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Cotinus coggygria Scop. is a valuable medicinal plant species with pronounced pharmacological potential due to its numerous biological activities. The herb is characterized by a high content of polyphenols among which is fustin. The anticancer activities of fustin, however, are extremely weakly studied. The aim of the present study was to investigate the in vitro antiproliferative potential of fustin isolated from the heartwood of C. coggygria against cell lines originating from two of the most common cancer types – breast (MDA-MB-231 and MCF7), and colon cancer (Colon 26).

In recent decades, natural products of plant origin have predominated among the sources of new therapeutic agents. Plants, which are intensively used in folk medicine, are the focus of particular interest, and being subjected to in-depth analyses for the assessment of their pharmacological properties. The objective of the present work was to evaluate the in vitro anticancer, antiviral, and antioxidant properties of a crude aqueous methanolic extract from the leaves of Rhus typhina L., which is a plant species with broad applications in traditional phytotherapy. The anticancer capacity of the extract was assessed on two human breast cancer cell lines (MCF7 and MDA-MB-231) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell proliferation assay, and its cell growth inhibitory effect on cancer cells was compared with its action on a non-cancerous breast epithelial cell line (MCF10A). Moreover, the in vitro antiviral activity of the plant extract was studied against viral strains of three taxonomic groups: herpes simplex virus type 1 (HSV-1), coxsackievirus B1 (CVB1), and influenza A virus (IAV/H3N2) using a cytopathic effect inhibition test, extract cytotoxicity evaluation through the neutral red uptake assay, a virucidal assay, a viral attachment assay, and cell pre-treatment with the extract. In turn, a radical scavenging assay with 2,2-diphenyl-1-picrylhydrazyl (DPPH) was applied to explore the antioxidant potential of R. typhina leaf extract. Results indicated that the plant extract possessed antiproliferative activity against the tested cell lines which was stronger toward cancer cells. A modest inhibitory effect on IAV/H3N2 replication was detected; as well as on an effect on herpes virions and on the adsorption of the HSV-1 and IAV/H3N2 strains; and a protective effect on uninfected cells before HSV-1 contact. The leaf extract of R. typhina also exhibited a strong free radical scavenging activity. The results of the present work demonstrated the pharmacological potentials of the plant extract, which warrants further and more detailed study in the future. [ABSTRACT FROM AUTHOR]

Despite significant efforts, cancer remains the second leading cause of mortality worldwide. The medicinal plant Nepeta nuda L. represents a valuable source of biologically active compounds with pharmacological activities including antioxidant, anti-inflammatory, antimicrobial, and antiviral. This study aimed to assess the antiproliferative potential and mechanisms of action of aqueous extract from the leaves of wild-grown N. nuda . Cancer cell lines, MDA-MB-231, MCF7 (breast), HT29, Colon 26 (colon), and HepG2 (liver cancer), and a non-cancerous skin cell line, BJ, were assessed for antiproliferative activity by MTT assay and observation of cell morphological alterations. The cancer cell line that was most sensitive to the extract was further studied for apoptotic alterations by Annexin V/propidium iodide staining, colony-forming assay, and qRT-PCR analysis. The results revealed that the plant extract inhibited the proliferation of all investigated cancer cell lines with the strongest cytostatic effect on Colon 26 cells with a half maximal inhibitory concentration (IC 50 ) value of 380.2 μg/mL and a selectivity index (SI) of 3.5. The extract significantly inhibited the ability of cells to form colonies, exhibited considerable proapoptotic potential involving the participation of the CASP8 gene, and increased the expression levels of ATG3 and the BECN1 gene, which suggests a role of autophagic cell death in the antitumor action.

The genetic bases of Alzheimer's disease (AD) and frontotemporal dementia (FTD) have been comprehensively studied, which is not the case for atypical cases not classified into these diagnoses. In the present study, we aim to contribute to the molecular understanding of the development of non-AD and non-FTD dementia due to hyperammonemia caused by mutations in urea cycle genes. The analysis was performed by pooled whole-exome sequencing (WES) of 90 patients and by searching for rare pathogenic variants in autosomal genes for enzymes or transporters of the urea cycle pathway. The survey returned two rare pathogenic coding mutations leading to citrullinemia type I: rs148918985, p.Arg265Cys, C>T; and rs121908641, p.Gly390Arg, G>A in the argininosuccinate synthase 1 ( ASS1 ) gene. The p.Arg265Cys variant leads to enzyme deficiency, whereas p.Gly390Arg renders the enzyme inactive. These variants found in simple or compound heterozygosity can lead to the late-onset form of citrullinemia type I, associated with high ammonia levels, which can lead to cerebral dysfunction and thus to the development of dementia. The presence of urea cycle disorder-causing mutations can be used for the early initiation of antihyperammonemia therapy in order to prevent the neurotoxic effects.

The aim of the present study was to synthesize lignin microparticles, to evaluate their physicochemical, spectral, morphological and structural characteristics, to examine their encapsulation and in vitro release potential and behaviour towards the flavonoid morin in simulated physiological medium and to assess the in vitro radical-scavenging potential of the morin-loaded lignin microcarrier systems. The physicochemical, structural and morphological characteristics of alkali lignin, lignin particles (LP) and morin-encapsulated lignin microparticles (LMP) were determined based on particle size distribution, SEM, UV/Vis spectrophotometric, FTIR and potentiometric titration analyses. The encapsulation efficiency of LMP was 98.1%. The FTIR analyses proved that morin was successfully encapsulated in the LP without unexpected chemical reactions between the flavonoid and the heteropolymer. The in vitro release performance of the microcarrier system was successfully mathematically described by Korsmeyer-Peppas and the sigmoidal models outlining the general role of diffusion during the initial stages of the in vitro release process in simulated gastric fluid (SGF), and the predominant contribution of biopolymer relaxation and erosion was determined in simulated intestinal medium (SIF). The higher radical-scavenging potential of LMP, as compared to that of LP, was proven via DPPH and ABTS assays. The synthesis of lignin microcarriers not only provides a facile approach for the utilization of the heteropolymer but also determines its potential for the design of drug-delivery matrices.

Background/aim: An increasing number of studies are reporting anticancer activity of widely used antiparasitic drugs and particularly benzimidazoles. Fenbendazole is considered safe and tolerable in most animal species at the effective doses as an anthelmintic. Little is known about the redox-modulating properties of fenbendazole and the molecular mechanisms of its antiproliferative effects. Our study aimed to investigate the possibility of selective redox-mediated treatment of triple-negative breast cancer cells by fenbendazole without affecting the viability and redox status of normal breast epithelial cells., Materials and Methods: The experiments were performed on three cell lines: normal breast epithelial cells (MCF-10A) and cancer breast epithelial cells (MCF7 - luminal adenocarcinoma, low metastatic; MDA-MB-231 - triple-negative adenocarcinoma, highly metastatic). Cells were treated with fenbendazole for 48-h and three parameters were analyzed using conventional assays: cell viability and proliferation, level of intracellular superoxide, and level of hydroperoxides., Results: The data demonstrated that MDA-MB-231 cells were more vulnerable to fenbendazole-induced oxidative stress than MCF-7 cells. In normal breast epithelial cells MCF-10A, fenbendazole significantly suppressed oxidative stress compared to untreated controls. These data correlate with the effect of fenbendazole on cell viability and the IC 50 values, which is indirect evidence of the potential targeting anticancer effect of the drug, especially in MDA-MB-231 cells., Conclusion: The difference in the levels of oxidative stress induced by fenbendazole in MDA-MB-231 and MCF-7 indicates that the two types of breast cancer respond to the drug through different redox-related mechanisms., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Due to the high prevalence of viral infections having no specific treatment and the constant emergence of resistant viral strains, searching for effective antiviral compounds is crucial. The present study explores in vitro the antiviral activity of ethanolic extract from aerial parts of., Aim: The aim of the current study was to evaluate antiviral activity of ethanolic extract from herbaceous plant., Materials and Methods: The crude aqueous ethanolic extract from aerial parts of., Results: The results show that the extract has the lowest toxicity on the MDBK cell line and similar cytotoxicity in Hep-2, whereas in the MDCK cells it has more than twice the highest toxicity. Testing the antiviral activity of., Conclusion: The crude extract from aerial parts of the medicinal plant., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Isolation and characterization of new biologically active substances affecting cancer cells is an important issue of fundamental research in biomedicine. Trehalose lipid was isolated from Rhodococcus wratislav i ensis strain and purified by liquid chromatography. The effect of trehalose lipid on cell viability and migration, together with colony forming assays, were performed on two breast cancer (MCF7-low metastatic; MDA-MB231-high metastatic) and one "normal" (MCF10A) cell lines. Molecular modeling that details the structure of the neutral and anionic form (more stable at physiological pH) of the tetraester was carried out. The tentative sizes of the hydrophilic (7.5 Å) and hydrophobic (12.5 Å) portions of the molecule were also determined. Thus, the used trehalose lipid is supposed to interact as a single molecule. The changes in morphology, adhesion, viability, migration, and the possibility of forming colonies in cancer cell lines induced after treatment with trehalose lipid were found to be dose and time dependent. Based on the theoretical calculations, a possible mechanism of action and membrane asymmetry between outer and inner monolayers of the bilayer resulting in endosome formation were suggested. Initial data suggest a mechanism of antitumor activity of the purified trehalose lipid and its potential for biomedical application., Competing Interests: The authors declare no conflict of interest.

Taking into account the rising trend of the incidence of cancers of various organs, effective therapies are urgently needed to control human malignancies. However, almost all chemotherapy drugs currently on the market cause serious side effects. Fortunately, several studies have shown that some non-toxic biological macromolecules, including algal polysaccharides, possess anti-cancer activities or can increase the efficacy of conventional chemotherapy drugs. Polysaccharides are characteristic secondary metabolites of many algae. The efficacy of polysaccharides on the normal and cancer cells is not well investigated, but our investigations proved a cell specific effect of a newly isolated extracellular polysaccharide from the red microalga Porphyridium sordidum . The investigated substance was composed of xylose:glucose and galactose:manose:rhamnose in a molar ratio of 1:0.52:0.44:0.31. Reversible electroporation has been exploited to increase the transport through the plasma membrane into the tested breast cancer tumor cells MCF-7 and MDA-MB231. Application of 75 µg/mL polysaccharide in combination with 200 V/cm electroporation induced 40% decrease in viability of MDA-MB231 cells and changes in cell morphology while control cells (MCF10A) remained with normal morphology and kept vitality., Competing Interests: The authors have declared no conflict of interest., (© 2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Breast cancer is currently the most common type of cancer in females. The majority of the hereditary forms of breast cancer are caused by mutations in the BRCA1 and BRCA2 genes, whose main function is the DNA repair of double-strand breaks. Genetic testing of females with a family history of breast cancer is recommended to determine their hereditary predisposition for this type of cancer. The variants with no clear clinical significance may represent a diagnostic challenge when performing targeted resequencing. In this study, DNA samples were obtained from 24 breast cancer patients (mean age, 35±10 years) with a positive family history and from 71 age-matched healthy controls. Informed consent was obtained from all the subjects. Sequence-targeted BRCA1 and BRCA2 libraries were prepared using the TruSeq Custom Amplicon method and sequenced on the Illumina MiSeq system. A wide range of variants were identified in the BRCA1 and BRCA2 genes. Two pathological/presumably pathological variants were detected in the breast cancer patient group: a mutation in BRCA2 at the chromosomal (chr) position chr13:32890665, which affected the first position of the 5' splice region following exon 2; and a mutation in BRCA1 at chr17:41219635, causing an in-frame triple nucleotide deletion of valine 1688 (8.3%). In the patient and control groups, 7 likely polymorphic variants and 13 common variants were detected in the BRCA1 and BRCA2 genes. To the best of our knowledge, this study was the first to identify 3 common polymorphisms in BRCA2, characteristic solely of the Bulgarian population, including chr13:32973737, T/-, a single-nucleotide polymorphism (SNP) within the 3'-UTR of exon 27; chr13:32973280, A/-, a mononucleotide deletion within the 5'-UTR of exon 27; and chr13:32973924, T/-, a mononucleotide deletion downstream of the gene sequence. To the best of our knowledge, this study was the first to apply next-generation sequencing of the BRCA1 and BRCA2 genes in a Bulgarian population, prompting further investigation for local founder mutations and variants characteristic for this particular region.

A single parenteral and oral administration of ammonium glycyrrhizinate in rat and mice experiments showed that the compound is related to practically nontoxic drugs. Its repeated administration (30 times) into the stomach in a maximum daily therapeutic dose (7 mg/kg) and in a four-fold dose (28 mg/kg) did not cause signs of intoxication, essential changes in the hematological and integral parameters, shifts in the activity of serum enzymes, morphological changes in the cell structures of the internal organs. Administration of the drug in a dose of 28 mg/kg for a second time led to changes in the activity of some enzymes in the brain, the development of parenchymatous dystrophy of the liver which changed to acidophilic necrosis attended with signs of regeneration. Under conditions of a subacute experiment the maximum daily therapeutic dose of ammonium glycyrrhizinate may be considered practically nontoxic.

An evaluation of the gonadotropic effect of Gastrofenzin has been carried out in conditions of 45-day and 90-day oral application (daily, 5 times per week) in male white rats. The experiments are performed in doses 1/20, 1/100 and 1/200 LD50, respectively 33.8, 6.7 and 3.4 mg.kg-1. Functional and morphologic methods of investigation have been used-count, character and mobility, acid and osmotic resistance of the sperm cells, mean number of sperm cells in the sperm tube, spermatogenesis' indices, morphological characteristic of the testes as well as autoradiographic method for determining the proteolytic activity of the acrosome. Irrespective of the application term the highest dose (33.8 mg.kg-1) causes systemic deviations in the functional indicators and physiologic fluctuation of the morphologic parameters characterizing the spermatogenic epithelium at preserved proteolytic activity of the acrosome. The dose 1/20 LD50 (33.8 mg.kg-1) is considered to be effective on the gonads in conditions of three-month chronic oral application of Gastrofensin and the threshold of the gonadotoxic activity is about 1/100 LD50-6.7 mg.kg-1.

The subacute (30 day) oral toxicity of Gastrofenzin has been investigated in white rats "Wistar" of both sexes, treated with 0.7 and 33 mg.kg-1 for the male and 0.9 and 44 mg.kg-1 for the female rats. The applied doses respond respectively to the control doses, 1/100 and 1/20 LD50 of the preparation. A complex of integral, behaviour, laboratory biochemical and histological methods has been used. The findings show that Gastrofenzin in doses 1/100 and 1/20 LD50 does not exert cumulative effect, reported by the lack of lethal effect among the animals. With the help of actograph "AIDA" an increased spontaneous activity is reported in the rats from both sexes treated with dose 1/20 LD50 of the preparation. Under the experimental conditions the doses of 7 and 9 mg.kg-1 (1/100 LD50) and 33 and 44 mg.kg-1 (1/20 LD50) do not exert toxic effect on the liver, kidneys and brain. Deviations are observed which show increasing of the oxidative-metabolic processes and trigger adaptation mechanisms in the above mentioned organs.

A risk evaluation has been carried out under conditions of chronic three-month experiment in oral application of Gastrofenzin in doses 1/20, 1/100 and 1/200 LD50 for male and female white rats, respectively 33.2 and 43.8; 6.7 and 8.8; 3.4 and 4.4 mg.kg-1. There have been applied integral, behavioural, laboratory, biochemical (serum, liver, kidney, brain, brain mitochondria), histologic and electron microscopic methods. The highest doses cause functional and biochemical changes in the nerve system, liver and the kidneys without involving the structural elements of the respective tissues. Significant changes have not been observed in the doses 1/100 LD50 and 1/200 LD50. A dose-effect increase has been found out in the level of cytochrome-P-450 in the liver tissue, but the data are insufficient for determining the type of the caused induction. The results of the complex study show that in the three-month application in doses 1/20, 1/100 and 1/200 LD50 Gastrofenzin does not cause development of significant deviation in the organism of the mice from both sexes and its toxicological characteristic is comparatively favourable.

The acute toxicity of the antiulcer drug "Gastrofenzin", synthesized in Bulgaria has been studied in oral, subcutaneous and intravenous application in white rats "Wistar" and white mice "ICR". The main toxicometric parameters (LD50, LD16, LD84 and others) have been determined. The clinical picture of intoxication is characterized mainly by symptoms deriving from in the central and vegetative nerve system. According to the parameters of acute oral toxicity (LD50 for male white rats is 665.0 mg.kg-1 and for female--876 mg.kg-1) and to the classification of Hodge & Stemer Gastrofenzin refers to the group of slightly toxic drugs. The LD50 in subcutaneous application is 938.0 mg.kg-1 for the male and 891.0 mg.kg-1 for the female rats. For the intravenous application LD50 is 50,1 mg.kg-1 for the male and 43.6 mg.kg-1 for the female rats. The coefficient of lethal intoxication danger is below 0.1 in the three ways of application which confirms its status according to the upper classification. A significant sex difference in the indicators of acute oral toxicity for the white rats and white mice has not been observed. The white mice of both sexes seem to be more sensitive to the drugs' effects than the white rats.

Toxic hygienic investigations were carried out involving a representative group of 131 workers (50 females and 81 males) distributed into three main workshops--preparatory, confection, and vulcanization--at "Dynamic" automobile tire plant in Sofia. The majority of male and female workers were in the age range beyond 40 years, having a general occupational experience in excess of 10 years and specialized occupational experience from 10 to 20 years or more. The chemical hazard was among the leading ones in the occupational environment, differing in nature according to the technologies used. Included were various chemical substances and compounds: synthetic rubbers, fillers (soot, chalk, kaolin); softeners (mazut, paraffin, etc.); accelerants (mercaptothiazoles--captax and altax); dithiocarbamates (thiuram); vulcacides (diphenylguanidine); antiwear agents (antioxidants and antiozonators-isopropyl-phenyl-paraphenylene diamine, naphthyl-beta-naphthylamine); antiaccelerants (phthalic anhydride, ets.); organic solvents and others. The indicated chemical substances and compounds, though often found at concentrations below the mean-shift MACs, do produce health impacts by virtue of prolonged and combined exposures. Use was made of the questionnaire method. Also, hematologic, clinical laboratory, and toxic chemical testing was performed. Findings pointed to changes in hemopoiesis, deviations in hepatic functional state, while sulfate and glucuronide values confirmed the workers' high exposures.

At the Preparatory Workshop of the Plant for Automobile Tires (PAT), Sofia, complex investigations were undertaken to reveal possible genotoxic exposure. The studies included chemical analyses for levels of identifiable human carcinogens in the occupational ambient air (benz(a)pyrene, mineral oils, 2-naphthylamine); special techniques--questionnaire investigations and cytogenetic analysis by cytokinesis-block micronucleus method in peripheral lymphocyte cultures from 23 workers in occupational groups at risk; and urinalysis for contents of mercapturic acids. An out-of-house control group of 13 nonexposed subjects was concurrently investigated. For contents of benz(a)pyrene and mineral oils exceeding 2.5 to 3.5 times the respective occupational environment MACs, evidence from cytogenetic analysis showed substantial, 4-fold, increase in indexes of genotoxic impairment (frequency of micronucleated-binucleated lymphocytes, number of micronuclei per 1000 binucleated lymphocytes) in the workers investigated. These results are an indicator of genotoxic exposure and point to an increased potential risk of cancer development in the group of workers studied.

These studies, centering on occupational environmental factors, biologic monitoring, and toxicodynamic investigations, involved a total of 105 workers distributed into eight job groups, who were 45 years, of age on the average and had from 5 to 10 years of special occupational experience at "Electrosteel" Works. Evidence was obtained for presence of unfavorable microclimate conditions, elevated equivalent levels of noise, excess of general and local vibrations, exposure to manganese aerosols, carbon monoxide, and nitrogen oxides; some of the subjects and deviations in hepatic status and connective tissue. Job groups found to be at risk were those of steel founders, crane workers, and pourers.

A representative group of 122 workers from shop "Predilen" with 7 to 15 years length of service in specialty is taken. The professional groups are formed on the basis of measured average-shift concentrations of carbon bisulphide in the air of the working place, which vary from 4 to 50 mg.m-3. In order to establish deviations in some of the basic links of the biochemical mechanism of the toxic compounds effect the following indices are traced: copper metabolism [copper concentration and activity of ceruloplasmin in the serum]; lipidic metabolism [content of cholesterol, cholesterol of high and low density, triglycerides, beta-lipoproteins and nonesterified lipidic acids in the serum]; intercellular substance of the connective tissue [glycoproteins, glycosaminoglycans and hexauronic acids in serum and urine]; immune status [immunoglobulins A, G and M in serum]; peripheral blood [leucocytes, DKK, morphology and lipid content in granulocytes]. Decrease of the lipids in granulocytes is registered, as well as reduction of the ceruloplasmin activity, increase of immunoglobulin M and glycosaminoglycans in urine. The already established deviations follow the "dose-effect" and "dose-response" dependence.

The acute oral and dermal toxicity was studied as well as subacute oral toxicity [30 successive days] and skin irritating effect on experimental animals of new drug form "Takal 9", "Takal 14" and "Takal 16" with proved bactericidal and virucidal activity. A complex of toxicometric, unspecific, haematological, biochemical and histological studies were performed. The compositions "Takal 9", "Takal 14" and "Takal 16" are slightly toxic at oral and dermal application. LD50 for "Takal 9" and "Takal 16" is above 15,000 mg/kg-1 while for preparation "Takal 14" is not reached. At unrepeated dermal application LD50 for the examined group of preparations surpasses 5000 mg/kg-1. The products have no skin-irritative effect. No cumulative effect is established in the conditions of a 30-day oral treatment. On the background of no changes in the serum indices an activation of the aerobic and anaerobic oxidation in the liver is registered in animals treated with ethyl alcohol, "Takal 9" and "Takal 16". These deviations are due, most probably, to the participation of ethyl alcohol as solvent, in "Takal 9" and "Takal 16". On the basis of the experiments, as most suitable for use, is established the preparation "Takal 14".

The purpose of this study is to give the toxicological characteristics of subacute oral, dermal and inhalation exposure of microbial preparation Bulmoscide, which is based on bacterium Bacillus thuringiensis, serotype H-14. The study was performed on sexually mature Wistar rats of both sexes. No significant changes in non-specific, clinico-laboratory and biochemical parameters as well as morphological examinations in any tested groups compared to the control groups were revealed. The doses 110 mg.kg-1 (1.32 x 10(9) sp.kg-1) at oral administration in duration of 90 days, 3000 mg.kg-1 (3.6 x 10(10) sp.kg-1) in 21 day dermal application and maximum attainable concentration of dust aerosol 18 mg.kg-3 (2.2 x 10(8) sp.m-3) during a 30 day inhalation exposure are "no toxic effect" levels. On the basis of the data, the selective bacterial insecticide Bulmoscide has been determined to be of low toxic and low hazardous preparation in compliance with the Hygiene Classification of pesticides.

The acute toxicity of a new Bulgarian bioinsecticide preparation is determined, produced on the basis of Bacillus thuringiensis containing 0.1% beta-exotoxin by oral, dermal, inhalational and intraperitoneal introduction in experimental animals. The evaluation of the toxicity is performed by a complex of toxicometric, integral, haematologic and pathologicoanatomic methods according to the WHO and USA criteria for studying the safety of the microbic agents for plant protection. It is already established that the preparation introduced orally in dose 10,000 mg.kg-1 (1.6.10(11) cell kg.-1 10 micrograms.kg-1 beta exotoxin), applied dermally in dose 6000 mg.kg-1 (9.6.10(10), 6 micrograms.kg-1 beta exotoxin) and in concentration 300 mg.m-3 (4.8.10(10) cell m-3, 300 micrograms.m-3 beta exotoxin) provokes no lethality, intoxication and changes in the integral, haematologic and pathologicoanatomic studies of test animals. LD50 at intraperitoneal introduction in white rats is 387.20 mg (6.2.10(10), kg-1, 387.2 micrograms kg-1 beta exotoxin) for male and 364.0 mg kg-1 (0.58.10(9) kg-1 364.0 micrograms kg-1 beta exotoxin) for female animals. The investigations point out that according to rate of acute toxicity the bacterial preparation containing 0.1% beta exotoxin is referred to the low toxic substances and reveals no danger for acute oral, dermal and inhalational poisonings when the regulations for production and use are observed.

In relation to the future implementation of the antibiotic bactericin in agriculture are carried out acute, subacute and chronic oral experiments on 128 male white rats and 88 female. In order to determine the parameters of acute oral toxicity, doses (200, 120, 80, 60, 50, 40 mg/kg) of the preparation dissolved in polyethylene glycol are applied. In the subacute--1/10 and 1/20 LD50, and in the chronic (four months)--1/50 and 1/100 LD50. The bactericin, meant for treatment of tomatoes before sowing, in rate of acute oral toxicity falls in class II of very toxic pesticides. The acute oral LD50 for male white rats is 73.0 (48.6-109.5) mg/kg-1 and for female--58.0 (39.9-84.0) mg/kg-1. In conditions of subacute (30 oral applications for 45 days) and chronic (four months) experiments no cumulative properties are proved as well as hepatotoxic, nephrotoxic and neurotoxic effect. On the basis of the complex study could be accepted, that the dose 1/100 LD50 (0.7 mg/kg-1) for male rats and 0.4 mg/kg-1 for female) is not active at chronic oral introduction.

This experiment was performed in Wistar rats of both sexes exposed subchronically to 1:100, 1:500, 1:1000 and 1:1500 LD50. The evaluation was based on endpoints measured on the 30th and 90th after starting exposure and after a recovery period of 30 days: these included clinical signs, functional changes, hematological parameters, urine analysis, biochemical, histochemical, immunomorphological endpoints, electron microscopy of internal organs, chromosome examination of bone marrow. A high lethality was shown to occur with a characteristic clinical picture: interruption of weight gain, behavioural changes, leucopenia mainly involving neutrophil leucocytes, biochemical changes characteristic of liver, cardio-vascular system (myocardium and aorta) together with pathologic, biochemical, histochemical and ultrastructural changes in liver, brain, thyroid gland, myocardium, spleen and bone marrow. Endpoints were shown to be clearly dose-dependently related with small variations with the low dose, i.e. 1:1500 LD50 (5 mg/kg-1 bw).

Changes in the liver of male rats were studied on the 1, 3, 5, 7, 10 and 14 days after a single oral application of 1/5 DL 50 of the chloracetanilic herbicide Acetochlor (DL50 = 1063 mg/kg-1). Two main periods in the action of acetochlor can be identified: between 1-2 days when the influence of the compound itself is predominant and between 5-7 days, when the toxic action of the slowly eliminated metabolites is most pronounced. These two periods provoke a biphasic activation/inhibition response of the liver. Remarkable is the compensatory effect of the cytochrome P-450 system responsible for the metabolism of acetochlor. The phase-specific changes were are followed by pathomorphological observations of liver tissue as well as by the time-course of the biochemical parameters studied in different liver fractions.

A study is performed on the long-term effect of the chloracetanilide herbicide "Acetochlor" in doses 21.0; 10.6: 5.5 and 2.6 mg/kg-1 in conditions of 6-month oral application and 2-month rehabilitation period on the metabolite processes and the balance of the connective-tissue components in the myocardium and aorta of male white rats. A complex of biochemical and histological methods are performed (activity of succinate dehidrogenase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, adenosin triphosphatase, cytochrome oxidase, fructoso-1,6-diphosphatase, level of the thiol groups, soluble globular, elastine, collagen fractions, insoluble collagen and elastine, general and sulphated glucosamino glycanes). The dose 21.0 mg/kg-1 leads to blocking of the thyol groups, inactivation of succinate dehydrogenase, cytochrome oxidase, adenosin triphosphatase, fructose-1,6-diphosphatase, glucose-6-phosphate dehydrogenase, activation of lactate dehydrogenase, decrease of the soluble globular, elastine, and collagen fractions and increase of the glucoseaminoglycanes in the heart muscle and aorta. The changes established in the heart muscle at 10,6 mg/kg-1 certify for stronger sensitivity of the organ of the aorta wall. The presence of single changes in the examined indices, their complete dying out after the rehabilitation period and absence of structural changes in the myocardium and aorta permit the dose of 5.5 mg/kg-1 to be accepted as not effective in the conditions of chronic experiment concerning the cardiovascular system.

The preparation "Mamestrine" developed in Bulgaria on the basis of NPV virus is meant for control of the Heliothis zea. Experiments are carried out on the toxic effect of the preparation, according to the requirements of FAO/WHO for assessment of the virus preparations and the acting in this country Bulgarian State Standards. On experimental animals (white rats of both sexes, white guinea pigs and white rabbits) are studied acute oral, dermal and inhalatory toxicity, subacute oral toxicity, dermal-irritation, eye-stimulation and skin-sensitizing activity, cytotoxicity and activity of the preparation in soils and waters. Toxicometric, integral, clinical and laboratory, biochemical and histological methods are used. Unrepeated oral application of dose 2.10(9) pol.kg-1, unrepeated dermal application of dose 1.10(9) pol.kg-1, in white rats and 0,4.10(7) pol.kg-1 in guinea pigs and 4 hrs inhalation unrepeated exposure of white rats to concentration 1.10(7) pol.m-3 provoke no signs of intoxication and lethal issue and are accepted as inoperative. During a 3-month oral application of the preparation in doses 1.10(7) and 1.10(9) pol.kg-1 are established no data for toxic effect on the organism of experimental white rats of both sexes. The preparation "Mamestrine" has no skin-irritative, eye-irritative, eye-stimulative and skin-sensitizing activity. There is no cytotoxic effect on animal (kidney of monkey) and human (carcinoma of the gullet) cellular cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

In the conditions of acute and subacute oral intoxication with acetanilidic preparation acetochlorine applied in doses respectively 1/5 LD50 for acute experiment and 1/20 and 1/100 LD50 for subacute experiment (LD50 for male animals--1063 mg/kg-1, and for females--768 mg/kg-1) are traced the changes in the capacity for methaemoglobin formation, the quantity of sulfhydryl groups in the serum, the activity of LDH, G-6-PhDH, IDH, MDH, SDH, Cyt Oxidasis and the quantity of soluble proteins in brain homogenates and isolated mitochondria of brain. The animals of the acute experiment are examined on the 1, 3, 5, 7, 10 and 14 day of the poisoning, and the animals of the subacute experiment--on the 24th hour after the last administration (42-day treatment with the preparation, 5 days weekly). The herbicide acetochlorine at unrepeated introduction of dose 212 6 mg/kg-1 (1/5 LD50) and multiple administration for a period of 42 days in doses 1/20 and 1/1000 LD50 in the stomach of white rats possess well expressed methaemoglobin formation capacity. In the conditions of acute and subacute experiment the preparation causes one-type changes in the enzymes activity, certifying for a destruction of the mitochondrial apparatus. A suppression of the activity of SDH, IDH, Cyt oxidasis and increase of the LDH, G-6-PhDH activity, could be a result of methaemoglobin formation. The latter is a predispose factor for appearing of chemical hypoxia leading to the inclusion of compensatory anaerobic oxidizing processes. The registered deviations have to be read at the hygiene standardization of the preparation.

The effect of the pesticide Fundazol (methyl-l-butyl-carbamoil-benzimidazol carbamate) on the development of sclerotic lesions in the heart muscle of experimental animals, caused by atherogenic diet, was studied. Investigations were carried out in a series of 144 albino rats of either sex, treated accordingly with 250 mg/kg and 1000 mg/kg Fundazol or atherogenic diet alone and with a combination of atherogenic factor and either dose of the pesticide. Using biochemical test (dehydrogenase and phosphatase activities, quantity of soluble and insoluble collagen and elastin proteins, content of glucosamineglycans and glucoproteins) and routine morphologic and histochemical methods, the authors studied the metabolic processes and the characteristics of the fibrous structures and basic intercellular substance in the heart muscle. Combined with atherogenic diet, Fundazol potentiated its effect: the developing pathologic process was more severe and progressed more rapidly than in animals exposed to the atherogenic factor alone.

Multigenerational studies were carried out on albino rats obtained from parent progeny - female-intact and male-perorally exposed to lead acetate, in the drinking water - 0.2 mg/kg (group I) and 20 mg/kg (group II); the data were compared with a control group. Changes were found in each progeny as follows : in PI - reduced erythrocyte count, increased reticulocytes (group II); enhanced ATP activity in brain homogenates (group II), as will as increased disulphide groups in homogenates from brain, liver and testis (group II), highly reduced indices of fertility - 50% and of gestation - 62% (group II), in 100% level of the same indices in the control animals respectively. In P2 - reticulocytosis, reduced CytO in homogenates of liver, reduced activity of ATP and SucDH, enhanced activity of LDH and G6PDH in brain homogenates (group I), reduced fertility index - 67% versus 100% of the controls. In P3 - increased erythrocyte count (group II), changes in the electrophoretic protein profile of serum (group II); reduction of ChEA (groups I and II) and CytO (group II) in liver, reduced ChEA in brain (group II). The results obtained suggest an eventual high real and potential risk for the human generation, when the males are exposed to considerable concentrations (doses) of lead under working conditions.

An experimental study was carried out on the effect of noise with intensity 85 and 95 dB on the changes in the vascular walls of albino rats of an atherogenic diet (cholic acid, cholesterol and vitamin D2) in the course of 30 daws. The single effect of noise did not induce essential deviations in aortic metabolism and structure. The atherogenic diet caused segmental increase of intracellular substance, disorientation of tissue elements, destruction of smooth muscular cells, accompanied by activation of anaerobic oxidation processes, increase of the quantity of collagenous proteins with reduced globular and elastin proteins content. The noise, with an intensity of 95 dB intensifies the alterations in the vascular wall to the origination of medionecroses.

Biochemical and histochemical studies are undertaken with the purpose to establish the state of the aortic wall groung substance in white rats, poisoned over a 10-day period with lead acetate (1/100 LD50) and manganese bichloride (1/100 LD50), separately and in combination. It is demonstrated that either of the metals, both separately and in combination, lead to an increase of the quantity of acid, and to a decrease of the quantity of neutral mucopolysaccharides. It is worth noting that upon combined action, a relative augmentation takes place also of hyaluronic acid in all the layers of the aortic wall. The changes observed point to quantitative and qualitative alterations in the intercellular substances of the aortic wall leading, in turn, to disturbances in its permeability.

Studies on the possibilities of origination of remote sequelae (embryotoxic and teratogenic, gonadotropic, mutagenic, carcinogenic, alterations in cardiovascular system, etc) under the effect of the wide application of pesticides in the practice is one of the most important aspects of the present-day toxicology. Numerous of our studies in that field are directed to the pesticides, to fungicides in particular, the greater part of them being with mechanisms of biological activity, triggering changes in DNA synthesis and disturbances in cellular respiration. The results from our experimental studies are presented in the communication, with an aspect of alterations in the gonads, embryotoxicity and teratogenicity, of representatives of various groups of chemical preparations for plant protection. The eventual use of those data in the prognosis of potential risk for humans is discussed. Model conditions are proposed for a more thorough assessment and more accurate determination of threshold levels of effect with a view to their utilization in hygienic standardization.

The activity of the enzymes: SDH,GIDH,LDH, GI-6-PDH, ATP-ase,PGM, G 6P-ase, PI, 6P-ase in myocardial tissue were studied under conditions of a 30-day experiment on albino rats, treated two hours daily, 5 days in the week, with noise with an intensity of 85 dB/A/ and 95 dB/A/. Under the effect of noise with intensity of 85 dB/A/ a tendency to inhibition of SDH and GIDH activity is observed, which after the treatment with 95 dB/A/ noise is statistically significant. With the latter noise level a significant enhancement of PI,6 P-ase activity is established as well as a tendency to enhancement of G6P-ase and ATP-ase activity. The data from the investigations carried out reveal the possibility of developing disturbances in the metabolism of myocardial tissue under noise effect.

The authors studied the changes in myocardium during a long-term effect of low carbon sulphide concentrations--50 and 10 mg/m3 by enzyme-histochemical, biochemical and classical histological and electron microscopic methods. THe data from the experiment provided evidence of the involvement of myocardium and vessels in destructive-adaptation reactions in case of carbon-sulphide effect, the destructive processes being with preponderance. They are conditioned both by metabolic disorders of energy-forming systems and the disturbed processes of transport and utilization of energy. Furthermore, the action coordination is disturbed as in the separate muscle cells and the totality of the tissue elements, forming the myocardium as well.

The vascular wall is rich in glucoseaminglicanes (GAG), which form the basic intercellular substance and determine its multiple functions. Using analytic and chromatographic methods the author examined hexauronic acid (HA), pentoses (P), sulphate groups and various derivatives of GAG (hyaluronic acid (HA), pentoses (P), sulphate groups and various derivatives of GAG (hyaluronic acid (HA), dermatan-sulfate (DS), keratansulfate (KS), chondroitinsulfate (HS), and cheransulfate (HES) in human aorta, obtained from persons at the age of 10 and over 70 years of age. Ten aortas of each group were examined. The studies showed that in the aortas of the adult persons the content of HA, P, HS, KS and sulphate groups was considerably higher than that of the aourtas, obtained form the young persons. There was an impression that the adult factor affected substantialy the qualitative characteristics of GAG--with advancement of age the lenght of polysaccharide chains was shortened and the degree of sulphatation was increased. The accumulation of acid GAG in the aorta of adult persons impaired the metabolism of substances between blood and tissue, which enhanced the infiltration of the blood vessels with lipids and proteins, especialy when there was a blood increase in their content (hyperlipemia, hypercholesterinemia, ect.)

Prenatal inhalation toxicity of xylene (industrial mixture of isomers) was studied in experiments of white Wistar rats exposed daily (6 hours a day, 5 days in a week) to concentrations of 10, 50 (MAC for xylene in the air of work environment in Bulgaria) and 500 mg.m-3 throughout the period of gestation from the first to the 21st day. Both routine teratological indices and biochemical and physiological methods of observation were used to evaluate the integrity of the individual organs - liver, brain, lungs and myocardium of the generation in the postnatal period of development. In concentrations of 50 and 500 mg.m-3, xylene exhibits pronounced embryotoxic and teratogenic effects. Postimplantation embryonal mortality increases, the process of physical development of the fetus is delayed, the incidence of induced anomalies of internal organs (hydrocephalus, microphthalmia, intracerebral haematomas, haemorrhages in the liver) is enhanced, the processes of ossification of the sternum and the skull are impaired. In concentrations of 50 and 500 mg.m-3, xylene causes disturbances in postnatal development of F1 generation. The concentration of 50 mg.m-3 is the threshold of the embryotropic effect of the solvent. Measures for the protection of women at work are proposed to reduce industrial hazard of developing antenatal pathology in the newborn of workwomen in xylene works.