Electrochemical treatment of mouse Ehrlich tumor with direct electric current.

Electrochemical treatment of cancer utilizes direct electric current (DEC) to produce direct alterations and chemical changes in tumors. However, the DEC treatment is not established and mechanisms are not well understood. In vivo studies were conducted to evaluate the effectiveness of DEC on animal tumor models. Ehrlich tumors were implanted subcutaneously in sixty male BALB/c mice. When the tumor volumes reached 850 mm(3), four platinum electrodes were inserted into the tumors. DEC of 4 mA was applied for 21 min to the treated group; the total charge was 5 C. The healthy and sick control groups were subjected to the same conditions but without DEC. Hematological and chemical parameters as well as histopathological and peritumoral findings were studied. After the electrochemical therapy it was observed that both tumor volume decrease and necrosis percentage increase were significant in the treated group. Moreover, 24 h after treatment an acute inflammatory response, as well as sodium ion decrease, and potassium ion and spleen weight increase were observed in this group. It was concluded that both electrochemical reactions (fundamentally those in which reactive oxygen species are involved), and immune system stimulation induced by cytotoxic action of the DEC could constitute the most important antitumor mechanisms.     

Electrochemical treatment of lung cancer

A pilot study of electrochemical treatment (ECT) as a therapy for 386 patients with nonsmall cell lung cancer was undertaken. There were 103 stage II cases, 89 stage IIIa cases, 122 stage IIIb cases, and 72 stage IV cases. Two ECT methods were used: For peripherally located lung cancer, platinum electrodes were inserted transcutaneously into the tumor under x-ray or CT guidance. For central type lung cancer or for those inoperable during thoracotomy, electrodes were inserted intraoperatively directly into the cancer. Voltage was 6–8 V, current was 40–100 mA, and electric charge was 100 coulombs per cm of tumor diameter. The number of electrodes was determined from the size of cancer mass, because the diameter of effective area around each electrode is approximately 3 cm. The short-term (6 months after ECT) results of the 386 lung cancer cases were: complete response (CR), 25.6% (99/386); partial response (PR), 46.4% (179/386); no change (NC), 15.3% (59/386); and progressive disease (PD), 12.7% (49/386). The total effective rate (CR + PR) was 72% (278/386). The 1, 3, and 5 year overall survival rates were 86.3% (333/386), 58.8% (227/386), and 29.5% (114/386), respectively. The main complication was traumatic pneumothorax, with an incidence rate of 14.8% (57/386). These clinical results show that ECT is simple, safe, effective, and minimally traumatic. ECT provides an alternative method for treating lung cancers that are conventionally inoperable, that are not responsive to chemotherapy or radiotherapy, or that cannot be resected after thoracotomy. Long-term survival rates suggest that ECT warrants further investigation. Bioelectromagnetics 18:8–13, 1997. © 1997 Wiley-Liss, Inc.     

Electric field and current density distribution in an anatomical head model during transcranial direct current stimulation for tinnitus treatment

Tinnitus is considered an auditory phantom percept. Recently, transcranial direct current stimulation (tDCS) has been proposed as a new approach for tinnitus treatment including, as potential targets of interest, either the temporal and temporoparietal cortex or prefrontal areas. This study investigates and compares the spatial distribution of the magnitude of the electric field and the current density in the brain tissues during tDCS of different brain targets. A numerical method was applied on a realistic human head model to calculate these field distributions in different brain structures, such as the cortex, white matter, cerebellum, hippocampus, medulla oblongata, pons, midbrain, thalamus, and hypothalamus. Moreover, the same distributions were evaluated along the auditory pathways. Results of this study show that tDCS of the left temporoparietal cortex resulted in a widespread diffuse distribution of the magnitude of the electric fields (and also of the current density) on an area of the cortex larger than the target brain region. On the contrary, tDCS of the dorsolateral prefrontal cortex resulted in a stimulation mainly concentrated on the target itself. Differences in the magnitude distribution were also found on the structures along the auditory pathways. A sensitivity analysis was also performed, varying the electrode position and the human head models. Accurate estimation of the field distribution during tDCS in different regions of the head could be valuable to better determine and predict efficacy of tDCS for tinnitus suppression.     

Variations of dose and electrode spacing for rat breast cancer electrochemical treatment

Electrochemical treatment (EChT) with direct current delivered through implanted electrodes has been used for local control of solid tumors in humans. This study tested the hypothesis that rat breast cancer responses to EChT are dependent on electrode spacing and dose, and explored suitable parameters for treating breast cancers with EChT. Rat breast cancers were initiated by injecting 1 x 10(6) MTF-7 cells to the right mammary gland fat pad of Fisher 344 female rats. The rats were randomly divided into designated experimental groups when the tumors grew to approximately 2 x 2 x 2 cm. One hundred and thirty rats were used for a survival study and 129 for a pathology study. A 4-channel EChT machine was used to administer coulometric doses. The survival study indicated that local tumor control rate is less than 40% in the 40 coulomb (C) and 60 C groups and more than 70% in the 80 and 100 C groups. Sixty six rats died of primary tumors, including all 10 rats in the control group. Once a rat's primary tumor was controlled, no recurrence was found. The main reason for terminating the primary tumor-free rats (51) was lymph node metastasis. Thirteen tumor-free rats survived for more than 6 months. The pathology study showed a significant dose effect on EChT induced tumor necrosis. At 10, 20, 40, and 80 C, the fraction showing necrosis were 39.7, 52.3, 62, and 77.7%, respectively (P 相似文献   

3D Stationary electric current density in a spherical tumor treated with low direct current: an analytical solution

Electrotherapy with direct current delivered through implanted electrodes is used for local control of solid tumors in both preclinical and clinical studies. The aim of this research is to develop a solution method for obtaining a three-dimensional analytical expression for potential and electric current density as functions of direct electric current intensity, differences in conductivities between the tumor and the surrounding healthy tissue, and length, number and polarity of electrodes. The influence of these parameters on electric current density in both media is analyzed. The results show that the electric current density in the tumor is higher than that in the surrounding healthy tissue for any value of these parameters. The conclusion is that the solution method presented in this study is of practical interest because it provides, in a few minutes, a convenient way to visualize in 3D the electric current densities generated by a radial electrode array by means of the adequate selection of direct current intensity, length, number, and polarity of electrodes, and the difference in conductivity between the solid tumor and its surrounding healthy tissue.     

经颅直流电刺激联合益生菌对脑卒中后认知功能障碍患者的作用

探讨经颅直流电刺激（tDCS）联合益生菌对脑卒中后认知功能障碍（PSCI）患者认知功能和肠道菌群的影响。

按随机数字表法将2020年6月至2021年6月我院收治的150例PSCI患者分为对照组和观察组,各75例。对照组患者给予tDCS治疗,观察组患者给予tDCS联合益生菌治疗。采用蒙特利尔认知功能评估量表（MoCA）和简易智力状态检查量表（MMSE）评估患者治疗前后的认知功能。采用荧光定量PCR法检测患者治疗前后肠道菌群数量变化。比较两组患者认知功能、肠道菌群、临床疗效以及不良反应发生情况。

治疗后,观察组患者肠道双歧杆菌和乳杆菌数量较治疗前显著升高,且双歧杆菌和乳杆菌数量显著高于对照组;而大肠埃希菌和肠球菌数量较治疗前显著降低,且大肠埃希菌和肠球菌数量显著低于对照组（均P＜0.05）。治疗后,两组患者MoCA和MMSE评分均升高,且观察组高于对照组（均P＜0.05）。观察组患者临床总有效率显著高于对照组（90.67% vs 78.67%,χ² = 12.482,P＜0.001）。对照组和观察组患者的不良反应发生情况比较差异无统计学意义（χ² = 0.150,P = 0.699）。

tDCS联合益生菌治疗能够有效改善PSCI患者的认知功能和肠道菌群状态,且不良反应少,安全系数高,值得临床推广。

     

Inhibition of the metabolism of nitrifying bacteria by direct electric current

The nitrifying bacteria in activated sludge and biofilms consisting of the bacteria immobilized on polypropylene packing were subjected to an electric current via two electrodes. In activated sludge, the metabolism of nitrifying bacteria was inhibited when the applied current was over 2.5 A m^–2, whilst in biofilms, inhibition began when the current reached 5 A m^–2. At 15 A m^–2, the nitrification rate of NH₄ ⁺-N in a biofilm with a bacterial density of 1.62 g total solids, dry wt m^–2 decreased to about 80% of its initial value. Ninety-two % of the initial biomass on the packing was retained after 36 h.     

Exposure of human leukemic cells to direct electric current

Treatment with direct electric current (DC) influences the growth of several cancer cells. In this work, we evaluated the effects of DC treatment on the human leukemic cell line HL60. Human cells were separately treated in the presence of the cathode or the anode or without contact with the electrodes. In all systems, DC-treated cells presented an impaired ability to proliferate. Growth inhibition was dependent on the generation of soluble products of electrolysis. Cathodic treatment of HL60 cells predominantly induced lysis, whereas treatment without contact with electrodes did not induce alterations in cell viability. In contrast, cell stimulation by the anode resulted in irreversible membrane damage, as demonstrated by trypan blue and 7-aminoactinomycin staining. Analysis of these cells by transmission electron microscopy indicated that necrosis is a major mechanism inducing cell death. In addition, apoptotic-like cells were observed under light microscopy after anodic treatment. Accordingly, DNA from anodic-treated cells presented a typical pattern of apoptosis. Apoptotic cell death was only generated after the treatment of HL60 cells in conditions in which the generation of chloride-derived compounds was favored. These results indicate that the nature of the products from cathodic or anodic reactions differently influences the mechanisms of cell death induced by DC-derived toxic compounds.     

Effects of transcranial direct current stimulation (tDCS) on balance improvement: a systematic review and meta-analysis

Background: Transcranial direct current stimulation (tDCS) has emerged as a promising therapeutic tool to improve balance and optimize rehabilitation strategies. However, current literature shows the methodological heterogeneity of tDCS protocols and results, hindering any clear conclusions about the effects of tDCS on postural control.

Objective: Evaluate the effectiveness of tDCS on postural control, and identify the most beneficial target brain areas and the effect on different populations.

Methods: Two independent reviewers selected randomized tDCS clinical-trials studies from PubMed, Scopus, Web of Science, and reference lists of retrieved articles published between 1998 and 2017. Most frequently reported centre of pressure (COP) variables were selected for meta-analysis. Other postural control outcomes were discussed in the review.

Results: Thirty studies were included in the systematic review, and 11 were submitted to a meta-analysis. A reduction of COP displacement area has been significantly achieved by tDCS, evidencing an improvement in balance control. Individuals with cerebral palsy (CP) and healthy young adults are mostly affected by stimulation. The analysis of the impact of tDCS over different brain areas revealed a significant effect after primary motor cortex (M1) stimulation, however, with no clear results after cerebellar stimulation due to divergent results among studies.

Conclusions: tDCS appears to improve balance control, more evident in healthy and CP subjects. Effects are observed when primary MI is stimulated. Cerebellar stimulation should be better investigated.     

Effects of direct electric current on Herpetomonas samuelpessoai: An ultrastructural study

The literature shows that the effects of direct electric currents on biological material are numerous, including bactericidal, fungicidal, parasiticidal, and anti‐tumoral, among others. Non‐pathogenic trypanosomatids, such as Herpetomonas samuelpessoai, have emerged as important models for the study of basic biological processes performed by a eukaryotic cell. The present study reports a dose‐dependent anti‐protozoan effect of direct electric treatment with both cathodic and anodic current flows on H. samuelpessoai cells. The damaging effects can be attributable to the electrolysis products generated during electric stimulation. The pH of the cell suspension was progressively augmented from 7.4 to 10.5 after the cathodic treatment. In contrast, the anodic treatment caused a pH decrease varying from 7.4 to 6.5. Transmission electron microscopy analyses revealed profound alterations in vital cellular structures (e.g., mitochondrion, kinetoplast, flagellum, flagellar pocket, nucleus, and plasma membrane) after exposure to both cathodic and anodic current flows. Specifically, cathodic current flow treatment induced the appearance of autophagic‐like structures on parasite cells, while those submitted to an anodic current flow presented marked disorganization of plasma membrane and necrotic appearance. However, parasites treated in the intermediary chamber (without contact with the electrodes) did not present significant changes in viability or morphology, and no pH variation was detected in this system. The use of H. samuelpessoai as a biological model and the direct electric current experimental approach used in our study provide important information for understanding the mechanisms involved in the cytotoxic effects of this physical agent. Bioelectromagnetics 33:334–345, 2012. © 2011 Wiley Periodicals, Inc.     

Enhanced biotransformations and product recovery in a membrane bioreactor through application of a direct electric current

The simultaneous enhancement of biotransformation coupled to product recovery, purification and concentration is presented. The nitrilase of Rhodococcus rhodochrous LL100-21 catalyses the single-step hydrolytic biotransformation of benzonitrile to benzoic acid and ammonia. When a direct electric current is applied across a bioreactor containing the bacterium and benzonitrile, the charged product (benzoic acid) can be removed in situ across an anion exchange membrane and recovered in a separate compartment. Over the course of a 24-hour biotransformation, benzonitrile was converted to benzoic acid which was completely removed from the bioreactor chamber and concentrated 3-fold in a separate chamber. The rate of production of benzoic acid increased by 42% when the current was applied (0.044 mmol/min/g dry cell weight in the presence of current as compared to 0.03 mmol/min/g dry cell weight in its absence). The enhanced reaction rate was achieved irrespective of product separation and therefore appears to be a direct effect upon the bacterial cells. This process has potential for enhanced productivity from biotransformations through a simultaneous increase in metabolic activity and in situ product recovery.     

Dielectric properties of mouse MCA1 fibrosarcoma at different stages of development

The in vitro bulk electrical properties of MCA1 fibrosarcoma induced in C57B1/6 male mice were measured at frequencies of 10 kHz to 100 MHz, with some tissues measured to 2 GHz. The properties of normal surrounding tissue also were measured. A comparison of the dielectric properties between three different stages of tumor development as well as that between various locations within the tumor is reported. Statistical analysis of the experimental results revealed statistically significant differences in the dielectric constant and conductivity of the tumor tissues at various stages of development as measured at frequencies below 10 MHz. Conductivity values at different stages also differ at a frequency of 100 MHz. At other frequencies these differences were found to be statistically insignificant.     

Combined effects of direct current stimulation and immobilized BMP‐2 for enhancement of osteogenesis

Direct current (DC) stimulation has been used to promote bone repair and osteogenesis, but problems associated with the implanted metal electrodes may limit its application and compromise the therapeutic results. The replacement of the metal electrodes with a biodegradable conductive polymer film can potentially overcome these problems. In our work, polypyrrole/chitosan films comprising polypyrrole nanoparticles dispersed in a chitosan matrix were prepared. The polypyrrole/chitosan film meets the requirements for DC delivery, as indicated by its electrical conductivity, biodegradability, and mechanical properties. The film supports osteoblast growth to the same degree as dentine discs (a bone‐like mineralized substrate), confirming that it is non‐cytotoxic. Our results showed that optimal DC stimulation was achieved with 200 µA for 4 h per day, and under this condition, osteoblast metabolic activity on Day 7 increased by 1.8‐fold over that without DC stimulation. To further improve osteogenesis on the polypyrrole/chitosan film, bone morphogenetic protein‐2 (BMP‐2) was covalently immobilized on the film surface. Osteoblasts cultured on the BMP‐2‐functionalized polypyrrole/chitosan film and subjected to the optimal DC stimulation exhibited a significant increase in cellular metabolic activity (2.3‐fold on Day 7), ALP activity (1.7‐fold on Day 21) and mineralization (twofold on Day 21) over those cultured on polypyrrole/chitosan film without DC stimulation. Osteogenic gene expression results showed that BMP‐2 and DC stimulation by itself enhanced osteoblast differentiation, and a combination of these two factors resulted in synergistic effects on osteoblast differentiation and maturation. Biotechnol. Bioeng. 2013; 110: 1466–1475. © 2012 Wiley Periodicals, Inc.     

Neoadjuvant gene delivery of feline granulocyte-macrophage colony-stimulating factor using magnetofection for the treatment of feline fibrosarcomas: a phase I trial

Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have high recurrence rates. Immunostimulatory gene therapy is a promising approach in veterinary oncology. This phase I dose-escalation study was performed to determine toxicity and feasibility of gene therapy with feline granulocyte-macrophage colony-stimulating factor (feGM-CSF) in cats with fibrosarcomas. Twenty cats were treated with plasmid coding for feGM-CSF attached to magnetic nanoparticles in doses of 50, 250, 750 and 1250 microg. Two preoperative intratumoral injections followed by magnetofection were given. Four control cats received only surgical treatment. Adverse events were recorded and correlated according to the veterinary co-operative oncology group toxicity scale. An enzyme-linked immunosorbent assay was performed to detect plasma feGM-CSF concentrations. No significant treatment related toxicity was observed. Preliminary recurrence results were encouraging as, on day 360, ten of 20 treated cats were recurrence-free. In conclusion, 1250 microg of feGM-CSF plasmid DNA applied by magnetofection is safe and feasible for phase II testing.     

Monitoring of artificial enzyme membrane systems by electric currents: I. Analytical treatment with direct current and buffered conductivity

Continuous electric fields (E) modify the transport flows and the intramembrane concentration profiles of protons or of ionic substrates or cofactors (inhibitors). These ‘mediators’ induce variations in enzyme activity, quantifiable by a generalized Damköhler group II Ψ distinguishing electrotransport reactions from diffusion reactions. For three typical reaction schemas, using only one mediator, the steady-state equations have been established. Depending on boundary conditions, the direction of electric current (for asymmetrical systems) and the value of Ψ. activations, inhibitions or activations followed by inactivations have been found. With buffered conductivity (supporting electrolyte), the limiting concentration profiles (E → ∞) are uniformly equal to the boundary values; i.e., diffusion constraints are suppressed and the regime is controlled by the reaction. The calculations give the relative activity variations for partially suppressed transport controls.     

Immunoregulatory cytokine release in rat spleen cell cultures after treatment with bleomycin and its analogues in vivo

Summary We have studied the immunological effects that accompany a change in the chemical structure of a group of antineoplastic antibiotics by comparing the immunoregulatory cytokine release during mitogen-stimulated spleen cell culture after in vivo drug treatment. Whereas bleomycin and peplomycin increased cytokine levels in culture supernatants when compared with supernatants from untreated control rat spleen cell cultures, liblomycin generally reduced cytokine levels under the same culture conditions. We then compared these results with the antitumor effects of equivalent doses of the three drugs against a highly antigenic rat fibrosarcoma, KMT-17, both in vivo and in vitro. The results suggest that the immunoaugmenting effects of these antitumor antibiotics are essential for an optimal antitumor effect in vivo, and that these effects can be drastically altered by modification of the chemical structure of the drugs employed.     

经颅电刺激对睡眠剥夺后双侧后扣带回皮质功能连接紊乱干预作用的初步研究

目的:探讨经颅电刺激对睡眠剥夺后双侧后扣带回皮质功能连接紊乱的干预作用。方法:研究采用自身前后对照的试验设计。16名受试者均接受2次24 h睡眠剥夺,2次睡眠剥夺间隔3周,受试者分别于第1次正常睡眠后、24 h睡眠剥夺后、经颅电刺激(真或假刺激)干预后(真、假刺激电流大小均为1 mA,电流作用时间分别为20 min、2 s,干预实验均持续20 min)及第2次经颅电刺激(假或真刺激)干预后采集静息态磁共振成像数据。以睡眠剥夺前收集静息态功能磁共振数据作为基线,选取双侧后扣带回皮质作为种子点进行全脑功能连接分析,观察睡眠剥夺前后及经颅电刺激真、假刺激后大脑的功能连接变化。结果:与正常睡眠后相比,24 h睡眠剥夺后双侧后扣带回皮质与双侧丘脑间的功能连接上升(P<0.01),与右侧楔前叶、海马旁回以及双侧岛叶间的功能下降(P<0.01)。与假刺激相比,给予真刺激后左侧后扣带回皮质与右侧楔前叶功能连接上升(P<0.01);与双侧丘脑、岛叶及右侧大脑皮质功能连接下降(P<0.01)。右侧后扣带回皮质与全脑的功能连接在双侧丘脑、右侧岛叶及大脑皮层间也存在下降(P<0....     

压力负荷性心衰小鼠左心室跨壁L-型钙电流的变化

为了观察正常和心衰时心内膜下和心外膜下心肌细胞L-型钙电流(ICa-L)的差别,我们采用主动脉弓狭窄的方法建立小鼠压力超负荷性心衰模型,采用全细胞膜片钳技术记录了正常、主动脉狭窄(band)及假手术对照(sham)组动物左心室游离壁内、外膜下心肌细胞的动作电位时程(action potential duration,APD)和ICa-L。结果显示:(1)与sham组同龄的正常小鼠左心室心内膜下细胞动作电位复极达90％的时程(APD90)为(38．2±6．44)ms,较心外膜下细胞的APD90(15.67±5.31)ms明显延长,二者的比值约为2．5:1;内膜下细胞和外膜下细胞ICa-L密度没有差异,峰电流密度分别为(-2.7±0.49)pA/pF和(-2.54±0．53)pA/pF;(2)Band组内、外膜下细胞的动作电位复极达50％的时程(APD50)、APD90均较sham组显著延长,尤以内膜下细胞延长突出,分别较sham组延长了400％和360％,内、外膜下细胞APD90的比值约为4.2:1;(3)与sham组相比, band组内膜下细胞ICa-L密度显著减小,在+10 mV～+40 mV的4个电压下分别降低了20．2％、21．4％、21.6％和25.7％(P< 0．01),但其激活电位、峰电位和翻转电位没有改变;band组外膜下细胞的ICa-L密度与同期sham组相比无明显变化;band组钙通道激活、失活及复活的动力学特征与sham组相比没有改变。以上结果提示,生理状态下小鼠左心室内、外膜下细胞ICa-L密度不存在明显差别,提示ICa-L与APD跨壁异质性的产生无关;心衰时左心室内、外膜下细胞APD明显延长,以内膜下细胞延长尤为突出,内膜下细胞ICa-L密度明显减少,而外膜下细胞ICa-L密度无明显改变,这种ICa-L的非同步变化在心衰时可能起到对抗APD延长、减少复极离散度的有益作用。