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Objective To evaluate the effect of sildenafil on the expression of hexokinase-2 (HK-2) in lung tissues in a rat model of pulmonary arterial hypertension. Methods Thirty-two male Sprague-Dawley rats, aged 2 months, weighing 200-220 g, were allocated into 4 groups with 8 rats in each group using a random number table: control group ( group C), pulmonary arterial hypertension group ( group PAH), low-dose sildenafil group (group S1 ) and high-dose sildenafil group (group S2 ). The model of pul-monary arterial hypertension was established through combining left pneumonectomy with subcutaneous in-jection of 60 mg∕kg monocrotaline. Two percent sildenafil 30 and 50 mg∕kg were administered by intragastric gavage once a day for 3 consecutive weeks starting from 5 weeks after pneumonectomy in S1 and S2 groups, respectively. The chest was opened after the end of administration for measurement of mean pulmonary arte-rial pressure (mPAP) and right ventricular systolic pressure (RVSP). The hearts and lungs were excised for determination of the percentage of the thickness of tunica media of pulmonary arterioles, size of right ventricular cardiomyocytes, α-smooth muscle actin (α-SMA) expression (by immunohistochemistry) and expression of hypoxia-inducible factor-1α (HIF-1α) and HK-2 ( by Western blot). Results Compared with group C, the mPAP, RVSP and percentage of MT were significantly increased, the size of right ven-tricular cardiomyocytes was enlarged, and the expression of HIF-1α, HK-2 and α-SMA was up-regulated in PAH and S1 groups, and the RVSP and percentage of MT were significantly increased, the size of right ventricular cardiomyocytes was enlarged, and the expression of HIF-1α, HK-2 and α-SMA was up-regula-ted (P<0. 05), and no significant change was found in mPAP in group S2 (P>0. 05). Compared with group PAH, the percentage of MT was significantly decreased, the size of right ventricular cardiomyocytes was decreased, and the expression of HIF-1α, HK-2 and α-SMA was down-regulated in group S1 , and the mPAP, RVSP and percentage of MT were significantly decreased, the size of right ventricular cardiomyo-cytes was decreased, and the expression of HIF-1α, HK-2 and α-SMA was down-regulated in group S2 (P<0. 05). Conclusion The mechanism by which sildenafil inhibits proliferation of pulmonary vascular smooth muscle cells is related to inhibiting the expression of HK-2 in lung tissues in a rat model of pulmona-ry arterial hypertension.
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OBJECTIVE To explore the clinical features of patients carrying deletions of the rod domain of the dystrophin gene. METHODS Clinical data of 12 Chinese patients with Becker muscular dystrophy (BMD) and such deletions was reviewed. RESULTS Most patients complained of muscle weakness of lower limbs. Two patients had muscle cramps, one had increased creatine kinase (CK) level, and one had dilated cardiomyopathy. CONCLUSION Compared with DMD, the clinical features of BMD are much more variable, particularly for those carrying deletions of the rod domain of the dystrophin gene. Muscular weakness may not be the sole complaint of BMD. The diagnosis of BMD cannot be excluded by moderately elevated CK. For male patients with dilated cardiomyopathy, the possibility of BMD should be considered.
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[Objective] To explore the clinical features,genetic characters in family amyotrophic lateral sclerosis (ALS10)patients.[Methods] TARDBP gene mutations in Chinese Han family patients with ALS10 diagnosed by the First Affiliated Hospital of Sun Yat-sen University in 2013 was screened by high-throughput sequencing.[Results] There were 5 patients in three generations in this family.The initial symptoms in all affected members were distal limb muscle weakness and dystrophy at their 50 age.With a rapid progression of symptoms about 8 to 18 months.A homozygous missense mutation (c.892G＞A) were detected in TARDBP gene exon 6 of the propositus,as well as the other three family members without any clinical symptoms.[Conclusion] ALS10 is a faster progressive and shorter survival time FALS.Since there was no effective treatment in ALS10,hereditary consultation and prenatal diagnosis play an important role in disease prevention and hereditary.
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Objective@#To investigate the delayed effect of liver injury and metabolism of dimethylformamide (DMF) after high exposures in rats.@*Methods@#A total of 12 rats were randomly divided into four groups and 3 rats were in each group. Rats in 1d DMF+2 d delayed group were dosed for 1 day and rested for 2 days, and sacrificed at the 4th day. Rats in 3 d DMF group were dosed for 3 days and sacrificed at the 4th day. Rats in 3 d DMF+3 d delayed group were dosed for 3 days and rested for 3 days, and sacrificed at the 7th day. Rats in control group were administrated with water for 3 days, sacrificed at the 7th day. The administrated dose was 1 000 mg/kg (body weight·d) DMF by oral. The daily observation and body weight were recorded during the study period. After the experiment, the blood biochemistry, including alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , lactic dehydrogenase (LDH) , alkaline phosphatase (ALP) , total bilirubin (TBIL) etc. were detected. Liver weight, kidney weight, liver/body ratio, kidney/body ratio and pathologic examination of liver and kidney were investigated. The concentrations of hemoglobin-adduct (NMHb) were detected.@*Results@#During the period of 1~3 d, body weight growth rate of rats in each treated group had no significant difference with control rats. In the 4~6 th day of the period, rats in group 3 became thinner than before, and the body weight was negative growth (-4.22±3.29 g/d) and significant lower than that of control rats (10.33±3.21 g/d, F=30.07, P<0.05) . AST and LDH levels of 3 d DMF group were significant higher than control group (P<0.05) . Liver/body ratio in 3 d DMF+3 d delayed group were significant higher than control group (P<0.05) . The gross inspection showed 1 rat and 3 rats were observed liver injury in 3 d DMF group and 3 d DMF+3 d delayed group, respectively. Histopathological lesions of 1d DMF+2 d delayed group, 3 d DMF group and 3 d DMF+3 d delayed group were mainly spotty necrosis, focal necrosis and large necrosis of liver cells, respectively. Only NMHb level of control group was undetectable. NMHb levels in 3 d DMF+3 d delayed group were significantly higher than 3 d DMF group (F=135.46, P<0.05) .@*Conclusion@#The DMF-induced liver injury and DMF metabolism may be delayed after high DMF exposures in rats.
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<p><b>OBJECTIVE</b>To explore the significance of SMN1 gene mutations among patients with spinal muscular atrophy (SMA) and the value of multiplex ligation dependent probe amplification (MLPA) for its diagnosis.</p><p><b>METHODS</b>Potential mutations of the SMN1 gene were detected among 78 SMA patients with a MLPA assay.</p><p><b>RESULTS</b>Homozygous deletion of SMN1 exons 7 and 8 was detected in 70 (89.7%) of all patients. Homozygous deletion of exons 7 and heterozygous deletion of exon 8 was detected in 3 patients (3.8%). Homozygous deletion of SMN1 exons 7 alone was detected in 3 patients (3.8%). Heterozygous deletion of SMN1 exons 7 and 8 was detected in 2 patients (2.6%). For 77 of the patients, both parents were found to carry heterozygous deletion of the SMN1 gene, which was consistent with the recessive inheritance of SMA. One patient with SMA type I was found to be rather rare. The patient was found to carry homozygous deletion of SMN1 exons 7 and 8, for which her mother was heterozygous, while no mutation was found in her father.</p><p><b>CONCLUSION</b>Homozygous deletion of the SMN1 gene have been detected in more than 95% of SMA patients. No homozygous deletion of exon 8 has been found. Homozygous deletion of exon 7 is more significant in the pathogenesis of SMA.</p>
Subject(s)
Female , Humans , Male , Exons , Gene Deletion , Multiplex Polymerase Chain Reaction , Muscular Atrophy, Spinal , Genetics , Mutation , Survival of Motor Neuron 1 Protein , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To develop a method for determination of 2, 4-dichlorophenoxyacetic acid (2, 4-D) in the air of workplace by high-performance liquid chromatography.</p><p><b>METHODS</b>2, 4-D was collected by ultrafine glass filters, desorbed by methanol, separated by a C18 column, and detected by a UV detector. Identification and quantification of 2, 4-D were performed by retention time and peak areas, respectively.</p><p><b>RESULTS</b>The linear range of the test was 2∼200 µg/ml; the elution efficiency was 94.6%- 95.9%; the limit of detection (S/N = 3) was 0.034 µg/ml (injection volume of 20 µl eluant); the lower limit of quantification (S/N = 10) was 0.11 µg/ml; the minimum detectable concentration was 0.011 mg/m(3); the minimum quantifiable concentration was 0.037 mg/m(3) (with sampled air volume of 45 L).</p><p><b>CONCLUSION</b>This method is convenient and simple in sample collection and preparation, and satisfies all methodological requirements. Therefore, this method is useful for the determination of 2, 4-D in the air of workplace.</p>