Down-regulation of murine testicular 17β-HSD3 and hepatic CYP1A2 enzymes by a bovine testes extract

Purpose  

We investigated the effects of a bovine testes extract (BTE), which was developed as an alternative product for andropausal men, on expression of testicular enzymes responsible for sex hormone synthesis genes and a carcinogen activation related gene.     

Effect of the maternal betaE-globin gene on hematologic responses to iron supplementation during pregnancy

BACKGROUND: It is customary in Southeast Asia to treat pregnant anemic women with iron supplements, but anemia in this region may be complicated by thalassemia and hemoglobinopathies, which lead to an ineffective response. OBJECTIVE: The aim was to determine whether routine iron supplementation during pregnancy in this area, which has a high prevalence of thalassemia and hemoglobinopathies, is an effective control strategy for iron deficiency anemia. DESIGN: A prospective study was conducted. Seventy-six pregnant women, including 43 who were heterozygous for the hemoglobin E (Hb E) gene, 20 who were heterozygous for Hb E and had alpha-thalassemia, and 13 who were homozygous Hb E, as well as 77 pregnant women who had no thalassemia gene, participated in this investigation. All pregnant women received a daily dose of 120 mg elemental Fe for an average of 133.5 d. Hematologic variables and serum ferritin concentrations were measured before supplementation and after supplementation at the gestational age of 28-32 wk. Differences in hematologic variables and serum ferritin were assessed. RESULTS: Significant differences in hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin responses were found between the nonthalassemia group and the 3 groups with the Hb E gene after adjustment for the following baseline values: age, body mass index, duration of iron supplementation, and ferritin concentration. Significant differences in the improvements in mean corpuscular volume and mean corpuscular hemoglobin values between the 3 groups indicate a poorer response at the cellular level in the pregnant women with the Hb E gene. Further analysis showed a significant difference in the hemoglobin response only for women who were homozygous for Hb E. CONCLUSION: Iron supplementation during pregnancy is not beneficial for pregnant women who are homozygous for Hb E, but a routine intervention should not cause iron overload, as judged from this short observation period.     

Molecular analysis of haemoglobin E in Southeast Asian populations

Haemoglobin (Hb) E is the most common Hb variant in Asia where its gene frequency approaches 0.3 in some areas. We studied genetic background of Hb E genes among Southeast Asian populations. This study examined β-globin gene haplotypes linked to haemoglobin E (Hb E) in diverse groups of Southeast Asian populations. The study was conducted on southern Thai (22 alleles), Cambodian (84 alleles), Laotian (120 alleles), Vietnamese (87 alleles) and Burmese (one allele) subjects. Results were compared with those of previous studies in northeast Thailand, the Yunnan of China, West India and Europe. Ten different haplotypes were observed. The four most common haplotypes were haplotypes 1 (–?+?–?+?+?+?–) and 2 (+?–?–?–?–?+?–) on chromosomes with framework 2 and haplotypes 6 (–?+?–?+?+?–?+) and 7 (+?– – – – –?+) on chromosomes with framework 3 variety. Phylogenetic analysis indicated that haplotype 1 is a relatively recent haplotype found in all populations, whereas haplotype 6 is found predominately in Cambodians. The results indicate that at least two genetic origins of Hb E are responsible for the high prevalence and spread of Hb E among Southeast Asian populations.     

Molecular and hematological profiles of hemoglobin EE disease with different forms of α-thalassemia

We describe hematologic and DNA characterization of hemoglobin (Hb) E homozygote with various forms of α-thalassemia in Thai individuals. Altogether, 131 unrelated adult subjects with Hb EE at routine Hb analysis were studied. Forty-two cases were found to carry α-thalassemia with ten different genotypes. These included 21 cases with α⁺-thalassemia heterozygote (–α^3.7/αα), one case with α⁺-thalassemia heterozygote (–α^4.2/αα), six cases with Hb Constant Spring heterozygote (α^CSα/αα), four cases with homozygous α⁺-thalassemia (–α^3.7/–α^3.7), one case with homozygous α⁺-thalassemia (–α^4.2/–α^4.2), two cases with compound α⁺-thalassemia/Hb Constant Spring (–α^3.7/α^CSα), one case with compound α⁺-thalassemia/Hb Paksé (–α^3.7/α^PSα), four cases with α⁰-thalassemia heterozygote (––^SEA/αα), and, unexpectedly, two cases with compound α⁰-thalassemia/α⁺-thalassemia [(––^SEA/–α^3.7) and (––^SEA/–α^4.2)]. The hematological expression of these Hb E homozygotes with various forms of α-thalassemia was presented comparatively with those of the 89 cases of pure Hb E homozygotes. Overlapping levels of Hb E, Hb F, and other hematological parameters were observed which did not predict clinical severity, indicating a need for α-globin gene analysis for accurate diagnosis and improved genetic counseling.     

Thalassemia and iron deficiency in a group of northeast Thai school children: relationship to the occurrence of anemia

The cross-sectional study assessed anemia, thalassemia, and hemoglobinopathies, as well as iron deficiency, among 190 northeastern Thai school children aged 10 to 11 years. The aim was to analyze the reasons for anemia among the group. Hemoglobin concentration and other hematological parameters were determined using an automated blood cell counter. Beta-thalassemia and other hemoglobinopathies were identified by high performance liquid chromatography (HPLC) analysis of hemoglobin. Alpha-thalassemia was identified by polymerase chain reaction (PCR) and related techniques. Iron deficiency was assessed using serum ferritin (SF) <20 ng/ml as indicator. Based on the WHO criteria, anemia was defined by hemoglobin (Hb) level <11.5 g/dl. Twenty five out of 190 children (13.2%; 95% CI = 8.7–18.8%) were anemic. Iron deficiency was found in only two out of 190 children (1.0%; 95% CI = 0.1–3.8%), but the two iron deficient children were not anemic. The proportion of thalassemia and hemoglobinopathies among the group was 61.1% (95% CI = 53.7–68.0%). As underlying reasons for anemia, thalassemia and hemoglobinopathies were found in 22 out of 25 (88.0%) anemic children. Beta-thalassemia and homozygous Hb E seem to be important, while this was less obvious for heterozygous α-thalassemia and heterozygous Hb E. Conclusion: The results suggest that thalassemia and hemoglobinopathies may be major contributing factors to the occurrence of anemia in this area among the children’s population.     

Mutation analysis of the GNE gene in distal myopathy with rimmed vacuoles (DMRV) patients in Thailand

Distal myopathy with rimmed vacuoles (DMRV) is an early-adult-onset, distal myopathy caused by a mutation of the UDP-N-acetylglucosamine 2 epimerase/N-acetylmannosamine kinase (GNE) gene. We herein report four Thai patients with DMRV who carried compound heterozygous mutations of the GNE gene including three novel (p.G89R, p.P511T, and p.I656N) and two known mutations (p.A524V and p.V696M). All patients shared p.V696M in one allele. Our study demonstrates the mutation spectrum of the GNE gene in Thai patients with DMRV.     

In vitro characterisation of the anti-intravasative properties of the marine product heteronemin

Metastases destroy the function of infested organs and are the main reason of cancer-related mortality. Heteronemin, a natural product derived from a marine sponge, was tested in vitro regarding its properties to prevent tumour cell intravasation through the lymph-endothelial barrier. In three-dimensional (3D) cell cultures consisting of MCF-7 breast cancer cell spheroids that were placed on lymph-endothelial cell (LEC) monolayers, tumour cell spheroids induce “circular chemorepellent-induced defects” (CCIDs) in the LEC monolayer; 12(S)-Hydroxyeicosatetraenoic acid (12(S)-HETE) and NF-κB activity are major factors inducing CCIDs, which are entry gates for tumour emboli intravasating the vasculature. This 3D co-culture is a validated model for the investigation of intravasation mechanisms and of drugs preventing CCID formation and hence lymph node metastasis. Furthermore, Western blot analyses, NF-κB reporter, EROD, SELE, 12(S)-HETE, and adhesion assays were performed to investigate the properties of heteronemin. Five micromolar heteronemin inhibited the directional movement of LECs and, therefore, the formation of CCIDs, which were induced by MCF-7 spheroids. Furthermore, heteronemin reduced the adhesion of MCF-7 cells to LECs and suppressed 12(S)-HETE-induced expression of the EMT marker paxillin, which is a regulator of directional cell migration. The activity of CYP1A1, which contributed to CCID formation, was also inhibited by heteronemin. Hence, heteronemin inhibits important mechanisms contributing to tumour intravasation in vitro and should be tested in vivo.