Eosinophil sequestration and activation are associated with the onset and severity of systemic adverse reactions following the treatment of onchocerciasis with ivermectin

To investigate the role of eosinophil activation and sequestration in the development and severity of adverse reactions after the treatment of Onchocerca volvulus infection, 40 O. volvulus-infected Ghanaians were randomized to receive placebo or standard- or high-dose ivermectin. Subjects were examined for typical physiologic and clinical events before and up to 48 h after treatment. Plasma samples were tested for interleukin (IL)-5 and eosinophil degranulation products (e.g., eosinophil-derived neurotoxin, EDN). After treatment, peripheral eosinophil counts declined in ivermectin-treated groups (P<.001), whereas circulating levels of IL-5 (P<.01) and EDN (P<.05) increased. Cumulative levels of IL-5 and EDN correlated with reaction scores (P<.01). High-dose ivermectin was associated with more-severe reactions, more-profound eosinopenia, and higher circulating levels of IL-5 and EDN, compared with the standard dose. These results suggest that eosinophil sequestration and activation/degranulation are associated with the initiation and severity of ivermectin-associated adverse reactions.     

The organization of automated information systems on occupational diseases and of the hygienic monitoring of working conditions

Creation of automated database "Archive of occupational diseases clinic" is an important task of informational support for occupational pathology centers. Constructing the database, the authors designed an "Accounting chart of patient with occupational disease for diagnostic survey in occupational pathology center" and a "Diagnosis of occupational disease" code book adjusted to X ICD with instruction. Analysis of the information obtained forms a basis for forecasting the course of pathologic process, for justifying a complex of treatment and prophylaxis.     

Morphological characteristics of lungs in embryos and fetuses in women living in regions contaminated with radionuclides after accident at the Chernobyl power plant

The possibility of transplacental passage of Cr-90 and Cs-137 as well as their traces appearance in descendants muscles and bones beginning from the 2nd pregnancy trimester (and this was sometimes associated with teratogenic effects) was demonstrated on the abortion material (human embryos and fetuses) from the controlled zones of the Bryansk region. Statistically significant inhibition of the bronchial branching (according to the morphometry of the lung histological section) this indicating the disturbance of the lung prenatal morphogenesis during the "pseudoglandular" developmental stage was observed in the 1st trimester of the pregnancy in the descendants of the irradiated mothers. Lung hypoplasia was observed in some cases in the 2nd and 3rd trimesters of the pregnancy. Activation of lymphoid cells in the fetal lungs and the tendency to the enhancement in them of the ectopic erythroid hemopoiesis was revealed. These processes are considered as a reflection of the compensatory adaptive cellular reaction in the descendants respiratory organs in response to the tissue hypoxia and antigenic stimuli from the organism of the pregnant woman irradiated after the Chernobyl accident.     

胃肠道间质瘤的诊断及预后探讨

目的探讨胃肠道间质瘤的诊断及预后相关因素。方法采用S-P免疫组化方法标记42例消化道及腹腔胃肠道间质瘤(GISTS)。结果42例GISTS中Des(+)4例(9.5%),SMA(+)14例(33%),Actin(+)12例(28.6%),CD34(+)36例(85.7%),CD117(+)40例(95.2%),S-100(+)12例(28.6%),Ki-67(+)22例(52.4%),bcl-2(+)28例(66.7%)。结论GISTS的诊断CD117阳性率高于CD34,但在诊断中应两者结合以提高诊断率;肿瘤的大小及核分裂的多少是判断良恶性的重要指标,而所有间质瘤具有潜在恶性。     

Characterization of the three-dimensional solution structure of human profilin: 1H, 13C, and 15N NMR assignments and global folding pattern

Human profilin is a 15-kDa protein that plays a major role in the signaling pathway leading to cytoskeletal rearrangement. Essentially complete assignment of the 1H, 13C, and 15N resonances of human profilin have been made by analysis of multidimensional, double- and triple-resonance nuclear magnetic resonance (NMR) experiments. The deviation of the 13C alpha and 13C beta chemical shifts from their respective random coil values were analyzed and correlate well with the secondary structure determined from the NMR data. Twenty structures of human profilin were refined in the program X-PLOR using a total of 1186 experimentally derived conformational restraints. The structures converged to a root mean squared distance deviation of 1.5 A for the backbone atoms. The resultant conformational ensemble indicates that human profilin is an alpha/beta protein comprised of a seven-stranded, antiparallel beta-sheet and three helices. The secondary structure elements for human profilin are quite similar to those found in Acanthamoeba profilin I [Archer, S. J., Vinson, V. K., Pollard, T. D., & Torchia, D. A. (1993), Biochemistry 32, 6680-6687], suggesting that the three-dimensional structure of Acanthamoeba profilin I should be analogous to that determined here for human profilin. The structure determination of human profilin has facilitated the sequence alignment of lower eukaryotic and human profilins and provides a framework upon which the various functionalities of profilin can be explored. At least one element of the actin-binding region of human profilin is an alpha-helix. Two mechanisms by which phosphatidylinositol 4,5-bisphosphate can interfere with actin-binding by human profilin are proposed.     

Adverse effects of pefloxacin in irradiated C3H/HeN mice: correction with glucan therapy

Opportunistic bacterial infections are the predominant cause of death following myelosuppressive radiation exposure. When used alone, a variety of immunomodulators and antibiotics have been reported to reduce radiation-induced death. In these studies, the combined therapeutic effects of the immunomodulator glucan and the quinolone antibiotic pefloxacin were evaluated for survival-enhancing effects in myelosuppressed C3H/HeN mice. Mice were exposed to 7.9 Gy of whole-body 60Co radiation and treated with saline, glucan (250 mg/kg of body weight intravenously, 1 h after irradiation), pefloxacin (64 mg/kg/day orally, days 3 to 24 after irradiation), or glucan plus pefloxacin. Survival 30 days after irradiation in mice receiving these respective treatments was 25, 48, 7, and 85%. Evaluation of granulocyte-macrophage progenitor cell (GM-CFC) recovery in mice receiving these treatments revealed that, compared with recovery in saline-treated mice, glucan stimulated GM-CFC recovery, pefloxacin suppressed GM-CFC recovery, and glucan administered in combination with pefloxacin could override pefloxacin's hemopoietic suppressive effect.     

Expression analysis of the mixed function oxidase system in rat brain by the polymerase chain reaction

To characterize the calcium (Ca2+)-releasing effects of histamine and GTP gamma S, the drug-induced tension developments were measured in beta-escin-treated skinned longitudinal smooth muscle of guinea pig ileum. Intracellular Ca2+ stores were loaded with Ca2+ by incubating the muscle for 10 min in a Ca(2+)-containing solution. Histamine (10-100 microM), applied after Ca(2+)-loading, produced a transient rise in tension. The effect of histamine was not preserved after treatment with 20 mM caffeine, a Ca(2+)-store releaser. The effect of histamine was potentiated by GTP; inhibited by GDP beta S, an antagonist of GTP for binding to G-proteins; or heparin, an antagonist of inositol 1,4,5-trisphosphate (IP3) for binding to its receptor; and mimicked by IP3. When GTP gamma S (20 microM) was applied and continued to be present for 15 min, a transient rise in tension followed by a small, sustained rise in tension was elicited. The effect of GTP gamma S was completely inhibited by GDP beta S. The initial, transient component of the biphasic GTP gamma S response was abolished or markedly inhibited after treatment with caffeine, heparin or the calcium ionophore A23187. The present results suggest that histamine and GTP gamma S cause a release of Ca2+ from caffeine-sensitive stores which is mediated by IP3 formed through a G-protein-coupled mechanism. The GTP gamma S-induced Ca2+ release is not considered to involve such an IP3-independent process as described in chemically-skinned arterial muscle.     

Myocardial perfusion and function in dogs with moderate coronary stenosis

MRI studies of first-pass contrast enhancement with polylysine-Gd-DTPA and myocardial tagging using spatial modulation of magnetization (SPAMM) were performed to assess the feasibility of a combined regional myocardial blood flow and 2D deformation exam. Instrumented closed-chest dogs were imaged at a baseline control state (Cntl) followed by two interventions: moderate coronary stenosis (St) achieved by partial occlusion of the left anterior descending (LAD) and moderate coronary stenosis with dobutamine loading (StD). Hypoperfusion of the anterior region (ANT) of the myocardium (LAD distribution) relative to the posterior wall (POS) based on the upslope of the signal intensity time curve from the contrast-enhanced MR images was demonstrated only with dobutamine loading (ANT:POS Cntl = 1.077 +/- 0.15 versus ANT:POS StD = 0.477 +/- 0.11, P < 0.03) and was confirmed with radiolabeled microspheres measurements (ANT:POS Cntl = 1.18 +/- 0.2 ml/min/g versus ANT:POS StD = 0.44 +/- 0.1 ml/min/g; P < 0.002). Significant changes in regional myocardial shortening were only seen in the StD state (P < 0.02); the anterior region showed impaired myocardial shortening with dobutamine loading (P = NS), whereas the nonaffected POS region showed a marked increase in shortening when compared with Cntl (Cntl = 0.964 +/- 0.02 versus StD = 0.884 +/- 0.03; P < 0.001). These results demonstrate that an integrated quantitative assessment of regional myocardial function and semiquantitative assessment of myocardial blood flow can be performed noninvasively with ultrafast MRI.