补虚颗粒对乙酰苯肼和环磷酰胺致血虚小鼠的补血作用研究

目的 研究补虚颗粒对乙酰苯肼和环磷酰胺联用致血虚小鼠的影响.方法 用乙酰苯肼和环磷酰胺联合作用于小鼠,建立小鼠血虚症模型,观察补虚颗粒对小鼠外周血常规、胸腺指数和脾脏指数的影响.结果 补虚颗粒给药组小鼠的红细胞、白细胞、血红蛋白和血小板计数均高于模型组,胸腺指数和脾脏指数也有一定程度的提高.结论 补虚颗粒对化学物质致血虚小鼠具有生血、补血作用.     

Glycidol exposure evaluation of humans who have ingested diacylglycerol oil containing glycidol fatty acid esters using hemoglobin adducts

Glycidol fatty acid esters (GEs) have been found as impurities in refined edible oils including diacylglycerol (DAG) oil, and concerns of possible exposure to glycidol (G), a known animal carcinogen, during digestion have been raised. We previously measured N-(2,3-dihydroxy-propyl)valine (diHOPrVal), a G hemoglobin adduct, for DAG oil exposed and non-exposed groups and showed there was no significant difference between them. In the present study, we conducted an additional analysis to verify the outcome of the previous report. The first experiment was designed as a matched case-control study to adjust variables with an increased sample size. The average levels of diHOPrVal were 6.9 pmol/g-globin (95%CI: 4.9–9.0) for 14 DAG oil exposed subjects and 7.3 pmol/g-globin (95%CI: 6.1–8.5) for 42 non-exposed volunteers, and no significant difference in levels was found between the two groups. In a second experiment, we compared the adduct levels of 12 DAG oil exposed subjects before and after discontinuing use of DAG oil, and found there was no significant change in diHOPrVal levels (from 7.1 ± 1.1 to 7.5 ± 1.4 pmol/g-globin). These results suggest that there was no increased exposure to G for humans who ingested DAG oil daily, although the evaluated population was limited.     

Monensin potentiates lead chelation efficacy of MiADMSA in rat brain post chronic lead exposure

The present study evaluates combination therapy with a chelating agent, MiADMSA and a Na⁺ ionophore, monensin against sub-chronic lead toxicity in rats. Animals were exposed to 0.1% lead in drinking water for 16 weeks and then treated with either MiADMSA at 50 mg/kg body weight, or monensin at 10 mg/kg, or both in combination for a period of 5 days was administered. Biomarkers indicative of oxidative stress like ROS, GSH, GSSG and TBARS demonstrated lead-induced toxic manifestations in blood, kidney and brain. Antioxidants like SOD, catalase and glutathione peroxidase along with specific lead biomarker, blood ALAD were also severely depleted in lead intoxicated animals. Serum parameters and histopathological findings supported the said results. MiADMSA treatment during both mono- and combination therapy with monensin, restored the antioxidant status and recovered biochemical and haematological variables due to lead. However, monensin alone was not found to be effective in the given scenario. Interestingly, combination therapy in its ability to revert lead-induced overall systemic toxicity was only found at par with the MiADMSA monotherapy except for its chelation potential. Monensin given in combination with MiADMSA potentiated its lead chelation ability especially from brain, along with maintaining the normal copper concentrations in the organ unlike MiADMSA monotherapy.     

Gender-specific association between iron status and the history of attempted suicide: implications for gender paradox of suicide behaviors

PURPOSE: Iron deficiency (ID) has been linked with high impulsivity, and an increased risk of ID was reported among suicide attempters. We hypothesized that poor iron status might be prevalent among suicide attempters, who have high impulsivity. METHODS: As a part of the third National Health and Nutrition Examination Survey (1988-1994), a set of iron indices were measured in 2598 men and 2975 women aged 17-39 years, who completed a mental disorder diagnostic interview. RESULTS: Using non-attempters as reference within each gender, we observed a gender-dependent association between poor iron status and the history of attempted suicide. For male attempters (n=74), the prevalence ratios (PR) of abnormal serum ferritin, serum iron and protoporphyrin were 18.3 (95%CI=3.3-101.7), 3.2 (1.1-9.4) and 5.4(1.8-15.6). In contrast, the PR of abnormal serum ferritin for female attempters (n=217) was 0.3 (0.1-0.6). The hematological indices did not differ significantly between attempters and non-attempters among either men or women. Compared with non-attempters, male attempters were prone to a higher odds [17.5 (4.2-72.4)] while female attempters to a lower odds [0.6 (0.3-1.1)] of ID. CONCLUSION: These data suggest new opportunities for exploring biological bases of gender paradox of suicidal behaviors and a novel way to enhance therapeutic and preventive interventions against suicide.     

Molecular characterization and origins of Hb Constant Spring and Hb Paksé in Southeast Asian populations

Hemoglobin Constant Spring (Hb CS) and Hb Paksé, two abnormal Hbs characterized by elongated α-globin chains resulting from mutations of the termination codon in the α2-globin gene, are the most prevalent nondeletional α-thalassemias in Southeast Asia. To determine the origins of these two variants in the region, we have determined α-globin gene haplotypes associated with these two variants on 120 Thai, eight Cambodian, and six Laos alleles, and the results were compared with those reported previously for the Chinese and Mediterranean. Five haplotypes were found to be associated with 131 α^CS genes examined, whereas a single haplotype was linked to all the α^Paksé genes in these Southeast Asian populations. All the α^CS haplotypes differed from those of the Mediterranean, but one of them was similar to a Chinese α^CS gene reported previously. It is concluded that there are multiple origins of the α^CS and a single origin of the α^Paksé mutations in Southeast Asia. Hematological findings confirm the mild thalassemia intermedia phenotypes for pure homozygous Hb CS and homozygous Hb CS with Hb E heterozygote and Hb E homozygote. The appearance of Hb CS peak by high-performance liquid chromatography analysis indicates the ability to form a tetrameric Hb molecule between the α^CS and β^E chains, leading to a novel derivative with similar characteristics to Hb CS.     

15例Hb Westmead复合东南亚缺失型α地中海贫血1分析

目的分析Hb Westmead（HbWS）复合东南亚缺失型α地中海贫血（地贫）1的临床和血液学特点,以更好指导临床遗传咨询。方法临床检查、血液学分析、血红蛋白分析和基因检测确诊的HbWS复合东南亚缺失型α地贫1患者15例,男6例,女9例,年龄2～34岁。以Cell Dyn1700全自动血细胞分析仪进行血细胞分析,以电泳法和高效液相法进行血红蛋白分析和血红蛋白F和血红蛋白A2定量检测,以Gap-PCR技术和反向斑点杂交技术分别检测缺失型和突变型α地贫基因。结果15例患者中只有6例有贫血,且均较轻,血红蛋白最低93g/L,平均红细胞体积和平均红细胞含量均低于正常,血红蛋白分析均无HbH区带,但均有较少量的HbBart＇s,基因型为αα^WS/--SEA。结论Hb WS复合东南亚缺失型α地贫1的临床特点有别于其它组合的HbH病,贫血较轻或不贫血。     

Changes in bone mass,biomechanical properties,and microarchitecture of calcium- and iron-deficient rats fed diets supplemented with inulin-type fructans

Feeding mineral-deficient diets enhances absorptive efficiency as an attempt of the body to compensate for the lack of an essential nutrient. Under certain circumstances, it does not succeed; and nutritional deficiency is produced. Our hypothesis was that inulin-type fructans (ITF), which are known to affect mineral absorption, could increase Ca and Fe bioavailability in Ca- and Fe-deficient rats. Male Wistar rats (n = 48, 4 weeks old) were assigned to 1 of 8 groups derived from 2 × 2 × 2 factorial design with 2 levels of added Fe (0 and 35 mg/kg), Ca (0 and 5 g/kg), and ITF (0 and 100 g/kg) for 33 days. The Fe status (hemoglobin, serum Fe, total Fe-binding capacity, transferrin saturation, liver minerals) was evaluated. Tibia minerals (Ca, Mg, and Zn), bone strength, and histomorphometry were determined. In nondeficient rats, ITF supplementation did not affect Fe status or organ minerals, with the exception of tibia Mg. Moreover, ITF improved bone resilience and led to a reduction in eroded surface per body surface and number of osteoclasts per area. In Ca-deficient rats, ITF increased liver (Fe and Zn) and tibia (Zn) mineral levels but impaired tibia Mg, yield load, and resilience. In conclusion, ITF worsened the tibia Mg levels and elastic properties when supplemented in Ca-deficient diets. In contrast, although bone Ca was not affected in nondeficient rats under the present experimental conditions, bone quality improved, as demonstrated by a moderate reduction in femur osteoclast resorption and significant increases in tibia Mg content and elasticity.     

Iron supplement prevents lead-induced disruption of the blood-brain barrier during rat development

Children are known to be venerable to lead (Pb) toxicity. The blood-brain barrier (BBB) in immature brain is particularly vulnerable to Pb insults. This study was designed to test the hypothesis that Pb exposure damaged the integrity of the BBB in young animals and iron (Fe) supplement may prevent against Pb-induced BBB disruption. Male weanling Sprague-Dawley rats were divided into four groups. Three groups of rats were exposed to Pb in drinking water containing 342 microg Pb/mL as Pb acetate, among which two groups were concurrently administered by oral gavage once every other day with 7 mg Fe/kg and 14 mg Fe/kg as FeSO(4) solution as the low and high Fe treatment group, respectively, for 6 weeks. The control group received sodium acetate in drinking water. Pb exposure significantly increased Pb concentrations in blood by 6.6-folds (p<0.05) and brain tissues by 1.5-2.0-folds (p<0.05) as compared to controls. Under the electron microscope, Pb exposure in young animals caused an extensive extravascular staining of lanthanum nitrate in brain parenchyma, suggesting a leakage of cerebral vasculature. Western blot showed that Pb treatment led to 29-68% reduction (p<0.05) in the expression of occludin as compared to the controls. Fe supplement among Pb-exposed rats maintained the normal ultra-structure of the BBB and restored the expression of occludin to normal levels. Moreover, the low dose Fe supplement significantly reduced Pb levels in blood and brain tissues. These data suggest that Pb exposure disrupts the structure of the BBB in young animals. The increased BBB permeability may facilitate the accumulation of Pb. Fe supplement appears to protect the integrity of the BBB against Pb insults, a beneficial effect that may have significant clinical implications.     

A novel gain-of-function PIP4K2A mutation elevates the expression of β-globin and aggravates the severity of α-thalassemia

Haemoglobin H (Hb H) disease (intermediate status of α-thalassemia) shows marked phenotypic variability from asymptomatic to severe anaemia. Apart from the combined β-thalassemia allele ameliorating clinical severity, reports of genetic modifier genes affecting the phenotype of Hb H disease are scarce which bring inconvenience to precise diagnosis and genetic counselling of the patients. Here, we present a novel mutation (c.948C>A, p.S316R) in the PIP4K2A gene in a female Hb H disease patient who displayed moderate anaemia and a relatively high Hb H level. Haematological analysis in her family members revealed that individuals carrying this mutation have upregulated β-globin expression, leading to a more imbalanced β/α-globin ratio and more Hb H inclusion bodies in peripheral red blood cells. According to functional experiments, the mutant PIP4K2A protein exhibits enhanced protein stability, increased kinase activity and a stronger regulatory effect on downstream proteins, suggesting a gain-of-function mutation. Moreover, introduction of the S316R mutation into HUDEP-2 cells increased expression of β-globin, further inhibiting erythroid differentiation and terminal enucleation. Thus, the S316R mutation is a novel genetic factor associated with β-globin expression, and the PIP4K2A gene is a new potential modifier gene affecting the α-thalassemia phenotype.     

Hydrops Fetalis Associated with Homozygosity for Hb Adana [α59(E8)Gly→Asp (α2)]

We describe cases of hydrops fetalis associated with nondeletional α-thalassemia (α-thal), in three unrelated Indonesian families. The genotypes of the fetuses and their parents were generated by DNA sequencing and by a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP)-based method to rapidly identify mutations detected by sequencing. Two of the fetuses had hydrops fetalis and homozygous α59(E8)Gly→Asp (α2), also known as Hb Adana. The third fetus was also suspected to be homozygous for Hb Adana because both parents were carriers of this mutation. This study shows that homozygosity for Hb Adana is associated with hydrops fetalis in the Indonesian population. We discuss this mutation and its various phenotypes including compound heterozygosity with other α-thal mutations and describe a simple approach to genetic testing that will clarify the risk of hydrops fetalis in the offspring of couples carrying this nondeletional mutation.