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Achieving health equity in the houseless population will take innovation, collaboration, and forward-thinking alternative models of health care. Using a foundation of disruptive innovation and an evidence-based care model, a group of nurses drew upon established partnerships to create Oregon's first nurse-owned and fully nurse-operated clinic serving the houseless population. The Harrington Health Clinic offers primary care, mental and behavioral health care, health and wellness, palliative care, and telemedicine services to men in a transitional housing program. Since its launch in January 2021, the clinic has served over 100 men spanning nearly 400 visits. The clinic attributes much of its success to registered nurses and nurse practitioners operating at the top of their scope, an academic affiliation that promotes learning-centered practices, and partnership with organizations similarly committed to just and equitable care. Through high quality, equitable primary care, this nurse managed and owned clinic has created a replicable solution that can impact houseless populations across the country.

The basic prerequisite for obtaining a quality casting according to the requirements and specifics of the customer is the production of the mould (in our case using low-pressure die-casting) without the occurrence of surface defects in the form of cracks, scabs, microshrinkages and local depressions. In this case, the mould segments for the tyre production are those which show tiny cracks or scabs on the functional surface of the castings that define the surface quality of the resulting product. It is necessary to analyse these defects in order to eliminate the causes of their formation in the casting process. For this reason, a new alloy of eutectic silumin AlSi9 alloyed with Mg, Mn and modified Sr was prepared in order to improve the fluidity and maintain the mechanical properties of the material up to 250 ℃ The subject of the study was the analysis of the surface defects of the mould, including the analysis of the chemical composition (energy-dispersive X-ray) and microstructure in the defect area. In order to investigate the subsurface layer of defects, metallographic specimens of cross-sections were prepared by means of mould, which were examined by light and electron microscopy. The detailed microstructural characterization of individual elements was performed on lamellas of the mould studied using transmission electron microscopy. An X-ray diffraction analysis was performed to investigate the residual stress at the defects area very closely. It has been found that a smaller number of defects on the functional surfaces can be obtained by changing the mould position during casting.

The public health crisis of chronic pain has only increased in recognition since the Institute of Medicine's (IOM) Relieving Pain in America (2011) called for a cultural transformation in the way pain is viewed, treated, and put forward specific recommendations for action. The National Pain Strategy (NPS) provides a roadmap for putting these recommendations into practice. We implemented a program that placed nurses and behavioral specialists at the head of an interdisciplinary team utilizing best practices. In this program, nurses enacted the NPS recommendations to advance care for patients with persistent pain on long-term opioid treatment. This program promoted professional growth in nurses along with fostering success for patients. Compared with patients receiving usual care, patients in the program achieved greater reductions in pain severity, pain-related disability, and pain-related functional interference and reported greater satisfaction with pain-related care and primary care services. This article will detail the NPS-aligned practice approaches these nurses and their teams used, describe the training for the nurses, and speak to opportunities to enhance the nurse's capacity for this role in hopes of providing a model for the future implementation of an NPS-based approach by nurses.

175 Background: Failure to address coordination of cancer survivorship care can result in physical disability, emotional distress, and increased health care costs. The Institute of Medicine (IOM) recommended Survivorship Care Plans (SCPs) to improve care coordination among cancer survivors. Despite evidence supporting SCPs there remains limited implementation of SCPs. The use of implementation science, frameworks, and strategies that address contextual and process factors, could improve use of SCPs in oncology clinics (Selove et al., 2016). Methods: This innovation used the Quality Implementation Framework (QIF) (Meyers, Durlak, & Wandersman, 2012) to guide implementation. The QIF outlines steps and strategies for four phases of implementation; initial considerations regarding the host setting, creating a structure for implementation, ongoing structure once implementation begins, and improving future application. Results: During the project period (January 29, 2018 through April 23, 2018), 17 SCP visits were conducted; all 17 patients completed study surveys. In response to, “My health care providers work together as a team to ensure that my needs are met,” 65% reported strongly agree, 29% reported agree, 5% reported disagree, and 0% reported strongly disagree. When asked “My health care providers have informed me of what my follow-up care should be” 65% reported strongly agree and 35% reported agree. Of the 17 PCP surveys mailed, four were returned. In response to “For this patient the SCP helps me coordinate follow-up care,” three PCPs responded “agree.” When asked “For this patient, the SCP helps me provide better care,” three responded “strongly agree.” One PCP reported neutral feelings toward both statements. All PCPs reported SCP helped them better understand cancer treatment given and side effects. Conclusions: Successful SCP implementation, replicating outcomes of trials supporting SCPs, is attributable to the use of implementation science. Results from this project demonstrated SCPs achieved care coordination and patient satisfaction. SCPs enhanced PCPs’ understanding of cancer treatment and side effects which could increase likelihood PCPs discuss survivorship issues, as demonstrated in literature.

Cultural heritage records and expresses the long processes of historic development, it forms the essence of diverse national, indigenous and local identities and it is an integral part of modern life. The dynamic interaction between tourism and cultural heritage continues to be among the foremost vehicles for cultural exchange providing a personal experience from the past, as well as of the contemporary life and society. It is appreciated as a positive force for natural and cultural conservation. Tourism can underline the economic characteristics of the heritage and points out the need for conservation by generating funding, educating the community and influencing policy. The achievement of a beneficial interaction between the conflicting expectations of visitors and the host or local communities presents many challenges and opportunities. The natural and cultural heritage, diversities and living cultures are major tourism attractions.

A rapid, sensitive, and specific high performance liquid chromatography procedure for the determination of stobadine in human plasma using electrospray tandem mass spectrometry (MS/MS) detection was developed. Multiple reaction monitoring (MRM) transitions at 202.9 > 160 (stobadine) and 166 > 103 (phenylalanine, I.S.) were selected to quantify stobadine by the internal standard method. Linear correlations (r∶ 0.9971–0.9981) of the calibration curves over the concentration range 20–500 ng mL−1 with lowest limit of quantitation (LOQ) of 10 ng mL−1 were established. An overall recovery of 94.3% of stobadine from plasma was attained using the SPE technique. The developed tandem mass spectrometry method was proven to be accurate and reproducible as a percent relative error (%RE) ranging from −3.5% to 3.0% and %RSD in the range of 1.4–8.3% were determined. Samples of stobadine in plasma were stable at −20°C for at least 5 weeks. The slope of the calibration curves was 0.00146 ± 0.000087, indicating goo...

Sympathetic storm phenomena are well known therapeutic problems in patients with severe brain injury. We have treated four patients with intrathecal baclofen (ITB) who suffered from severe hypertension, tachycardia and other sympathetic storm phenomena after different primary events. In all patients conventional therapy with sedatives and antiadrenergic medication had been taken to the upper limits before initiating ITB. Autonomic dysfunction immediately improved in three of four patients. In all patients ITB, via lumbar or ventricular route, proved safe and without complications. The anatomical and pharmacological basis of the GABA-B agonist action on such sympathetic storm phenomena are not yet fully understood. However, the positive results observed in three out of four patients are promising and require further investigation. ITB is a new therapeutic approach to control otherwise unresponsive sympathetic storm phenomena in severe brain injury.

The present work deals with the kinetics of hydrolysis of the acyl derivatives of stobadine, an originally synthesized potential antiarrhythmic and antihypoxic drug, which was found to have also an excellent scavenging effect on reactive oxygen species. The acyl derivatives of stobadine, which possess high lipophilicity, represent model blood-brain barrier penetrating agents. It is assumed that the acyl derivatives of stobadine may act as prodrugs which are hydrolysed in different biological tissues to release the active drug. The decomposition of three acyl derivatives of stobadine was studied in acidic, basic and neutral buffer solutions at constant ionic strength (0.1 mol/L) at 25 degrees and 70 degrees C using UV spectrophotometric method. The pseudo first-order rate constants and the pH-rate profile for the degradation of acetyl-, valeroyl- and nicotinoyl-derivatives of stobadine were determined. Confirmation that stobadine was the first degradation product was provided by thin-layer chromatography.

The effect of oral controlled-release (CR), oral transmucosal (buccal; TMD) and transdermal (TDD) drug delivery systems on plasma concentrations of melatonin (MT) and its principal metabolite in human subjects using a crossover, single dose design was evaluated. Twelve adult male volunteers participated in the study and received all three dosage forms on three separate occasions. All patch dosage forms were removed after 10 h of wear. Plasma concentrations of the parent drug and its metabolite, 6-sulfatoxymelatonin (MT6s) were measured by radioimmunoassay. Between-subject plasma concentrations of MT were very variable following both oral CR and TDD. Use of the oral CR system gave plasma MT profiles in some subjects that were initially similar to physiological levels, but then differed substantially from physiological in the rate of MT offset; in a few subjects, plasma MT levels remained consistently much below normal nocturnal physiological levels. Also, the ratio of metabolite to parent drug by the oral CR route was many times greater than physiological. TDD resulted in a significant delay in systemic drug levels and a gradual decline in drug delivery after patch removal, possibly due to deposition of melatonin in the skin. TDD failed to simulate the physiological plasma profile of MT (rapid achievement of steady-state blood levels and rapid decline after removal of the patch; i.e., so-called "square-wave" profile). TMD provided prompt systemic drug levels with less variability than oral CR or TDD delivery. Also, plasma MT levels fell promptly and rapidly after removal of the patch. No indication of mucosal deposition was observed. TMD was able to mimic the physiological plasma profiles of both MT and its principal metabolite.

Freehand three-dimensional ultrasound imaging (3D-US) is increasingly used in image-guided surgery. During image acquisition, a set of B-scans is acquired that is distributed in a non-parallel manner over the area of interest. Reconstructing these images into a regular array allows 3D visualization. However, the reconstruction process may introduce artefacts and may therefore reduce image quality. The aim of the study is to compare different algorithms with respect to image quality and diagnostic value for image guidance in neurosurgery.3D-US data sets were acquired during surgery of various intracerebral lesions using an integrated ultrasound-navigation device. They were stored for post-hoc evaluation. Five different reconstruction algorithms, a standard multiplanar reconstruction with interpolation (MPR), a pixel nearest neighbour method (PNN), a voxel nearest neighbour method (VNN) and two voxel based distance-weighted algorithms (VNN2 and DW) were tested with respect to image quality and artefact formation. The capability of the algorithm to fill gaps within the sample volume was investigated and a clinical evaluation with respect to the diagnostic value of the reconstructed images was performed.MPR was significantly worse than the other algorithms in filling gaps. In an image subtraction test, VNN2 and DW reliably reconstructed images even if large amounts of data were missing. However, the quality of the reconstruction improved, if data acquisition was performed in a structured manner. When evaluating the diagnostic value of reconstructed axial, sagittal and coronal views, VNN2 and DW were judged to be significantly better than MPR and VNN.VNN2 and DW could be identified as robust algorithms that generate reconstructed US images with a high diagnostic value. These algorithms improve the utility and reliability of 3D-US imaging during intraoperative navigation.

According to their strategic location, intraaxial lesions of the foramen magnum may cause severe symptoms. The primary goal of surgery is to decompress the lower brain stem and upper cervical cord without additionally impairing the neurological function, or, as in vascular lesions, to eliminate the risk of recurrent bleeding. Secondary goals of surgery are to preserve the atlanto-occipital stability, to minimize traumatization of various muscles in the craniovertebral region, to preserve the sigmoid sinus and jugular bulb and to avoid air embolism or excessive venous bleeding during surgery. The most common intraaxial lesions encountered at the level of the foramen magnum are cavernous malformations, gliomas, ependymomas, and hemangioblastomas. They are located either in the medulla oblongata (up to the pontomedullary junction) or within the cervical cord at the level of C1. These lesions may be located either totally intraaxially, with or without contact to the surface of the brain stem or spinal cord, or, in other instances, they may be partially exophytic (1). Moreover, from the surgical point of view, particularly in terms of accessibility, lesions located in the dorsal and lateral region of the brain stem and spinal cord significantly differ from those located anteriorly or anterolaterally. Hemangioblastomas may sometimes involve the proximal intradural vertebral artery and its branches.

Caspases are enzymes which play a key role in programmed cell death--apoptosis. Dysregulation of this process results in a series of disorders in which apoptosis is involved in pathogenesis. Diseases could be divided into two groups--diseases with pathological inhibition of apoptosis (cancer, some autoimmune disorders) and diseases with pathological induction of apoptosis (neurodegenerative disorders, AIDS). The paper lists the most significant activators and inhibitors of caspases as they control apoptosis and hence they are widely studied nowadays. The effects of stobadine, theophylline and adenine derivatives on the activity of caspase 1 was investigated with the use of spectrophotometry. The compounds under study showed an inhibitory effect on the enzyme tested; in one case the inhibitory effect exceeded 80%.

CRLR (calcitonin receptor-like receptor) and CD 117, the gene product of c-kit have been shown to be expressed in cells of glial tumors, especially in those with higher malignancy. Here we report the distribution of these peptides in various cellular compartments within those tumors.Both receptor proteins have been investigated in 95 glial tumor biopsies of different grades.Both proteins were visualized by immunohistochemistry with antibodies either commercially available or raised for this purpose.Both receptor peptides can be identified in or around tumor blood vessels. CRLR occurs in some endothelial cells, especially in the microvascular proliferations of glioblastoma multiforme, whereas CD 117 preferentially occurs in cells of the thickened vascular wall within cells of pericyte or fibroblast morphology. Both antigens are found in addition in few neoplastic cells of overt astrocyte morphology.The occurrence of identical antigens in glial tumor blood vessels and in neighboring tumor cells underlines the common origin of "mesenchymal" and "neuroepithelial" components of such (malignant) glial neoplasms.

The paper studies the adsorption of nine stobadin acylderivatives on active charcoal. Freundlich model of adsorption was employed to evaluate the course of adsorption in dependence on the concentration of substances. At the same time, the dependence of adsorption on lipophilicity and structural parameters of substances was evaluated. The dependence of the amount of the adsorbed substance on time served for the calculation of the rate constant of the 1st order of adsorption process. These values correlate with the parameters characterizing the size of the molecule.

Nitrogen oxide is a relatively stable, highly reactive radical, which develops in the organism by oxidation of the guanidine nitrogen of the amino acid L-arginine by the action of NO-synthase with the development of L-citrulline. It participates in a number of physiological and pathological processes. The difference between the physiological and pathological concentration of nitrogen oxide is very small, and for that reason we search for suitable methods of its determination and the substances influencing the level of nitrogen and thus decreasing its overproduction. Testing of scavenger activity against NO was performed by the method following Griess (spectrophotometric determination of nitrites as the oxidation products of NO), which was compared with the HPLC (high-performance liquid chromatography) method developed by the present authors. The antiradical effect of the compounds being assayed (acetylsalicylic acid, piracetam, paracetamol, serotonin, stobadin dihydrochloride, 5-hydroxy-L-tryptophan, N-acetyl-L-cysteine, L-glutathion, and N-acetyl-DL-penicillamine) against NO was compared with the so-called total antioxidant activity--TRAP (total radical-trapping antioxidant parameter), which corresponds to the capability to trap peroxyl radicals. On the basis of the obtained data, piracetam and acetylsalicylic acid show no antioxidant activity, paracetamol shows probably moderate scavenging action against nitrogen oxide, and other compounds tested (primarily 5-hydroxy-L-tryptophan, serotonin, stobadin) are strong antioxidants against both NO and peroxyl radical.

The central role in apoptosis, which is a precondition of the normal development of the organism, as played by caspases, a family of highly specific cysteine proteases. Caspases released from procaspases in a certain surplus induce apoptosis, with simultaneous cleavage of some cellular proteins essential for cellular growth. Caspase activity (initiative or effector one) is the resultant and final physiological as well as pathological stimulus, in which impairment of the cell membranes, function of mitochondria and other organelles, and also DNA takes place. The interest is focused on caspases inhibitors, which could influence, at some stages, some diseases which are difficult to control or which are still untreatable (tumours, neurodegenerative diseases, viral liver diseases, inflammatory diseases). The caspases family includes 14 enzymes, the best examined ones being caspase-1 and caspase-3. The therapeutically usable protease inhibitors include, for the time being, serine proteases and some metaloproteases, whereas the inhibitors of cysteine proteases have not been introduced into practice yet. Synthesis of caspases inhibitors, in particularly those of non-peptidic character, the so-called small molecules, is one of the strategic aims of contemporary research of the treatment of the above-mentioned diseases.

The spatial arrangement of single stereoisomers may influence pharmacodynamic, pharmacokinetic and toxicological properties of a drug. Trapencaine (I. N. N.), (+/-)-trans-2-(pyrrolidin-1-yl)cyclohexylester of 3-(n)-pentyloxycarbanilic acid, was developed as an antiulcer drug with gastroprotective, local anaesthetic and spasmolytic effects. Limited information is available about the potential pharmacodynamic differences of the enantiomers of trapencaine. Therefore, the enantiomers of (+/-)-trans- or cis-2-(pyrrolidin-1-yl)cyclohexylester of 3-(n)-pentyloxy carbanilic acid were synthesised and tested on models of acute gastric damage induced by indomethacin and/or ethanol. A difference was found between their antiulcer effect, with the (+)-trans-enantiomer being the most effective and the (-)-cis-enantiomer the least effective in the models used.

The luminol-enhanced chemiluminiscence method was used to investigate the antioxidative activity of N-(alkoxyphenyl)-2-(2-oxo-1-aza-1-cykloalkyl) acetamides studied as potential cognitive enhancers and stobadine acylderivatives which form prodrugs with increased lipophilicity. The effect on the production of reactive oxygen metabolites by activated leukocytes was studied in vitro. Furthermore, the total radical-trapping antioxidant parameter was evaluated as the peroxyl radical-trapping capacity and the scavenging effect on the superoxide anion radical (generated by the enzymatic system hypoxanthine/xanthine oxidase) and on the hydroxyl radical (produced in Fenton reaction) were studied. The antioxidative properties of the tested substances were compared with that of stobadine dihydrochloride. Only stobadine and its butyrylderivative have been demonstrated to possess free radical scavenging activity in all systems. Cinnamoylstobadine inhibited only the leukocyte chemiluminiscence activity. The potential cognitive enhancers did not show any antioxidant activity.

The formation of phases during the intercalation of amino alcohols (2-aminoethanol, 3-aminopropanol, 4-aminobutanol, 5-aminopentanol and 6-aminohexanol) into alfa-Zr(HPO4)2 . H2O was studied. The existence of three phases with general formula alfa-Zr(HPO4)2 .xNH2(CH2)nOH . zH2O (x=0.5, 1, 2; n=2-6; z=0.2-1.2) depends on the molar ratio of the starting compounds in the reaction mixture. The compounds alfa-Zr(HPO4)2 .2NH2(CH2)nOH . 1.2H2O (n=5 and 6) lose water and one molecule of amino alcohol upon heating to about 200 °C, as observed by thermal X-ray diffraction measurements.

The goal of this study was to evaluate factors for the prognosis of patients with metastatic spinal tumors. 139 patients with vertebral metastases were studied. The modified Tokuhashi Score (a preoperative score composed of six parameters) and single factors were analysed with statistical methods. The modified Tokuhashi Score showed a significant correlation (p = 0,0019) with survival time of patients. Additionally, only the Karnofsky Index as single parameter showed statistically significant correlation(p = 0.0016). Regarding the logistic regression, primary tumor, age, sex and Karnofsky Index were identified as prognostic factors for survival time. This trial could demonstrate that the Tokuhashi Score is a successful predicting tool for the assessment of prognosis of patients with vertebral metastases.

Chirality is a stereochemical phenomenon in the area of drugs, influencing pharmacodynamic, pharmacokinetic, and biotransformation processes. On an example of known drugs, the present paper describes the relations of chirality to drug efficacy, safety, toxicity, manifestations of drug interactions, and some other factors with a feedback action on the chirality-drug relationship.

The free radical scavenging effect of the hydrochloride of (+/-)-trans-2-(1-pyrrolidinyl-)cyclohexylester of 3-(n)-pentyloxy carbanilic acid, pentacaine (trapencaine I.N.N), and its derivatives and other substances, lidocaine, stobadine, mannitol, and ascorbic acid was tested in the presence of diphenyl-p-picrylhydrazyl (decrease in absorbance). In this method, more pronounced antiradical activity was observed with trapencaine, more effective than stobadine, ascorbate, and mannitol. Trapencaine derivatives and lidocaine were less effective in comparison with trapencaine. After introducing a methylene group into the hydrophilic moiety of the trapencaine molecule (stereoisomers P-18, P-20), there was a loss of antiradical activity, but the cis-isomer is more effective than the transisomer. The results demonstrate the existence of relationships between the chemical structure, antiradical and gastric-cytoprotective activity.

Viral liver diseases, particularly hepatitides of type B (HBV) and C (HCV) show an increasing trend, the number of infected people in the world being several hundred million people. With the exception of other forms (HAV, HDV, HEV, and HGV), where infectivity is also high, possible transmission and infection in HBV and HCV are often independent of the affected person (blood transfusion, stomatological operations, surgery, etc.). Treatment of hepatitides not proceeding into a chronic stage is without any problems at the moment. In the case of HBV, besides chemical drugs which are being developed, vaccination is available. Hepatitis C remains to be a problem of world importance. Its growth in recent years runs parallel to an increase in drug addicts and HIV infection. The difficulties in the development of vaccines are related to rapid mutation of the virus and continuous formation of other serotypes. Progress in many biological disciplines is a certain warranty that the so-called NS3 proteases inhibitors and medicaments of other types, including vaccines, will be introduced into practice for HCV treatment.

The effect of cis- and trans-isomers of 2-(1-pyrrolidinyl) and of 2-(1-pyrrolidinylmethyl)cyclohexyl alkoxycarbanilates was tested in acute gastric injury induced by phenylbutazone and/or 96% ethanol administration in rats. In both models a more pronounced antiulcer and gastroprotective activity was observed after pretreatment with the trans-isomer of 2-(1-pyrrolidinyl)cyclohexyl ester of 3(n)-pentyloxycarbanilic acid. Its cis-isomer, by comparison, was less effective against ethanol-induced gastric injury and failed to prevent the gastric damage induced by phenylbutazone. After introducing a methylene group into the hydrophilic part of the molecule, there was a loss of stereospecific difference, with both stereoisomers exerting a similar gastroprotective activity.

Monitoring of partial pressure of brain tissue oxygenation P(ti)O2, brain tissue ph (brph), partial pressure of brain tissue CO2 [P(ti)CO2] and intracranial pressure (ICP) by invasive methods, calculation of cerebral perfusion pressure (CPP), and hemodynamic monitoring of middle arterial blood pressure (MABP) are the main strategies in multimodal neuromonitoring. Using this multimodal approach the therapy of raised intracranial pressure with diffuse brain edema has undergone fundamental changes during recent years [2, 3, 7, 9, 19, 24, 25, 40, 42].

During the 10th meeting of the WSSFN in Maebashi in 1989, we discussed 'endoscopic stereotaxy', and presented our preliminary results. This technique was first designed to optimize stereotactic biopsy, but it proved to be effective for other neurosurgical indications as well, including endoscopic stereotactic evacuation of intraparenchymal and intraventricular space-occupying cysts, endoscopic stereotactic cystoventriculostomy, third ventriculostomy, evacuation of brain abscess and intracerebral hematoma, and retrieval of adherent or free-floating ventricular catheters. Our results with endoscopic stereotaxy in different indications are encouraging, compared to conventional microsurgical techniques and pure stereotactic techniques. From 1989 to 1997 we have performed more than 400 stereotactic endoscopic procedures. The mortality rate is below 1%, the operative morbidity is below 3%.

Der Beitrag befast sich mit der Anatomie der Lymphdrusen und -ge-fase sowie einer Methode zum sicheren Auffinden von Lymphknotenmetastasen mit sterilem Methylenblau. Das Methylenblau wird 3–5 cm oberhalb des Magens in einer Menge von 3–6 ml injiziert. Nach wenigen Minuten werden die Drusen gut sichtbar und eine Lymphadenektomie durchfuhrbar. Desweiteren wird ein statistischer Vergleich unterschiedlicher Magenoperationstechniken gefuhrt. Ferner werden die Bekampfung des Operationsschockes mit vegetativer Dekonnektion nach Laborit und Hugenard dargestellt. Mit diesem Verfahren ist die Sterblichkeit auf 0,87% zu senken. Auserdem wird der Zusammenhang zwischen Erstdiagnose und Behandlungsmoglichkeit nach Aufnahme in das Krankenhaus dargelegt und statistisch ausgewertet.

The optically active isomers of carbisocaine [1-methyl-2-diethylaminoethyl ester of 2-(n)-heptyloxycarbonilic acid] were prepared. The blocking activity of equimolar concentrations of the carbisocaine and its corresponding enantiomers was tested on isolated rat sciatic nerves. There were no significant differences between the anesthetic action of racemic form and enantiomers, however, lower activity for the (--)-enantiomer was observed. The results may indicate negligible stereoselectivity of action of highly lipophilic local anesthetic carbisocaine in the excitable membrane.

The genotoxic effect of stobadine (1) was studied in vitro using the micronucleus test. Hamster and human fibroblastoid cells were used. In hamster cells, the highest concentration of 1 (1.10(-3) mol/l) caused a significant elevatin in the number of micronuclei, while in human cells no positive response was found for either of the concentrations used. Stobadine had no genotoxic effect on human fibroblastoid cells.

The preceding study of the effect of the branching of the connecting chain by the metoxymethyl-, ethoxymethyl- and propoxymethyl group on the alpha carbon on local anaesthetic activity was a stimulus for the preparation of 16 drugs of the group of 1-ethoxyethoxymethyl-2-(1-pyrrolidinyl-), 2-piperidino- and 2-(1-perhydroazepinyl) ethyl esters of o-, m- and p-alkoxyphenylcarbamic acids. The discontinuation of the substituent on the alpha carbon of the connecting chain by another oxygen atom (introduction of an ethoxyethoxymethyl group) has a positive effect on surface and infiltration anaesthesia. Of the prepared agents, 2-piperidino- and 2-(1-perhydroazepinyl-) derivatives with a hexyl or heptyloxy group in the o-position of the benzene ring were most effective; they exceeded the standards cocaine and procaine more than one hundred times. p-Derivatives were least effective; in some cases their indices of effectiveness did not achieve the effectiveness of the standards in both surface and infiltration anaesthesia under study. Acute toxicity of all drugs lies within the range of the toxicities of the standards.

The activity of peptidases (trypsin from bovine pancreas and trypsin-like enzymes from the liver rat homogenate) was influenced by five preparation of Kampo medicine, TJ-9 (Sho-Saiko-To), TJ-15 (Oren-Gedoku-To), TJ-23 (Toki-Shakuyaku-San), TJ-96 (Saiboku-To), and TJ-114 (Sairei-To) and studied in relation to their effect on the uptake of free oxygen radicals demonstrated earlier. On the basis of increased activity of trypsin and trypsin-like enzymes and the previously found capability of uptaking free oxygen radicals, the mechanism of action of the Kampo preparations may be assumed to be connected not only with a direct support of enzymes of digestion and increased activity of peptidases, capable of eliminating oxidatively damaged proteins, but with an antioxidative effect as well, which prevents increased cumulation of oxidatively damaged macromolecules and the action of superoxide radicals developed earlier by the well-known and trypsin-stimulated conversion of xanthinedehydrogenase to xanthinoxidase.