Modulation of action potential duration by inhibition of the transient outward current in sheep cardiac Purkinje fibers

In sheep cardiac Purkinje fibers concentration-dependent inhibition of transient outward current (i_to) by 4-aminopyridine (4-AP, 3-1000 mol/l) was recorded with the two-microelectrode voltage-clamp technique, and correlated effects on action potential duration measured at — 70 mV (APD-70) were investigatigated.Half-maximal inhibition of i_to-amplitude occurred at 15 mol/l 4-AP. The drug exhibited no major effect on voltage-dependent control of inactivation but reduced the maximally available i_to-current. At different activation frequencies (0.05 Hz, 0.25 Hz, 1 Hz) an equal amount of i_to-current, measured as percentage of the respective control, was inhibited by 4-AP. The APD-70 was on the average increased by 4-AP (3–500 mol/l) in a concentration-dependont manner up to 151 % of control. The drug-induced prolongation, measured as percentage of the respective control, was independent of stimulation frequency (0.05 Hz, 0.25 Hz, 1 Hz). Prolongation of APD-70 was on the average more pronounced for short action potentials (APD-70<150 ms: 169 % of reference) than for longer ones (APD-70 150–300 ms: prolongation to 117 % of reference; 500 mol/l 4-AP; 0.25 Hz stimulation rate). Few long control signals (APD-70 >300 ms) were shortened by 4-AP. These results indicate that inhibition of i_to-current by appropriate drugs will result in a reduction of inhomogeneity of action potential duration.     

Lipoic (thioctic) acid increases brain energy availability and skeletal muscle performance as shown by in vivo31P-MRS in a patient with mitochondrial cytopathy

A woman affected by chronic progressive external ophthalmoplegia and muscle mitochondrial DNA deletion was studied by phosphorus magnetic resonance spectroscopy (³¹P-MRS) prior to and after 1 and 7 months of treatment with oral lipoic acid. Before treatment a decreased phosphocreatine (PCr) content was found in the occipital lobes, accompanied by normal inorganic phosphate (Pi) level and cytosolic pH. Based on these findings, we found a high cytosolic adenosine diphosphate concentration [ADP] and high relative rate of energy metabolism together with a low phosphorylation potential. Muscle MRS showed an abnormal work-energy cost transfer function and a low rate of PCr recovery during the post-exercise period. All of these findings indicated a deficit of mitochondrial function in both brain and muscle. Treatment with 600 mg lipoic acid daily for 1 month resulted in a 55% increase of brain [PCr], 72% increase of phosphorylation potential, and a decrease of calculated [ADP] and rate of energy metabolism. After 7 months of treatment MRS data and mitochondrial function had improved further. Treatment with lipoate also led to a 64% increase in the initial slope of the work-energy cost transfer function in the working calf muscle and worsened the rate of PCr resynthesis during recovery. The patient reported subjective improvement of general conditions and muscle performance after therapy. Our results indicate that treatment with lipoate caused a relevant increase in levels of energy available in brain and skeletal muscle during exercise.     

Extracellular site of action of phenylalkylamines on L-type calcium current in rat ventricular myocytes

The effects of the phenylalkylamines verapamil, gallopamil, and devapamil on L-type calcium currents (I_Ca) were studied in ventricular myocytes from rat hearts using the whole-cell patch-clamp technique. In particular, the question was addressed, whether the pharmacological binding sites for these drugs were located at the inner and/or at the outer surface of the cell membrane. Therefore, tertiary verapamil, gallopamil, and devapamil and their corresponding quaternary derivatives were applied either from the outside or the inside of the cell membrane. Extracellular application of verapamil, gallopamil and devapamil (each at 3 M) reduced Ica to 16.1 ±8.6%, 11 ± 8.9 %, and 9.3 ± 6 % of control, respectively. Intracellular application of the same substances, via the patch pipette filled with 30 M of either verapamil, gallopamil, or devapamil, failed to depress I_Ca. The quaternary derivatives of the phenylalkylamines (30 M) were ineffective both when applied extracellularly or intracellularly. It is suggested that phenylalkylamines block I_Ca in ventricular myocytes by acting on a binding site of the calcium channel molecule located at the outer surface of the cell membrane.     

Defining harm reduction

Harm reduction attempts to reduce the adverse consequences of drug use among persons who continue to use drugs. It developed in response to the excesses of a “zero tolerance approach”. Harm reduction emphasizes practical rather than idealized goals. It has been expanded from illicit drugs to legal drugs and is grounded in the evolving public health and advocacy movements. Harm reduction has proved to be effective and it has gained increasing official acceptance; for example, it is now the basis of Canada's Drug Strategy. However, the concept is still poorly defined, as virtually any drug policy or programme, even abstinence-oriented programmes, attempt to reduce drug-related harm. The principle feature of harm reduction is the acceptance of the fact that some drug users cannot be expected to cease their drug use at the present time. Harm reduction is neutral about the long term goals of intervention while according a high priority to short-term realizable goals. Harm reduction should be neutral about legalization. The essence of the concept is to ameliorate adverse consequences of drug use while, at least in the short term, drug use continues.     

The impacts of breast conserving treatment and mastectomy on the quality of life in early-stage breast cancer patients

The quality of life (QOL) in 55 early-stage breast cancer patients after surgery was prospectively assessed using a newly developed Japanese QOL questionnaire: The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD). The impacts of breast conserving treatment (BCT) (22 cases) and modified radical mastectomy (MRM) (33 cases) on the QOL in those subjects were compared. The overall QOL scores were evaluated during four periods (before surgery, 0–2, 3–12, and 13–24 months after surgery). The mean scores of the four categories of the QOL-ACD (activity, physical condition, psychological condition, and social relationships) were also compared. The results demonstrated that a significant improvement was observed in the overall QOL scores among the three periods after surgery (0–2, 3–12, and 13–24 months) only in the BCT group (P<0.05). There were no significant differences between the two groups in the overall QOL scores during any of the three periods after surgery, and the mean score of the ‘psychological condition’ during 0–2 months period in the BCT group was significantly lower than that in the MRM group (P< 0.05).     

The effect of the illumination time when treating port-wine stains

This paper reports the electron microscopy results obtained from two patients who were treated with 5 W of yellow (578 nm) light from a copper vapour laser with an illumination time of 3.6 ms and a 0.3 mm spot diameter. The endpoint of treatment was transient blanching. Following treatment, erythema was observed. There was minimal damage to the epidermis and non-vascular tissue such as the nerve fibres. There was severe damage to the endothelial cells of the ectatic vessels. Twenty-four hours after treatment, platelet activation and collagen were present, indicating that these vessels were no longer viable. Theoretical calculations are used to determine the flow of heat within and away from a 50m diameter vessel. From this, heating of the entire vessel is shown to occur with illumination times of 4 ms, with minimal heating of the non-vascular tissue. Shorter illuminations do not heat the entire vessel, while the use of longer illumination times will cause excessive damage to the surrounding non-vascular tissue. Illumination times close to 4 ms must be regarded as optimal.     

基于神经营养因子探讨经颅直流电刺激对缺血性脑卒中患者的影响

目的 探讨经颅直流电刺激（tDCS）对缺血性脑卒中患者的影响,以及与外周血神经营养因子的相关性。 方法 将40例缺血性脑卒中患者按随机数字表法分为对照组与治疗组,每组20例。2组患者均给予常规药物治疗及康复训练,治疗组在此基础上增加tDCS,强度2.0 mA,每次20 min,每日1次,共14次,对照组给予伪刺激。治疗前及治疗2周后（治疗后）,采用改良Barthel指数（MBI）、简易精神状态量表(MMSE) 、汉密尔顿抑郁量表（HAMD）、抑郁自评量表(SDS)对2组患者进行评估,用ELISA法测定外周血脑源性神经营养因子(BDNF）、神经生长因子(NGF）水平。 结果 治疗前,2组患者MBI、MMSE、HAMD、SDS评分及外周血BDNF、NGF水平比较,差异均无统计学意义（P>0.05）。与组内治疗前比较,2组患者治疗后上述指标均改善（P<0.05）。与对照组比较,治疗组治疗后MBI评分［（68.00±14.81）分］、MMSE评分［（24.85±3.12）分］较高（P<0.05）,HAMD评分［（19.70±2.11）分］较低（P<0.05）,外周血BDNF水平［（108.20±36.96）pg/ml］、NGF水平［（2.90±1.03）pg/ml］较高（P<0.05）。 结论 tDCS可以有效改善缺血性脑卒中患者的认知功能,减轻抑郁症状,提高生活自理能力,其作用机制可能与神经营养因子水平升高有关。     

城市生活垃圾无害化处理的研究

目的：研究城市生活垃圾无害化自理问题。方法：用微生物对１００吨城市生活垃圾进行自理第六天使垃圾的温度超过７０℃,且在此温度下保持７天,然后温度逐渐下降到１５天。结果：自理后在垃圾固有微生物中,细菌总数、真菌数、产气荚膜杆菌量及烘大肠菌的量分别下降了９５．５１％、９９．０９％、８７．６０％和９９．７０％。对金黄色葡萄球菌１大肠杆菌、枯草芽孢杆菌、白色念球菌、乙型肝炎病毒及蛔虫卵的杀灭率分别是９９．９     

蛛网膜下腔出血的院前诊治体会—附6例病例报告

蛛网膜下腔出血要强调诊断快速、准确,本病特点为突发,“头要裂开”样剧痛,重者伴有颅内压增高表现和神经根刺激征。脑膜刺激征是本病的主要体征。处置：应减少搬动,镇静、止痛,必要时降低血压或颅内压。尽早转入医院治疗。强调：行脑血管形象学检查是进一步找出病因、进行根冶的必须手段。