Phagocytosis of Hemozoin (Native and Synthetic Malaria Pigment), and Plasmodium falciparum Intraerythrocyte-Stage Parasites by Human and Mouse Phagocytes

Hemozoin, the detoxification product of hemoglobin heme, piles up as electron-dense material in the food vacuole (FV) of intraerythrocytic malaria parasites (malaria pigment). In infected individuals, pigment is internalized by both circulating and resident phagocytes, thus modulating their functions. Synthetic beta-hematin, prepared in vitro from hematin (ferriprotoporphyrin IX hydroxide) in acidic condition, is spectroscopically identical to hemozoin. In this electron microscopy study, native and synthetic hemozoin also prove to be morphologically indistinguishable (large polygonal crystals with apparent transverse banding) and to undergo the same process when internalized by phagocytes (primarily a direct uptake of crystals, similar to what is described for asbestos fibers). On the contrary,whole parasites appear to follow a classical endocytic pathway. This suggests that there may be differences between the ingestion of free particles and whole parasites in terms of modulation of phagocytes' functions.     

双氢青蒿素对人骨肉瘤细胞TE85细胞内尿激酶型纤溶酶原激活物和色素上皮衍生因子表达的影响

目的 观察双氢青蒿素(DHA)对人骨肉瘤细胞活性、转移能力以及细胞中尿激酶型纤溶酶原激活物(uPA)和色素上皮衍生因子(PEDF)表达的影响.方法 将不同浓度的DHA(5、10、20、40、80 μmol/L)作用于体外培养的正常人成骨细胞和人骨肉瘤细胞TE85 12、24、48 h后,噻唑蓝(MTT)法测定DHA对细胞活性的影响,反转录-聚合酶链反应(RT-PCR)法检测细胞中uPA和PEDF mRNA水平的表达,Westen blot法检测uPA和PEDF蛋白水平的表达.结果 DHA对人成骨细胞活性无明显影响(P＞0.05).DHA能够明显抑制人骨肉瘤细胞TE85的活性(P＜0.05).不同作用时间下DHA对人骨肉瘤细胞TE85的半数抑制浓度(IC50)分别为(12 h)=(41.66±0.53) μmol/L、IC50(24 h)=(32.28 ±0.27)μmol/L和IC50 (48 h)=(22.53±1.26) μmol/L.DHA能够明显减少人骨肉瘤细胞的迁移和细胞中uPA的表达水平,同时细胞中PEDF表达升高(P＜0.05).结论 DHA对正常人体骨组织无害,能够有效抑制骨肉瘤细胞生长和转移.     

Evaluating pancreatitis in primary care: a population-based cohort study

Background

Pancreatitis is an important condition with significant mortality. Primary care may have an important role to play in its prevention, early diagnosis, and ongoing management.

Aim

To evaluate incidence, case fatality, and clinical features of acute and chronic pancreatitis in a large population.

Design and setting

Population-based cohort study using a primary care database in the UK from 1990 to 2013.

Method

Use of general practice records from 16 491 patients diagnosed with pancreatitis. Age-standardised incidence rates and case fatality were estimated. Clinical features, aetiology, and patterns of recurrence were evaluated.

Results

Incidence of pancreatitis increased from 14.8 in 100 000 (1990–1994) to 31.2 in 100 000 (2010–2013) in males, and from 14.5 to 28.3 in 100 000 in females (2010–2013). Overall case fatality after diagnosis was 4.3% (95% CI = 4.0% to 4.6%) at 90 days and 7.9% (95% CI = 7.5% to 8.4%) at 365 days. In 1990–1994, 10% of patients with acute pancreatitis were recorded as heavy drinkers, increasing to 12% in 2010–2012; for patients with chronic pancreatitis the proportions were 13%, rising to 21%. Among patients who died in the 90 days after diagnosis, 92% consulted with their general practice in the 2 months before first diagnosis.

Conclusion

The incidence of pancreatitis is increasing over time. Alcohol abuse may now account for at least one in eight cases of acute, and one in five cases of chronic pancreatitis. Consultations among those who subsequently died may have offered potential for earlier diagnosis and intervention.     

Jaundice

Jaundice is a yellow discoloration of body tissues usually observed in the skin secondary to excess bilirubin in the serum. This occurs due to imbalance between production and clearance of bilirubin. It is important to understand the pathophysiology of jaundice to understand its aetiology. Careful history and physical examination, together with appropriate urine and blood tests will guide further investigations to obtain an appropriate diagnosis. It is important to assess and address associated sepsis, dehydration, electrolyte imbalance and clotting abnormality to reduce morbidity prior to instituting any treatment plan. This often involves specialists from the multidisciplinary team.     

Radiologic appearance of gallstones and its relationship with biliary symptoms and awareness of having gallstones

In the course of two cross-sectional epidemiological surveys carried out by the Rome Group for Epidemiology and Prevention of Cholelithiasis (GREPCO), cholecystography was performed in 82 of 126 subjects identified by means of ultrasonography as having gallstones. In four subjects gallstones were not detected by cholecystography. The x-ray characteristics of the gallbladder and gallstones of the remaining 78 subjects were related to age, sex, presence of biliary symptoms in the five years prior to the study, and awareness of having gallstones. Twenty-three of the 78 gallstone subjects (29.5%) showed a nonvisualized gallbladder. Among the 55 subjects with visualized gallbladder, 16 (29.1%) and 28 (50.9%) showed radiopaque and solitary stones, respectively. The mean diameter of the largest stone was 19.7 mm±11.2 (sd). Age was related inversely to the number of stones. X-ray characteristics of gallstones did not differ between men and women. Presence of biliary symptoms in the five years prior to the study or awareness of having gallstones were not related to any radiologic feature, either in univariate or multivariate statistical analysis which included age, sex, weight, and height as possible confounding variables. Nineteen (24.3%) of the 78 subjects showed gallstones which would have been suitable for medical therapy with bile acids (ie, radiolucent, with a diameter of less than 20 mm, and in a visualized gallbladder).Rome Group for the Epidemiology and Prevention of Cholelithiasis (GREPCO) (For the composition of GREPCO, see appendix).This study was supported by a grant from Ministero della Sanità, No. CS/30/245/3458.     

PEDF抑制大鼠角膜移植术后新生血管作用的实验研究

目的：探讨局部应用色素上皮细胞衍生因子（pigment epithelium derived factor,PEDF）滴眼液抑制角膜移植术后角膜新生血管（corneal neovascularization,CNV）的作用及其可能机制。方法：建立大鼠同种异体间穿透性角膜移植模型,术后把72只大鼠随机平均分为实验组（10nM的PEDF眼液）和对照组（赋形剂滴眼液）。对术眼角膜用裂隙灯显微镜观察和照相,定量分析角膜新生血管面积,术后1w,2w,3w,1月,2月,3月,每个组随机处死6只动物,取其角膜标本进行免疫组化染色和透射电镜观察。结果：实验组角膜新生血管面积较对照组在术后1w,2w,3w,1月,2月显著减少（P〈0．01或P〈0．05）。结论：局部应用PEDF滴眼液可以抑制角膜移植术后角膜新生血管生长。     

Number and size of stones in patients with asymptomatic and symptomatic gallstones and gallbladder carcinoma: A prospective study of 592 cases

The development of gallbladder carcinoma has been correlated with the presence of a single large gallstone in two retrospective studies. The objective of the present study was to determine the number and size of gallstones in patients with gallbladder carcinoma compared to asymptomatic and symptomatic female patients with gallstones. The following three groups of patients were included in this prospective trial: (A) 78 asymptomatic patients with gallstones; (B) 365 symptomatic patients with gallstones; and (C) 149 patients with gallbladder carcinoma. At the end of the operation, the resected gallbladder was opened and the number of stones counted. The maximum size of the stones was determined using calipers. Patients with gallbladder carcinoma were significantly older than patients in the other two groups (P <0.001). In the group with asymptomatic gallstones, there were significantly more patients with one single stone, whereas in the group with gallbladder carcinoma there were significantly more patients with multiple stones (more than 11; P <0.01). Patients with gallbladder carcinoma had significantly larger stones, regardless of the number of stones present (P <0.001). We postulate that the increase in the number and size of the stones among patients with gallbladder carcinoma could simply be an effect of aging or it could be a reflection of the long-term presence of stones in the gallbladder rather than some particular chemical or physical influence.