Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients

Background

Treatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting.

Methods

The study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained.

Results

Baseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased.

Conclusions

In renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damage.

     

Acquired immunodeficiency syndrome-associated non-Hodgkin's lymphomas and other malignancies in patients with hemophilia

Non-Hodgkin's lymphoma (NHL) is the most common human immunodeficiency virus (HIV)-associated malignancy in hemophiliacs. We studied the incidence and clinicopathologic features of NHL in 3,041 hemophiliacs followed at 18 US Hemophilia Centers between 1978 and 1989. Of the 1,295 (56.6%) who were HIV(+), 253 (19.5%) developed acquired immunodeficiency syndrome (AIDS), of whom 14 (5.5%) developed NHL. Three NHL occurred in HIV(-) hemophiliacs, for a 36.5-fold greater risk in HIV(+) than HIV(-) hemophiliacs (P < .001). The NHL incidence rate was 29-fold greater than in the US population by Surveillance, Epidemiology, and End Results (SEER) estimates (P < .001). Between 0 and 4 lymphomas have been observed per year between 1978 and 1989. At presentation 13 (92.9%) of the HIV(+) NHL were extranodal. Ten were stage IV, 1 stage II, and 3 stage IE. Ten (71.4%) were high-grade, 3 (21.4%) intermediate-grade, and 1 (7.1%) was a low-grade B-cell lymphoma. Epstein-Barr virus (EBV) DNA was detected in 36% by in situ hybridization, including one central nervous system (CNS) lymphoma. The mean CD4 cell count at NHL diagnosis was 64/mm3, the mean latency from initial HIV infection was estimated to be 59 months, and the median survival was 7 months. The incidence of basal cell carcinoma in HIV(+) hemophiliacs was 18.3-fold greater than in HIV(-) hemophiliacs (P < .001) and 11.4-fold greater than in the US population (P < .001). In conclusion, incidence rates of NHL and basal cell carcinoma in HIV(+) hemophiliacs are significantly increased over rates in HIV(-) hemophiliacs and over rates in the US population. Clinicopathologic presentation of NHL in HIV(+) hemophiliacs is similar to that in HIV(+) homosexual men.     

B-cell lymphoma after angioimmunoblastic lymphadenopathy: a case with oligoclonal gene rearrangements associated with Epstein-Barr virus

We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), who subsequently developed large-cell immunoblastic lymphoma of B-cell immunophenotype. At the time of the initial diagnosis, histologic examination of an inguinal lymph node showed typical features of AILD, and there was no evidence of a monoclonal B-cell population by immunohistochemical analysis. In situ hybridization and Southern blot analysis for Epstein-Barr virus (EBV) were negative. At autopsy 2 years later, the patient had widespread lymph node and organ involvement by large-cell immunoblastic lymphoma of B-cell immunophenotype. Southern blot analysis performed on DNA extracted from lymph nodes, liver, and spleen showed two patterns of Ig heavy chain and kappa light chain gene rearrangements. The T-cell receptor beta chain gene was in the germline configuration. Analysis with an EBV terminal repeat region probe showed two clonal populations that paralleled the Ig gene rearrangement studies. Double-labeling immunohistochemistry and in situ hybridization confirmed the presence of EBV within the neoplastic B cells. The data support the hypothesis that EBV was not etiologically related to AILD in this case, and that EBV proliferation may occur after the onset of the disease. Further, the data suggest that some B-cell lymphomas that arise in the setting of AILD resemble EBV-associated B-cell lymphomas that arise in other immunodeficiency states.     

高效液相色谱法测定消痰咳片的含量

目的：采用反相色谱法同时测定消痰咳片中两种主要成分甲氧苄啶和磺胺体的含量。方法：以乙腈：0.1%H3PO4(15:85)为流动相，检测波长254nm，HPLC法测定含量。结果：试验表明，甲氧苄啶和磺胺林在0.8-8ug范围内呈良好的线性关系，回归方程分别为Y＝－1127.1＋110.2x(r=0.9994),Y=-1852.3 256.2x(r=0.9996),相对标准偏差分别为2.1%和0.8%。结论：该方法简便、准确、可靠。     

Stimulus generalization of fear responses: effects of auditory cortex lesions in a computational model and in rats

The conditioning of fear responses to a simple acoustic stimulus (pure tone) paired with footshock can be mediated by the transmission of auditory information to the lateral nucleus of the amygdala from either the auditory thalamus or the auditory cortex. We examined the processing capacity of the thalamo-amygdala pathway by making lesions of the auditory cortex and testing the extent to which conditioned fear responses generalized to tones other than the one paired with footshock. Two studies were performed, one in an anatomically constrained computational model of the fear conditioning network and the other in rats. Stimulus generalization was unaffected in both. These findings support the validity of the model as an approach to studying the neural basis of conditioned fear learning, and in addition suggest that the thalamo-amygdala pathway, possibly by the use of population coding, is capable of performing at least crude stimulus discriminations.      

Apoptosis in peripheral lymphocytes in systemic lupus erythematosus: a review

There is increasing evidence to suggest that abnormalities in apoptosis may play a part in the pathogenesis of systemic lupus erythematosus (SLE). For example, there is now considerable evidence that bel-2 expression is enhanced in a proportion of peripheral T cells, but not in B cells, in SLE patients and correlates with overall disease activity regardless of the activity index employed. Further work is required to establish whether enhanced bel-2 expression by some T cells in SLE patients is related to their activation or intrinsically enhanced by genetic predisposition. Mutations in Fas result in a lymphoproliferative syndrome and may play a role in accelerating autoimmune disease. A report of three children with mutations in Fas has once again focused attention on this regulator of apoptosis. The relationships between inducers and inhibitors of apoptosis may differ in different cell types, and must be elucidated before the implications of observations made in lymphocytes from SLE patients can be fully understood.      

非相关成分参比一倍率导数光谱法测定制剂中甲氧苄啶和磺胺甲(口恶)唑

提出了非相关成分参比一倍率导数光谱法用于测定混合组分体系的基本原理和实验方法。本法可用于待测成分和非相关成分导数光谱严重重叠且待测成分含量较低时的不经分离直接测定。试用本法消除了甲氧苄啶(TMP)和磺胺甲嚼唑(SMZ)及附加剂之间的相互干扰,从而测定了部分制剂中的TMP:用“零交法”测定了SMZ,平均回收率分别为:102.5±1.63%(CV)和100.3±0.99%(CV)。     

Secular trends in breastfeeding and parental smoking

To explore the association between smoking and breastfeeding, we obtained data from a retrospective questionnaire-based national survey comprising a random sample (n = 34 799) of all mothers giving birth in Norway 1970-91. Variables studied were postpartum smoking habits for both parents, duration of breastfeeding, infant's year of birth and parental age. The response rate was 70% (n = 24 438). During the study period, the maternal postpartum smoking prevalence decreased from 38% to 26%. The proportion breastfeeding at 6 months increased from 15% to 44% among smokers, and from 30% to 72% among non-smokers. In spite of a considerable increase in breastfeeding both among smokers and non-smokers, the proportion of breastfeeding, non-smoking women at 6 months was twice that of smoking women during the whole period. Furthermore, the duration of breastfeeding was shorter among young mothers and when the fathers were smoking. There was epidemiological evidence that the effect on breastfeeding of smoking might represent both biological and social mechanisms.     

鼠尾静脉流体力学转染技术对绿色荧光蛋白表达质粒器官靶向分布的影响

目的:观察流体力学尾静脉注射对绿色荧光蛋白基因器官靶向性的影响,为今后质粒载体的基因治疗和功能研究寻找潜在的靶器官。方法:实验于2005-12/2006-04在江西省分子医学重点实验室完成。选用健康雄性昆明鼠40只,将32只小鼠按随机数字表法分为流体力学注射和常规注射两大组,每大组再分为转染组和对照组两个小组(n=8),并设正常对照组(n=8)。①流体力学转染组将100μg/只绿色荧光蛋白表达质粒溶液2mL在5s内快速注入尾静脉;对照组仅在5s内注入林格氏液2mL。②常规注射组则将2mL林格氏液或绿色荧光蛋白表达质粒溶液在30s左右注入尾静脉。注射结束后24h采集各组小鼠血清检测转氨酶,并采集肝、脾、心、肾、肺和脑组织进行冰冻切片,部分肝组织采用多聚甲醛固定后切片,荧光显微镜下观察。结果:40只小鼠全部进入结果分析,无脱失。①流体力学注射组和常规注射组小鼠血清转氨酶与正常对照组比较差异均无显著性意义(P>0.05)。②常规尾静脉注射引起少数肾小球细胞表达绿色荧光蛋白,而肝、脾、心、肺及脑等组织未见明显绿色荧光蛋白表达。③流体力学注射引起肝内绿色荧光蛋白高水平表达,肝细胞表达率接近45%,其他组织则无绿色荧光蛋白表达。结论:流体力学方法是肝靶向性的活体基因转染方法,绿色荧光蛋白可作为该方法进行目的基因研究的一个可靠和方便的示踪剂。