole-genome gene expression profiling by RNA-seq was performed in livers of mice with acute liver failure and analyzed by Gene Ontology Enrichment Analysis. Efficacy of histone acetyltransferase inhibitor garcinol and LDH inhibitor galloflavin at reducing liver damage was evaluated in mice with induced hepatotoxicity. Levels and activities of PDHC and LDH were increased in cytoplasmatic and nuclear fractions of livers of mice with acute liver failure. The increase of nuclear PDHC and LDH was associated with increased concentrations of acetyl-coA and lactate in nuclear fractions, and histone H3 hyper-acetylation. Gene expression in livers of mice with acute liver failure suggested that increased histone H3 acetylation induces the expression of genes related to response to damage. Reduced histone acetylation by the histone acetyltransferase inhibitor garcinol decreased liver damage and improved survival in mice with acute liver failure. Knock-down of PDHC or LDH improved viability in cells exposed to a pro-apoptotic stimulus. Treatment with the LDH inhibitor galloflavin that was also found to inhibit PDHC, reduced hepatic necrosis, apoptosis, and expression of pro-inflammatory cytokines in mice with acute liver failure. Mice treated with galloflavin also showed a dose-response increase in survival. PDHC and LDH translocate to the nucleus and are targets for therapy of acute liver failure. Acute liver failure is a rapidly progressive and life-threatening deterioration of liver function resulting in high mortality and

  19. Toxicity of Nitrification Inhibitors on Dehydrogenase Activity in Soils

    OpenAIRE

    Ferisman Tindaon; Gero Benckiser; Johannes C. G. Ottow

    2011-01-01

    The objective of this research was to determine the effects of nitrification inhibitors (NIs) such as 3,4-dimethylpyrazolephosphate=DMPP, 4-Chlor-methylpyrazole phosphate=ClMPP and dicyandiamide,DCD) which might be expected to inhibit microbial activity, on dehydrogenase activity (DRA),in three different soils in laboratory conditions. Dehydrogenase activity were assessed via reduction of 2-p-Iodophenyl-3-p-nitrophenyl-5-phenyltetrazoliumchloride (INT). The toxicity and dose response curve of...

  20. ald of Mycobacterium tuberculosis Encodes both the Alanine Dehydrogenase and the Putative Glycine Dehydrogenase

    Science.gov (United States)

    Giffin, Michelle M.; Modesti, Lucia; Raab, Ronald W.; Wayne, Lawrence G.

    2012-01-01

    The putative glycine dehydrogenase of Mycobacterium tuberculosis catalyzes the reductive amination of glyoxylate to glycine but not the reverse reaction. The enzyme was purified and identified as the previously characterized alanine dehydrogenase. The Ald enzyme was expressed in Escherichia coli and had both pyruvate and glyoxylate aminating activities. The gene, ald, was inactivated in M. tuberculosis, which resulted in the loss of all activities. Both enzyme activities were found associated with the cell and were not detected in the extracellular filtrate. By using an anti-Ald antibody, the protein was localized to the cell membrane, with a smaller fraction in the cytosol. None was detected in the extracellular medium. The ald knockout strain grew without alanine or glycine and was able to utilize glycine but not alanine as a nitrogen source. Transcription of ald was induced when alanine was the sole nitrogen source, and higher levels of Ald enzyme were measured. Ald is proposed to have several functions, including ammonium incorporation and alanine breakdown. PMID:22210765

  1. Kinetics of soil dehydrogenase in response to exogenous Cd toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Xiangping [College of Natural Resources and Environment, Northwest A& F University, Yangling, 712100, Shaanxi (China); Key Laboratory of Vegetation Restoration and Management of Degraded Ecosystems, South China Botanical Garden, Chinese Academy of Sciences, CAS 723 Xingke Rd., Tianhe District, Guangzhou 510650 (China); Wang, Ziquan; Lu, Guannan [College of Natural Resources and Environment, Northwest A& F University, Yangling, 712100, Shaanxi (China); He, Wenxiang, E-mail: wenxianghe@nwafu.edu.cn [College of Natural Resources and Environment, Northwest A& F University, Yangling, 712100, Shaanxi (China); Key Laboratory of Plant Nutrition and Agro-environment in Northwest China, Ministry of Agriculture, Northwest A& F University, Yangling, 712100, Shaanxi (China); Wei, Gehong [College of Life Sciences, Northwest A& F University, Yangling, 712100, Shaanxi (China); Huang, Feng; Xu, Xinlan; Shen, Weijun [Key Laboratory of Vegetation Restoration and Management of Degraded Ecosystems, South China Botanical Garden, Chinese Academy of Sciences, CAS 723 Xingke Rd., Tianhe District, Guangzhou 510650 (China)

    2017-05-05

    Highlights: • pH explained 30–45% of the dehydrogenase activity (DHA), V{sub max}, and K{sub m} variations across soils. • Different inhibition mechanism of Cd to DHA varied soil types. • Soil properties and inhibition constant affect the toxicity of Cd. • Reaction constant (k) could indicate sensitively the toxicity of Cd to DHA. - Abstract: Soil dehydrogenase plays a role in the biological oxidation of soil organic matter and can be considered a good measure of the change of microbial oxidative activity under environmental pollutions. However, the kinetic characteristic of soil dehydrogenase under heavy metal stresses has not been investigated thoroughly. In this study, we characterized the kinetic characteristic of soil dehydrogenase in 14 soil types, and investigated how kinetic parameters changed under spiked with different concentrations of cadmium (Cd). The results showed that the K{sub m} and V{sub max} values of soil dehydrogenase was among 1.4–7.3 mM and 15.9–235.2 μM h{sup −1} in uncontaminated soils, respectively. In latosolic red soil and brown soil, the inhibitory kinetic mechanism of Cd to soil dehydrogenase was anticompetitive inhibition with inhibition constants (K{sub i}) of 12 and 4.7 mM, respectively; in other soils belonged to linear mixed inhibition, the values of K{sub i} were between 0.7–4.2 mM. Soil total organic carbon and K{sub i} were the major factors affecting the toxicity of Cd to dehydrogenase activity. In addition, the velocity constant (k) was more sensitive to Cd contamination compared to V{sub max} and K{sub m}, which was established as an early indicator of gross changes in soil microbial oxidative activity caused by Cd contamination.

  2. Radioprotective effects of ocimum flavonoids on leukocyte oxidants and antioxidants in oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    Reshma, K [Department of Biochemistry, Kasturba Medical College, Mangalore (India); Rao, A V [Fr. Muller' s Medical College, Mangalore (India); Dinesh, M [Department of Oncology, Amritha Institute of Medical Sciences, Cochin (India); Vasudevan, D M [Dept. of Biochemistry, Amritha Institute of Medical Sciences, Cochin (India)

    2008-04-15

    Oxidants (NADPH oxidase and myeloperoxidase) and antioxidants (GSH, GSH peroxidase, SOD and glucose 6 phosphate dehydrogenase, that provides NADPH for antioxidants) were assayed in the neutrophils from oral cancer patients, in three stages viz, baseline samples, 15 days after radiation and 30 days following radiation. These samples were obtained from 2 groups of patients. Group A that received radiation alone and Group B that received radiation and ocimum flavonoids, a radioprotector. The results showed a significant fall in the SOD levels in the second follow up of group B. Glucose 6 phosphate dehydrogenase showed significant increase only in the first follow up of patients who received Ocimum flavonoids. Except for these findings all other parameters remained statistically nonsignificant. (author)

  3. Radioprotective effects of ocimum flavonoids on leukocyte oxidants and antioxidants in oral cancer

    International Nuclear Information System (INIS)

    Reshma, K.; Rao, A.V.; Dinesh, M.; Vasudevan, D.M.

    2008-01-01

    Oxidants (NADPH oxidase and myeloperoxidase) and antioxidants (GSH, GSH peroxidase, SOD and glucose 6 phosphate dehydrogenase, that provides NADPH for antioxidants) were assayed in the neutrophils from oral cancer patients, in three stages viz, baseline samples, 15 days after radiation and 30 days following radiation. These samples were obtained from 2 groups of patients. Group A that received radiation alone and Group B that received radiation and ocimum flavonoids, a radioprotector. The results showed a significant fall in the SOD levels in the second follow up of group B. Glucose 6 phosphate dehydrogenase showed significant increase only in the first follow up of patients who received Ocimum flavonoids. Except for these findings all other parameters remained statistically nonsignificant. (author)

  4. Modulation of low dose radiation effect on pentose phosphate pathway enzymes by B-multivitamin deficiency

    International Nuclear Information System (INIS)

    Zimatkina, T.I.; Lashak, L.K.; Moiseenok, A.G.

    1997-01-01

    Blood, liver, thymus and spleen of albino rats injected subcutaneously with antivitamins (othythiamine and methotrexate) and subjected to prolonger γ-irradiation in the overall dose of 0.75 Gy were assayed for transketolase and glucose-6-phosphate dehydrogenase after 12h, 1, 2, 5 and 40 days from the last radiation dose. High transketolase sensitivity was found both to radiation (activation) and the combined effects of vitamin deficiency and radiation (potentiation of antivitamin inhibitory action) in all the tissues studied. The activity of glucose-6-phosphate dehydrogenase was little changed under the given experimental manipulations, but the combined effect of the factors considerably inhibited the enzyme activities in the organs of the immune system. Consequently, in B-multivitamin deficiency the effect of low radiation doses was subjected to a considerable modulation resulting in profound inhibition of the oxidation and nonoxidative branches of the pentose phosphate pathway. (author). 9 refs, 2 tabs

  5. The Role of Pyruvate Dehydrogenase Kinase in Diabetes and Obesity

    Directory of Open Access Journals (Sweden)

    In-Kyu Lee

    2014-06-01

    Full Text Available The pyruvate dehydrogenase complex (PDC is an emerging target for the treatment of metabolic syndrome. To maintain a steady-state concentration of adenosine triphosphate during the feed-fast cycle, cells require efficient utilization of fatty acid and glucose, which is controlled by the PDC. The PDC converts pyruvate, coenzyme A (CoA, and oxidized nicotinamide adenine dinucleotide (NAD+ into acetyl-CoA, reduced form of nicotinamide adenine dinucleotide (NADH, and carbon dioxide. The activity of the PDC is up- and down-regulated by pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase, respectively. In addition, pyruvate is a key intermediate of glucose oxidation and an important precursor for the synthesis of glucose, glycerol, fatty acids, and nonessential amino acids.

  6. Aminotransferase and glutamate dehydrogenase activities in lactobacilli and streptococci

    Directory of Open Access Journals (Sweden)

    Guillermo Hugo Peralta

    Full Text Available ABSTRACT Aminotransferases and glutamate dehydrogenase are two main types of enzymes involved in the initial steps of amino acid catabolism, which plays a key role in the cheese flavor development. In the present work, glutamate dehydrogenase and aminotransferase activities were screened in twenty one strains of lactic acid bacteria of dairy interest, either cheese-isolated or commercial starters, including fifteen mesophilic lactobacilli, four thermophilic lactobacilli, and two streptococci. The strains of Streptococcus thermophilus showed the highest glutamate dehydrogenase activity, which was significantly elevated compared with the lactobacilli. Aspartate aminotransferase prevailed in most strains tested, while the levels and specificity of other aminotransferases were highly strain- and species-dependent. The knowledge of enzymatic profiles of these starter and cheese-isolated cultures is helpful in proposing appropriate combinations of strains for improved or increased cheese flavor.

  7. Catalytic properties of thermophilic lactate dehydrogenase and halophilic malate dehydrogenase at high temperature and low water activity.

    Science.gov (United States)

    Hecht, K; Wrba, A; Jaenicke, R

    1989-07-15

    Thermophilic lactate dehydrogenases from Thermotoga maritima and Bacillus stearothermophilus are stable up to temperature limits close to the optimum growth temperature of their parent organisms. Their catalytic properties are anomalous in that Km shows a drastic increase with increasing temperature. At low temperatures, the effect levels off. Extreme halophilic malate dehydrogenase from Halobacterium marismortui exhibits a similar anomaly. Increasing salt concentration (NaCl) leads to an optimum curve for Km, oxaloacctate while Km, NADH remains constant. Previous claims that the activity of halophilic malate dehydrogenase shows a maximum at 1.25 M NaCl are caused by limiting substrate concentration; at substrate saturation, specific activity of halophilic malate dehydrogenase reaches a constant value at ionic strengths I greater than or equal to 1 M. Non-halophilic (mitochondrial) malate dehydrogenase shows Km characteristics similar to those observed for the halophilic enzyme. The drastic decrease in specific activity of the mitochondrial enzyme at elevated salt concentrations is caused by the salt-induced increase in rigidity of the enzyme, rather than gross structural changes.

  8. Abundance and distribution of the highly iterated palindrome 1 (HIP1) among prokaryotes

    OpenAIRE

    Delaye, Luis; Moya, Andrés

    2011-01-01

    We have studied the abundance and phylogenetic distribution of the Highly Iterated Palindrome 1 (HIP1) among sequenced prokaryotic genomes. We show that an overrepresentation of HIP1 is exclusive of some lineages of cyanobacteria, and that this abundance was gained only once during evolution and was subsequently lost in the lineage leading to marine pico-cyanobacteria. We show that among cyanobacterial protein sequences with annotated Pfam domains, only OpcA (glucose 6-phosphate dehydrogenase...

  9. p73 regulates basal and starvation-induced liver metabolism in vivo

    OpenAIRE

    He, Zhaoyue; Agostini, Massimiliano; Liu, He; Melino, Gerry; Simon, Hans-Uwe

    2015-01-01

    As a member of the p53 gene family, p73 regulates cell cycle arrest, apoptosis, neurogenesis, immunity and inflammation. Recently, p73 has been shown to transcriptionally regulate selective metabolic enzymes, such as cytochrome c oxidase subunit IV isoform 1, glucose 6-phosphate dehydrogenase and glutaminase-2, resulting in significant effects on metabolism, including hepatocellular lipid metabolism, glutathione homeostasis and the pentose phosphate pathway. In order to further investigate th...

  10. Chemienzymatic synthesis of Uridine. Nucleotides labeled with [15N] and [13C

    DEFF Research Database (Denmark)

    Gilles, Anne-Marie; Cristea, Ioan; Palibroda, Nicolae

    1995-01-01

    +necessary for the oxidation of glucose 6-phosphate and 6-phosphogluconate was recycled by glutamate dehydrogenase and excess of ammonia and a-oxoglutarate. Despite the number and complexity of the enzymatic steps, the synthesis of [15N,13C]UTP is straightforward with an overall yield exceeding 60%. This method, extended...... and diversified to the synthesis of all natural ribonucleotides, is a more economical alternative for obtaining nucleic acids for structural analysis by heteronuclear NMR spectroscopy....

  11. Reversible inactivation of CO dehydrogenase with thiol compounds

    Energy Technology Data Exchange (ETDEWEB)

    Kreß, Oliver [Department of Microbiology, University of Bayreuth, 95440 Bayreuth (Germany); Gnida, Manuel [Department of Chemistry, University of Paderborn, 33098 Paderborn (Germany); Pelzmann, Astrid M. [Department of Microbiology, University of Bayreuth, 95440 Bayreuth (Germany); Marx, Christian [Institute of Biochemistry and Biophysics, Friedrich-Schiller-University of Jena, 07745 Jena (Germany); Meyer-Klaucke, Wolfram [Department of Chemistry, University of Paderborn, 33098 Paderborn (Germany); Meyer, Ortwin, E-mail: Ortwin.Meyer@uni-bayreuth.de [Department of Microbiology, University of Bayreuth, 95440 Bayreuth (Germany)

    2014-05-09

    Highlights: • Rather large thiols (e.g. coenzyme A) can reach the active site of CO dehydrogenase. • CO- and H{sub 2}-oxidizing activity of CO dehydrogenase is inhibited by thiols. • Inhibition by thiols was reversed by CO or upon lowering the thiol concentration. • Thiols coordinate the Cu ion in the [CuSMo(=O)OH] active site as a third ligand. - Abstract: Carbon monoxide dehydrogenase (CO dehydrogenase) from Oligotropha carboxidovorans is a structurally characterized member of the molybdenum hydroxylase enzyme family. It catalyzes the oxidation of CO (CO + H{sub 2}O → CO{sub 2} + 2e{sup −} + 2H{sup +}) which proceeds at a unique [CuSMo(=O)OH] metal cluster. Because of changing activities of CO dehydrogenase, particularly in subcellular fractions, we speculated whether the enzyme would be subject to regulation by thiols (RSH). Here we establish inhibition of CO dehydrogenase by thiols and report the corresponding K{sub i}-values (mM): L-cysteine (5.2), D-cysteine (9.7), N-acetyl-L-cysteine (8.2), D,L-homocysteine (25.8), L-cysteine–glycine (2.0), dithiothreitol (4.1), coenzyme A (8.3), and 2-mercaptoethanol (9.3). Inhibition of the enzyme was reversed by CO or upon lowering the thiol concentration. Electron paramagnetic resonance spectroscopy (EPR) and X-ray absorption spectroscopy (XAS) of thiol-inhibited CO dehydrogenase revealed a bimetallic site in which the RSH coordinates to the Cu-ion as a third ligand ([Mo{sup VI}(=O)OH{sub (2)}SCu{sup I}(SR)S-Cys]) leaving the redox state of the Cu(I) and the Mo(VI) unchanged. Collectively, our findings establish a regulation of CO dehydrogenase activity by thiols in vitro. They also corroborate the hypothesis that CO interacts with the Cu-ion first. The result that thiol compounds much larger than CO can freely travel through the substrate channel leading to the bimetallic cluster challenges previous concepts involving chaperone function and is of importance for an understanding how the sulfuration step in

  12. Alcohol consumption, alcohol dehydrogenase 3 polymorphism, and colorectal adenomas

    NARCIS (Netherlands)

    Tiemersma, E.W.; Wark, P.A.; Ocké, M.C.; Bunschoten, A.; Otten, M.H.; Kok, F.J.; Kampman, E.

    2003-01-01

    Alcohol is a probable risk factor with regard to colorectal neoplasm and is metabolized to the carcinogen acetaldehyde by the genetically polymorphic alcohol dehydrogenase 3 (ADH3) enzyme. We evaluated whether the association between alcohol and colorectal adenomas is modified by ADH3 polymorphism.

  13. [Genetic variations in alcohol dehydrogenase, drinking habits and alcoholism

    DEFF Research Database (Denmark)

    Tolstrup, J.S.; Rasmussen, S.; Tybjaerg-Hansen, A.

    2008-01-01

    Alcohol is degraded primarily by alcohol dehydrogenase (ADH), and genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. By genotyping 9,080 white men and women from the general population, we found that men and women with ADH1B slow versus fast alcohol degrad...

  14. Efficiency of superoxide anions in the inactivation of selected dehydrogenases

    International Nuclear Information System (INIS)

    Rodacka, Aleksandra; Serafin, Eligiusz; Puchala, Mieczyslaw

    2010-01-01

    The most ubiquitous of the primary reactive oxygen species, formed in all aerobes, is the superoxide free radical. It is believed that the superoxide anion radical shows low reactivity and in oxidative stress it is regarded mainly as an initiator of more reactive species such as · OH and ONOO - . In this paper, the effectiveness of inactivation of selected enzymes by radiation-generated superoxide radicals in comparison with the effectiveness of the other products of water radiolysis is examined. We investigate three enzymes: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), alcohol dehydrogenase (ADH) and lactate dehydrogenase (LDH). We show that the direct contribution of the superoxide anion radical to GAPDH and ADH inactivation is significant. The effectiveness of the superoxide anion in the inactivation of GAPDH and ADG was only 2.4 and 2.8 times smaller, respectively, in comparison with hydroxyl radical. LDH was practically not inactivated by the superoxide anion. Despite the fact that the studied dehydrogenases belong to the same class of enzymes (oxidoreductases), all have a similar molecular weight and are tetramers, their susceptibility to free-radical damage varies. The differences in the radiosensitivity of the enzymes are not determined by the basic structural parameters analyzed. A significant role in inactivation susceptibility is played by the type of amino acid residues and their localization within enzyme molecules.

  15. Efficiency of superoxide anions in the inactivation of selected dehydrogenases

    Energy Technology Data Exchange (ETDEWEB)

    Rodacka, Aleksandra, E-mail: olakow@biol.uni.lodz.p [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Serafin, Eligiusz, E-mail: serafin@biol.uni.lodz.p [Laboratory of Computer and Analytical Techniques, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Puchala, Mieczyslaw, E-mail: puchala@biol.uni.lodz.p [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland)

    2010-09-15

    The most ubiquitous of the primary reactive oxygen species, formed in all aerobes, is the superoxide free radical. It is believed that the superoxide anion radical shows low reactivity and in oxidative stress it is regarded mainly as an initiator of more reactive species such as {sup {center_dot}}OH and ONOO{sup -}. In this paper, the effectiveness of inactivation of selected enzymes by radiation-generated superoxide radicals in comparison with the effectiveness of the other products of water radiolysis is examined. We investigate three enzymes: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), alcohol dehydrogenase (ADH) and lactate dehydrogenase (LDH). We show that the direct contribution of the superoxide anion radical to GAPDH and ADH inactivation is significant. The effectiveness of the superoxide anion in the inactivation of GAPDH and ADG was only 2.4 and 2.8 times smaller, respectively, in comparison with hydroxyl radical. LDH was practically not inactivated by the superoxide anion. Despite the fact that the studied dehydrogenases belong to the same class of enzymes (oxidoreductases), all have a similar molecular weight and are tetramers, their susceptibility to free-radical damage varies. The differences in the radiosensitivity of the enzymes are not determined by the basic structural parameters analyzed. A significant role in inactivation susceptibility is played by the type of amino acid residues and their localization within enzyme molecules.

  16. Expanding the clinical spectrum of 3-phosphoglycerate dehydrogenase deficiency

    NARCIS (Netherlands)

    Tabatabaie, L; Klomp, L W J; Rubio-Gozalbo, M E; Spaapen, L J M; Haagen, A A M; Dorland, L; de Koning, T J

    UNLABELLED: 3-Phosphoglycerate dehydrogenase (3-PGDH) deficiency is considered to be a rare cause of congenital microcephaly, infantile onset of intractable seizures and severe psychomotor retardation. Here, we report for the first time a very mild form of genetically confirmed 3-PGDH deficiency in

  17. Nicotinoprotein methanol dehydrogenase enzymes in Gram-positive methylotrophic bacteria

    NARCIS (Netherlands)

    Hektor, Harm J.; Kloosterman, Harm; Dijkhuizen, Lubbert

    2000-01-01

    A novel type of alcohol dehydrogenase enzyme has been characterized from Gram-positive methylotrophic (Bacillus methanolicus, the actinomycetes Amycolatopsis methanolica and Mycobacterium gastri) and non-methylotrophic bacteria (Rhodococcus strains). Its in vivo role is in oxidation of methanol and

  18. Medium-chain acyl-CoA dehydrogenase deficiency

    DEFF Research Database (Denmark)

    Waddell, Leigh; Wiley, Veronica; Carpenter, Kevin

    2006-01-01

    The fatty acid oxidation disorder most commonly identified by tandem mass spectrometry newborn screening is the potentially fatal medium-chain acyl-CoA dehydrogenase deficiency (MCAD). In clinically presenting cases, 80% are homozygous for the common mutation, c.985A > G and 18% heterozygous. We ...

  19. New enzymatic assay, parasite lactate dehydrogenase in diagnosis ...

    African Journals Online (AJOL)

    Background: The unique ability of plasmodial lactate dehydrogenase p(LDH) to utilise 3-acetyl pyridine dinucleotide (APAD) in lieu of NAD as a coenzyme in the conversion of pyruvate to lactate, led to the development of a biochemical assay for the detection of plasmodial parasitaemia. Researchers have reported that ...

  20. Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

    DEFF Research Database (Denmark)

    Tolstrup, J.S.; Nordestgaard, Børge; Rasmussen, S.

    2008-01-01

    Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 whi...

  1. Cloning and expression of chicken 20-hydroxysteroid dehydrogenase

    Czech Academy of Sciences Publication Activity Database

    Bryndová, Jana; Klusoňová, Petra; Kučka, Marek; Vagnerová, Karla; Mikšík, Ivan; Pácha, Jiří

    2006-01-01

    Roč. 37, č. 3 (2006), s. 453-462 ISSN 0952-5041 R&D Projects: GA AV ČR(CZ) IAA6011201 Grant - others:GA UK(CZ) 216/2004 Institutional research plan: CEZ:AV0Z50110509 Keywords : 20-hydroxysteroid dehydrogenase * SDR family Subject RIV: CE - Biochemistry Impact factor: 2.988, year: 2006

  2. Cofactor engineering of Lactobacillus brevis alcohol dehydrogenase by computational design

    NARCIS (Netherlands)

    Machielsen, M.P.; Looger, L.L.; Raedts, J.G.J.; Dijkhuizen, S.; Hummel, W.; Henneman, H.G.; Daussmann, T.; Oost, van der J.

    2009-01-01

    The R-specific alcohol dehydrogenase from Lactobacillus brevis (Lb-ADH) catalyzes the enantioselective reduction of prochiral ketones to the corresponding secondary alcohols. It is stable and has broad substrate specificity. These features make this enzyme an attractive candidate for

  3. Purification and characterization of xylitol dehydrogenase from Fusarium oxysporum

    DEFF Research Database (Denmark)

    Panagiotou, Gianni; Kekos, D.; Macris, B.J.

    2002-01-01

    An NAD(+)-dependent xylitol dehydrogenase (XDH) from Fusarium oxysporum, a key enzyme in the conversion of xylose to ethanol, was purified to homogeneity and characterised. It was homodimeric with a subunit of M-r 48 000, and pI 3.6. It was optimally active at 45degreesC and pH 9-10. It was fully...

  4. Aldehyde Dehydrogenase 1 and Raf Kinase Inhibitor Protein ...

    African Journals Online (AJOL)

    Aldehyde Dehydrogenase 1 and Raf Kinase Inhibitor Protein Expression Defines the Proliferative Nature of Cervical Cancer Stem Cells. ... of cervical cancer stem cells and also to validate them in initial and advanced stages of cervical cancer. Keywords: Cervical cancer, ALDH1, BALB/c-nu/nu, HeLa cells, RKIP, Sox2 ...

  5. Assay of partially purified glutamate dehydrogenase isolated from ...

    African Journals Online (AJOL)

    Glutamate dehydrogenase (E C 1.4.1.1) isolated from the seeds of asparagus beans was partially purified to a factor of 22 by dialysis after fractional precipitation with solid ammonium sulphate at 40 and 60% saturation. A specific activity of 11.78μmol min-1 mg-1 protein was calculated for the partially purified enzyme when ...

  6. Crystallization behaviour of glyceraldehyde dehydrogenase from Thermoplasma acidophilum

    Czech Academy of Sciences Publication Activity Database

    Lermark, L.; Degtjarik, Oksana; Steffler, F.; Sieber, V.; Kutá-Smatanová, Ivana

    2015-01-01

    Roč. 71, č. 12 (2015), s. 1475-1480 ISSN 2053-230X Institutional support: RVO:67179843 Keywords : TaAlDH * Thermoplasma acidophilum * bioproduction * cell-free enzyme cascade * glyceraldehyde dehydrogenase Subject RIV: CE - Biochemistry Impact factor: 0.647, year: 2015

  7. Novel thidiazuron-derived inhibitors of cytokinin oxidase/dehydrogenase

    Czech Academy of Sciences Publication Activity Database

    Nisler, Jaroslav; Kopečný, D.; Končitíková, R.; Zatloukal, Marek; Bazgier, Václav; Berka, K.; Zalabák, D.; Briozzo, P.; Strnad, Miroslav; Spíchal, Lukáš

    2016-01-01

    Roč. 92, 1-2 (2016), s. 235-248 ISSN 0167-4412 R&D Projects: GA MŠk(CZ) LO1204; GA ČR GA15-22322S Institutional support: RVO:61389030 Keywords : Cytokinin oxidase/dehydrogenase * Crystal structure * Molecular docking Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.356, year: 2016

  8. Phosphorylation of formate dehydrogenase in potato tuber mitochondria

    DEFF Research Database (Denmark)

    Bykova, N.V.; Stensballe, A.; Egsgaard, H.

    2003-01-01

    Two highly phosphorylated proteins were detected after two-dimensional (blue native/SDS-PAGE) gel electrophoretic separation of the matrix fraction isolated from potato tuber mitochondria. These two phosphoproteins were identified by mass spectrometry as formate dehydrogenase (FDH) and the E1alpha...

  9. Characterization of the L-lactate dehydrogenase from Aggregatibacter actinomycetemcomitans.

    Directory of Open Access Journals (Sweden)

    Stacie A Brown

    Full Text Available Aggregatibacter actinomycetemcomitans is a Gram-negative opportunistic pathogen and the proposed causative agent of localized aggressive periodontitis. A. actinomycetemcomitans is found exclusively in the mammalian oral cavity in the space between the gums and the teeth known as the gingival crevice. Many bacterial species reside in this environment where competition for carbon is high. A. actinomycetemcomitans utilizes a unique carbon resource partitioning system whereby the presence of L-lactate inhibits uptake of glucose, thus allowing preferential catabolism of L-lactate. Although the mechanism for this process is not fully elucidated, we previously demonstrated that high levels of intracellular pyruvate are critical for L-lactate preference. As the first step in L-lactate catabolism is conversion of L-lactate to pyruvate by lactate dehydrogenase, we proposed a model in which the A. actinomycetemcomitans L-lactate dehydrogenase, unlike homologous enzymes, is not feedback inhibited by pyruvate. This lack of feedback inhibition allows intracellular pyruvate to rise to levels sufficient to inhibit glucose uptake in other bacteria. In the present study, the A. actinomycetemcomitans L-lactate dehydrogenase was purified and shown to convert L-lactate, but not D-lactate, to pyruvate with a K(m of approximately 150 microM. Inhibition studies reveal that pyruvate is a poor inhibitor of L-lactate dehydrogenase activity, providing mechanistic insight into L-lactate preference in A. actinomycetemcomitans.

  10. Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood

    NARCIS (Netherlands)

    Lapalme-Remis, S.; Lewis, E.C.; De Meulemeester, C.; Chakraborty, P.; Gibson, K.M.; Torres, C.; Guberman, A.; Salomons, G.; Jakobs, C.; Ali-Ridha, A.; Parviz, M.; Pearl, P.L.

    2015-01-01

    Objective: The natural history of succinic semialdehyde dehydrogenase (SSADH) deficiency in adulthood is unknown; we elucidate the clinical manifestations of the disease later in life. Methods: A 63-year-old man with long-standing intellectual disability was diagnosed with SSADH deficiency following

  11. Assessment of creatine kinase and lactate dehydrogenase activities ...

    African Journals Online (AJOL)

    Ina bid to investigate the influence of menopausal on coronary heart disease, plasma creatine kinase (CK) and lactate dehydrogenase (LDH) enzymes were analysed on a prospective cohort of 100 women attending Irrua Specialist Teaching Hospital (ISTH), Irrua, Edo state-Nigeria. They were divided into two groups; ...

  12. Serum creatine kinase and lactate dehydrogenase activities in ...

    African Journals Online (AJOL)

    ... in thyroid function are common endocrine disorders affecting 5-10% of individuals over ... Key words: Hyperthyroidism, hypothyroidism, lactate dehydrogenase, serum creatine kinase ... individuals depends on age, race, lean body mass and physical activity. ... measured by radioimmunoassay on AXSYM System (Abbott.

  13. Novel guanidine-based inhibitors of inosine monophosphate dehydrogenase.

    Science.gov (United States)

    Iwanowicz, Edwin J; Watterson, Scott H; Liu, Chunjian; Gu, Henry H; Mitt, Toomas; Leftheris, Katerina; Barrish, Joel C; Fleener, Catherine A; Rouleau, Katherine; Sherbina, N Z; Hollenbaugh, Diane L

    2002-10-21

    A series of novel guanidine-based small molecule inhibitors of inosine monophosphate dehydrogenase (IMPDH) was explored. IMPDH catalyzes the rate determining step in guanine nucleotide biosynthesis and is a target for anticancer, immunosuppressive and antiviral therapy. The synthesis and the structure-activity relationships (SARs), derived from in vitro studies, for this new series of inhibitors is given.

  14. Zinc and glutamate dehydrogenase in putative glutamatergic brain structures.

    Science.gov (United States)

    Wolf, G; Schmidt, W

    1983-01-01

    A certain topographic parallelism between the distribution of histochemically (TIMM staining) identified zinc and putative glutamatergic structures in the rat brain was demonstrated. Glutamate dehydrogenase as a zinc containing protein is in consideration to be an enzyme synthesizing transmitter glutamate. In a low concentration range externally added zinc ions (10(-9) to 10(-7) M) induced an increase in the activity of glutamate dehydrogenase (GDH) originating from rat hippocampal formation, neocortex, and cerebellum up to 142.4%. With rising molarity of Zn(II) in the incubation medium, the enzyme of hippocampal formation and cerebellum showed a biphasic course of activation. Zinc ions of a concentration higher than 10(-6) M caused a strong inhibition of GDH. The effect of Zn(II) on GDH originating from spinal ganglia and liver led only to a decrease of enzyme activity. These results are discussed in connection with a functional correlation between zinc and putatively glutamatergic system.

  15. Optic neuropathy in a patient with pyruvate dehydrogenase deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Small, Juan E. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States); Gonzalez, Guido E. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Radiology, Boston, MA (United States); Clinica Alemana de Santiago, Departmento de Imagenes, Santiago (Chile); Nagao, Karina E.; Walton, David S. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Ophthalmology, Boston, MA (United States); Caruso, Paul A. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Radiology, Boston, MA (United States)

    2009-10-15

    Pyruvate dehydrogenase (PDH) deficiency is a genetic disorder of mitochondrial metabolism. The clinical manifestations range from severe neonatal lactic acidosis to chronic neurodegeneration. Optic neuropathy is an uncommon clinical sequela and the imaging findings of optic neuropathy in these patients have not previously been described. We present a patient with PDH deficiency with bilateral decreased vision in whom MRI demonstrated bilateral optic neuropathy and chiasmopathy. (orig.)

  16. Optic neuropathy in a patient with pyruvate dehydrogenase deficiency

    International Nuclear Information System (INIS)

    Small, Juan E.; Gonzalez, Guido E.; Nagao, Karina E.; Walton, David S.; Caruso, Paul A.

    2009-01-01

    Pyruvate dehydrogenase (PDH) deficiency is a genetic disorder of mitochondrial metabolism. The clinical manifestations range from severe neonatal lactic acidosis to chronic neurodegeneration. Optic neuropathy is an uncommon clinical sequela and the imaging findings of optic neuropathy in these patients have not previously been described. We present a patient with PDH deficiency with bilateral decreased vision in whom MRI demonstrated bilateral optic neuropathy and chiasmopathy. (orig.)

  17. Influence of thorax irradiation on lactic dehydrogenase isoenzyme activity

    International Nuclear Information System (INIS)

    Valle, C.; Munnich, A.; Pasquier, C.

    The right hemi-thorax of rats was irradiated with 1200 and 3000 rads ( 60 Co) and blood samples were taken sequentially. The five lactic dehydrogenase (LDH) isoenzymes which have proved to be useful as biochemical indicators of acute pulmonary injury in other experimental animals (dogs), were assayed, after irradiation, as a function of time and as a functon of dose. There was no significant change in LDH isoenzyme activities after lung irradiation in rats [fr

  18. Bioelectrochemical fuel cell and sensor based on quinoprotein alcohol dehydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    Davis, G; Hill, H A.O.; Aston, W J; Higgins, I J; Turner, A P.F.

    1983-09-01

    A biofuel cell, yielding a stable and continuous low-power output, based on the enzymatic oxidation of methanol to formic acid has been designed and investigated. The homogeneous kinetics of the electrochemically-coupled enzymatic oxidation reaction were investigated and optimized. The biofuel cell also functioned as a sensitive method for the detection of primary alcohols. A method for medium-scale preparation of the enzyme alcohol dehydrogenase (alcohol: (acceptor) oxidoreductase, EC 1.1.99.8) is described. (Refs. 14).

  19. Cloning, purification and crystallization of Thermus thermophilus proline dehydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    White, Tommi A.; Tanner, John J., E-mail: tannerjj@missouri.edu [Departments of Chemistry and Biochemistry, University of Missouri-Columbia, Columbia, Missouri 65211 (United States)

    2005-08-01

    Cloning, purification and crystallization of T. thermophilus proline dehydrogenase is reported. The detergent n-octyl β-d-glucopyranoside was used to reduce polydispersity, which enabled crystallization. Nature recycles l-proline by converting it to l-glutamate. This four-electron oxidation process is catalyzed by the two enzymes: proline dehydrogenase (PRODH) and Δ{sup 1}-pyrroline-5-carboxylate dehydrogenase. This note reports the cloning, purification and crystallization of Thermus thermophilus PRODH, which is the prototype of a newly discovered superfamily of bacterial monofunctional PRODHs. The results presented here include production of a monodisperse protein solution through use of the detergent n-octyl β-d-glucopyranoside and the growth of native crystals that diffracted to 2.3 Å resolution at Advanced Light Source beamline 4.2.2. The space group is P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 82.2, b = 89.6, c = 94.3 Å. The asymmetric unit is predicted to contain two protein molecules and 46% solvent. Molecular-replacement trials using a fragment of the PRODH domain of the multifunctional Escherichia coli PutA protein as the search model (24% amino-acid sequence identity) did not produce a satisfactory solution. Therefore, the structure of T. thermophilus PRODH will be determined by multiwavelength anomalous dispersion phasing using a selenomethionyl derivative.

  20. Cloning, purification and crystallization of Thermus thermophilus proline dehydrogenase

    International Nuclear Information System (INIS)

    White, Tommi A.; Tanner, John J.

    2005-01-01

    Cloning, purification and crystallization of T. thermophilus proline dehydrogenase is reported. The detergent n-octyl β-d-glucopyranoside was used to reduce polydispersity, which enabled crystallization. Nature recycles l-proline by converting it to l-glutamate. This four-electron oxidation process is catalyzed by the two enzymes: proline dehydrogenase (PRODH) and Δ 1 -pyrroline-5-carboxylate dehydrogenase. This note reports the cloning, purification and crystallization of Thermus thermophilus PRODH, which is the prototype of a newly discovered superfamily of bacterial monofunctional PRODHs. The results presented here include production of a monodisperse protein solution through use of the detergent n-octyl β-d-glucopyranoside and the growth of native crystals that diffracted to 2.3 Å resolution at Advanced Light Source beamline 4.2.2. The space group is P2 1 2 1 2 1 , with unit-cell parameters a = 82.2, b = 89.6, c = 94.3 Å. The asymmetric unit is predicted to contain two protein molecules and 46% solvent. Molecular-replacement trials using a fragment of the PRODH domain of the multifunctional Escherichia coli PutA protein as the search model (24% amino-acid sequence identity) did not produce a satisfactory solution. Therefore, the structure of T. thermophilus PRODH will be determined by multiwavelength anomalous dispersion phasing using a selenomethionyl derivative

  1. Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study

    DEFF Research Database (Denmark)

    Ferrari, P.; McKay, J. D.; Jenab, M.

    2012-01-01

    BACKGROUND/OBJECTIVES: Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian populati...

  2. Cloning and cDNA sequence of the dihydrolipoamide dehydrogenase component of human α-ketoacid dehydrogenase complexes

    International Nuclear Information System (INIS)

    Pons, G.; Raefsky-Estrin, C.; Carothers, D.J.; Pepin, R.A.; Javed, A.A.; Jesse, B.W.; Ganapathi, M.K.; Samols, D.; Patel, M.S.

    1988-01-01

    cDNA clones comprising the entire coding region for human dihydrolipoamide dehydrogenase have been isolated from a human liver cDNA library. The cDNA sequence of the largest clone consisted of 2082 base pairs and contained a 1527-base open reading frame that encodes a precursor dihydrolipoamide dehydrogenase of 509 amino acid residues. The first 35-amino acid residues of the open reading frame probably correspond to a typical mitochondrial import leader sequence. The predicted amino acid sequence of the mature protein, starting at the residue number 36 of the open reading frame, is almost identical (>98% homology) with the known partial amino acid sequence of the pig heart dihydrolipoamide dehydrogenase. The cDNA clone also contains a 3' untranslated region of 505 bases with an unusual polyadenylylation signal (TATAAA) and a short poly(A) track. By blot-hybridization analysis with the cDNA as probe, two mRNAs, 2.2 and 2.4 kilobases in size, have been detected in human tissues and fibroblasts, whereas only one mRNA (2.4 kilobases) was detected in rat tissues

  3. Pyruvate Dehydrogenase and Pyruvate Dehydrogenase Kinase Expression in Non Small Cell Lung Cancer and Tumor-Associated Stroma

    Directory of Open Access Journals (Sweden)

    Michael I. Koukourakis

    2005-01-01

    Full Text Available Pyruvate dehydrogenase (PDH catalyzes the conversion of pyruvate to acetyl-coenzyme A, which enters into the Krebs cycle, providing adenosine triphosphate (ATP to the cell. PDH activity is under the control of pyruvate dehydrogenase kinases (PDKs. Under hypoxic conditions, conversion of pyruvate to lactate occurs, a reaction catalyzed by lactate dehydrogenase 5 (LDH5. In cancer cells, however, pyruvate is transformed to lactate occurs, regardless of the presence of oxygen (aerobic glycolysis/Warburg effect. Although hypoxic intratumoral conditions account for HIFia stabilization and induction of anaerobic metabolism, recent data suggest that high pyruvate concentrations also result in HIFia stabilization independently of hypoxia. In the present immunohistochemical study, we provide evidence that the PDH/PDK pathway is repressed in 73% of non small cell lung carcinomas, which may be a key reason for HIFia stabilization and “aerobic glycolysis.” However, about half of PDHdeficient carcinomas are not able to switch on the HIF pathway, and patients harboring these tumors have an excellent postoperative outcome. A small subgroup of clinically aggressive tumors maintains a coherent PDH and HIF/LDH5 expression. In contrast to cancer cells, fibroblasts in the tumor-supporting stroma exhibit an intense PDH but reduced PDK1 expression favoring maximum PDH activity. This means that stroma may use lactic acid produced by tumor cells, preventing the creation of an intolerable intratumoral acidic environment at the same time.

  4. High-fat diet enhanced retinal dehydrogenase activity, but suppressed retinol dehydrogenase activity in liver of rats

    Directory of Open Access Journals (Sweden)

    Mian Zhang

    2015-04-01

    Full Text Available Evidence has shown that hyperlipidemia is associated with retinoid dyshomeostasis. In liver, retinol is mainly oxidized to retinal by retinol dehydrogenases (RDHs and alcohol dehydrogenases (ADHs, further converted to retinoic acid by retinal dehydrogenases (RALDHs. The aim of this study was to investigate whether high-fat diet (HFD induced hyperlipidemia affected activity and expression of hepatic ADHs/RDHs and RALDHs in rats. Results showed that retinol levels in liver, kidney and adipose tissue of HFD rats were significantly increased, while plasma retinol and hepatic retinal levels were markedly decreased. HFD rats exhibited significantly downregulated hepatic ADHs/RDHs activity and Adh1, Rdh10 and Dhrs9 expression. Oppositely, hepatic RALDHs activity and Raldh1 expression were upregulated in HFD rats. In HepG2 cells, treatment of HFD rat serum inhibited ADHs/RDHs activity and induced RALDHs activity. Among the tested abnormally altered components in HFD rat serum, cholesterol reduced ADHs/RDHs activity and RDH10 expression, while induced RALDHs activity and RALDH1 expression in HepG2 cells. Contrary to the effect of cholesterol, cholesterol-lowering agent pravastatin upregulated ADHs/RDHs activity and RDH10 expression, while suppressed RALDHs activity and RALDH1 expression. In conclusion, hyperlipidemia oppositely altered activity and expression of hepatic ADHs/RDHs and RALDHs, which is partially due to the elevated cholesterol levels.

  5. Characterization of human short chain dehydrogenase/reductase SDR16C family members related to retinol dehydrogenase 10.

    Science.gov (United States)

    Adams, Mark K; Lee, Seung-Ah; Belyaeva, Olga V; Wu, Lizhi; Kedishvili, Natalia Y

    2017-10-01

    All-trans-retinoic acid (RA) is a bioactive derivative of vitamin A that serves as an activating ligand for nuclear transcription factors, retinoic acid receptors. RA biosynthesis is initiated by the enzymes that oxidize retinol to retinaldehyde. It is well established that retinol dehydrogenase 10 (RDH10, SDR16C4), which belongs to the 16C family of the short chain dehydrogenase/reductase (SDR) superfamily of proteins, is the major enzyme responsible for the oxidation of retinol to retinaldehyde for RA biosynthesis during embryogenesis. However, several lines of evidence point towards the existence of additional retinol dehydrogenases that contribute to RA biosynthesis in vivo. In close proximity to RDH10 gene on human chromosome 8 are located two genes that are phylogenetically related to RDH10. The predicted protein products of these genes, retinol dehydrogenase epidermal 2 (RDHE2, SDR16C5) and retinol dehydrogenase epidermal 2-similar (RDHE2S, SDR16C6), share 59% and 56% sequence similarity with RDH10, respectively. Previously, we showed that the single ortholog of the human RDHE2 and RDHE2S in frogs, Xenopus laevis rdhe2, oxidizes retinol to retinaldehyde and is essential for frog embryonic development. In this study, we explored the potential of each of the two human proteins to contribute to RA biosynthesis. The results of this study demonstrate that human RDHE2 exhibits a relatively low but reproducible activity when expressed in either HepG2 or HEK293 cells. Expression of the native RDHE2 is downregulated in the presence of elevated levels of RA. On the other hand, the protein encoded by the human RDHE2S gene is unstable when expressed in HEK293 cells. RDHE2S protein produced in Sf9 cells is stable but has no detectable catalytic activity towards retinol. We conclude that the human RDHE2S does not contribute to RA biosynthesis, whereas the low-activity RA-sensitive human RDHE2 may have a role in adjusting the cellular levels of RA in accord with

  6. Erythromycin and Sulfisoxazole

    Science.gov (United States)

    ... dehydrogenase (G-6-PD) deficiency, yellowing of the skin or eyes, colitis, or stomach problems.tell your doctor if you ... rash If you experience any of the following symptoms, call your doctor immediately: severe skin rash itching hives difficulty breathing or swallowing wheezing ...

  7. 9-Hydroxyprostaglandin dehydrogenase activity in the adult rat kidney. Regional distribution and sub-fractionation.

    Science.gov (United States)

    Asciak, C P; Domazet, Z

    1975-02-20

    1. Catabolism of prostaglandin F2alpha in the adult rat kidney takes place by the following sequence of enzymatic steps: (1) 15-hydroxyprostaglandin dehydrogenase; (2) prostaglandin delta13-reductase; and (3) 9-hydroxyprostaglandin dehydrogenase. 2. 9-Hydroxyprostaglandin dehydrogenase activity was highest in the cortex with lesser amounts in the medulla and negligible activity detected in the papilla. A similar distribution was observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 3. Most of the 9-hydroxyprostaglandin dehydrogenase activity in the homogenate was found in the high-speed supernatant as also observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 4. These observations indicate that the rat kidney contains an abundance of prostaglandin-catabolising enzymes which favour formation of metabolites of the E-type.

  8. Molecular structure of the pyruvate dehydrogenase complex from Escherichia coli K-12.

    Science.gov (United States)

    Vogel, O; Hoehn, B; Henning, U

    1972-06-01

    The pyruvate dehydrogenase core complex from E. coli K-12, defined as the multienzyme complex that can be obtained with a unique polypeptide chain composition, has a molecular weight of 3.75 x 10(6). All results obtained agree with the following numerology. The core complex consists of 48 polypeptide chains. There are 16 chains (molecular weight = 100,000) of the pyruvate dehydrogenase component, 16 chains (molecular weight = 80,000) of the dihydrolipoamide dehydrogenase component, and 16 chains (molecular weight = 56,000) of the dihydrolipoamide dehydrogenase component. Usually, but not always, pyruvate dehydrogenase complex is produced in vivo containing at least 2-3 mol more of dimers of the pyruvate dehydrogenase component than the stoichiometric ratio with respect to the core complex. This "excess" component is bound differently than are the eight dimers in the core complex.

  9. Purification of 2-oxo acid dehydrogenase multienzyme complexes from ox heart by a new method.

    OpenAIRE

    Stanley, C J; Perham, R N

    1980-01-01

    A new method is described that allows the parallel purification of the pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase multienzyme complexes from ox heart without the need for prior isolation of mitochondria. All the assayable activity of the 2-oxo acid dehydrogenase complexes in the disrupted tissue is made soluble by the inclusion of non-ionic detergents such as Triton X-100 or Tween-80 in the buffer used for the initial extraction of the enzyme complexes. The yields of the pyruvate...

  10. Reproductive strategies and genetic variability in tropical freshwater fish

    Directory of Open Access Journals (Sweden)

    Maria Dolores Peres Lassala

    2007-01-01

    Full Text Available We estimated the genetic variability of nine fish species from the Brazilian upper Paraná River floodplain (Astyanax altiparanae, Hoplias malabaricus, Leporinus lacustris, Loricariichthys platymetopon, Parauchenipterus galeatus, Pimelodus maculatus, Rhaphiodon vulpinus, Roeboides paranensis and Serrasalmus marginatus based on data for 36 putative allozyme loci obtained using corn starch gel electrophoresis of 13 enzymatic systems: aspartate aminotransferase (EC 2.6.1.1, acid phosphatase (EC 3.1.3.2, esterase (EC 3.1.1.1, glycerol-3-phosphate dehydrogenase (EC 1.1.1.8, glucose-6-phosphate dehydrogenase (EC 1.1.1.49, glucose-6-phosphate isomerase (EC 5.3.1.9, Iditol dehydrogenase (EC 1.1.1.14, isocitrate dehydrogenase - NADP+ (EC 1.1.1.42, L-lactate dehydrogenase (EC 1.1.1.27, malate dehydrogenase (EC 1.1.1.37, malate dehydrogenase-NADP+ (EC 1.1.1.40, phosphoglucomutase (EC 5.4.2.2 and superoxide dismutase, (EC 1.15.1.1. The mean expected heterozygosity varied from zero to 0.147. When data from the literature for 75 species of tropical fish were added to the nine species of this study, the heterozygosity values differed significantly among the groups of different reproductive strategies. The highest mean heterozygosity was for the non-migratory without parental care, followed by the long-distance migratory, and the lowest mean was for the non-migratory with parental care or internal fecundation.

  11. Increased superoxide accumulation in pyruvate dehydrogenase complex deficient fibroblasts.

    Science.gov (United States)

    Glushakova, Lyudmyla G; Judge, Sharon; Cruz, Alex; Pourang, Deena; Mathews, Clayton E; Stacpoole, Peter W

    2011-11-01

    The pyruvate dehydrogenase complex (PDC) oxidizes pyruvate to acetyl CoA and is critically important in maintaining normal cellular energy homeostasis. Loss-of-function mutations in PDC give rise to congenital lactic acidosis and to progressive cellular energy failure. However, the subsequent biochemical consequences of PDC deficiency that may contribute to the clinical manifestations of the disorder are poorly understood. We postulated that altered flux through PDC would disrupt mitochondrial electron transport, resulting in oxidative stress. Compared to cells from 4 healthy subjects, primary cultures of skin fibroblasts from 9 patients with variable mutations in the gene encoding the alpha subunit (E1α) of pyruvate dehydrogenase (PDA1) demonstrated reduced growth and viability. Superoxide (O(2)(.-)) from the Qo site of complex III of the electron transport chain accumulated in these cells and was associated with decreased activity of manganese superoxide dismutase. The expression of uncoupling protein 2 was also decreased in patient cells, but there were no significant changes in the expression of cellular markers of protein or DNA oxidative damage. The expression of hypoxia transcription factor 1 alpha (HIF1α) also increased in PDC deficient fibroblasts. We conclude that PDC deficiency is associated with an increase in O(2)(.-) accumulation coupled to a decrease in mechanisms responsible for its removal. Increased HIF1α expression may contribute to the increase in glycolytic flux and lactate production in PDC deficiency and, by trans-activating pyruvate dehydrogenase kinase, may further suppress residual PDC activity through phosphorylation of the E1α subunit. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Identification, Cloning, and Characterization of l-Phenylserine Dehydrogenase from Pseudomonas syringae NK-15

    Directory of Open Access Journals (Sweden)

    Sakuko Ueshima

    2010-01-01

    Full Text Available The gene encoding d-phenylserine dehydrogenase from Pseudomonas syringae NK-15 was identified, and a 9,246-bp nucleotide sequence containing the gene was sequenced. Six ORFs were confirmed in the sequenced region, four of which were predicted to form an operon. A homology search of each ORF predicted that orf3 encoded l-phenylserine dehydrogenase. Hence, orf3 was cloned and overexpressed in Escherichia coli cells and recombinant ORF3 was purified to homogeneity and characterized. The purified ORF3 enzyme showed l-phenylserine dehydrogenase activity. The enzymological properties and primary structure of l-phenylserine dehydrogenase (ORF3 were quite different from those of d-phenylserine dehydrogenase previously reported. l-Phenylserine dehydrogenase catalyzed the NAD+-dependent oxidation of the β-hydroxyl group of l-β-phenylserine. l-Phenylserine and l-threo-(2-thienylserine were good substrates for l-phenylserine dehydrogenase. The genes encoding l-phenylserine dehydrogenase and d-phenylserine dehydrogenase, which is induced by phenylserine, are located in a single operon. The reaction products of both enzymatic reactions were 2-aminoacetophenone and CO2.

  13. Two different dihydroorotate dehydrogenases from yeast Saccharomyees kluyveri

    DEFF Research Database (Denmark)

    Zameitat, E.; Knecht, Wolfgang; Piskur, Jure

    2004-01-01

    Genes for two structurally and functionally different dihydroorotate dehydrogenases (DHODHs, EC 1.3.99.11), catalyzing the fourth step of pyrimidine biosynthesis, have been previously found in yeast Saccharomyces klujveri. One is closely related to the Schizosaccharomyces pombe mitochondrial family...... for their biochemical properties and interaction with inhibitors. Benzoates as pyrimidine ring analogs were shown to he selective inhibitors of cytosolic DHODs. This unique property of Saccharomyces DHODHs could appoint DHODH as a species-specific target for novel anti-fungal therapeutics....

  14. Deracemization of Secondary Alcohols by using a Single Alcohol Dehydrogenase

    KAUST Repository

    Karume, Ibrahim

    2016-03-01

    © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. We developed a single-enzyme-mediated two-step approach for deracemization of secondary alcohols. A single mutant of Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase enables the nonstereoselective oxidation of racemic alcohols to ketones, followed by a stereoselective reduction process. Varying the amounts of acetone and 2-propanol cosubstrates controls the stereoselectivities of the consecutive oxidation and reduction reactions, respectively. We used one enzyme to accomplish the deracemization of secondary alcohols with up to >99% ee and >99.5% recovery in one pot and without the need to isolate the prochiral ketone intermediate.

  15. In vitro hydrogen production by glucose dehydrogenase and hydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    Woodward, J. [Oak Ridge National Lab., TN (United States)

    1996-10-01

    A new in vitro enzymatic pathway for the generation of molecular hydrogen from glucose has been demonstrated. The reaction is based upon the oxidation of glucose by Thermoplasma acidophilum glucose dehydrogenase with the concomitant oxidation of NADPH by Pyrococcus furiosus hydrogenase. Stoichiometric yields of hydrogen were produced from glucose with continuous cofactor recycle. This simple system may provide a method for the biological production of hydrogen from renewable sources. In addition, the other product of this reaction, gluconic acid, is a high-value commodity chemical.

  16. [Genetic variations in alcohol dehydrogenase, drinking habits and alcoholism

    DEFF Research Database (Denmark)

    Tolstrup, J.S.; Rasmussen, S.; Tybjaerg-Hansen, A.

    2008-01-01

    Alcohol is degraded primarily by alcohol dehydrogenase (ADH), and genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. By genotyping 9,080 white men and women from the general population, we found that men and women with ADH1B slow versus fast alcohol...... degradation drank approximately 30% more alcohol per week and had a higher risk of everyday and heavy drinking, and of alcoholism. Individuals with ADH1C slow versus fast alcohol degradation had a higher risk of heavy drinking Udgivelsesdato: 2008/8/25...

  17. Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets.

    Science.gov (United States)

    Marimuthu, Srinivasan; Chivukula, Raghavender S V; Alfonso, Lloyd F; Moridani, Majid; Hagen, Fred K; Bhat, G Jayarama

    2011-11-01

    Epidemiological and clinical observations provide consistent evidence that regular intake of aspirin may effectively inhibit the occurrence of epithelial tumors; however, the molecular mechanisms are not completely understood. In the present study, we determined the ability of aspirin to acetylate and post-translationally modify cellular proteins in HCT-116 human colon cancer cells to understand the potential mechanisms by which it may exerts anti-cancer effects. Using anti-acetyl lysine antibodies, here we demonstrate that aspirin causes the acetylation of multiple proteins whose molecular weight ranged from 20 to 200 kDa. The identity of these proteins was determined, using immuno-affinity purification, mass spectrometry and immuno-blotting. A total of 33 cellular proteins were potential targets of aspirin-mediated acetylation, while 16 were identified as common to both the control and aspirin-treated samples. These include enzymes of glycolytic pathway, cytoskeleton proteins, histones, ribosomal and mitochondrial proteins. The glycolytic enzymes which were identified include aldolase, glyceraldehyde-3-phosphate dehydrogenase, enolase, pyruvate kinase M2, and lactate dehydrogenase A and B chains. Immunoblotting experiment showed that aspirin also acetylated glucose-6-phosphate dehydrogenase and transketolase, both enzymes of pentose phosphate pathway involved in ribonucleotide biosynthesis. In vitro assays of these enzymes revealed that aspirin did not affect pyruvate kinase and lactate dehydrogenase activity; however, it decreased glucose 6 phosphate dehydrogenase activity. Similar results were also observed in HT-29 human colon cancer cells. Selective inhibition of glucose-6-phosphate dehydrogenase may represent an important mechanism by which aspirin may exert its anti-cancer effects through inhibition of ribonucleotide synthesis.

  18. Increased salivary aldehyde dehydrogenase 1 in non-reticular oral lichen planus.

    Science.gov (United States)

    Mansourian, Arash; Shanbehzadeh, Najmeh; Kia, Seyed Javad; Moosavi, Mahdieh-Sadat

    2017-01-01

    Oral lichen planus is a potentially malignant disorder. One of the malignant transformation markers is cancer stem cells. One of the proposed marker for the detection of cancer stem cells's in head and neck cancer is aldehyde dehydrogenase. Recently it is shown that aldehyde dehydrogenase 1 expression in tissue samples is associated with oral lichen planus malignant transformation. This study evaluates salivary aldehyde dehydrogenase 1 in oral lichen planus. Thirty patients and 30 age and sex-matched healthy volunteers were recruited. Oral lichen planus was diagnosed based on the modified World Health Organization criteria. Subjects in the case group were divided into reticular and non-reticular forms. Unstimulated salivary samples were collected at 10-12 AM. Saliva concentrations of aldehyde dehydrogenase 1 were measured by ELISA. The differences between aldehyde dehydrogenase levels in the oral lichen planus group compared with the control group were not significant but aldehyde dehydrogenase in non-reticular oral lichen planus was significantly higher than that of the reticular form. This is a cross-sectional study, thus longitudinal studies in oral lichen planus may present similar or different results. The mechanism of malignant transformation in oral lichen planus is not defined. Previous analyses revealed that the aldehyde dehydrogenase 1 expression is significantly correlated with increased risk of transformation. This finding is consistent with our results because in the erosive and ulcerative forms of oral lichen planus, which have an increased risk of transformation, salivary aldehyde dehydrogenase 1 was overexpressed. A higher salivary aldehyde dehydrogenase level in non-reticular oral lichen planus can be a defensive mechanism against higher oxidative stress in these groups. Aldehyde dehydrogenase may be one of the malignant transformation markers in oral lichen planus. Further studies are needed for introducing aldehyde dehydrogenase as a prognostic

  19. Increased salivary aldehyde dehydrogenase 1 in non-reticular oral lichen planus*

    Science.gov (United States)

    Mansourian, Arash; Shanbehzadeh, Najmeh; Kia, Seyed Javad; Moosavi, Mahdieh-Sadat

    2017-01-01

    Background Oral lichen planus is a potentially malignant disorder. One of the malignant transformation markers is cancer stem cells. One of the proposed marker for the detection of cancer stem cells's in head and neck cancer is aldehyde dehydrogenase. Recently it is shown that aldehyde dehydrogenase 1 expression in tissue samples is associated with oral lichen planus malignant transformation. Objective This study evaluates salivary aldehyde dehydrogenase 1 in oral lichen planus. Method Thirty patients and 30 age and sex-matched healthy volunteers were recruited. Oral lichen planus was diagnosed based on the modified World Health Organization criteria. Subjects in the case group were divided into reticular and non-reticular forms. Unstimulated salivary samples were collected at 10-12 AM. Saliva concentrations of aldehyde dehydrogenase 1 were measured by ELISA. Results The differences between aldehyde dehydrogenase levels in the oral lichen planus group compared with the control group were not significant but aldehyde dehydrogenase in non-reticular oral lichen planus was significantly higher than that of the reticular form. Limitations of the study This is a cross-sectional study, thus longitudinal studies in oral lichen planus may present similar or different results. Conclusions The mechanism of malignant transformation in oral lichen planus is not defined. Previous analyses revealed that the aldehyde dehydrogenase 1 expression is significantly correlated with increased risk of transformation. This finding is consistent with our results because in the erosive and ulcerative forms of oral lichen planus, which have an increased risk of transformation, salivary aldehyde dehydrogenase 1 was overexpressed. A higher salivary aldehyde dehydrogenase level in non-reticular oral lichen planus can be a defensive mechanism against higher oxidative stress in these groups. Aldehyde dehydrogenase may be one of the malignant transformation markers in oral lichen planus. Further

  20. Coenzyme- and His-tag-induced crystallization of octopine dehydrogenase

    International Nuclear Information System (INIS)

    Smits, Sander H. J.; Mueller, Andre; Grieshaber, Manfred K.; Schmitt, Lutz

    2008-01-01

    The crystal structure of octopine dehydrogenase revealed a specific role of the His 5 tag in inducing the crystal contacts required for successful crystallization. Over the last decade, protein purification has become more efficient and standardized through the introduction of affinity tags. The choice and position of the tag, however, can directly influence the process of protein crystallization. Octopine dehydrogenase (OcDH) without a His tag and tagged protein constructs such as OcDH-His 5 and OcDH-LEHis 6 have been investigated for their crystallizability. Only OcDH-His 5 yielded crystals; however, they were multiple. To improve crystal quality, the cofactor NADH was added, resulting in single crystals that were suitable for structure determination. As shown by the structure, the His 5 tag protrudes into the cleft between the NADH and l-arginine-binding domains and is mainly fixed in place by water molecules. The protein is thereby stabilized to such an extent that the formation of crystal contacts can proceed. Together with NADH, the His 5 tag obviously locks the enzyme into a specific conformation which induces crystal growth

  1. High-pressure-induced water penetration into 3-isopropylmalate dehydrogenase

    International Nuclear Information System (INIS)

    Nagae, Takayuki; Kawamura, Takashi; Chavas, Leonard M. G.; Niwa, Ken; Hasegawa, Masashi; Kato, Chiaki; Watanabe, Nobuhisa

    2012-01-01

    Structures of 3-isopropylmalate dehydrogenase were determined at pressures ranging from 0.1 to 650 MPa. Comparison of these structures gives a detailed picture of the swelling of a cavity at the dimer interface and the generation of a new cleft on the molecular surface, which are accompanied by water penetration. Hydrostatic pressure induces structural changes in proteins, including denaturation, the mechanism of which has been attributed to water penetration into the protein interior. In this study, structures of 3-isopropylmalate dehydrogenase (IPMDH) from Shewanella oneidensis MR-1 were determined at about 2 Å resolution under pressures ranging from 0.1 to 650 MPa using a diamond anvil cell (DAC). Although most of the protein cavities are monotonically compressed as the pressure increases, the volume of one particular cavity at the dimer interface increases at pressures over 340 MPa. In parallel with this volume increase, water penetration into the cavity could be observed at pressures over 410 MPa. In addition, the generation of a new cleft on the molecular surface accompanied by water penetration could also be observed at pressures over 580 MPa. These water-penetration phenomena are considered to be initial steps in the pressure-denaturation process of IPMDH

  2. Idiopathic intracranial hypertension, hormones, and 11ß-hydroxysteroid dehydrogenases

    Directory of Open Access Journals (Sweden)

    Markey KA

    2016-04-01

    Full Text Available Keira A Markey,1 Maria Uldall,2 Hannah Botfield,1 Liam D Cato,1 Mohammed A L Miah,1 Ghaniah Hassan-Smith,1 Rigmor H Jensen,2 Ana M Gonzalez,1 Alexandra J Sinclair1 1Neurometabolism, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; 2Danish Headache Center, Clinic of Neurology, Rigshospitalet-Glostrup, University of Copenhagen, Glostrup, Denmark Abstract: Idiopathic intracranial hypertension (IIH results in raised intracranial pressure (ICP leading to papilledema, visual dysfunction, and headaches. Obese females of reproductive age are predominantly affected, but the underlying pathological mechanisms behind IIH remain unknown. This review provides an overview of pathogenic factors that could result in IIH with particular focus on hormones and the impact of obesity, including its role in neuroendocrine signaling and driving inflammation. Despite occurring almost exclusively in obese women, there have been a few studies evaluating the mechanisms by which hormones and adipokines exert their effects on ICP regulation in IIH. Research involving 11ß-hydroxysteroid dehydrogenase type 1, a modulator of glucocorticoids, suggests a potential role in IIH. Improved understanding of the complex interplay between adipose signaling factors such as adipokines, steroid hormones, and ICP regulation may be key to the understanding and future management of IIH. Keywords: 11beta-hydroxysteroid dehydrogenase type 1, steroid and adipokines, obesity, leptin

  3. The Alcohol Dehydrogenase Isoenzyme as a Potential Marker of Pancreatitis.

    Science.gov (United States)

    Jelski, Wojciech; Piechota, Joanna; Orywal, Karolina; Szmitkowski, Maciej

    2018-05-01

    Human pancreas parenchyma contains various alcohol dehydrogenase (ADH) isoenzymes and also possesses aldehyde dehydrogenase (ALDH) activity. The altered activities of ADH and ALDH in damaged pancreatic tissue in the course of pancreatitis are reflected in the human serum. The aim of this study was to investigate a potential role of ADH and ALDH as markers for acute (AP) and chronic pancreatitis (CP). Serum samples were collected for routine biochemical investigations from 75 patients suffering from acute pancreatitis and 70 patients with chronic pancreatitis. Fluorometric methods were used to measure the activity of class I and II ADH and ALDH activity. The total ADH activity and activity of class III and IV isoenzymes were measured by a photometric method. There was a significant increase in the activity of ADH III isoenzyme (15.06 mU/l and 14.62 mU/l vs. 11.82 mU/l; ppancreatitis or chronic pancreatitis compared to the control. The diagnostic sensitivity for ADH III was about 84%, specificity was 92 %, positive and negative predictive values were 93% and 87% respectively in acute pancreatitis. Area under the Receiver Operating Curve (ROC) curve for ADH III in AP and CP was 0.88 and 0.86 respectively. ADH III has a potential role as a marker of acute and chronic pancreatitis. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. Signatures of cinnamyl alcohol dehydrogenase deficiency in poplar lignins.

    Science.gov (United States)

    Lapierre, Catherine; Pilate, Gilles; Pollet, Brigitte; Mila, Isabelle; Leplé, Jean-Charles; Jouanin, Lise; Kim, Hoon; Ralph, John

    2004-02-01

    A series of transgenic poplars down-regulated for cinnamyl alcohol dehydrogenase (CAD) was analyzed by thioacidolysis. Among the lignin-derived monomers, the indene compounds that were recently shown to originate from sinapaldehyde incorporated into lignins through 8-O-4-cross-coupling, were found to increase as a function of CAD deficiency level. While these syringyl markers were recovered in substantial amounts in the most severely depressed lines, the markers for coniferaldehyde incorporation were recovered in only low amounts. In conjunction with these additional sinapaldehyde units and relative to the control samples, lignins in CAD-deficient poplar lines had less conventional syringyl-units and beta-O-4-bonds and more free phenolic groups. We found that almost half of the polymers in the most deficient lines could be solubilized in alkali and at room temperature. This unusual behavior suggests that lignins in CAD-deficient poplars occur as small, alkali-leachable lignin domains. That mainly sinapaldehyde incorporates into the lignins of CAD-deficient poplars suggests that the recently identified sinapyl alcohol dehydrogenase (SAD), which is structurally distinct from the CAD enzyme targeted herein, does not play any substantial role in constitutive lignification in poplar.

  5. The radiation inactivation of glutamate and isocitrate dehydrogenases

    International Nuclear Information System (INIS)

    El Failat, R.R.A.

    1980-12-01

    The reaction of free radicals produced by ionizing radiation with the enzymes glutamate dehydrogenase (GDH) and NADP + -specific isocitrate dehydrogenase (ICDH) have been studied by steady-state and pulse radiolysis techniques. In de-aerated GDH solutions, hydroxyl radicals have been found to be the most efficient of the primary radicals generated from water in causing inactivation. The effect of reaction with the enzyme of selective free radicals (SCN) 2 - , (Br) 2 - and (I) 2 - on its activity has also been studied. In neutral solutions, the order of inactivating effectiveness is (I) 2 - > (Br) 2 - > (SCN) 2 - . In the case of the thiocyanate radical anion (SCN) 2 - , the inactivation efficiency is found to depend on KSCN concentration. The radiation inactivation of GDH at both neutral and alkaline pH is accompanied by the loss of sulphydryl groups. Pulse radiolysis was also used to determine the rate constants and the transient absorption spectra following the reaction of the free radicals with GDH. 60 Co-γ-radiolysis and pulse radiolysis were also used to study the effect of ionizing radiation on the activity of ICDH. The results obtained were similar to those of GDH. (author)

  6. Orthodontic Force Application in Correlation with Salivary Lactate Dehydrogenase Activity

    Directory of Open Access Journals (Sweden)

    Erik Husin

    2013-07-01

    Full Text Available Orthodontic tooth movement generate mechanical forces to periodontal ligament and alveolar bone. The forces correlate with initial responses of periodontal tissues and involving many metabolic changes. One of the metabolic changes detected in saliva is lactate dehydrogenase (LDH activity. Objectives: To evaluate the correlation between orthodontic interrupted force application, lactate dehydrogenase activity and the distance of tooth movement. Methods: upper premolar, pre-retraction of upper canine and 1, 7, 14, 21 and 28 days post-retraction of upper canine with 100g interrupted orthodontic force. Results: duration of force (F=11.926 p 14 and 28 days post-retraction of canine. The region of retraction correlated with the distance of tooth movement (F=7.377 p=0.007. The duration of force correlated with the distance of tooth movement (F=66.554 p=0.000. retraction of canine. Conclusion: This study concluded that orthodontic interrupted force application on canine could increase the distance of tooth movement and LDH activity in saliva.

  7. Effect of radon inhalations on certain oxyda-reductive enzymes in adrenols of white rats

    International Nuclear Information System (INIS)

    Robaczynski, J.; Kaplonska, J.; Lozinska, E.

    1974-01-01

    Histochemical investigations were carried out on adrenals of white rats after radon inhalations from inhalers in Swieradow-spa. Increased reactions of oxydo-reductive enzymes: NAD tetrazolium reductase, succinic dehydrogenase and glucose-6-phosphate dehydrogenase were observed in the adrenal cortex, particularly in the zona reticularis which was hypertrophied. Raised activity of oxydo-reductive enzymes in the cells of adrenal cortex evidences increased metabolism in these cells which may reflect increased production of hormones. Finding of stimulation of adrenocortical cells after radon inhalations is of essential importance for explanation of the biological mechanism of action of radon used in balneotherapy. (author)

  8. [Age-related characteristics of structural support for ovarian function].

    Science.gov (United States)

    Koval'skiĭ, G B

    1984-12-01

    Histoenzymological assay was used to investigate various structures of the ovaries of rats of two groups aged 3-4 and 12-14 months during estral cycle. The activity of 3 beta-, 17 beta- and 20 alpha-steroid dehydrogenases, glucose-6-phosphate dehydrogenase, NAD and NADP-diaphorases, esterase, acid and alkaline phosphatases was studied. It has been shown that transport alterations in the microcirculation including the hematofollicular barrier play, the leading part in age-dependent depression of reproductive and endocrine functions. Ageing rats demonstrated no linkage between endothelial, thecal and granular cells, which points to the injury of the histophysiological mechanisms of the follicular system integration.

  9. Inosine monophosphate dehydrogenase messenger RNA expression is correlated to clinical outcomes in mycophenolate mofetil-treated kidney transplant patients, whereas inosine monophosphate dehydrogenase activity is not

    NARCIS (Netherlands)

    Sombogaard, Ferdi; Peeters, Annemiek M. A.; Baan, Carla C.; Mathot, Ron A. A.; Quaedackers, Monique E.; Vulto, Arnold G.; Weimar, Willem; van Gelder, Teun

    2009-01-01

    Measurement of the pharmacodynamic biomarker inosine monophosphate dehydrogenase (IMPDH) activity in renal transplant recipients has been proposed to reflect the biological effect better than using pharmacokinetic parameters to monitor mycophenolate mofetil therapy. The IMPDH assays are however

  10. New recombinant bacterium comprises a heterologous gene encoding glycerol dehydrogenase and/or an up-regulated native gene encoding glycerol dehydrogenase, useful for producing ethanol

    DEFF Research Database (Denmark)

    2010-01-01

    dehydrogenase encoding region of the bacterium, or is inserted into a phosphotransacetylase encoding region of the bacterium, or is inserted into an acetate kinase encoding region of the bacterium. It is operably linked to an inducible, a regulated or a constitutive promoter. The up-regulated glycerol......TECHNOLOGY FOCUS - BIOTECHNOLOGY - Preparation (claimed): Producing recombinant bacterium having enhanced ethanol production characteristics when cultivated in growth medium comprising glycerol comprises: (a) transforming a parental bacterium by (i) the insertion of a heterologous gene encoding...... glycerol dehydrogenase; and/or (ii) up-regulating a native gene encoding glycerol dehydrogenase; and (b) obtaining the recombinant bacterium. Preferred Bacterium: In the recombinant bacterium above, the inserted heterologous gene and/or the up-regulated native gene is encoding a glycerol dehydrogenase...

  11. Cloning and mRNA Expression of NADH Dehydrogenase during Ochlerotatus taeniorhynchus Development and Pesticide Response

    Science.gov (United States)

    NADH dehydrogenase, the largest of the respiratory complexes, is the first enzyme of the mitochondrial electron transport chain. We have cloned and sequenced cDNA of NADH dehydrogenase gene from Ochlerotatus (Ochlerotatus) taeniorhynchus (Wiedemann) adult (GeneBank Accession number: FJ458415). The ...

  12. Role and structural characterization of plant aldehyde dehydrogenases from family 2 and family 7

    Czech Academy of Sciences Publication Activity Database

    Končitíková, R.; Vigouroux, A.; Kopečná, M.; Andree, T.; Bartoš, Jan; Šebela, M.; Moréra, S.; Kopečný, D.

    2015-01-01

    Roč. 468, Part: 1 (2015), s. 109-123 ISSN 0264-6021 R&D Projects: GA ČR GA15-22322S; GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : aldehyde dehydrogenase 2 (ALDH2) * aldehyde dehydrogenase 7 (ALDH7) * benzaldehyde Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.562, year: 2015

  13. The Diagnostic Significance of Serum Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase Activity in Urinary Bladder Cancer Patients.

    Science.gov (United States)

    Orywal, Karolina; Jelski, Wojciech; Werel, Tadeusz; Szmitkowski, Maciej

    2017-07-01

    The aim of this study was to investigate a potential role of alcohol dehydrogenase and aldehyde dehydrogenase as tumor markers for urinary bladder cancer. Serum samples were obtained from 41 patients with bladder cancer and 52 healthy individuals. Class III and IV of ADH and total ADH activity were measured by the photometric method. For measurement of class I and II ADH and ALDH activity, the fluorometric method was employed. Significantly higher total activity of ADH was found in sera of both, low-grade and high-grade bladder cancer patients. The diagnostic sensitivity for total ADH activity was 81.5%, specificity 98.1%, positive (PPV) and negative (NPV) predictive values were 97.4% and 92.3% respectively. Area under ROC curve for total ADH activity was 0.848. A potential role of total ADH activity as a marker for bladder cancer, is herein proposed. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  14. Evaluation of alcohol dehydrogenase and aldehyde dehydrogenase enzymes as bi-enzymatic anodes in a membraneless ethanol microfluidic fuel cell

    Science.gov (United States)

    Galindo-de-la-Rosa, J.; Arjona, N.; Arriaga, L. G.; Ledesma-García, J.; Guerra-Balcázar, M.

    2015-12-01

    Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (AldH) enzymes were immobilized by covalent binding and used as the anode in a bi-enzymatic membraneless ethanol hybrid microfluidic fuel cell. The purpose of using both enzymes was to optimize the ethanol electro-oxidation reaction (EOR) by using ADH toward its direct oxidation and AldH for the oxidation of aldehydes as by-products of the EOR. For this reason, three enzymatic bioanode configurations were evaluated according with the location of enzymes: combined, vertical and horizontally separated. In the combined configuration, a current density of 16.3 mA cm-2, a voltage of 1.14 V and a power density of 7.02 mW cm-2 were obtained. When enzymes were separately placed in a horizontal and vertical position the ocp drops to 0.94 V and to 0.68 V, respectively. The current density also falls to values of 13.63 and 5.05 mA cm-2. The decrease of cell performance of bioanodes with separated enzymes compared with the combined bioanode was of 31.7% and 86.87% for the horizontal and the vertical array.

  15. Direct Electron Transfer of Dehydrogenases for Development of 3rd Generation Biosensors and Enzymatic Fuel Cells

    Directory of Open Access Journals (Sweden)

    Paolo Bollella

    2018-04-01

    Full Text Available Dehydrogenase based bioelectrocatalysis has been increasingly exploited in recent years in order to develop new bioelectrochemical devices, such as biosensors and biofuel cells, with improved performances. In some cases, dehydrogeases are able to directly exchange electrons with an appropriately designed electrode surface, without the need for an added redox mediator, allowing bioelectrocatalysis based on a direct electron transfer process. In this review we briefly describe the electron transfer mechanism of dehydrogenase enzymes and some of the characteristics required for bioelectrocatalysis reactions via a direct electron transfer mechanism. Special attention is given to cellobiose dehydrogenase and fructose dehydrogenase, which showed efficient direct electron transfer reactions. An overview of the most recent biosensors and biofuel cells based on the two dehydrogenases will be presented. The various strategies to prepare modified electrodes in order to improve the electron transfer properties of the device will be carefully investigated and all analytical parameters will be presented, discussed and compared.

  16. Krebs cycle metabolite profiling for identification and stratification of pheochromocytomas/paragangliomas due to succinate dehydrogenase deficiency

    NARCIS (Netherlands)

    Richter, S; Peitzsch, M.; Rapizzi, E.; Lenders, J.W.M.; Qin, N.; Cubas, A.A. de; Schiavi, F.; Rao, J.U.; Beuschlein, F.; Quinkler, M.; Timmers, H.J.L.M.; Opocher, G.; Mannelli, M.; Pacak, K.; Robledo, M.; Eisenhofer, G.

    2014-01-01

    CONTEXT: Mutations of succinate dehydrogenase A/B/C/D genes (SDHx) increase susceptibility to development of pheochromocytomas and paragangliomas (PPGLs), with particularly high rates of malignancy associated with SDHB mutations. OBJECTIVE: We assessed whether altered succinate dehydrogenase

  17. Identification and Overexpression of a Bifunctional Aldehyde/Alcohol Dehydrogenase Responsible for Ethanol Production in Thermoanaerobacter mathranii

    DEFF Research Database (Denmark)

    Yao, Shuo; Just Mikkelsen, Marie

    2010-01-01

    Thermoanaerobacter mathranii contains four genes, adhA, adhB, bdhA and adhE, predicted to code for alcohol dehydrogenases involved in ethanol metabolism. These alcohol dehydrogenases were characterized as NADP(H)-dependent primary alcohol dehydrogenase (AdhA), secondary alcohol dehydrogenase (Adh....... Overexpressions of AdhE in strain BG1E1 with xylose as a substrate facilitate the production of ethanol at an increased yield. Copyright © 2010 S. Karger AG, Basel...

  18. Lactate dehydrogenase inhibition: exploring possible applications beyond cancer treatment.

    Science.gov (United States)

    Di Stefano, Giuseppina; Manerba, Marcella; Di Ianni, Lorenza; Fiume, Luigi

    2016-04-01

    Lactate dehydrogenase (LDH) inhibition is considered a worthwhile attempt in the development of innovative anticancer strategies. Unfortunately, in spite of the involvement of several research institutions and pharma-companies, the discovery of LDH inhibitors with drug-like properties seems a hardly resolvable challenge. While awaiting new advancements, in the present review we will examine other pathologic conditions characterized by increased glycolysis and LDH activity, which could potentially benefit from LDH inhibition. The rationale for targeting LDH activity in these contexts is the same justifying the LDH-based approach in anticancer therapy: because of the enzyme position at the end of glycolytic pathway, LDH inhibitors are not expected to hinder glucose metabolism of normal cells. Moreover, we will summarize the latest contributions in the discovery of enzyme inhibitors and try to glance over the reasons underlying the complexity of this research.

  19. Over-Expression, Purification and Crystallization of Human Dihydrolipoamide Dehydrogenase

    Science.gov (United States)

    Hong, Y. S.; Ciszak, Ewa; Patel, Mulchand

    2000-01-01

    Dehydrolipoamide dehydrogenase (E3; dihydrolipoan-tide:NAD+ oxidoreductase, EC 1.8.1.4) is a common catalytic component found in pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase complex, and branched-chain cc-keto acid dehydrogenase complex. E3 is also a component (referred to as L protein) of the glycine cleavage system in bacterial metabolism (2). Active E3 forms a homodimer with four distinctive subdomain structures (FAD binding, NAD+ binding, central and interface domains) with non-covalently but tightly bound FAD in the holoenzyme. Deduced amino acids from cloned full-length human E3 gene showed a total of 509 amino acids with a leader sequence (N-terminal 35 amino acids) that is excised (mature form) during transportation of expressed E3 into mitochondria membrane. So far, three-dimensional structure of human E3 has not been reported. Our effort to achieve the elucidation of the X-ray crystal structure of human E3 will be presented. Recombinant pPROEX-1 expression vector (from GIBCO BRL Life Technologies) having the human E3 gene without leader sequence was constructed by Polymerase Chain Reaction (PCR) and subsequent ligation, and cloned in E.coli XL1-Blue by transformation. Since pPROEX-1 vector has an internal His-tag (six histidine peptide) located at the upstream region of a multicloning site, one-step affinity purification of E3 using nickelnitriloacetic acid (Ni-NTA) agarose resin, which has a strong affinity to His-tag, was feasible. Also a seven-amino-acid spacer peptide and a recombinant tobacco etch virus protease recognition site (seven amino acids peptide) found between His-tag and first amino acid of expressed E3 facilitated the cleavage of His-tag from E3 after the affinity purification. By IPTG induction, ca. 15 mg of human E3 (mature form) was obtained from 1L LB culture with overnight incubation at 25C. Over 98% of purity of E3 from one-step Ni-NTA agarose affinity purification was confirmed by SDS-PAGE analysis. For

  20. Idiopathic intracranial hypertension, hormones, and 11β-hydroxysteroid dehydrogenases

    Science.gov (United States)

    Markey, Keira A; Uldall, Maria; Botfield, Hannah; Cato, Liam D; Miah, Mohammed A L; Hassan-Smith, Ghaniah; Jensen, Rigmor H; Gonzalez, Ana M; Sinclair, Alexandra J

    2016-01-01

    Idiopathic intracranial hypertension (IIH) results in raised intracranial pressure (ICP) leading to papilledema, visual dysfunction, and headaches. Obese females of reproductive age are predominantly affected, but the underlying pathological mechanisms behind IIH remain unknown. This review provides an overview of pathogenic factors that could result in IIH with particular focus on hormones and the impact of obesity, including its role in neuroendocrine signaling and driving inflammation. Despite occurring almost exclusively in obese women, there have been a few studies evaluating the mechanisms by which hormones and adipokines exert their effects on ICP regulation in IIH. Research involving 11β-hydroxysteroid dehydrogenase type 1, a modulator of glucocorticoids, suggests a potential role in IIH. Improved understanding of the complex interplay between adipose signaling factors such as adipokines, steroid hormones, and ICP regulation may be key to the understanding and future management of IIH. PMID:27186074

  1. Lactate dehydrogenase (LDH isoenzymes patterns in ocular tumours

    Directory of Open Access Journals (Sweden)

    Singh Rajendra

    1991-01-01

    Full Text Available Estimation of lactate dehydrogenase (LDH isoenzymes in the serum and aqueous humor was carried out in 15 cases of benign ocular tumour, 15 cases of malignant tumor and 15 normal cases. Cases of both sexes aged between 1 year and 75 years were included. LDH, isoenzymes specially LDH4 and LDH5 are higher and LDH1 and LDH2 lower in sera of patients with malignant tumor specially retinoblastoma as compared to benign tumor cases and control cases. LDH isoenzymes in aqueous humor are significantly higher and show a characteristic pattern in retinoblastoma cases, the concentration was presumably too low in the control, malignant tumor other than retinoblastoma and benign tumor cases as its fractionation was not possible.

  2. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase

    DEFF Research Database (Denmark)

    Madiraju, Anila K; Erion, Derek M; Rahimi, Yasmeen

    2014-01-01

    Metformin is considered to be one of the most effective therapeutics for treating type 2 diabetes because it specifically reduces hepatic gluconeogenesis without increasing insulin secretion, inducing weight gain or posing a risk of hypoglycaemia. For over half a century, this agent has been...... prescribed to patients with type 2 diabetes worldwide, yet the underlying mechanism by which metformin inhibits hepatic gluconeogenesis remains unknown. Here we show that metformin non-competitively inhibits the redox shuttle enzyme mitochondrial glycerophosphate dehydrogenase, resulting in an altered...... hepatocellular redox state, reduced conversion of lactate and glycerol to glucose, and decreased hepatic gluconeogenesis. Acute and chronic low-dose metformin treatment effectively reduced endogenous glucose production, while increasing cytosolic redox and decreasing mitochondrial redox states. Antisense...

  3. A Case of Hyperammonemia Associated with High Dihydropyrimidine Dehydrogenase Activity

    Directory of Open Access Journals (Sweden)

    Keiki Nagaharu

    2016-01-01

    Full Text Available Over the past decades, 5-Fluorouracil (5-FU has been widely used to treat several types of carcinoma, including esophageal squamous cell carcinoma. In addition to its common side effects, including diarrhea, mucositis, neutropenia, and anemia, 5-FU treatment has also been reported to cause hyperammonemia. However, the exact mechanism responsible for 5-FU-induced hyperammonemia remains unknown. We encountered an esophageal carcinoma patient who developed hyperammonemia when receiving 5-FU-containing chemotherapy but did not exhibit any of the other common adverse effects of 5-FU treatment. At the onset of hyperammonemia, laboratory tests revealed high dihydropyrimidine dehydrogenase (DPD activity and rapid 5-FU clearance. Our findings suggested that 5-FU hypermetabolism may be one of the key mechanisms responsible for hyperammonemia during 5-FU treatment.

  4. 17 beta-hydroxysteroid dehydrogenase activity in canine pancreas

    International Nuclear Information System (INIS)

    Mendoza-Hernandez, G.; Lopez-Solache, I.; Rendon, J.L.; Diaz-Sanchez, V.; Diaz-Zagoya, J.C.

    1988-01-01

    The mitochondrial fraction of the dog pancreas showed NAD(H)-dependent enzyme activity of 17 beta-hydroxysteroid dehydrogenase. The enzyme catalyzes oxidoreduction between androstenedione and testosterone. The apparent Km value of the enzyme for androstenedione was 9.5 +/- 0.9 microM, the apparent Vmax was determined as 0.4 nmol mg-1 min-1, and the optimal pH was 6.5. In phosphate buffer, pH 7.0, maximal rate of androstenedione reduction was observed at 37 degrees C. The oxidation of testosterone by the enzyme proceeded at the same rate as the reduction of the androstenedione at a pH of 6.8-7.0. The apparent Km value and the optimal pH of the enzyme for testosterone were 3.5 +/- 0.5 microM and 7.5, respectively

  5. Pyruvate Dehydrogenase Kinase as a Novel Therapeutic Target in Oncology

    Directory of Open Access Journals (Sweden)

    Gopinath eSutendra

    2013-03-01

    Full Text Available Current drug development in oncology is non-selective as it typically focuses on pathways essential for the survival of all dividing cells. The unique metabolic profile of cancer, which is characterized by increased glycolysis and suppressed mitochondrial glucose oxidation provides cancer cells with a proliferative advantage, conducive with apoptosis resistance and even increased angiogenesis. Recent evidence suggests that targeting the cancer-specific metabolic and mitochondrial remodeling may offer selectivity in cancer treatment. Pyruvate dehydrogenase kinase (PDK is a mitochondrial enzyme that is activated in a variety of cancers and results in the selective inhibition of pyruvate dehydrogenase (PDH, a complex of enzymes that converts cytosolic pyruvate to mitochondrial acetyl-CoA, the substrate for the Krebs’ cycle. Inhibition of PDK with either small interfering RNAs or the orphan drug dichloroacetate (DCA shifts the metabolism of cancer cells from glycolysis to glucose oxidation and reverses the suppression of mitochondria-dependent apoptosis. In addition, this therapeutic strategy increases the production of diffusible Krebs’ cycle intermediates and mitochondria-derived reactive oxygen species (mROS, activating p53 or inhibiting pro-proliferative and pro-angiogenic transcription factors like nuclear factor of activated T-cells (NFAT and hypoxia-inducible factor 1α (HIF1α. These effects result in decreased tumor growth and angiogenesis in a variety of cancers with high selectivity. In a small but mechanistic clinical trial in patients with glioblastoma, a highly aggressive and vascular form of brain cancer, DCA decreased tumor angiogenesis and tumor growth, suggesting that metabolic targeting therapies can be translated directly to patients. Therefore, reversing the mitochondrial suppression with metabolic-modulating drugs, like PDK inhibitors holds promise in the rapidly expanding field of metabolic oncology.

  6. Functional consequences of piceatannol binding to glyceraldehyde-3-phosphate dehydrogenase.

    Science.gov (United States)

    Gerszon, Joanna; Serafin, Eligiusz; Buczkowski, Adam; Michlewska, Sylwia; Bielnicki, Jakub Antoni; Rodacka, Aleksandra

    2018-01-01

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is one of the key redox-sensitive proteins whose activity is largely affected by oxidative modifications at its highly reactive cysteine residue in the enzyme's active site (Cys149). Prolonged exposure to oxidative stress may cause, inter alia, the formation of intermolecular disulfide bonds leading to accumulation of GAPDH aggregates and ultimately to cell death. Recently these anomalies have been linked with the pathogenesis of Alzheimer's disease. Novel evidences indicate that low molecular compounds may be effective inhibitors potentially preventing the GAPDH translocation to the nucleus, and inhibiting or slowing down its aggregation and oligomerization. Therefore, we decided to establish the ability of naturally occurring compound, piceatannol, to interact with GAPDH and to reveal its effect on functional properties and selected parameters of the dehydrogenase structure. The obtained data revealed that piceatannol binds to GAPDH. The ITC analysis indicated that one molecule of the tetrameric enzyme may bind up to 8 molecules of polyphenol (7.3 ± 0.9). Potential binding sites of piceatannol to the GAPDH molecule were analyzed using the Ligand Fit algorithm. Conducted analysis detected 11 ligand binding positions. We indicated that piceatannol decreases GAPDH activity. Detailed analysis allowed us to presume that this effect is due to piceatannol ability to assemble a covalent binding with nucleophilic cysteine residue (Cys149) which is directly involved in the catalytic reaction. Consequently, our studies strongly indicate that piceatannol would be an exceptional inhibitor thanks to its ability to break the aforementioned pathologic disulfide linkage, and therefore to inhibit GAPDH aggregation. We demonstrated that by binding with GAPDH piceatannol blocks cysteine residue and counteracts its oxidative modifications, that induce oligomerization and GAPDH aggregation.

  7. Functional consequences of piceatannol binding to glyceraldehyde-3-phosphate dehydrogenase.

    Directory of Open Access Journals (Sweden)

    Joanna Gerszon

    Full Text Available Glyceraldehyde-3-phosphate dehydrogenase (GAPDH is one of the key redox-sensitive proteins whose activity is largely affected by oxidative modifications at its highly reactive cysteine residue in the enzyme's active site (Cys149. Prolonged exposure to oxidative stress may cause, inter alia, the formation of intermolecular disulfide bonds leading to accumulation of GAPDH aggregates and ultimately to cell death. Recently these anomalies have been linked with the pathogenesis of Alzheimer's disease. Novel evidences indicate that low molecular compounds may be effective inhibitors potentially preventing the GAPDH translocation to the nucleus, and inhibiting or slowing down its aggregation and oligomerization. Therefore, we decided to establish the ability of naturally occurring compound, piceatannol, to interact with GAPDH and to reveal its effect on functional properties and selected parameters of the dehydrogenase structure. The obtained data revealed that piceatannol binds to GAPDH. The ITC analysis indicated that one molecule of the tetrameric enzyme may bind up to 8 molecules of polyphenol (7.3 ± 0.9. Potential binding sites of piceatannol to the GAPDH molecule were analyzed using the Ligand Fit algorithm. Conducted analysis detected 11 ligand binding positions. We indicated that piceatannol decreases GAPDH activity. Detailed analysis allowed us to presume that this effect is due to piceatannol ability to assemble a covalent binding with nucleophilic cysteine residue (Cys149 which is directly involved in the catalytic reaction. Consequently, our studies strongly indicate that piceatannol would be an exceptional inhibitor thanks to its ability to break the aforementioned pathologic disulfide linkage, and therefore to inhibit GAPDH aggregation. We demonstrated that by binding with GAPDH piceatannol blocks cysteine residue and counteracts its oxidative modifications, that induce oligomerization and GAPDH aggregation.

  8. Evaluation of Serum Lactate Dehydrogenase Activity in a Virtual Environment

    Directory of Open Access Journals (Sweden)

    V.M.T. Trindade

    2013-05-01

    Full Text Available Int