Anti-migraine effect of wine-processed Radix scutellariae: Pharmacodynamic verification in nitroglycerin-induced rats and correlation study between compounds dissolution and the fractal dimension.

ETHNOPHARMACOLOGICAL RELEVANCE: Wine-processed Radix scutellariae (RS) is the processed product of RS, which is the dried root of Scutellaria baicalensis Georgi. It is recorded in Chinese traditional formula that wine-processed RS has the effect of anti-migraine, while the effect has not been confirmed and the possible mechanism remains unclear. AIM OF THE STUDY: To verify the anti-migraine effect of wine-processed RS in nitroglycerin (NTG)-induced rats and explore the correlation between compounds dissolution and the pore structure based on fractal theory. MATERIALS AND METHODS: In the validation of pharmacodynamics, the effects of wine-processed RS on migraines were firstly evaluated by observing the number of head-scratching of rats, then investigated by determining the levels of nitric oxide (NO), calcitonin gene-related peptide (CGRP) and the expression of c-Fos in the brain of NTG-induced rat models using ELISA and immunohistochemical assessments. In the correlation study, the stir-frying time of RS was set to 5 min, 10 min and 15 min. The scanning electron microscope (SEM) and mercury intrusion method were used to explore the pore structure and main parameters of the pore structure including pore size distribution, pore volume, porosity, surface area and fractal dimension. The compounds dissolution of total flavonoids and five major components containing baicalein, baicalin, scutellarin, wogonin and wogonoside was determined by UV-Vis spectrophotometry and HPLC separately. RESULTS: The animal experiments had shown that wine-processed RS could significantly reduce the head-scratching times of NTG-induced rat models (p < 0.01) and markedly decrease the levels of NO (p < 0.01), CGRP (p < 0.05) and the expression of c-Fos (p < 0.01) compared with model group. The data indicated that wine-processing would affect the dissolution of compounds by changing the pore structure of RS. The order of positive correlation between pore structure parameters and compounds' dissolution was total surface area > fractal dimension (r > 0) and the order of negative correlation was average pore size > total porosity > total volume (r < 0). Compared with the other sample groups (p < 0.05), the wine-processed RS stir-fried for 10 min had a pore structure which was more favorable for compounds dissolution. CONCLUSIONS: Wine-processing could strengthen the anti-migraine effect of RS by changing the pore structure of RS, which is linked to the dissolution of compounds. The RS stir-fried for 10 min may be more effective in treating migraine.

Traditional Chinese medicine practices used in COVID-19 (Sars-cov 2/Coronavirus-19) treatment in clinic and their effects on the cardiovascular system.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of plants used in the formulations of traditional Chinese medicine (TCM), which were also used in clinical trials to treat patients with the novel coronavirus COVID-19, and to assess their effects on the cardiovascular system. METHODS: A literature review of PubMed, ResearchGate, ScienceDirect, the Cochrane Library, and TCM monographs was conducted and the effects of the plants on the cardiovascular system and the mechanisms of action in COVID-19 treatment were evaluated. RESULTS: The mechanism of action, cardiovascular effects, and possible toxicity of 10 plants frequently found in TCM formulations that were used in the clinical treatment of COVID-19 were examined. CONCLUSION: TCM formulations that had been originally developed for earlier viral diseases have been used in COVID-19 treatment. Despite the effectiveness seen in laboratory and animal studies with the most commonly used plants in these formulations, the clinical studies are currently insufficient according to standard operating procedures. More clinical studies are needed to understand the safe clinical use of traditional plants.

Metabolite profiling, arginase inhibition and vasorelaxant activity of Cornus mas, Sorbus aucuparia and Viburnum opulus fruit extracts.

The present study investigated the effects of Cornus mas, Sorbus aucuparia and Viburnum opulus fruit extracts on arginase activity and arterial vasodilation. V. opulus fruit extract exerted the highest vasorelaxant activity in phenylephrine precontracted rat aortic rings (EC50 = 6.31 ±â€¯1.61 µg/mL) and a significant inhibition of arginase (IC50 = 71.02 ±â€¯3.06 µg/mL). By contrast, S. aucuparia and C. mas fruit extracts showed no important anti-arginase activity and a significantly weaker activity in the rat aortic rings relaxation assay (EC50 = 100.9 ±â€¯11.63 and 78.52 ±â€¯8.59 µg/mL, respectively). For all extracts, the main mechanism of vasodilation was proven to be endothelium-dependent. HPLC-ESI-Q-TOF-MS/MS studies revealed a very complex metabolite profiling in all three extracts with chlorogenic acid accounting for 30.89, 0.72 and 2.03 mg/g in V. opulus, C. mas and S. aucuparia fruit extracts, respectively. All extracts were declared non-toxic in the brine shrimp acute toxicity test. Our study highlights potential benefits of V. opulus fruit extract in diseases associated with endothelial dysfunction and impaired vasodilation.

Analysis of the main constituents of Changshu tablet and its spasmolysis effect against contraction induced by acetylcholine in the rat-isolated intestinal smooth muscle.

The Changshu tablet (CST), one kind of Chinese patent medicine with astringent to the intestine and relieving diarrhea, was made by the root of Rose odorata Sweet var. gigantean (Coll.et Hemsl.) Rehd.et Wils. Although CST has a long history of clinical application, but the research of its chemical composition is less. So the objective of this study was to investigate the main constituents and preliminarily research its effect of the contraction of isolated intestine in vitro. The contents of total polyphenols (126.23mg/g) and total triterpenoids (132.75mg/g) in CST were determined by ultraviolet spectrophotometry. Procyanidin B3, epigallo catechin, catechin, epicatechin, (-)-fisetinidol-(4α, 8)-(-)-catechin, (4α, 8)-(-)-fisetinidol-(-)-epicatechins and (+)-guibourtinidol-(4ß, 8)-epicatechin were identified and determined by high performance liquid chromatography and their contents were distributed from 0.04mg/g to 1.46 mg/g. CST showed significant inhibitory effect against acetylcholine-induced contraction on the rat-isolated intestinal smooth muscle with a dose-dependent manner from 0.06 to 0.6mg/mL. The maxim inhibition rates of CST on duodenum, jejunum, ileum and colon were 65.70±3.47%, 79.74±1.27%, 58.90±1.87% and 45.75±2.21% respectively. These results indicated that CST has a spasmolytic role in gastrointestinal motility which was probably mediated through inhibition of muscarinic receptors. All these findings promote the improvement of the quality control standard of CST and provide pharmacological foundation for clinical application of CST in gastrointestinal tract.

Lipid emulsion alleviates the vasodilation and mean blood pressure decrease induced by a toxic dose of verapamil in isolated rat aortae and an in vivo rat model.

This study aimed to examine the effects of lipid emulsion on the vasodilation and cardiovascular depression induced by toxic doses of calcium channel blockers. The effects of lipid emulsion on the vasodilation induced by bepridil, verapamil, nifedipine, and diltiazem were investigated in isolated endothelium-denuded rat aortae. The effect of lipid emulsion on the comparable hemodynamic depression induced by the continuous infusion of a toxic dose of either verapamil or diltiazem was examined in an in vivo rat model. The results showed the following decreasing order for the magnitude of lipid emulsion-mediated inhibition of vasodilation: bepridil, verapamil, nifedipine, and diltiazem. Lipid emulsion (0.5-2%) reversed the vasodilation induced by a toxic dose of verapamil, whereas only a higher concentration (2%) reversed the vasodilation induced by a toxic dose of diltiazem. Pretreatment with lipid emulsion alleviated the systolic and mean blood pressure decreases induced by a toxic dose of verapamil, whereas it had no effect on the decrease induced by diltiazem. Taken together, these results suggest that lipid emulsion alleviates the severe vasodilation and systolic blood pressure decrease induced by a toxic dose of verapamil, and this alleviation appears to be associated with the relatively high lipid solubility of verapamil.

Chemical composition, vasorelaxant, antioxidant and antiplatelet effects of essential oil of Artemisia campestris L. from Oriental Morocco.

BACKGROUND: Artemisia campestris L. (Asteraceae) is a medicinal herb traditionally used to treat hypertension and many other diseases. Hence, this study is aimed to analyze the essential oil of A. campestris L (AcEO) and to investigate the antiplatelet, antioxidant effects and the mechanisms of its vasorelaxant effect. METHODS: The chemical composition of AcEO was elucidated using GC/MS analysis. Then, the antioxidant effect was tested on DPPH radical scavenging and on the prevention of ß-carotene bleaching. The antiplatelet effect was performed on the presence of the platelet agonists: thrombin and ADP. The mechanism of action of the vasorelaxant effect was studied by using the cellular blockers specified to explore the involvement of NO/GC pathway and in the presence of calcium channels blockers and potassium channels blockers. RESULTS: AcEO is predominated by the volatiles: spathulenol, ß-eudesmol and p-cymene. The maximal antioxidant effect was obtained with the dose 2 mg/ml of AcEO. The dose 1 mg/ml of AcEO showed a maximum antiplatelet effect of, respectively 49.73% ±9.54 and 48.20% ±8.49 on thrombin and ADP. The vasorelaxation seems not to be mediated via NOS/GC pathway neither via the potassium channels. However, pretreatment with calcium channels blockers attenuated this effect, suggesting that the vasorelaxation is mediated via inhibition of L-type Ca2+ channels and the activation of SERCA pumps of reticulum plasma. CONCLUSION: This study confirms the antioxidant, antiplatelet and vasorelaxant effects of A.campestris L essential oil. However, the antihypertensive use of this oil should be further confirmed by the chemical fractionation and subsequent bio-guided assays.

Forskolin: genotoxicity assessment in Allium cepa.

Forskolin, a diterpene, 7ß-acetoxy-8,13-epoxy-1α,6ß,9α-trihydroxy-labd-14-en-11-one (C22H34O7) isolated from Coleus forskohlii, exerts multiple physiological effects by stimulating the enzyme adenylate cyclase and increasing cyclic adenosine monophosphate (cAMP) concentrations. Forskolin is used in the treatment of hypertension, congestive heart failure, eczema, and other diseases. A cytogenetic assay was performed in Allium cepa to assess possible genotoxic effects of forskolin. Forskolin was tested at concentrations 5-100 µM for exposure periods of 24 or 48 h. Treated samples showed significant reductions in mitotic index (p < 0.05) and increases in the frequency of chromosome aberrations (p < 0.01) at both exposure times. The treated meristems showed chromosome aberrations including sticky metaphases, sticky anaphases, laggard, anaphase bridges, micronuclei, polyploidy, fragments, breaks, and C-mitosis. Forskolin may cause genotoxic effects and further toxicological evaluations should be conducted to ensure its safety.

Pharmacological evidence that spinal α(2C)- and, to a lesser extent, α(2A)-adrenoceptors inhibit capsaicin-induced vasodilatation in the canine external carotid circulation.

During a migraine attack capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), producing cranial vasodilatation and central nociception; hence, trigeminal inhibition may prevent this vasodilatation and abort migraine headache. This study investigated the role of spinal α2-adrenoceptors and their subtypes (i.e. α(2A), α(2B) and/or α(2C)-adrenoceptors) in the inhibition of the canine external carotid vasodilator responses to capsaicin. Anaesthetized vagosympathectomized dogs were prepared to measure arterial blood pressure, heart rate and external carotid conductance. The thyroid artery was cannulated for one-min intracarotid infusions of capsaicin, α-CGRP and acetylcholine. A cannula was inserted intrathecally for spinal (C1-C3) administration of 2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazolo-[5,4-d]-azepin-dihydrochloride (B-HT 933; a selective α2-adrenoceptor agonist) and/or the α2-adrenoceptor antagonists rauwolscine (α(2A/2B/2C)), 2-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole maleate (BRL44408; α(2A)), imiloxan (α(2B)) or acridin-9-yl-[4-(4-methylpiperazin-1-yl)-phenyl]amine (JP-1302; α(2C)). Infusions of capsaicin, α-CGRP and acetylcholine dose-dependently increased the external carotid conductance. Intrathecal B-HT 933 (1000 and 3100 µg) inhibited the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine. This inhibition, abolished by rauwolscine (310 µg), was: (i) unaffected by 3,100 µg imiloxan; (ii) partially blocked by 310 µg of BRL44408 or 100 µg of JP-1302; and (iii) abolished by 1,000 µg of BRL44408 or 310 µg of JP-1302. Thus, intrathecal B-HT 933 inhibited the external carotid vasodilator responses to capsaicin. This response, mediated by spinal α2-adrenoceptors unrelated to the α(2B)-adrenoceptor subtype, resembles the pharmacological profile of α(2C)-adrenoceptors and, to a lesser extent, α(2A)-adrenoceptors.

Severe hypoglycemia associated with an illegal sexual enhancement product adulterated with glibenclamide: MR imaging findings.

PURPOSE: To describe the magnetic resonance (MR) imaging findings associated with severe hypoglycemia after consumption of an illegal sexual enhancement product (Power 1 Walnut) adulterated with glibenclamide, an oral hypoglycemic agent used to treat diabetes mellitus. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective study. Records in eight male patients with severe hypoglycemia of unknown cause, without prior treatment for diabetes, and with positive blood toxicology results for glibenclamide were reviewed. MR imaging included diffusion-weighted imaging and, in some patients, MR angiography, dynamic contrast material-enhanced perfusion MR imaging, and MR spectroscopy. RESULTS: In seven patients, there were hyperintense abnormalities on diffusion-weighted and T2-weighted images in the hippocampus and cerebral cortex, sparing the subcortical white matter and cerebellum. Three patients had abnormalities of the splenium of the corpus callosum, and one had widespread involvement, including the caudate nucleus, basal ganglia, and internal capsule bilaterally. In three patients, unilateral cortical involvement, which did not conform to the typical cerebral arterial territories, was noted. In one patient, perfusion MR imaging showed slightly increased relative cerebral blood volume, and MR spectroscopy revealed no evidence of abnormal lactate in the affected cerebral cortex. CONCLUSION: Diffusion-weighted MR imaging findings in patients with severe hypoglycemia showed typical lesions in the hippocampus and cerebral cortex, but the caudate nucleus and basal ganglia were involved in only the most severely affected patient. The splenium of the corpus callosum and internal capsule were also abnormal in three patients, and unilateral cortical lesions could be distinguished from acute ischemic stroke by the pattern of involvement and MR angiographic, perfusion, and spectroscopic findings.

Penile oleogranuloma among Wisconsin Hmong.

Injection of viscous or semisolid materials into the penile shaft to increase its size, to correct erectile dysfunction, and/or to satisfy a sexual partner has only been sporadically reported in Eastern and Western European and American men. However, this practice appears to be more widespread in the countries of Southeast Asia. We present 3 cases of Hmong patients seen in a urology clinic in Wausau, Wis. We describe the presentation, correction, and difficulties experienced in convincing patients to undergo adequate treatment.

The enhancement of the hyperglycemic effect of S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine by vitamin C in an animal model.

BACKGROUND: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetlypenicillamine (SNAP) are two of the most common sources of nitric oxide (NO) in the biomedical field. Vitamin C has been known to accelerate the decomposition of GSNO and SNAP increasing the release and availability of NO which is cytotoxic at non-physiological concentrations. The study investigates any potential detrimental effect of vitamin C and GSNO, vitamin C and SNAP on glucose metabolism in normotensive and normoglycemic dogs. RESULTS: The results showed that administration of vitamin C (50 mg/kg) and GSNO (35 mg/kg & 50 mg/kg), or vitamin C (50 mg/kg) and SNAP (10 mg/kg) to overnight fasted dogs resulted in significant elevation of the blood glucose levels, attaining maximum level at the 2.0 or 2.5 h time point postprandially. The elevated blood glucose levels were due to significant reduction in plasma insulin levels in the dogs treated with vitamin C and GSNO, or vitamin C and SNAP (P < 0.05). The decreased insulin response was associated with significant elevation of nitric oxide produced from GSNO and SNAP co-administered with vitamin C, as assessed by plasma nitrate/nitrite levels. CONCLUSIONS: The results indicate that enhanced NO release by vitamin C affects postprandial blood glucose and plasma insulin levels and the reduced glucose tolerance is mainly due to impaired insulin release. The clinical relevance of the findings of this study suggest that hypertensive diabetic patients treated with GSNO or SNAP, who are on vitamin C supplements may be more predisposed to further decrease in their glycemic control.

[Effectivity versus toxicity of minoxidil as antiproliferative agent for lens epithelial cells. In vitro study]. / Efectividad versus toxicidad del minoxidil como agente antiproliferativo de células epiteliales de cristalino. Estudio in vitro.

PURPOSE: To evaluate the inhibitory effect of minoxidil on cultured proliferating lens epithelial cells (LECs) versus cytotoxic effect over corneal endothelial cells in culture, because minimum side effects over anterior chamber structures and particularly on corneal endothelium are required for successful therapy and prevention of posterior capsular opacification (PCO). METHODS: New Zealand Rabbit LECs and corneal endothelium were cultured in DMEM at 35 degrees C in 5% CO2 in multiwells during 7 days. Both types of cells were exposed to minoxidil (1, 2 and 4 mM) for 1 and 24 hours. Control group and balanced salt solution group were included. After seven days multiwells were processed for light microscopy study. Morphometric study of cellular population of LECs and corneal endothelium cells were done using a computed planimetry system. RESULTS: Dose-dependent effect on LECs proliferation was noted and non-confluent colonies of cells were observed on all treated groups. Morphologic changes in normal appearance of corneal endothelial cells after 1 hour of minoxidil treatment was observed and intracellular alterations were confirmed even with the lowest dose exposure. CONCLUSIONS: Although effectiveness of minoxidil suppressing in vitro LECs proliferation could be suggest as a useful therapeutic agent to prevent PCO, however the inhibitory effect of different concentrations on corneal endothelial cells conditioned its possible use on ocular surgery.

Acute and subacute toxicity and efficacy of S-nitrosylated captopril, an ACE inhibitor possessing nitric oxide activities.

The toxicity and efficacy of S-nitrosocaptopril (CapNO), a novel vasodilator possessing the capacities of both a nitric oxide donor and an angiotensin converting enzyme (ACE) inhibitor, were examined in rodents. In single-dose acute toxicity studies in ICR mice, the median lethal dose (LD(50)) for CapNO was 674+/-94 mg/kg (iv) and 2078+/-100 mg/kg (po), whereas for oral captopril was 4286+/-173 mg/kg. S-nitrosoglutathione, containing the same S-nitroso moiety as CapNO, showed an LD(50) equal to CapNO when the values were expressed by the mol/kg. The cause of acute death by the high doses of CapNO was lethal hypotension. In the subacute toxicity studies, oral CapNO was well tolerated in normotensive and hypertensive rats at doses up to 500 mg/kg/day for 3 months, except for considerable reductions in food consumption and growth rate observed in the 500 mg/kg/day group. Serum chemistry and hematology tests performed in the subacute toxicity studies revealed no adverse effects of oral CapNO except for a significant decrease in cholesterol levels in hypertensive SHR rat. At autopsy, no histopathological changes in major organs were observed over the subacute period. Administration of a therapeutic dose of CapNO (iv, 250 microg/kg which produced 25% decreases in blood pressure) revealed no changes in the hematological parameters. Subchronic treatment of SHR and SS/Jr rats with oral CapNO (50 mg/kg/day) significantly reduced mean arterial pressure to the normotensive level. Considering the absence of adverse effects of CapNO in the subchronic toxicity study, CapNO appears to be a safe drug for further clinical trials, but particular caution must be taken because it can cause hypotension when overdosed.

Evidence for toxic effects of alkylphenols from Ginkgo biloba in the hen's egg test (HET).

Extracts from the leaves of the Gingko tree (Ginkgo biloba L.) are therapeutically used for the treatment of peripheral and cerebral vascular disorders as well as multi-infarct or Alzheimer-type dementia. As constituents with potential contact allergenic and toxic properties in crude Ginkgo extracts a group of alkylphenols (e.g., ginkgolic acids, ginkgol, bilobol) has been described. Thus, for reasons of drug safety a maximal concentration (< or = 5 ppm) of ginkgolic acids is requested by the Monograph of the Commission E of the former German Federal Health Agency (Bundesgesundheitsamt, BGA). During production of the standardized Ginkgo extract EGb 761, alkylphenols are largely eliminated as water insoluble compounds (decanter sludge) from the primary acetone extract. To further assess the adverse properties of alkylphenols, different fractions derived from the decanter sludge were evaluated for their embryotoxic effects in the hen's egg test (HET). A fraction enriched for ginkgolic acids (16%) and biflavones (6.7%) was found to induce death of 50% of the chick embryos (LD50) at a dose of 1.8 mg/egg (approximately/= 33 ppm). A similar strong lethal effect (LD50: 3.5 mg/egg; 64 ppm) was oberserved for a fraction which contained 58% ginkgolic acids but less than 0.02% biflavones. In contrast, an extreme low toxic potential (LD50: 250 mg/egg or 4540 ppm) was established for a fraction containing 16% biflavones and 1% ginkgolic acids. Thus, the present investigations confirm the high toxic potential of ginkgolic acids, although it can not be excluded that biflavones or some other constituents in the different fractions may amplify the adverse effect of these substances. Since no contribution of alkylphenols to the therapeutic efficacy of Ginkgo extracts has been confirmed and their elimination during the manufacturing process does not cause technical problems, these results further support the requirement for the completest possible removal of these compounds under toxicological considerations.

Bioenergetic consequences of opening the ATP-sensitive K(+) channel of heart mitochondria.

There is an emerging consensus that pharmacological opening of the mitochondrial ATP-sensitive K(+) (K(ATP)) channel protects the heart against ischemia-reperfusion damage; however, there are widely divergent views on the effects of openers on isolated heart mitochondria. We have examined the effects of diazoxide and pinacidil on the bioenergetic properties of rat heart mitochondria. As expected of hydrophobic compounds, these drugs have toxic, as well as pharmacological, effects on mitochondria. Both drugs inhibit respiration and increase membrane proton permeability as a function of concentration, causing a decrease in mitochondrial membrane potential and a consequent decrease in Ca(2+) uptake, but these effects are not caused by opening mitochondrial K(ATP) channels. In pharmacological doses (<50 microM), both drugs open mitochondrial K(ATP) channels, and resulting changes in membrane potential and respiration are minimal. The increased K(+) influx associated with mitochondrial K(ATP) channel opening is approximately 30 nmol. min(-1). mg(-1), a very low rate that will depolarize by only 1-2 mV. However, this increase in K(+) influx causes a significant increase in matrix volume. The volume increase is sufficient to reverse matrix contraction caused by oxidative phosphorylation and can be observed even when respiration is inhibited and the membrane potential is supported by ATP hydrolysis, conditions expected during ischemia. Thus opening mitochondrial K(ATP) channels has little direct effect on respiration, membrane potential, or Ca(2+) uptake but has important effects on matrix and intermembrane space volumes.

The Ginkgo biloba extract (EGb 761) protects and rescues hippocampal cells against nitric oxide-induced toxicity: involvement of its flavonoid constituents and protein kinase C.

An excess of the free radical nitric oxide (NO) is viewed as a deleterious factor involved in various CNS disorders. Numerous studies have shown that the Ginkgo biloba extract EGb 761 is a NO scavenger with neuroprotective properties. However, the mechanisms underlying its neuroprotective ability remain to be fully established. Thus, we investigated the effect of different constituents of EGb 761, i.e., flavonoids and terpenoids, against toxicity induced by NO generators on cells of the hippocampus, a brain area particularly susceptible to neurodegenerative damage. Exposure of rat primary mixed hippocampal cell cultures to either sodium nitroprusside (SNP; 100 microM) or 3-morpholinosydnonimine resulted in both a decrease in cell survival and an increase in free radical accumulation. These SNP-induced events were blocked by either EGb 761 (10-100 microg/ml) or its flavonoid fraction CP 205 (25 microg/ml), as well as by inhibitors of protein kinase C (PKC; chelerythrine) and L-type calcium channels (nitrendipine). In contrast, the terpenoid constituents of EGb 761, known as bilobalide and ginkgolide B, as well as inhibitors of phospholipases A [3-[(4-octadecyl)benzoyl]acrylic acid (OBAA)] and C (U-73122), failed to display any significant effects. Moreover, EGb 761 (50 microm) CP 205 (25 microg/ml), and chelerythrine were also able to rescue hippocampal cells preexposed to SNP (up to 1 mM). Finally, EGb 761 (100 microg/ml) was shown to block the activation of PKC induced by SNP (100 microM). These data suggest that the protective and rescuing abilities of EGb 761 are not only attributable to the antioxidant properties of its flavonoid constituents but also via their ability to inhibit NO-stimulated PKC activity.

Evaluation of linear polyethyleneimine/nitric oxide adduct on wound repair: therapy versus toxicity.

A full-thickness wound model was used to evaluate the effects of a topically applied polyethyleneimine-based nitric oxide donor on wound repair in aged rats. Polymer applications were applied over a 10-day period on days 0, 2, 4, 6, and 8 comparing treatment (linear polyethyleneimine-nitric oxide) and control groups (linear polyethyleneimine). Urinary nitrate excretion was quantified as a measure of nitric oxide released. The nitric oxide released from the linear polyethyleneimine-nitric oxide group was significant compared with controls (p

[Experimental data on the toxicity of nonachlazine, a new antianginal agent]. / Eksperimental'nye dannye o toksichnosti nonakhlazina--novogo antianginalinogo sredstva

The results obtained by a study of acute and chronic toxicity of nonachlazine--a new original coronary-active agent endowed with antianginal properties are reported. Nonachlazine has been found to have a sufficiently wide range of therapeutic action. With its repeated (for 36 days) oral introduction to rats in an effective dose of 10 mg/kg the drug does not produce any adverse effect on the general condition of the animals, reduces but insignificantly their weight gain, fails to exert any damaging effect on the blood system, does not change biochemical characteristics featuring the function of the liver, nor evokes any pathohistological changes of the internal organs. Nonachlazine has no locally irritating effect on the gastro-intestinal tract and is a compound producing but a slight stress action.