Modulation of in vitro eosinophil progenitors by hydrocortisone: role of accessory cells and interleukins

The growth of human eosinophil progenitors (CFU-Eo) and the modulation of growth by hydrocortisone were studied as functions of the presence of lymphocytes and monocytes in marrow cells under study; and the source of colony-stimulating factors, specifically, media conditioned by macrophage-like cell line, GCT; phytohemagglutinin-stimulated mononuclear cells (PHA-LCM); or the T cell line, MO. CFU-Eo growth was greatest in marrow containing accessory cells as compared to marrow depleted of accessory cells; and in marrow treated with phytohemagglutinin-stimulated leukocyte conditioned media (PHA-LCM) or MO (T cell line)-conditioned medium (MO-CM) as compared with GCT cell- conditioned medium (GCT-CM). Hydrocortisone reproducibly inhibited eosinophil progenitor growth in unfractionated marrow stimulated by GCT- CM. This effect was abrogated by admixing irradiated mononuclear cells or T lymphocytes with the target marrow or by adding interleukin 1 or interleukin 2 (IL-1, IL-2). Inhibition by hydrocortisone did not occur when monocyte and T lymphocyte depleted marrow was studied. Unlike GCT- CM, MO-CM and PHA-LCM stimulated equal proportions of eosinophil progenitors in nondepleted and accessory cell-depleted marrow and demonstrated less hydrocortisone inhibition. However, both GCT-CM and PHA-LCM produced in the presence of hydrocortisone stimulated significantly fewer CFU-Eos in both unfractionated and accessory cell- depleted marrow target populations. These results indicate that the growth of CFU-Eo and inhibition of growth by hydrocortisone is a direct function of a monocyte-T cell interaction and probably is mediated through effects on the production/release of eosinophil colony stimulating factor (Eo-CSF).     

Substrate for endothelial prostacyclin production in the presence of platelets exposed to collagen is derived from the platelets rather than the endothelium

Interactions between vascular endothelial cells and blood platelets have been investigated using a model microcirculation consisting of microcarrier beads colonized with human umbilical vein endothelial cells (HUVECs) and perfused with washed platelet suspensions. To simulate the effects of endothelial desquamation and exposure of subendothelium, fibrillar collagen in suspension was coinjected with the platelets. In this model, neither the passage of platelets alone nor collagen alone stimulated prostacyclin (PGI2) production by the HUVECs. Platelets activated by coinjection with collagen released thromboxane A2 (TXA2), and this was associated with the simultaneous production of PGI2 by the HUVECs. By means of double-isotope experiments with [3H]arachidonic acid (AA) incorporated into platelets and [14C]-AA into HUVECs, it was shown that all the PGI2 generated was derived from platelet AA and/or endoperoxides. This interpretation was strengthened by the finding that PGI2 production was not prevented by treatment of HUVECs with indomethacin followed by perfusion with collagen-stimulated platelets. AA metabolites in double-isotope label experiments were further characterized by reverse-phase chromatography, and it was shown that both cyclooxygenase and lipoxygenase products of the HUVECs were derived from platelet membrane lipid. Thrombin regularly produced transient PGI2 release, but showed rapid tachyphylaxis. Platelet-derived compounds including ADP, ATP, and platelet-activating factor (PAF) did not produce PGI2 release by HUVECs in this system. Thus, the transfer of AA and metabolites from collagen- stimulated platelets is likely to be the mechanism for PGI2 production in the context of minor degrees of endothelial desquamation.     

吸氧对听感觉门控P50的影响

目的研究呼吸纯氧对健康人听感觉门控P50的影响。方法右利手、健康男性大学生志愿者28名,根据随机数字表分为对照组(n=12)和实验组(n=16)。佩戴面罩,对照组呼吸空气,实验组呼吸医用纯氧60 min。应用条件-测试刺激,记录吸氧前(pre0)、吸氧20 min(Oxy20)、吸氧50 min(Oxy50)、吸氧后30 min(post30)的脑电图,计算听觉P50潜伏期和P50感觉门控电位(S1与S2振幅之差)。结果 S1刺激在4个时间点各组P50潜伏期相对稳定(P0.7);吸氧50 min时,实验组比对照组P50潜伏期缩短(P0.05)。S2刺激在4个时间点各组P50潜伏期相对稳定(P0.30),两组间比较无显著性差异(P0.05)。对照组P50门控电位比较稳定(P=0.70),而实验组随吸氧时间逐渐延长,电位越来越高,停止吸氧后,电位迅速回落,Oxy20和post30(P=0.04)、Oxy50和post30(P=0.02)相比均有显著性差异。组间比较,4个时间点均无显著性差异(P0.05)。结论健康人吸60 min纯氧,可能缩短对刺激的反应时间,有增强听觉门控电位的趋势。     

In vivo anti-plasmodial activities and toxic impacts of lime extract of a combination of Picralima nitida,Alstonia boonei and Gongronema latifolium in mice infected with Chloroquine-sensitive Plasmodium berghei

Background

Lime extracts of powdered combination of seeds of Picralima nitida, stem bark of Alstonia boonei and leaves of Gongronema latifolium is a common remedy used in the treatment of malaria in South Western Nigeria.

Objective

To determine the antiplasmodial activities of the combined herbal extracts and its impact on the haematological, hepatological and renological parameters in mice.

Methods

The 4-day suppressive and curative tests were used to assess the antiplasmodial activities of the extract in mice infected with chloroquine-sensitive Plasmodium berghei at concentration of 200mg/kg, 400mg/kg and 800mg/kg body weight. The haematological parameters including red blood cells, white blood cells, packed cell volume and haemoglobin count were analysed with an auto analyser. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were determined, while urea, protein and creatinine were analysed by standard procedural methods.

Results

The 4-day suppressive test revealed that the test extract achieved percentage suppression of 39.0%, 41.6% and 54.68% for the 200mg/kg, 400mg/kg and 800mg/kg concentration respectively. Additionally, the curative test achieved a high percentage suppression of 80.97%, 83.84% and 86.16% at the 200mg/kg, 400mg/kg and 800mg/kg concentration respectively. The extracts did not induce significant change on haematological parameters (P>0.05), while significant elevation in the values of the ALT and AST (P<0.05) was observed and elevation of creatinine (P<0.05) at 800mg/kg.

Conclusions

The results support the traditional use of the herbal combination in the treatment of malaria, however the liver cells were impacted by the extracts in bioassay conducted with mice.     

Laminar flow reduces cases of surgical site infections in vascular patients

Introduction

Numerous strategies are employed routinely in an effort to lower rates of surgical site infections (SSIs). A laminar flow theatre environment is generally used during orthopaedic surgery to reduce rates of SSIs. Its role in vascular surgery, especially when arterial bypass grafts are used, is unknown.

Methods

A retrospective review of a prospectively maintained database was undertaken for all vascular procedures performed by a single consultant over a one-year period. Cases were performed, via random allocation, in either a laminar or non-laminar flow theatre environment. Demographic data, operative data and evidence of postoperative SSIs were noted. A separate subgroup analysis was undertaken for patients requiring an arterial bypass graft. Univariate and multivariate logistical regression was undertaken to identify significant factors associated with SSIs.

Results

Overall, 170 procedures were analysed. Presence of a groin incision, insertion of an arterial graft and a non-laminar flow theatre were shown to be predictive of SSIs in this cohort. In the subgroup receiving arterial grafts, only a non-laminar flow theatre environment was shown to be predictive of an SSI.

Conclusions

This study suggests that laminar flow may reduce incidences of SSI, especially in the subgroup of patients receiving arterial grafts.     

Sirolimus-associated diffuse alveolar hemorrhage

Sirolimus is an immunosuppressive medication used in transplant recipients. To our knowledge, we describe the third reported case of alveolar hemorrhage in association with sirolimus. Fever, dyspnea, hemoptysis, and lung infiltrates resolved rapidly with cessation of sirolimus therapy both initially and after reinstitution of the drug. Unlike previous reports, our patient had no evidence of lymphocytic alveolitis but rather marked macrophage hemosiderosis, suggesting that sirolimus pulmonary toxicity may manifest through 2 separate mechanisms. Our case highlights an uncommon but potentially lethal manifestation of sirolimus pulmonary toxicity.     

Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm of human chromosome 12 in malignant hematologic diseases

Translocations and deletions of the short arm of chromosome 12 [t(12p) and del(12p)] are common recurring abnormalities in a broad spectrum of hematologic malignant diseases. We studied 20 patients and one cell line whose cells contained 12p13 translocations and/or 12p deletions using fluorescence in situ hybridization (FISH) with phage, plasmid, and cosmid probes that we previously mapped and ordered on 12p12-13. FISH analysis showed that the 12p13 translocation breakpoints were clustered between two cosmids, D12S133 and D12S142, in 11 of 12 patients and in one cell line. FISH analysis of 11 patients with deletions demonstrated that the deletions were interstitial rather than terminal and that the distal part of 12p12, including the GDI-D4 gene and D12S54 marker, was deleted in all 11 patients. Moreover, FISH analysis showed that cells from 3 of these patients contained both a del(12p) and a 12p13 translocation and that the affected regions of these rearrangements appeared to overlap. We identified three yeast artificial chromosome (YAC) clones that span all the 12p13 translocation breakpoints mapped between D12S133 and D12S142. They have inserts of human DNA between 1.39 and 1.67 Mb. Because the region between D12S133 and D12S142 also represents the telomeric border of the smallest commonly deleted region of 12p, we also studied patients with a del(12p) using these YACs. The smallest YAC, 964c10, was deleted in 8 of 9 patients studied. In the other patient, the YAC labeled the del(12p) chromosome more weakly than the normal chromosome 12, suggesting that a part of the YAC was deleted. Thus, most 12p13 translocation breakpoints were clustered within the sequences contained in the 1.39 Mb YAC and this YAC appears to include the telomeric border of the smallest commonly deleted region. Whether the same gene is involved in both the translocations and deletions is presently unknown.     

Transcranial Doppler in the management of extracranial cerebrovascular disease: implications in diagnosis and monitoring

Transcranial Doppler (TCD) insonation permits quantitative noninvasive evaluation of intracerebral arterial velocity. With the use of a 2 MHz Doppler through a transtemporal approach, middle cerebral artery blood velocity (MCA-V, centimeters per second) and major collaterals were measured in 96 patients, including 15 normal control subjects, 66 patients with extracranial cerebrovascular disease (ECCVD), and 15 patients with other medical problems without ECCVD. MCA-V was higher in control subjects (62.7 +/- 15.1) than in patients with ECCVD (45.0 +/- 16.3, p less than 0.05). There was a significant inverse correlation between MCA-V and the degree of internal carotid artery stenosis present by duplex examination. Twenty-three patients monitored during carotid endarterectomy had a mean MCA-V under anesthesia of 37.0 +/- 16.9, which decreased to 22.4 +/- 14.8 during cross-clamping (p less than 0.01). MCA-V during cross-clamping correlated directly with stump pressure (R = 0.87) and was higher when major collaterals were identified before operation by TCD than when none were seen (31.7 +/- 9.5 vs. 8.8 +/- 8.5, p less than 0.01). Shunt function was verified in all 11 patients shunted. Electroencephalographic changes occurred in four patients with an MCA-V of 14.7 +/- 8.5 compared with an average of 24.1 +/- 15.5 for patients with normal electroencephalograms. MCA-V increased from 46.6 +/- 21.2 before operation to 61.0 +/- 22.4 after carotid endarterectomy (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)