Research on needle-acupointomics / 中国针灸

The concept of needle-acupointomics should be clarified initially in order to discuss the relative researches. The comprehension can be deepened through the aspects of researching methods, content and goals. Proper researching model and analysis method should be selected so as to bring the advantages of the ancient acupuncture literatures, case records and clinical experiences of famous physicians into full play. Only in this way can the domestic needle acupointomics studies achieve a breakthrough.

Histopathological observation of acquired immunity in skin of hamsters elicited by Necator americanus third-stage infective larvae / 中国地方病学杂志

Objective To obtain acquired immunity evidence in hamsters elicited by third stage hookworm larvae of Necator americanas(NaL3).morphology changes of NaL3 and inflammatory responses in the skin and undedying subcutaneous tissue and muscles of hamsters were observed.Methods Hamsters were immunized subcutaneously with one dose of 150 NaL3 at 2 weeks earlier,and then challenged pereutaneously with 900 NaL3.Skins were excised from post-challenge hamsters at 6,24,72 hours and 1,2 weeks,and then examined under light microscopy.Non-immunized hamsters served as negative controls.Results In non-immunized hamsters the number of NaL3 were 15,33,11.0 and 0 at 6,24,72 hours and 1,2 weeks post-infection.No damaged or dead NaL3 section was observed.All NaL3 exhibited no structural damage and infihrating inflammatory cells were absent from the sunDunding tissues.There were no cutaneous changes.In contrast.the total number of Nak sections in the skin of immunized hamsters were 25,53,15,5 and 4 at 6,24,72 hours and 1,2 weeks post-challenge.Among these NaL3 sections,damaged and dead section number were 0,24,6,0,0 and 0,0,7,5,4.At 24 hours post-challenge the Nak exhibited cutieular swelling and damage.By 72 hours post-challenge pyknosis of the somatic cells nuclei and sparseness or loss of definition in the internal structures of NaL3 were seen.One or two weeks after chanenge,the NaL3 showed severe damage or even dead with remnants.Inflammatory responses including macrophages,epithelioid cells and eosinophils infiltrating and granulomata forming were mainly seen around the NaL3 sections in the skin of immunized hamsters.Conclusions Hamsters initially immunized with NaL3 exhibited obvious acquired immunity protection against percutaneously challenged infection as evidenced by vigorous inflammatory responses in the skin and underlying subcutaneous tissue and muscle.

Evaluation of the in vivo activity of tribendimidine against Schistosoma mansoni, Fasciola hepatica, Clonorchis sinensis, and Opisthorchis viverrini.

We examined the in vivo activity of tribendimidine against selected trematodes. A single 150-mg/kg dose of tribendimidine achieved a 99.1% reduction of Clonorchis sinensis in rats. A 400-mg/kg dose of tribendimidine reduced Opisthorchis viverrini in hamsters by 95.7%. High doses of tribendimidine showed no activity against Schistosoma mansoni and Fasciola hepatica.

Effect of artesunate and artemether against Clonorchis sinensis and Opisthorchis viverrini in rodent models.

Food-borne trematodiasis is an emerging public health problem and there is a need to develop novel treatment options. We examined the in vivo efficacy of single oral doses of artesunate and artemether administered to rodents experimentally infected with either Clonorchis sinensis or Opisthorchis viverrini. Rats infected with adult C. sinensis were administered artesunate or artemether at doses of 75, 150 or 300 mg/kg. Hamsters infected with adult O. viverrini were administered artesunate or artemether at doses of 200, 400 or 600 mg/kg. Treatment efficacy was assessed according to reductions in worm burden compared with infected but untreated control animals. Worm burden reductions of 98.6-100% were found in C. sinensis-infected rats after a single dose of artesunate and artemether at 150 mg/kg. Administration of artesunate and artemether at a dose of 400mg/kg to O. viverrini-infected hamsters resulted in worm burden reductions of 77.6% and 65.5%, respectively. However, both drugs showed toxic effects when administered to O. viverrini-infected hamsters at a dose > or =400mg/kg. Our study demonstrates that artesunate and artemether possess excellent clonorchicidal activities in vivo. These findings provide a foundation for subsequent clinical trials. More laboratory investigations are warranted to investigate further the opisthorchicidal properties of the artemisinins.

Effect of tribendimidine on adult Echinostoma caproni harbored in mice, including scanning electron microscopic observations.

Food-borne trematodiasis is an emerging public health problem with more than 10% of the world's population at risk of infection, yet there are only 2 drugs available for treatment and morbidity control. We assessed the effect of a promising broad-spectrum anthelmintic drug, i.e., tribendimidine, with an experimental focus on adult Echinostoma caproni. Female NMRI mice were infected with 30 E. caproni for 2 wk and then administered single oral doses of tribendimidine ranging between 25 and 500 mg/kg. Three days post-treatment, mice were necropsied, and adult worms were recovered from their intestines. Worm burden reductions were assessed against untreated control mice. In addition, scanning electron microscopic observations were done on adult E. caproni recovered from mice given a single dose of 150 mg/kg tribendimidine intragastrically 2, 4, and 8 hr post-treatment. Worm burden reductions of 100% were achieved at doses of 125 mg/kg and above. Severe damage of the tegument, including extensive peeling, formation of blebs, and structural loss of the definition of collar and tegumentary spines already occurred within 2 hr after drug administration. Our findings call for further investigations using tribendimidine in other trematode-animal models, because this compound shows promising trematocidal activity.

Effect of artemether administered alone or in combination with praziquantel to mice infected with Plasmodium berghei or Schistosoma mansoni or both.

The artemisinins have become key drugs for the treatment and control of malaria, particularly within artemisinin-based combination therapies. Since the artemisinins also exhibit antischistosomal properties, their use in areas where malaria and schistosomiasis are co-endemic may have an effect on both diseases and co-infection might alter drug efficacy. We assessed the antimalarial and antischistosomal efficacies of artemether in mice infected with Plasmodium berghei or Schistosoma mansoni or both parasites concurrently. Three oral doses of 400 mg/kg artemether at 14-day intervals reduced total and female S. mansoni worm burdens by 98.7-100%, regardless of a concurrent P. berghei infection. When four daily doses of 55 mg/kg artemether were administered, which is a standard treatment schedule to cure P. berghei-infected mice, significantly lower total and female S. mansoni worm burden reductions were observed (73.1-89.2%). Artemether, administered at both of the above-mentioned treatment schemes, showed excellent antimalarial efficacy with no indications of delayed clearance of P. berghei or recrudescence, also in mice co-infected with S. mansoni. Co-infection with P. berghei had no effect on S. mansoni worm burden reductions following artemether-praziquantel combinations. Our findings point to the need for epidemiological studies in areas where malaria and schistosomiasis co-exist and where artemisinin-based combination therapies are introduced, since artemisinin-based combination therapies as part of a malaria control package may have ancillary benefits against schistosomiasis.

Artesunate and artemether are effective fasciolicides in the rat model and in vitro.

OBJECTIVES: To study the fasciocidal properties of artesunate and artemether in the rat model and in vitro. METHODS: Adult Fasciola hepatica were exposed in vitro to 1, 10 and 100 microg/mL of artesunate, artemether and dihydroartemisinin for 72 h. Female Wistar rats were administered a single oral dose of artesunate and artemether (100-400 mg/kg) commencing 3 or 10-14 weeks post-infection and worm burden reductions were assessed against infected but untreated control rats. F. hepatica were also observed by scanning electron microscopy (SEM) after recovery from bile ducts of rats given a single oral dose of 200 mg/kg artesunate 24 and 72 h post-treatment. RESULTS: F. hepatica exposed for 72 h to 10 microg/mL of artesunate, artemether and dihydroartemisinin in vitro showed poor mobility, swelling of the worm body, roughness, damage of the tegument and blebbing. Exposure to drug concentrations of 100 microg/mL resulted in the death of all F. hepatica by 72 h. One hundred per cent worm burden reductions were achieved in rats infected with adult F. hepatica after treatment with artesunate and artemether at 400 and 200 mg/kg, respectively. Administration of artesunate and artemether at a dose of 200 mg/kg to rats harbouring juvenile F. hepatica resulted in worm burden reductions of 46% and 82%, respectively. F. hepatica recovered from rats' bile ducts 24 h after administration of 200 mg/kg artesunate showed normal activity and SEM observations revealed that there was no visible damage. Seventy-two hours post-treatment F. hepatica displayed very poor mobility and there was focal swelling of the tegument and spines. CONCLUSIONS: Artesunate and artemether exhibit promising fasciocidal activities, with the latter showing better tolerability by the hosts.

Protective immunity elicited by ultraviolet-irradiated third-stage infective hookworm (Necator americanus and Ancylostoma caninum) larvae in mice and hamsters.

The protective immunity elicited by ultraviolet-irradiated third-stage infective larvae of Necator americanus (UV-NaL3) and Ancylostoma caninum (UV-AcL3) was evaluated in laboratory mice (a non-permissive model) and hamsters (a permissive model). After optimizing the time of exposure to UV-irradiation, both oral and subcutaneous vaccination routes with UV-AcL3 in mice were explored. Oral vaccination was more effective at reducing the number of challenge AcL3 entering the lungs, whereas subcutaneous vaccination was more effective at blocking muscle entry. When UV-irradiated NaL3 and non-irradiated AcL3 were used as vaccines in hamsters, both of them were effective at reducing adult hookworm burdens. However, the length of protection afforded by UV-irradiated L3 was substantially greater than that resulting from immunization with non-irradiated L3. A single dose was less effective than multiple doses. The protective immunity elicited by UV-irradiated NaL3 given once every other week for a total of three immunizations was similar to that elicited by non-irradiated AcL3 given during the same schedule. Protection was not significantly affected by administering the L3 on a weekly basis for a total of three immunizations, even though the antibody titers were reduced using this schedule. These studies will facilitate the elucidation of the mechanisms underlying larval protection.

Necator americanus: optimization of the golden hamster model for testing anthelmintic drugs.

Laboratory golden hamsters (Mesocricetus auratus) were infected with Necator americanus under several different parasite and host conditions to optimize the model for testing anthelminthic drugs. The results confirmed that male hamsters were more susceptible to infection than females. Host age in the range of 5-15 weeks was not a factor that impacted on adult worm burden, and similar worm burdens were achieved using doses of 150, 250 or 500 N. americanus L3 (NaL3). The largest numbers of adult hookworms were recovered on days 21-28 post-infection, with a significant decrease at days 40-50 post-infection. Therefore adult worm recovery is maximal approximately 11-18 days prior to patency and host blood loss. From these studies a drug evaluation protocol was developed using 150 NaL3 as the infectious dose and then evaluating the anthelminthic effects of the drugs albendazole, tribendimidine, and pyrantel pamoate on days 21-28 post-infection. The model confirms the anthelminthic activity of albendazole, tribendimidine, and pyrantel pamoate and has the potential as a laboratory animal model to detect emerging drug resistance.

Tissue distribution and excretion of bromotetrandrine in rats / 药学学报

<p><b>AIM</b>To study the tissue distribution and excretion of bromotetrandrine (W198) in rats.</p><p><b>METHODS</b>The concentrations of W198 in biological samples were determined by an HPLC method with UV detection.</p><p><b>RESULTS</b>After a single i.v. dose of 20 mg x kg(-1) W198 in rats, the parent drug concentrations in tissues were higher than those in blood at the same time. Parent drug was mainly distributed in lung, kidney, heart and liver, the peak levels were attained at 0.25 h and decreasing at 2 h after dosing in most tissues. After a single iv dose of 20 mg x kg(-1) W198 in rats, the excretion of the parent drug in urine, feces and bile amounted to 0. 150%, 2.1% and 0.063% of the dose, respectively.</p><p><b>CONCLUSION</b>W198 was mostly distributed in lung. The parent drug excretion was less than 3% via urine, feces and bile.</p>

Triggering of high-level resistance against Schistosoma mansoni reinfection by artemether in the mouse model.

Artemether, a methyl ether derivative of dihydroartemisinin, not only exhibits antimalarial properties, but also possesses strong activity against schistosomula, the immature stages of a parasitic worm that can cause schistosomiasis. To test if the effect would be similar to that of irradiation with respect to the induction of immunologic protective responses, groups of mice were infected with Schistosoma mansoni cercariae and treated with artemether at 1-3 weeks post-infection. Control mice were either infected with normal cercariae or with cercariae exposed to radiation that permitted early development but not maturation of the parasites. The mice were challenged six weeks after the initial infection, and the mean numbers of schistosomes recovered in the various groups were calculated upon dissection eight weeks post-challenge. The administration of artemether two weeks after the initial infection resulted in 58% protection, while giving the drug three weeks post-infection increased the level of protection to 81%. This level of protection is as high as that normally obtained by immunization with irradiated cercariae (84% in the present study) and is superior to the level of resistance obtained with any individual schistosome vaccine candidate antigen thus far reported.

Necator americanus: maintenance through one hundred generations in golden hamsters (Mesocricetus auratus). I. Host sex-associated differences in hookworm burden and fecundity.

The human hookworm Necator americanus was maintained through one hundred generations in the golden hamster (Mesocricetus auratus). The parasite strain employed here was ultimately adapted to hamsters without the requirement for exogenous steroids or other immunosuppressive agents. Moreover, there was no requirement to use neonatal hamsters--successful infections were obtained in 9- to 10-week-old hamsters infected subcutaneously with 250 hookworm larvae. This unique adaptation of N. americanus to hamsters permits its use for purposes of anthelminthic drug and vaccine development.

Necator americanus: maintenance through one hundred generations in golden hamsters (Mesocricetus auratus). II. Morphological development of the adult and its comparison with humans.

Through 100 passages, the human hookworm Necator americanus was adapted to the golden hamster, Mesocricetus auratus, without either the requirement for exogenous steroids or other immunosuppressive agents, nor the requirement to infect hamsters as pups. Adult N. americanus recovered from infected hamsters were morphologically similar to those from infected humans in Sichuan Province, China, although they were smaller and the females produced fewer eggs. The natural history and kinetics of N. americanus infection was different in female and male hamsters. Female hamsters supported low intensity infections that lasted for approximately two months. In contrast, the peak intensity of infection in male hamsters was high, but this situation lasted less than for 4 weeks at which time many of the hookworms were expelled. However, even after the major parasite expulsion, the total number of hookworms consistently remained higher in chronically infected male hamsters compared with female hamsters. The hamster model of N. americanus is potentially useful for studying the development of new anthelminthic drugs and vaccines.

Bioavailability of ubiquinone 10 tablets in healthy volunteers / 中国临床药理学与治疗学

Aim To compare the bioavailability of two ubiquinone tablets in healthy volunteers. Methods A HPLC method was used to determine the serum ubiquinone 10 concentrations at 0,1,2,3,4,6,8 and 12 h after oral administration for 7 days ( 20 mg, tid ) in a cross-over test. Results AUC, Cmax and Tpeak of the test tablets were (5.91?1.78)?g?h?ml-1 ,(0.66?0.17)?g?ml-1 and (4.00?1.25) h, respectively,and these of the reference tablets were (6.30?2.09)?g?h?ml-1,(0.70?0.20)?g?ml-1 and (4.60?1.58)h , respectively . All of these parameters between the two kinds of tablets were not significantly different statistically. Conclusion The related bioavailability of the test tablets versus the reference tablets is 93.9%. The two formulations of ubiquinone 10 are bioequivalent.