Journeys to tuberculosis treatment: a qualitative study of patients, families and communities in Jogjakarta, Indonesia

Background  

Many tuberculosis (TB) patients in Indonesia are diagnosed late. We seek to document patient journeys toward TB diagnosis and treatment and factors that influence health care seeking behavior.     

Ulcerative and granulomatous colitis in children. Comparison of double- and single-contrast studies

The authors reviewed 49 double-contrast and 27 single-contrast barium-enema examinations (BE) in 71 children with suspected inflammatory bowel disease. The diagnosis was proved in 41 patients, of whom 36 underwent proctoscopy and 5 had advanced disease which was treated surgically within 3 to 30 days after BE; the other 30 children served as controls. BE and proctoscopy were compared with regard to sensitivity (detection of disease) and accuracy (categorization as ulcerative or granulomatous colitis). Sensitivity was 93% for double-contrast and 82% for single-contrast BE. Both detected all cases of advanced disease; in early disease, double-contrast BE detected 91% of cases and single-contrast BE 70%. Colitis was correctly categorized as ulcerative or granulomatous in 93% with double-contrast BE and 86% with single-contrast BE. Specificity within the control group was 100% with both techniques. The authors conclude that both types of BE exhibit similar sensitivity in advanced disease, but the double-contrast technique is more accurate in detecting early disease.     

Magnetic resonance imaging of the heart: a review of the experience in 172 subjects

Gated magnetic resonance (MR) imaging was used to evaluate central cardiovascular anatomy in 172 subjects, 31 of whom were healthy volunteers. Using the spin-echo technique, images of diagnostic quality were obtained in 93% of cases with TE = 28 msec and in 65% of cases with TE = 56 msec. Transverse multisection sequences encompassing most of the left ventricle required approximately 6-8 minutes. Corroborative studies were available in 134 of 141 patients who had cardiovascular disease; two dimensional echocardiograms and angiography in 133 and 100 patients, respectively. Gated MR demonstrated the wall thinning and complications caused by prior myocardial infarctions and high signal intensity of the myocardium at the site of acute myocardial infarctions. MR accurately demonstrated anatomic abnormalities owing to hypertrophic and congestive cardiomyopathies, congenital abnormalities of the heart and great vessels, rheumatic heart disease, pulmonary hypertension, and cardiac and paracardiac masses. Depiction of cardiovascular anatomy and pathoanatomy was attained without the use of any contrast media. Consequently, gated MR is an effective technique for cardiac diagnosis. The short time required for tomographic examination of the entire heart using the multisection technique renders this a practical cardiac imaging modality.     

化学修饰小干扰RNA作为治疗药物的研究进展

化学修饰为小干扰RNA（siRNA）治疗面临的诸多挑战提供了解决方法。此综述考察现有的各种siRNA修饰方法,包括RNA和双链siRNA结构的各个方面。然后考察化学修饰siRNA的应用,重点关注其作用的专一性（消除免疫反应和杂交依赖性的脱靶作用）和转运方法,同时对酶稳定性和效价也进行了讨论。     

Peripheral and central sites of action for the non-selective cannabinoid agonist WIN 55,212-2 in a rat model of post-operative pain

Background and purpose:

Activation of cannabinoid (CB) receptors decreases nociceptive transmission in inflammatory or neuropathic pain states. However, the effects of CB receptor agonists in post-operative pain remain to be investigated. Here, we characterized the anti-allodynic effects of WIN 55,212-2 (WIN) in a rat model of post-operative pain.

Experimental approach:

WIN 55,212-2 was characterized in radioligand binding and in vitro functional assays at rat and human CB₁ and CB₂ receptors. Analgesic activity and site(s) of action of WIN were assessed in the skin incision-induced post-operative pain model in rats; receptor specificity was investigated using selective CB₁ and CB₂ receptor antagonists.

Key results:

WIN 55,212-2 exhibited non-selective affinity and agonist efficacy at human and rat CB₁ versus CB₂ receptors. Systemic administration of WIN decreased injury-induced mechanical allodynia and these effects were reversed by pretreatment with a CB₁ receptor antagonist, but not with a CB₂ receptor antagonist, given by systemic, intrathecal and supraspinal routes. In addition, peripheral administration of both CB₁ and CB₂ antagonists blocked systemic WIN-induced analgesic activity.

Conclusions and implications:

Both CB₁ and CB₂ receptors were involved in the peripheral anti-allodynic effect of systemic WIN in a pre-clinical model of post-operative pain. In contrast, the centrally mediated anti-allodynic activity of systemic WIN is mostly due to the activation of CB₁ but not CB₂ receptors at both the spinal cord and brain levels. However, the increased potency of WIN following i.c.v. administration suggests that its main site of action is at CB₁ receptors in the brain.British Journal of Pharmacology (2009) 157, 645–655; doi:10.1111/j.1476-5381.2009.00184.x; published online 3 April 2009     

富硒麦芽对阿霉素致小鼠心脏毒性的保护作用

目的：探讨含硒制剂诱导金属硫蛋白在对抗阿霉素心脏毒性中的作用,比较无机硒制剂亚硒酸钠与有机硒制剂富硒麦芽。方法：不同时间给小鼠喂予硒制剂后取血分离血清,按常规查ＧＯＴ和ＣＫ活性,按ＤＴＮＢ法测ＧＳＨ－Ｐｘ活性;取心、肝、肾组织按Ｈｇ－Ｃｈｅｌｅｘ法测金属硫蛋白（）含量并做心脏病理学检查。结果：两种含硒制剂均能减轻阿霉素引起的体重下降,ＧＯＴ与ＣＫ酶升高及心脏病理损害,其中富硒麦芽的效果略优于亚硒酸     

Heparin cofactor activities in a family with hereditary antithrombin III deficiency: evidence for a second heparin cofactor in human plasma

Plasma levels of antithrombin-heparin cofactor, determined by heparin- dependent antithrombin assay, and antithrombin III antigen were measured in 22 members of a large kindred predisposed to venous thrombosis. While 11 members had reduced plasma levels of both antithrombin-heparin cofactor and antithrombin III antigen, the levels of antithrombin-heparin cofactor were always greater than the levels of antithrombin III antigen: 66% (+/- 7%) and 49% (+/- 5%) of normal plasma, respectively. Pooled normal plasma and plasma from one of the affected family members (60% antithrombin-heparin cofactor and 47% antithrombin III antigen) were fractionated by heparin-agarose affinity chromatography. Antithrombin-heparin cofactor, which eluted from heparin-agarose with buffer containing 0.4 M NaCl and did not cross- react with antibody specific for antithrombin III and did not inhibit factor Xa at an appreciable rate in the presence of heparin, was designated heparin cofactor A. Antithrombin-heparin cofactor, which eluted from heparin-agarose with buffer containing 2.0 M NaCl, was functionally and antigenically identified as antithrombin III. The concentrations of heparin cofactor A in normal and patient plasma were similar (4.5 x 10(-7) M), while the concentration of antithrombin III in patient plasma (8.0 x 10(-7) M) was only 50% of normal (1.6 x 10(-6) M). The functional properties of both heparin cofactor A and antithrombin III obtained from patient plasma were normal. From the results of the present study it would appear that the antithrombin- heparin cofactor concentrating measured in patient plasma reflects the combined concentrations of heparin cofactor A and antithrombin III. Since heparin cofactor A does not cross-react with antibody to antithrombin III, the concentration of antithrombin III antigen in patient plasma is thus lower than the concentration of antithrombin- heparin cofactor.     

Urban legends series: oral candidosis

Candida species (spp) are commensal yeast that can only instigate oral infection (oral candidosis – OC) when there is an underlying predisposing condition in the host. We investigated four controversial topics on OC: (i) How can a microbiological determination of OC be made as Candida spp. are commensal yeasts and not all of them form hyphae or pseudohyphae during infection? (ii) Is median rhomboid glossitis (MRG) a manifestation of candidal infection? (iii) Can candidal infection cause palate papillary hyperplasia (PPH)? (iv) What is the best therapeutic treatment for denture‐associated erythematous stomatitis (DAES)? Results from extensive literature searches, including a systematic review, suggested the following: (i) the diagnosis of OC merely on the basis of the presence of yeasts is an oversimplification of a complex process. No convincing evidence of a single test or method better able to discriminate the transition from candidal saprophytism to pathogenicity has been reported in the literature; (ii–iii) conclusive evidence of a direct aetiopathogenic relationship between MRG and PPH and candidal infection has not been found; and (iv) only limited evidence is available for any DAES treatment, thus making it impossible to make strong therapeutic recommendations.