一叶萩生物碱类成分研究

目的对一叶萩的生物碱类成分进行研究。方法采用各种色谱技术对一叶萩的总生物碱部位进行分离,应用理化常数和波谱技术(NMR、MS等)鉴定化合物的结构。结果自一叶萩枝叶的总碱部位中分离得到2个新的生物碱类化合物,分别命名为叶下珠碱B(phyllanthidine B,4α-methoxy-phyllanthidine,Ⅰ)和一叶萩醇D(securi-nolD,14β-hydroxyviroallosecurinine,Ⅱ)。结论化合物和均为新化合物。     

Presence and consequence of uracil in preneoplastic DNA from folate/methyl-deficient rats

Uracil can arise in DNA by misincorporation of dUTP into nascent DNA and/or by cytosine deamination in established DNA. Based on recent findings, both pathways appear to be promoted in the methyl-deficient model of hepatocarcinogenesis. A chronic increase in the ratio dUTP:dTTP with folate/methyl deficiency can result in a futile cycle of excision and reiterative uracil misincorporation leading to premutagenic apyrimidinic (AP) sites, DNA strand breaks, DNA fragmentation and apoptotic cell death. The progressive accumulation of unmethylated cytosines with chronic methyl deficiency will increase the potential for cytosine deamination to uracil and further stress uracil mismatch repair mechanisms. Uracil is removed by a highly specific uracil-DNA glycosylase (UDG) leaving an AP site that is subsequently repaired by sequential action of AP endonuclease, 5'-phosphodiesterase, a DNA polymerase and DNA ligase. Since the DNA polymerases cannot distinguish between dUTP and dTTP, an increase in dUTP:dTTP ratio will promote uracil misincorporation during both DNA replication and repair synthesis. The misincorporation of uracil for thymine (5-methyluracil) may constitute a genetically significant form of DNA hypomethylation distinct from cytosine hypomethylation. In the present study a significant increase in the level of uracil in liver DNA as early as 3 weeks after initiation of folate/methyl deficiency was accompanied by parallel increases in DNA strand breaks, AP sites and increased levels of AP endonuclease mRNA. In addition, uracil was also detected within the p53 gene sequence using UDG PCR techniques. Increased levels of uracil in DNA implies that the capacity for uracil base excision repair is exceeded with chronic folate/methyl deficiency. It is possible that enzyme-induced extrahelical bases, AP sites and DNA strand breaks interact to negatively affect the stability of the DNA helix and stress the structural limits of permissible uracil base excision repair activity. Thus substitution of uracil for thymine induces repair- related premutagenic lesions and a novel form of DNA hypomethylation that may relate to tumor promotion in the methyl-deficient model of hepatocarcinogenesis.      

Effects of an oxalate load on urinary oxalate excretion in calcium stone formers.

OBJECTIVE: To investigate the oxalate intake and the effect of an oxalate load on urinary oxalate excretion in calcium stone-forming (CSF) patients. DESIGN: Prospective study. SETTING: University-affiliated outpatient Renal Lithiasis Unit. Patients and controls: Seventy (70) CSF and 41 healthy subjects (HS) collected a 24-hour urine sample and were submitted to a 3-day dietary record to determine mean oxalate (Ox), calcium (Ca) and vitamin C intake. Fifty-eight (58) CSF patients were randomly selected to receive milk (N = 28) or dark (N = 30) chocolate as an oxalate load. INTERVENTION: Administration of either milk (94 mg Ox + 430 mg Ca) or dark chocolate (94 mg Ox + 26 mg Ca) for 3 days. A 24-hour urine sample was obtained before and after the load to determine calcium, oxalate, sodium, potassium, urea, and creatinine. MAIN OUTCOME MEASURE: Oxalate intake and excretion. RESULTS: CSF patients presented mean Ox intake of 98 +/- 137 mg/d, similar to that of HS (108 +/- 139 mg/d). Mean Ox and vitamin C intake was directly correlated with Ox excretion only in CSF. The consumption of dark chocolate induced a significant increase in mean urinary Ox (36 +/- 14 versus 30 +/- 10 mg/24 hr) not observed in the milk chocolate group. Thus, a 2-fold increase in Ox intake in this population of CSF patients produced a significant 20% increase in oxaluria, not observed when Ca was consumed simultaneously. CONCLUSION: The present study suggests that even small increases in Ox intake affect oxalate excretion and the mitigation of urinary oxalate increase by Ca consumption reinforces that Ca and Ox intakes for CSF patients should be in balance. Further studies are necessary to assess whether or not a 20% increase in oxaluria will lead to a higher risk of stone formation.     

Induction of TrkA expression by differentiation inducers in human myeloid leukemia KG-1 cells

We have recently reported that retinoic acid (RA) induced the expression of trkA, the high affinity receptor for nerve growth factor (NGF), in human myeloid leukemia KG-1 cells. In the present study, we report that the expression of trkA was also induced by several other differentiation inducers, including 1alpha, 25-dihydroxyvitamin D3 (Vit D3), 1-beta-D-arabinofuranosyl cytosine (Ara-C), sodium butyrate (NaBut), and phorbol 12-myristate 13-acetate (PMA). Interestingly, RA in combination with NaBut or PMA synergistically induced cellular differentiation as well as the expression of trkA in KG-1 cells. Furthermore, activation of the induced trkA receptor by exogenous NGF potentiated the differentiating effects of RA and NaBut. Our results demonstrated that the induction of trkA is an event associated with the differentiation of KG-1 cells. Our findings suggest that NGF, in addition to its pivotal roles in the nervous system, may also play important roles in hematopoietic differentiation.     

Effects of <Emphasis Type="Italic">Lactobacillus casei</Emphasis> and <Emphasis Type="Italic">Bifidobacterium breve</Emphasis> on urinary oxalate excretion in nephrolithiasis patients

It had been suggested that lactic acid bacteria (LAB) may degrade oxalate in the intestinal lumen, reducing urinary oxalate excretion. We aimed to evaluate the effect of a LAB mixture containing Lactobacillus casei (LC) and Bifidobacterium breve (BB) (LC + BB) upon urinary oxalate reduction in stone-forming (SF) patients without hyperoxaluria under conditions of an oxalate-rich diet. After an oxalate restriction period (7 days washout), 14 SF patients consumed an oxalate-rich diet during 4 weeks (200 mg/day) and a lyophilized LC + BB preparation was given t.i.d. after meals during the last 2 weeks. Twenty-four-hour urine samples were collected for determination of oxalate, calcium, magnesium, citrate, sodium, potassium and creatinine at baseline, after 2 weeks (DIET) and 4 weeks (DIET + LC + BB). The mean urinary oxalate excretion was significantly higher after DIET versus baseline (27 ± 8 vs. 35 ± 11 mg/24 h), but the mean decrease was not significant between DIET + LC + BB and DIET periods (35 ± 11 vs. 33 ± 10 mg/24 h). Seven out of 14 patients presented a reduction in oxaluria after LC + BB versus DIET, being the reduction higher than 25% in 4, and up to 50% in 2 of them. The latter two patients were those who had presented the greatest increase in oxaluria in response to dietary oxalate. In conclusion, this mixture of L. casei and B. breve was shown to possess a variable lowering effect upon urinary oxalate excretion that may be dependent on dietary oxalate intake.     

Association of alcohol dehydrogenase and aldehyde dehydrogenase 2 genetic polymorphisms with serum lipid profile： meta-analysis of mendelian randomisation studies

Background Alcohol dehydrogenase （ADH） and aldehyde dehydrogenase 2 （ALDH2） are the key en- zymes for alcohol metabolism. Several genetic studies have investigated the association between ADH and ALDH2 genetic polymorphisms and serum lipid profile （SLP）, however, the results were inconsistent. Methods Fourteen articles involving 27,917 participants were included in this meta-analysis. Weighted mean difference （WMD） and 95% confidence intervals （CIs） were presented using random effects model. Publication bias was evaluated by funnel plot and Begg＇s test. In addition, to further explore the heterogeneity, subgroup analysis were performed. Results Overall, there was no association between ADH genetic polymorphisms and SLP with no regard for drinking status. However, compared with ALDH2 wild homozygous genotype, ALDH2 mutant genotypes were associated with significant decrease in serum high density lipoprotein cholesterol （HDL- C） （WMD -1.80 mg/dL, 95% CI -1.88 to -1.72, P 〈 0.001） and total cholesterol （TC） levels （WMD -1.]0 mg/dL, 95% CI -1.59 to -0.62, P 〈 0.001）, and significant increase in serum low density lipoprotein choles- terol （LDL-C） level （WMD 0.30 mg/dL, 95% CI 0.18 to 0.43, P 〈 0.001）. Although there was no significant difference in serum triglyceride level in the overall population, subgroup analysis revealed that compared with ALDH2 ＊ 1 wild homozygote, ALDH2 ＊ 2 allele displayed a significant difference in serum triglyceride level between the female and male （female： WMD 1.69 mg/dl, 95% CI 1.08 to 2.30, P 〈 0.001; male： WMD -6.42 mg/dL, 95% CI -12.15 to -0.68, P = 0.028）. Conclusion ADH genetic polymorphism has no association with SLP, regardless of sex category and drinking status. ALDH2 genetic polymorphism has slight association with HDL-C, LDL-C and TC levels and sex-specific association with serum triglyceride level. Whether or not the association between ADH2 genetic polymorphisms and SLP is resulted from alcohol con-sumption nee     

Noncitrus alkaline fruit: a dietary alternative for the treatment of hypocitraturic stone formers

Background and Purpose: Fruits and vegetables are natural suppliers of potassium, bicarbonate, or bicarbonate precursors such as citrate, malate and others-hence, possessing potential effects on citraturia. We aimed to compare the acute effects of a noncitrus (melon) fruit vs citric ones (orange and lime) on citraturia and other lithogenic parameters. Patients and Methods: Two-hour urine samples were collected from 30 hypocitraturic stone-forming patients after an overnight fast and 2, 4, and 6 hours after the consumption of 385?mL (13 oz) of either freshly squeezed orange juice (n=10), freshly blended melon juice (n=10), or freshly squeezed lime juice (n=10). Urinary citrate, potassium, pH, and other lithogenic parameters were determined and net gastrointestinal alkali absorption (NGIA) was calculated. Potential renal acid load (PRAL) and pH from juices were determined. Results: Significant and comparable increases of mean urinary citrate were observed in all groups, whereas mean urinary potassium, pH, and NGIA were significantly increased only after consumption of melon and orange juices. The pH of melon juice was higher and the PRAL value was more negative compared with orange juice, indicating a higher alkalinity. Conclusions: These findings suggested that melon, a noncitrus source of potassium, citrate, and malate, yielded an increase in urinary citrate excretion equivalent to that provided by orange, and hence represents another dietary alternative for the treatment of hypocitraturic stone-formers. Despite its low potassium content, lime also produced comparable increases in citraturia possibly because of its high citric acid content.