It is well known that dichlorvos (DDVP), an organophosphate insecticide in common use, is so easily and rapidly hydrolyzed and excreted that it has usually little toxic effect on human body. In these days, however, it is widely used as an industrial and domestic insecticide and as an anthelmintic agent for animals, so that the accident of chemical poisoning occurs frequently. DDVP acts as a powerful inhibitor of carboxylic esterase, which can cause accumulation of acetylcholine at the synapses so paralysis of muscle and the transmission failure in cholinergic synapses dueing to desensitization of acetylcholin receptor may occure. Moreover accumulation of the acetylcholine brings about the elevation of the cyclic-AMP, which alters the cellular metabolisms of nucleic acid, carbohydrate, protein and lipid. Present study has undertaken to investigate the cardiotoxic effect of DDVP by electron microscopic study. A total of 30 Sprague-Dawley strain rats, weighing about 250gm were used as experimental animals. 2mg/kg/day of DDVP is intraperitonealy injected 3 times with intervals of every other day. On 1 day, 3 days, 5 days, 7 days and 14 days after drug administration, the animals were sacrified by cervical dislocation. Left ventricular cardiac muscles were resected and sliced into $1mm^3$. The specimens were embedded with Epon 812 and prepared by routine methods for electron microscopical observation. All preparations were stained with lead citrate and uranyl acetate and then observed with Hitachi-600 transmission electron microscope. The results were as follows: 1. In the cardiac muscle of DDVP treated rats, mitochondria with disorganized double membrane and mitochondrial crista, and vacuole formation in mitochondrial matrix were observed. But structures of mitochondria were recovered to normal in 14 days group. 2. In the cardiac muscle of DDVP treated rats, cisternae of sarcoplasmic reticulum were dilated and sacculated. But these changes were recovered to normal in 14 days group. 3. In the cardiac muscle of DDVP treated rats, glycogen particles around damaged myofibrils were decreased. But amount of glycogen particles were restored in 14 days group. 4. In the cardiac muscle of DDVP treated rats, disruption and discontinuation of myofilaments and disorganization of Z-disc were observed. But the structures of myofibrils were recovered to normal in 14 days group. It is consequently suggested that DDVP would induce the reversible degenerative changes on the ultrastructures in cardiac muscle of rat.
Dryopteris crassirhizoma is one of the naturally occurring substance wood ferns and is known for having anti-inflammatory, antiviral and anthelmintic activities. However, there is less report about its anticancer effect in human cancer cell lines. In the present study, the effect of methanol extract of dryopteris crassirhizoma (MEDC) on apoptosis in human oral cancer cell lines (MC3 and HN22 cells) was investigated. MEDC inhibited cell viability and induced apoptosis. MEDC significantly increased Bak and truncated Bid proteins in MC3 cells and elevated only truncated Bid compared to the control while other Bcl-2 family proteins were not altered. MEDC has anticancer activity by inducing apoptotic cell death through the regulation of either Bak or Bid. These findings suggest that its extract possibly may be used for treating oral cancer.
Journal of agricultural medicine and community health
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v.10
no.1
/
pp.26-35
/
1985
The present study was undertaken to evaluate the prevalence rate of Taenia species infection and distribution of taeniasis caused by Taenia solium among Koreans in Seoul and Cheju Do In Korea during the period from August to December 1984. A total of 4,256 stool specimens from the students of Mapo Ku and 360 stool specimens from the inhabitants of Guro-Ku in Seoul was collected and examined by cellophane thick smear technique. On the other hand 1,015 stool specimens from the students of Jocheon Myun and 265 specimens from the students of Jocheon Myun and 265 specimens from the inhabitants of Aeweol Myun and Gujwa Myun in Cheju Do were also examined. The results were summarized as follows ; Four (0.1%) out of 4.256 students were positive and 2 (0.6%) out of 360 inhabitants in Seoul were positive (Table 1, 2). Positive rates of taeniasis in Cheju Do were 1.7% (17) out of 1,015 students and 12.5% (33) out of 5 villagers (Table 3, 4). In order to observe the distribution of Taenia solium infection, the scolex or a part of Taenia spp. were collected from the stool of positive cases by anthelmintic treatment. For the species identification, expelled proglottides were examined microscopically by the number of branches of the uterus, presence of vaginal sphincter or the accessory ovarian lobe etc. Three cases were infected with Taenia solium among 6 egg positive cases in Seoul. But only 1 case was infected with Taenia solium out of 7 students taking anthelmintics voluntarily by recommendation of Korean Association for Parasite Eradication (KAFPE). On the other hand, among 32 cases of egg positive cases of this study and 26 cases of KAFPE in Cheju Do, 13 cases (22.4%) were infected with Taenia solium. But 13 cases who were not examined and complained expulsion of proglottides in their stool were infected with Taenia saginata (Table 5). Among 62 persons infected with Taenia saginata, only 4 cases did not know their infection of this worm. Rut in 17 cases with Taenia solium, 7 persons did not know their infection until stool examinations were performed (Table 6).
A total of 32 human diphyllobothriasis cases have been reported so far in Korea, exclud- ing 21 egg-positive cases from stool examinations. Authors experienced five more human cases of DiphHllobothrium latum infection, especially infected due to eating raw flesh of redlip mullet, Lizc hoematocheiln. Five cases were neighbors residing in the Puchon area, Kyonggi-do, who ate raw mullets (L. hQematocheila) in a party in February 1996. The mul- lets were purchased at the Noryangjin fisheries market in Seoul. All of cases (2 males and 3 females) were 35 to 43 years old and healthy with the body weight range of 56-62 kg. They complained about gastrointestinal trouble and abdominal discomfort, but were in normal ranges of their hematology and urinalysis data. None revealed any sign of anemia The patients experienced natural discharge of a chain of segments before, and showed diphyllobothriid eggs in their stool specimens when they visited our laboratory. They were administered with praziquantel (15 mg/kg of body weight) and 30 g of magnesium sulfate as a purgative. Two whole worms with the scolices (310-340 cm in length; 8-13 mm in width) were expelled each from two out of five cases after anthelmintic treatment, and the others expelled the parts of strobilae without scolex. The worms were identified as D. Ictum, based on the following biological characters. external morphologies, coiling of uterus, the number of uterine loops, position of genital opening, morphologies of cirrus, cirrus sac and seminal vesicle on the histological sections, position of vagina and uterine pore , and microscopical and SEM morphologies of the eggs.
Beta-asarone is one of the main bioactive constituents in traditional Chinese medicine Acorus calamu. Previous studies have shown that it has antifungal and anthelmintic activities. However, little is known about its anticancer effects. This study aimed to determine inhibitory effects on LoVo colon cancer cell proliferation and to clarify the underlying mechanisms in vitro and in vivo. Dose-response and time-course anti-proliferation effects were examined by MTT assay. Our results demonstrated that LoVo cell viability showed dose- and time-dependence on ${\beta}$-asarone. We further assessed anti-proliferation effects as ${\beta}$-asarone-induced apoptosis by annexin V-fluorescein isothiocyanate/propidium iodide assay usinga flow cytometer and observed characteristic nuclear fragmentation and chromatin condensation of apoptosis by microscopy. Moreover, we found the apoptosis to be induced through the mitochondrial/caspase pathway by decreasing mitochondrial membrane potential (MMP) and reducing the Bcl-2-to-Bax ratio, in addition to activating the caspase-9 and caspase-3 cascades. Additionally, the apoptosis could be inhibited by a pan-caspase inhibitor, carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK). When nude mice bearing LoVo tumor xenografts were treated with ${\beta}$-asarone, tumor volumes were reduced and terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assays of excised tissue also demonstrated apoptotic changes. Taken together, these findings for the first time provide evidence that ${\beta}$-asarone can suppress the growth of colon cancer and the induced apoptosis is possibly mediated through mitochondria/caspase pathways.
The critical role of heat shock protein 90 (Hsp90) in tumorigenesis led to the development of several first- and second-generation Hsp90 inhibitors, which have demonstrated promising responses in cancers. In this study, we found second-generation Hsp90 inhibitor BIIB021-resistant multidrug-resistant (MDR) human cancer cells, although BIIB021 was shown to be active in first-generation Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-resistant MDR cells. MCF7-MDR and HeyA8- MDR cells were more resistant to BIIB021 than their parental counterparts, indicating that BIIB021 cannot be applicable to all cancer cells expressing MDR proteins. We revealed that dimethyl-celecoxib (DMC), one of the non-steroidal anti-inflammatory drugs (NSAIDs), potentiated cytotoxicity of BIIB021 against both BIIB021-resistant and BIIB021-sensitive MDR cells. The effectiveness of NSAIDs involving celecoxib and DMC in combination with BIIB021 led to the autophagic degradation/down-regulation of mutant p53 (mutp53) that overexpressed MDR cells and the suppression of Hsp70 induction. This resulted in sensitization of MDR cells to BIIB021. Moreover, autophagy induction by sulindac sulfide, another type of NSAID, and niclosamide, an FDA-approved anthelmintic drug, potentiated 17-AAG-mediated autophagic degradation/down-regulation of mutp53 and c-Myc, client proteins of Hsp90. Therefore, our results suggest that NSAIDs and niclosamide positively enhance the anticancer activity of Hsp90 inhibitors through an autophagic pathway. They may also be new candidates for sensitizing MDR cells to Hsp90 inhibitors.
Soil-transmitted helminth (STH) infections are still a considerable challenge in Myanmar. We undertook a control program for STH infections (especially Trichuris trichiura) among schoolchildren in Myanmar using mass drug administration (MDA) and health education. Around 1,700 schoolchildren from 15 primary schools in 3 suburban districts (Shwe Pyi Thar, Twantay, and Kyauktan) of the Yangon Region were subjected in this study during 2017-2019. All of the schoolchildren in each school were orally administered albendazole (400 mg in a single dose) 2, 3, and 4 times a year in 2017, 2018, and 2019, respectively. The results revealed that the egg positive rate of any intestinal helminths (including STH) was reduced from 37.6% (649/1,724) in 2017 to 22.8% (352/1,542) in 2019. The egg positive rate of Ascaris lumbricoides was decreased remarkably from 23.3% (402/1,724) in 2017 to 3.6% (56/1,542) in 2019. However, that of T. trichiura was only slightly reduced from 26.9% (464/1,724) in 2017 to 20.2% (312/1,542) in 2019. The intensity of infection with A. lumbricoides and T. trichiura was both more or less reduced, and the proportion of light infection cases with A. lumbricoides and T. trichiura increased from 35.6% in 2017 to 64.3% in 2019 and from 70.3% in 2017 to 81.7% in 2019, respectively. The results indicated that repeated MDAs (2-4 times a year for 3 years) using albendazole on schoolchildren in Myanmar failed to control T. trichiura infection. For a successful control of trichuriasis in Myanmar, new MDA strategies, using a modified albendazole regimen (multiple daily doses for 2 or 3 days) or an alternative anthelmintic drug, such as oxantel pamoate, is strongly recommended.
Standard- and large-sized eggs of Trichuris trichiura were found in the feces of schoolchildren in Yangon, Myanmar during epidemiological surveys and mass deworming with albendazole in 2017-2019. The standard-sized eggs were identified as those of T. trichiura, but it was necessary to exclude the possibility of the large-sized eggs belonging to Trichuris vulpis, a dog whipworm. We conducted morphological and molecular studies to determine the species of the 2 types of Trichuris eggs. Individual eggs of both sizes were isolated from Kato-Katz fecal smears (n=20) and mechanically destroyed using a 23G injection needle. Nuclear DNA was extracted, and the 18S rRNA region was sequenced in 15 standard-sized eggs and 15 large-sized eggs. The average size of standard-sized eggs (T. trichiura) was 55.2×26.1 ㎛ (range: 51.7-57.6×21.3-28.0 ㎛; n=97), whereas the size of large-sized eggs was 69.3×32.0 ㎛ (range: 65.1-76.4×30.1-34.5 ㎛; n=20), slightly smaller than the known size of T. vulpis. Regarding standard-sized eggs, the 18S rRNA nucleotide sequences exhibited 100% homology with T. trichiura deposited in GenBank and 88.6-90.5% homology with T. vulpis. Regarding large-sized eggs, the nucleotide sequences showed 99.8-100% homology with T. trichiura in GenBank and 89.6-90.7% homology with T. vulpis. Both standard- and large-sized eggs of Trichuris spp. found in Myanmar schoolchildren during 2017-2019 were morphologically and molecularly confirmed to belong to T. trichiura. The conversion of eggs from smaller to large sizes might be due to anthelmintic treatments with albendazole.
Eun Young Kim;Sungwon Choi;Sungsook Lee;Hyerim Son;Jin Ee Baek;Jae Hoon Shin;Deaho Kim
Journal of Korean Society of Occupational and Environmental Hygiene
/
v.33
no.4
/
pp.403-411
/
2023
Objectives: Formalin is used as an anthelmintic in farms where flounder are raised. In this study, we aim to identify formaldehyde exposure levels for aquaculture industry workers and provide basic data for managing formaldehyde exposure. Methods: Exposure levels of formaldehyde in the air, including formalin spraying operations, were assessed separately for personal and area samples. In addition, considering the formalin administration method, dermal exposure to the hands was estimated when administering the chemical, and dermal exposure to the legs during water tank work was estimated by collecting water in the water tank and evaluating the amount of formaldehyde remaining. Finally, the respiratory exposure level and the estimated dermal exposure level were added to derive the total exposure level and compared with the maximum allowable human dose. Results: As a result of the airborne evaluation, the formaldehyde concentration of the worker (1 person) who performed the formalin spraying and flounder sorting was 33.61 ppb, and the arithmetic mean of formaldehyde concentrations of the workers (3 people) who only performed the flounder sorting was 3.28 ppb (range: 2.25-4.89 ppb). In the case of dermal exposure, when spraying formalin once, the amount was estimated to be 0.33-2.62 mg when wearing protective gear and 3.27-26.12 mg when not wearing it. Conclusions: There was a difference in the formaldehyde exposure level of workers depending on their operation of handling formalin and whether or not protective gear was worn. In particular, because the level of formaldehyde exposure due to dermal exposure can be significant, there is a need to improve formalin administration methods in a way that avoids skin contact as much as possible.
Avermectin (AVM) $B_{1a}$ produced by Streptomyces avermitilis via polyketide pathway is a secondary metabolite with powerful anthelmintic and insecticidal activities, thus being used as an efficient agent in the field of agriculture and animal health. It has been reported that a precursor for AVM $B_{1a}$ biosynthesis was isoleucine and the biosynthetic pathway of AVM $B_{1a}$ was closely similar to that of fatty acid. Based on understanding of the biosynthetic pathway of AVM $B_{1a}$, we intended to screen various mutants resistant against O-methyl threonine (OMT), an isoleucine-anti metabolite, and/or mutants resistant against p-fluoro phenoxy acetic acid (pFAC), an inhibitor of fatty acid biosynthesis. It was inferred that these mutants could produce AVM $B_{1a}$ more efficiently, due to the acquired capability of not only overproducing isoleucine intracellularly but also channelling metabolized carbon-sources into the polyketide pathway, thus leading to enhanced biosynthesis of AVM $B_{1a}$. The resulting mutant (PFA-1 strain) resistant against 100 ppm of pFAC was able to produce approximately 42 fold higher amount of AVM $B_{1a}$ compared to the parallel mother strain (4,200 vs. 100 units/l). In addition, through the process of continuous strain improvement program carried out by gradually increasing the OMT concentration, it was possible to obtain a more attractive mutant with greater AVM $B_{1a}$ production capacity (9,000 units/l). Notable was that significantly higher producer (12,000 units/l) could be selected through further screening of the resistant mutants, this time, to even higher concentration of PFAC. Meanwhile, through the analysis of AVM Bla production histograms (i.e., number of strains according to their AVM $B_{1a}$ biosynthetic ability) for the earlier strains in comparison with the high producers having the characteristics of resistance to OMT and pFAC, it was found that production stability of the high-yielding producers were remarkably improved, as demonstrated by the fact that larger proportion of the mutated strains had greater capability of AVM $B_{1a}$ biosynthesis ($71\%$ in the range between 5,000 and 7,000 units/L; $47\%$ in the range between 6,000 and 7,000 units/l). Based on these consequences, it was concluded that the rational screening strategy based on the understanding of the biosynthetic pathway of AVM $B_{1a}$ was very effective in obtaining high-yielding mutants with the features of enhanced production stability.
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