Modulation of insulin resistance in ovariectomized rats by endurance exercise training and estrogen replacement

Estrogen is known to play a role in fat metabolism, but its role in carbohydrate metabolism remains controversial. We investigated alterations in carbohydrate and fat metabolism after prolonged estrogen deprivation by determining body weight, food intake, visceral fat content, serum lipids, glucose tolerance, and insulin action on glucose transport activity in isolated soleus and extensor digitorum longus muscles. In addition, effects of endurance exercise training with or without estrogen replacement on metabolic alterations occurring under estrogen deficiency were examined. Female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated (SHAM). The OVX rats remained sedentary, received 5 μg of 17β-estradiol (E₂), performed exercise training (ET), or underwent both estrogen treatment and exercise training (E₂ + ET) for 12 weeks. Compared with SHAM, OVX animals had greater final body weights, visceral fat content, and serum levels of total and low-density lipoprotein cholesterol (P < .05). Exercise training and E₂ significantly reduced body weights (6% and 25%), visceral fat (37% and 51%), and low-density lipoprotein cholesterol level (19% and 26%). Exercise training alone improved whole-body glucose tolerance (29%), which was enhanced to the greatest extent (51%) in the ET rats that also received E₂. Insulin-stimulated glucose transport activity in OVX group was lower than that in SHAM by 29% to 44% (P < .05). Exercise training and E₂ corrected the diminished insulin action on skeletal muscle glucose transport in OVX animals, which was partly due to elevated glucose transporter-4 protein expression. These findings indicate that 12 weeks of ovariectomy caused metabolic alterations mimicking features of the insulin resistance syndrome. Furthermore, these metabolic disturbances were attenuated by ET or E₂, whereas the beneficial interactive effects of ET and E₂ on these defects were not apparent.     

Thalassemia intermedia associated with the Hb Constant Spring EE Bart's disease in pregnancy: a molecular and hematological analysis

We defined the molecular basis and analyzed hematological phenotype associated with an unusual form of thalassemia intermedia caused by interaction of the hemoglobin Constant Spring (Hb CS), homozygous Hb E and alpha degrees -thalassemia found in two unrelated pregnant Thai women. Both patients had moderate anemia and characteristic of thalassemia intermedia. Hb-HPLC analysis demonstrated in both cases, Hb E and Hb Constant Spring with 3-4% Hb Bart's. Hb F was marginally elevated (3-5%). Both of them were diagnosed hematologically as the Hb CS EE Bart's disease. DNA analysis revealed the homozygosity for Hb E in both cases and identified the Hb CS mutation in trans to the alpha degrees -thalassemia allele with the SEA deletion in one case and with the Thai deletion in another. The appearance of Hb-HPLC peak resembling the Hb CS in peripheral blood of the two cases indicated the ability to form a tetrameric Hb molecule between alpha(CS) and beta(E) chains leading to a hybrid Hb namely the Hb E-CS (alpha2(CS)beta2(E)) with similar characteristics to Hb CS (alpha2(CS)beta2(A)). Hematological data of the patients were presented comparatively with other forms of related disorders in our series including 2 Hb H/Hb EE diseases, 16 homozygous Hb CS with and without Hb E, 14 Hb H diseases and 35 Hb H-CS diseases. Different genotype-phenotype correlations observed in these Thai patients with these disorders are illustrated.     

Validation of different pediatric triage systems in the emergency department

BACKGROUND: Triage system in children seems to be more challenging compared to adults because of their different response to physiological and psychosocial stressors. This study aimed to determine the best triage system in the pediatric emergency department.     

Modified expression of cytochrome P450 mRNAs by growth hormone in mouse liver

The expression of eight mouse hepatic cytochrome P450s (P450s) genes was investigated at the mRNA level in relation with the pattern of growth hormone (GH) administration. The constitutive expression of five sex-dependent P450s was sexually dimorphic, namely female>male for CYP2A4, CYP2B9, CYP2B10, and CYP3A41, and male>female for CYP2D9. In mice neonatally treated with monosodium L-glutamate to produce GH-deficiency, GH was found to be an essential factor with GH archetype as a determinant in the regulatory mechanism of hepatic CYP2D9 and CYP3A41 expression, and GH was shown to be a repressive factor for the constitutive expression in females. Implantation with micro-osmotic pump containing GH (to yield a constant release of GH to mimic the plasma GH profile in females) to male mice increased CYP2A4, CYP2B9, CYP2B10, and CYP3A41, but decreased CYP2D9, expression to female levels, while conversely, twice-daily administration of GH (to produce the so-called male pattern of plasma GH levels) to female mice resulted in the repression of female-specific, CYP2B9 and CYP3A41, as well as female-predominant, CYP2A4 and CYP2B10, expression, and induction of male-specific CYP2D9 expression. Thus, the sex-dependent plasma GH profile (referred to hereafter as the GH archetype) was a decisive factor for the expression of sex-specific P450 genes in adult mouse liver. On the other hand, the regulation of CYP1A2, CYP2C29, and CYP3A11 expression was either sex-independent or GH archetype-independent, considering the comparable levels between sexes of the constitutive expression and GH-inducible expression of these isoforms. Moreover, the observations suggested for the first time that the expression of CYP2B9 and CYP2A4 was not entirely GH-independent, but rather involved an imprinting GH-related factor that participated in the regulatory mechanism of P450 expression in females.     

Nutritional status of pregnant women in Northeast Thailand

A comparative study on the nutritional status of primiparous and multiparous women in the first trimester of pregnancy was conducted in the northeastern province of Thailand, Khon Kaen, to investigate differences in protein-energy-malnutrition, iron deficiency anaemia, vitamin A deficiency and carotenoid status between both parity groups. 94 subjects were recruited at first attendance of antenatal clinic. Data about weight, height, haemoglobin and haematocrit were obtained from hospital records. Anthropometric measurements of mid-upper arm circumference and triceps skinfold were done on a sub sample. Retinol, carotenoids and alpha-tocopherol were analysed using a reversed-phase high-performance liquid chromatography method. Ferritin, transthyretin and retinol-binding protein were determined by enzyme-linked immunosorbent assay. Primiparous women showed lower body mass index, mid-upper arm circumference, corrected arm muscle area (P<0.001) as well as lower retinol, cholesterol and triceps skinfold (P<0.05). After adjusting for age and socio-economical status the significant difference persisted for all parameters but triceps skinfold. No significant differences of alpha-tocopherol, serum proteins, carotenoids and iron indices could be observed, even though a tendency to higher values for ferritin, haemoglobin and haematocrit was shown in multiparous women. Prevalence of protein-energy-malnutrition (body mass index <18.5 kg/m2) in the primiparous group was significantly higher compared to the multiparous group (P<0.05). Prevalence of protein-energy-malnutrition, iron deficiency anaemia and vitamin A deficiency were 15.1%,6.3% and 3.3%, respectively, in the total study population. No differences between parity groups could be observed for prevalence of iron deficiency anaemia and vitamin A deficiency.     

Compound heterozygote states for Hb C/Hb Malay and Hb C/Hb E in pregnancy: a molecular and hematological analysis

Hemoglobin (Hb) C (alpha2beta(2)6Glu-Lys) is a variant Hb found mainly in West Africa where individuals carrying both Hb C and Hb S (alpha2beta(2)6Glu-Val) usually have a disease similar to sickle cell disease. The Hb C molecule has reduced solubility leading to crystal formation and hemolytic anemia. We report a hitherto undescribed interaction of Hb C and Hb Malay (alpha2beta(2)19Asn-Ser) in a Thai individual. She was a 24-year-old pregnant woman with moderate anemia who had the following hematologic data; Hb 8.9 g/dl, Hct 30.0%, MCV 81.0 fl, MCH 24.1 pg, MCHC 29.7 g/dl, RDW 17.1% and instead of Hb crystal a marked number of target cell in peripheral blood was observed. Hb analysis revealed 22.5% Hb Malay, 64.6% Hb C and 4.5% Hb A2. Globin gene analyses demonstrated that she carried the betaC mutation (beta6: GAG-AAG) in trans to the betaMalay mutation (beta19: AAC-AGC). Hematologic data of the patient were compared to those of the compound heterozygote for Hb C and Hb E (alpha2beta(2)26Glu-Lys) found in 5 other unrelated Thai pregnant women and 11 pregnant women with Hb C heterozygote with or without co-inheritance of alpha-thalassemia who had much lower Hb C levels and the non-pregnant women with Hb C heterozygote and a compound Hb E/Hb Malay syndrome. Different genotype-phenotype correlations observed in these Thai patients with Hb C disorders are illustrated.     

Allelic loss on chromosome band 18p11.3 occurs early and reveals heterogeneity in breast cancer progression

We examined the stage specificity and heterogeneity of 18p11 alterations in a series of tumors representing 96 microdissected samples. Significant loss of heterozygosity (LOH) (63%) was found, with 56% occurring early in ductal carcinoma in situ. Although most cases indicated LOH was clonally inherited, heterogeneity for 18p LOH occurred in 27% of tumors. When compared with other LOH data, 18p LOH was found in conjunction with allelic deletion on 3p, 9p, 17p and 17q, while 13q, 16q, and 11p were less frequently associated. These analyses suggest chromosome 18p11 alteration is a common and early event in breast disease.     

Sexual dimorphic expression of mouse hepatic CYP2B: alterations during development or after hypophysectomy

The constitutive expression of CYP2B mRNA in the livers of mice in the prepubertal stage was sex-independent, with CYP2B9 as the principal isoform. During the maturation stage, CYP2B10 was expressed in both sexes, whereas CYP2B9 was diminished markedly in the males, resulting in a sexually dimorphic expression in adult mice. Hypophysectomy eliminated the sexual dimorphism in the mouse CYP2B subfamily by markedly increasing the expression of both CYP2B9 and CYP2B10 in males to levels similar to those in females.     

Molecular and hematological characterization of HPFH-6/Indian deletion-inversion Ggamma(Agammadeltabeta)0-thalassemia and Ggamma(Agammadeltabeta)0-thalassemia/HbE in Thai patients

The hereditary persistence of fetal hemoglobin (HPFH)-6 is sporadically found in Thailand whereas the deletion-inversion type (G)gamma((A)gamma delta beta)(0)-thalassemia is described among Indians. We report a hitherto un-described case in which these two defects co-segregate. He was a 3-year-old Thai boy who had a feature of thalassemia intermedia phenotype with the following hematologic data; Hb 8.8 g/dL, Hct 29.2%, MCV 66.9 fL, MCH 20 pg, and MCHC 30.1 g/dL. Hemoglobin analysis revealed 100% Hb F with only (G)gamma-globin chain. Globin gene analyses demonstrated that he carried the HPFH-6 deletion in trans to the Indian deletion-inversion (G)gamma((A)gamma delta beta)(0)-thalassemia. Hematologic data of the patient was compared to those of the HPFH-6 heterozygote found in his father, to (G)gamma((A)gamma delta beta)(0)-thalassemia heterozygotes detected in his mother and sister, and to that of an unrelated Thai patient who was a compound heterozygote for the deletion-inversion (G)gamma((A)gamma delta beta)(0)-thalassemia and HbE.     

Bimodal action of miroestrol and deoxymiroestrol,phytoestrogens from Pueraria candollei var. mirifica, on hepatic CYP2B9 and CYP1A2 expressions and antilipid peroxidation in mice

Miroestrol and deoxymiroestrol are phytoestrogens isolated from Pueraria candollei var. mirifica. The influence of miroestrol and dexoymirosestrol on hepatic cytochrome P450 (P450) enzymes and antioxidative activity in brain was examined in C57BL/6 mice compared with that of a synthetic female sex hormone estradiol. We hypothesized that miroestrol and deoxymiroestrol would induce CYP2B9 expression, whereas CYP1A2 expression would be suppressed compared with estradiol. Miroestrol and deoxymiroestrol treatment significantly increased uterus weight and volume. In addition, both of these phytoestrogens induced the expression of CYP2B9 and suppressed the expression of CYP1A2, as expected. Hepatic P450 activities correspondingly showed that both compounds increased benzyloxyresorufin O-dealkylase activity, whereas methoxyresorufin O-dealkylase activity was reduced. These observations suggested that miroestrol and deoxymiroestrol might affect hepatic P450 enzymes, including the CYP2B9 and CYP1A2 P450 isoforms. Assessment of lipid peroxidation demonstrated that miroestrol and deoxymiroestrol markedly decreased levels of malondialdehyde formation in the mouse brain. This is the first report suggesting miroestrol and deoxymiroestrol as potential alternative medicines to estradiol because of their distinctive ability to regulate mouse hepatic P450 expression and their beneficial antioxidative activities.