涂圈压电传感器提取频移法测定微量麻黄碱及其在制剂分析中的应用

麻黄碱在受热时可挥发,在蒸除提取溶剂时相随挥发损失,不能用常规的提取重量法测定。使用本室新近研制的涂圈压电传感器作为超微量质量敏感元件,取常规提取重量法的基本原理,并加以改进,可以实现麻黄碱的快速分析,从而扩大该经典方法的应用范围。本法可测定低至亚μg级的麻黄碱,具有方法简便、灵敏度高等优点。     

Serum levels of DDT and liver function of malaria control personnel

The levels of DDT and metabolites in serum of 23 applicators involved in malaria control operations in Natal were determined using gas chromatography with electron capture detection. The mean levels (microgram/l, ppb) were 61.7 DDT, 129.3 DDE, 11.0 DDD and 202.0 sigma DDT. Percentage DDT was 33.4%. These levels were higher than for an age matched sample of the general population in KwaZulu, who are protected by DDT against malaria. Percentage DDT correlated negatively with age (P less than 0.05) for the applicators, suggesting a change in pharmacodynamics with age. Mean serum albumin, alkaline phosphatase, aspartate transferase and gamma-glutamyltransferase (GGT) levels did not differ significantly from an age-matched control group, but the mean GGT value for the applicators was higher than the maximum of the laboratory normal range. Although not clinically significant, the alanine transferase was significantly higher in the applicators than in the control group. These higher levels suggest a possible risk to the health of the sprayers, but uncertainties remain.     

"Hemicrania continua": another headache absolutely responsive to indomethacin

Two cases suffering from a headache apparently at variance with well recognized headaches are described. It is characterized by a steady, non-paroxysmal, probably severe to moderately severe hemicrania localized anteriorly or anteroposteriorly and is not associated with nausea. Indomethacin exerts an absolute, persistent and clearly dose-dependent effect on this headache, which differs from unilateral headache syndromes such as cluster headache and cervicogenic headache in its temporal pattern and indomethacin response. It differs from chronic paroxysmal hemicrania in its temporal pattern and in the lack of accompanying symptoms.     

Associations between FTO genotype and total energy and macronutrient intake in adults: a systematic review and meta‐analysis

Risk variants of fat mass and obesity‐associated (FTO) gene have been associated with increased obesity. However, the evidence for associations between FTO genotype and macronutrient intake has not been reviewed systematically. Our aim was to evaluate the potential associations between FTO genotype and intakes of total energy, fat, carbohydrate and protein. We undertook a systematic literature search in OVID MEDLINE, Scopus, EMBASE and Cochrane of associations between macronutrient intake and FTO genotype in adults. Beta coefficients and confidence intervals (CIs) were used for per allele comparisons. Random‐effect models assessed the pooled effect sizes. We identified 56 eligible studies reporting on 213,173 adults. For each copy of the FTO risk allele, individuals reported 6.46 kcal day^?1 (95% CI: 10.76, 2.16) lower total energy intake (P = 0.003). Total fat (P = 0.028) and protein (P = 0.006), but not carbohydrate intakes, were higher in those carrying the FTO risk allele. After adjustment for body weight, total energy intakes remained significantly lower in individuals with the FTO risk genotype (P = 0.028). The FTO risk allele is associated with a lower reported total energy intake and with altered patterns of macronutrient intake. Although significant, these differences are small and further research is needed to determine whether the associations are independent of dietary misreporting.     

Prophylactic window therapy with the clinical poly(ADP‐ribose) polymerase inhibitor olaparib delays BRCA1‐deficient mammary tumour formation in mice

Women with heterozygous germline mutations in the BRCA1 tumour suppressor gene are strongly predisposed to developing early‐onset breast cancer through loss of the remaining wild‐type BRCA1 allele and inactivation of TP53. Although tumour prevention strategies in BRCA1‐mutation carriers are still limited to prophylactic surgery, several therapeutic strategies have been developed to target the DNA repair defects (also known as ‘BRCAness’) of BRCA1‐deficient tumours. In particular, DNA‐damaging agents such as platinum drugs and poly(ADP‐ribose) polymerase (PARP) inhibitors show strong activity against BRCA1‐mutated tumours. However, it is unclear whether drugs that target BRCAness can also be used to prevent tumour formation in BRCA1‐mutation carriers, especially as loss of wild‐type BRCA1 may not be the first event in BRCA1‐associated tumourigenesis. We performed prophylactic treatments in a genetically engineered mouse model in which de novo development of BRCA1‐deficient mammary tumours is induced by stochastic loss of BRCA1 and p53. We found that prophylactic window therapy with nimustine, cisplatin or olaparib reduced the amount and size of mammary gland lesions, and significantly increased the median tumour latency. Similar results were obtained with intermittent prophylactic treatment with olaparib. Importantly, prophylactic window therapy with nimustine and cisplatin resulted in an increased fraction of BRCA1‐proficient mammary tumours, suggesting selective survival and malignant transformation of BRCA1‐proficient lesions upon prophylactic treatment with DNA‐damaging agents. Prophylactic therapy with olaparib significantly prolonged mammary tumour‐free survival without any significant increase in the fraction of BRCA1‐proficient tumours, warranting the evaluation of this PARP inhibitor in prophylactic trials in BRCA1‐mutation carriers. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Invasion of erythrocytes by Plasmodium falciparum malaria parasites: evidence for receptor heterogeneity and two receptors

Plasmodium falciparum malaria parasites with different capabilities of invading sialic acid-deficient erythrocytes were identified. Thai-2 parasites cultured in Tn erythrocytes invaded neuraminidase-treated and Tn erythrocytes twice as efficiently as Thai-2 parasites cultured in normal erythrocytes and seven to ten times more efficiently than a cloned line of Camp parasites cultured in normal erythrocytes. All three parasite lines required sialic acid for optimal invasion, but Thai-2 parasites cultured in Tn erythrocytes invaded neuraminidase- treated erythrocytes with 45% efficiency whereas Camp parasites invaded neuraminidase-treated erythrocytes with less than 10% efficiency. P falciparum malaria parasites probably possess two receptors: one that binds to a sialic acid-dependent ligand and another that binds to a sialic acid-independent ligand. Parasites may differ in the quantity or affinity of their receptors for the sialic acid-independent ligand.     

Expression of bcl-xL can confer a multidrug resistance phenotype

It has been suggested that genes that regulate apoptotic cell death may play an important role in determining the sensitivity of tumor cells to chemotherapy. We have recently cloned a member of the bcl-2 family, bcl- x. To test whether bcl-XL expression affects the sensitivity of tumor cells to chemotherapy, we have created stable cell lines overexpressing bcl-XL and have tested these cells for resistance to cell death induced by metabolic inhibitors and chemotherapeutic agents. Bcl-XL expression dramatically reduces the cytotoxicity of bleomycin, cisplatin, etoposide, vincristine, hygromycin B, and mycophenolic acid for up to 4 days in culture. Bcl-XL does not prevent cells from undergoing cell cycle arrest in response to these drugs, but rather prevents treated cells from undergoing apoptosis. Cell-cycle analysis on cells treated with the chemotherapeutic agents bleomycin, cisplatin, etoposide, and vincristine, show that the drugs cause growth arrest in different positions within the cell cycle. Bcl-XL expressing cells treated with chemotherapeutic drugs retain their proliferative ability after the drugs are removed. Interestingly, vincristine-treated cells expressing bcl-XL become polyploid after drug removal. These data show that bcl-XL protects cells from a wide variety of apoptotic stimuli, acts in multiple positions within the cell cycle, and confers a multidrug resistance phenotype. The ability of bcl-XL to prevent apoptotic cell death in response to chemotherapy-induced DNA damage and cell-cycle arrest may contribute to the accumulation of chromosomal aberrations within tumors. The expression of bcl-XL in tumor cells is likely to be an important indicator of chemotherapeutic efficacy.     

Gastrojejunostomy: is it helpful for patients with pancreatic cancer?

A retrospective review of palliative outcome of gastrojejunostomy in patients with pancreatic cancer was conducted. Eighty-one patients were analyzed in two groups depending on duodenal patency. Forty-five patients (group I) had no evidence of duodenal obstruction. Thirty-six patients (group II) had evidence of impingement on the duodenum by the pancreatic cancer. A third subset of patients was also studied for outcome. These 21 patients (five group I and 16 group II) had nausea and vomiting as major symptoms and were judged to have the most to gain from gastrojejunostomy. Patients were categorized by outcome. Poor outcome was defined as either death during the hospitalization for gastrojejunostomy or death within 30 days of operation even if the patient left the hospital. Risk for poor outcome depended on group. In group I, 18 of 45 patients (40%) had a poor outcome compared with 25 of 36 (70%) patients in group II (p less than 0.001). Nineteen of the 21 (90%) patients with nausea and vomiting had a poor outcome. It is an unfortunate paradox that the more patients need gastrojejunostomy for pancreatic cancer, the less likely they are to have a favorable outcome. Gastric outlet obstruction in pancreatic cancer appears to be a terminal event. A prospective study is needed to see if any true palliation of vomiting can be affected in these patients.