Low dose short duration pulsed electromagnetic field effects on cultured human chondrocytes: An experimental study

Background:

Pulsed electromagnetic field (PEMF) is used to treat bone and joint disorders for over 30 years. Recent studies demonstrate a significant effect of PEMF on bone and cartilage proliferation, differentiation, synthesis of extracellular matrix (ECM) and production of growth factors. The aim of this study is to assess if PEMF of low frequency, ultralow field strength and short time exposure have beneficial effects on in-vitro cultured human chondrocytes.

Materials and Methods:

Primary human chondrocytes cultures were established using articular cartilage obtained from knee joint during joint replacement surgery. Post characterization, the cells were exposed to PEMF at frequencies ranging from 0.1 to 10 Hz and field intensities ranging from 0.65 to 1.95 μT for 60 min/day for 3 consecutive days to analyze the viability, ECM component synthesis, proliferation and morphology related changes post exposure. Association between exposure doses and cellular effects were analyzed with paired''t’ test.

Results:

In-vitro PEMF exposure of 0.1 Hz frequency, 1.95 μT and duration of 60 min/day for 3 consecutive days produced the most favorable response on chondrocytes viability (P < 0.001), ECM component production (P < 0.001) and multiplication. Exposure of identical chondrocyte cultures to PEMFs of 0.65 μT field intensity at 1 Hz frequency resulted in less significant response. Exposure to 1.3 μT PEMFs at 10 Hz frequency does not show any significant effects in different analytical parameters.

Conclusions:

Short duration PEMF exposure may represent a new therapy for patients with Osteoarthritis (OA).     

Predictors of incident atrial fibrillation and influence of medications: a retrospective case�Ccontrol study

Background

Atrial fibrillation (AF) is a common condition, associated with raisedmortality and risk of majormorbidity, and is predicted to increase due to an aging population.

Aim

To update earlier research of AF predictors using UK data.

Design and setting

Case–control analysis of adults aged 18 years and older with a diagnosis of AF in practices registered with the General Practice Research Database (GPRD) in the UK.

Method

Using the GPRD, a case.control analysis was performed using logistic regression to compare 55 412 incident AF cases to 216 400 controls, for medical history and prior use of drugs. The association between time since start of diagnosis or drug use and AF risk was summarised using Spline regression.

Results

The following were confirmed as risk factors for AF: heart failure (risk ratio [RR] 2.91 [95% CI = 2.59 to 3.27]); ischaemic heart disease (IHD) (RR 2.00 [95% CI = 1.78 to 2.24]); hypertension (RR 2.60 [95% CI = 2.32 to 2.92]); hyperthyroidism (RR 1.56 [95% CI = 1.39 to 1.75]); being a heavy drinker (RR 1.43 [95% CI = 1.27 to 1.60]); cerebrovascular accident (RR 1.48 [95% CI = 1.32 to 1.66]); and obesity (bodymass index ≥30 kg/m² RR 1.29 [95% CI = 1.15 to 1.45]). Current use of oral glucocorticoids (RR 1.62 [95% CI = 1.44 to 1.82]) and of beta-2 agonists (RR 1.30 [95% CI = 1.16 to 1.46]) were identified as significant risk factors, and statins (RR 0.82 [95% CI = 0.73 to 0.92]) as a significant protective factor. No effect was found for current use of bisphosphonates (RR 0.95 [95% CI = 0.85 to 1.07]), renin.angiotensin.aldosterone system (RAAS) agents (RR 1.04 [95% CI = 0.93 to 1.17]), or xanthine derivatives (RR 1.09 [95% CI = 0.97 to 1.22]). Spline regression analysis found the effect of heart failure, IHD, use of oral glucocorticoids, and use of statins on the likelihood of developing AF was sustained over a number of years.

Conclusion

These findings update the risk factors that are associated with AF, and confirmthe protective properties of statins and the risks of beta-2 agonists in developing AF, but not the supposed protective qualities of glucocorticoids and RAAS agents.     

Ex-vivo evaluation of gene therapy vectors in human pancreatic （cancer） tissue slices

AIM： To culture human pancreatic tissue obtained from small resection specimens as a pre-clinical model for examining virus-host interactions.
METHODS： Human pancreatic tissue samples （malignant and normal） were obtained from surgical specimens and processed immediately to tissue slices. Tissue slices were cultured ex vivo for 1-6 d in an incubator using 95% 02. Slices were subsequently analyzed for viability and morphology. In addition the slices were incubated with different viral vectors expressing the reporter genes GFP or DsRed. Expression of these reporter genes was measured at 72 h after infection.
RESULTS： With the Krumdieck tissue slicer, uniform slices could be generated from pancreatic tissue but only upon embedding the tissue in 3% low melting agarose. Immunohistological examination showed the presence of all pancreatic cell types. Pancreatic normal and cancer tissue slices could be cultured for up to 6 d, while retaining viability and a moderate to good morphology. Reporter gene expression indicated that the slices could be infected and transduced efficiently by adenoviral vectors and by adeno associated viral vectors, whereas transduction with lentiviral vectors was limited. For the adenoviral vector, the transduction seemed limited to the peripheral layers of the explants.
CONCLUSION： The presented system allows reproducible processing of minimal amounts of pancreatic tissue into slices uniform in size, suitable for pre-clinical evaluation of gene therapy vectors.     

The effect on the safety of intravenous immunoglobulin of testing plasma for antibody to hepatitis C

BACKGROUND: The safety of intravenous immunoglobulin (IGIV), manufactured from units testing negative for antibody to hepatitis C virus (anti-HCV), was investigated. STUDY DESIGN AND METHODS: A study involving five chimpanzees was performed to determine whether the safety of IGIV would be compromised if units of plasma that reacted for anti-HCV were withheld from pools from which IGIV is manufactured. In the first phase of the experiment, two chimpanzees were infused with 25 mL per kg of unprocessed, pooled plasma from 2887 donors who did not react for anti-HCV in single-antigen (c100-3) enzyme-linked immunosorbent assays. In the second phase, each of three chimpanzees was infused with 1000 mg per kg of IGIV manufactured from the same plasma units. The immunoglobulin was made by seven United States- licensed manufacturers, each using its own approved method. Each chimpanzee received an equal dose of each manufacturer's IGIV. RESULTS: The two chimpanzees that received anti-c100-3-nonreactive, unprocessed pooled plasma became infected with HCV. The three chimpanzees infused with IGIV did not show any evidence of infection with HCV 15 months after inoculation. Two of these animals were challenged with human non- A,non-B hepatitis-infectious plasma, and both subsequently showed evidence of HCV infection. CONCLUSION: These studies demonstrate that, as determined by infectivity for chimpanzees, 1) the withholding of plasma units that react for anti-c100-3 from pools from which plasma products are manufactured does not render the source material noninfectious, and 2) the safety of IGIV manufactured from such plasma pools is not compromised by withholding the units that react for anti- c100-3.     

白细胞三烯拮抗剂ONO-1078对豚鼠迷走神经电刺激引起气道痉挛及微血管渗漏作用

阿托品预先处理的豚鼠,电刺激迷走神经(10Hz,5ms,2V或10V,90s)引起气道阻力增高,气管、主支气管和肺内气道的依文思蓝渗出量增加,并随刺激强度加大而增强。白细胞三烯拮抗剂ONO-1078(0.03,0.1mg·kg^-1,iv)对气道阻力的增高无明显影响;但显著抑制微血管渗漏,在刺激强度低(2V)时更明显。结果提示白细胞三烯类参与神经原性炎症时的气道微血管渗漏反应。     

查耳酮类化合物对过敏性慢反应物质拮抗作用的构效关系

查耳酮类化合物对过敏性慢反应物质拮抗作用的构效关系何克勤，程桂芳，奚凤德，郭宗儒，朱秀媛（中国医学科学院，中国协和医科大学药物研究所，北京１０００５０）过敏性慢反应物质（ＳＲＳＡ），主要含白三烯Ｃ４（ＬＴＣ４）、白三烯Ｄ４（ＬＴＤ４）和白三烯Ｅ４（Ｌ...     

New diphosphonate compounds for skeletal imaging: comparison with methylene diphosphonate

Three-hour biodistribution of Tc-99m complexes of six diphosphonates was compared in rabbits with tibial lesions to determine which was best for detection of focal bone lesions. Sr-85 was used as a standard. N,N-dimethylaminomethylene diphosphonate (DMAD) was the only agent with a higher lesion/normal bone ratio than methylene diphosphonate (MDP), attributable to lower concentration in normal bone. Hydroxymethane diphosphonate (HDP) and 2,3-dicarboxypropane-1, 1-diphosphonate (DPD) demonstrated higher concentration than MDP in normal bone without improving lesion contrast. They also exhibited much higher uptake in the liver and kidney, as well as muscle and red marrow in the case of DPD. None was superior to MDP as an all-purpose skeletal agent, though others may be better for specific applications.