Laws, regulations, guidelines, and principles pertaining to laboratory animals in Southeast Asia

Southeast Asia is a subregion of Asia, consisting of the following countries: Brunei or the Nation of Brunei; Cambodia or the Kingdom of Cambodia; Christmas Island (a territory of Australia); Indonesia or the Republic of Indonesia; Laos or the Lao People's Democratic Republic; Malaysia; Myanmar; Philippines or the Republic of the Philippines; Singapore or the Republic of Singapore; East Timor or Timor-Leste or the Democratic Republic of Timor-Leste; Thailand or the Kingdom of Thailand; and Vietnam or the Socialist Republic of Vietnam. All these countries are members of the World Organisation for Animal Health (OIE). The OIE Terrestrial Animal Health Code (the Terrestrial Code) sets out standards for the improvement of animal health and welfare and veterinary public health worldwide, including standards for safe international trade in terrestrial animals (mammals, birds, and bees) and their products. This is achieved through the detailing of animal health measures to be used by the veterinary authorities of importing and exporting countries to avoid the transfer of agents pathogenic for animals or humans, while avoiding unjustified trade barriers. The Terrestrial Code is a reference document for use by veterinary authorities, import/export services, epidemiologists and all those involved in international trade. Section 7 of the Terrestrial Code covers animal welfare and Chapter 7.1 is called, “Introduction to the Recommendations for Animal Welfare.” There is no specific overarching legislation applied for animal welfare relevant directly to laboratory animals for research, testing, and teaching in Southeast Asia. This chapter describes current laws, regulations, guidelines, and principles pertaining to laboratory animals used for research, teaching, and testing in some countries of Southeast Asia region including Cambodia, Indonesia, Philippines, Thailand and Singapor

Radical curative efficacy of tafenoquine combination regimens in Plasmodium cynomolgi-infected Rhesus monkeys (Macaca mulatta)

<p>Abstract</p> <p>Background</p> <p>Tafenoquine is an 8-aminoquinoline being developed for radical cure (blood and liver stage elimination) of <it>Plasmodium vivax</it>. During monotherapy treatment, the compound exhibits slow parasite and fever clearance times, and toxicity in glucose-6-phosphate dehydrogenase (G6PD) deficiency is a concern. Combination with other antimalarials may mitigate these concerns.</p> <p>Methods</p> <p>In 2005, the radical curative efficacy of tafenoquine combinations was investigated in <it>Plasmodium cynomolgi</it>-infected naïve Indian-origin Rhesus monkeys. In the first cohort, groups of two monkeys were treated with a three-day regimen of tafenoquine at different doses alone and in combination with a three-day chloroquine regimen to determine the minimum curative dose (MCD). In the second cohort, the radical curative efficacy of a single-day regimen of tafenoquine-mefloquine was compared to that of two three-day regimens comprising tafenoquine at its MCD with chloroquine or artemether-lumefantrine in groups of six monkeys. In a final cohort, the efficacy of the MCD of tafenoquine against hypnozoites alone and in combination with chloroquine was investigated in groups of six monkeys after quinine pre-treatment to eliminate asexual parasites. Plasma tafenoquine, chloroquine and desethylchloroquine concentrations were determined by LC-MS in order to compare doses of the drugs to those used clinically in humans.</p> <p>Results</p> <p>The total MCD of tafenoquine required in combination regimens for radical cure was ten-fold lower (1.8 mg/kg <it>versus </it>18 mg/kg) than for monotherapy. This regimen (1.8 mg/kg) was equally efficacious as monotherapy or in combination with chloroquine after quinine pre-treatment to eliminate asexual stages. The same dose of (1.8 mg/kg) was radically curative in combination with artemether-lumefantrine. Tafenoquine was also radically curative when combined with mefloquine. The MCD of tafenoquine monotherapy for radical cure (18 mg/kg) appears to be biologically equivalent to a 600-1200 mg dose in humans. At its MCD in combination with blood schizonticidal drugs (1.8 mg/kg), the maximum observed plasma concentrations were substantially lower than (20-84 <it>versus </it>550-1,100 ng/ml) after administration of 1, 200 mg in clinical studies.</p> <p>Conclusions</p> <p>Ten-fold lower clinical doses of tafenoquine than used in prior studies may be effective against <it>P. vivax </it>hypnozoites if the drug is deployed in combination with effective blood-schizonticidal drugs.</p

A Study Identifying the Medical Regions : An Analysis by Hierarchical Clustering Using Inter-districtional Transfer Rate

1)千葉県医療実態調査の資料により,「市町村内受診率」「地区間移動率」「隣接市町村間の患者相互移動数」「移動指数」を求め,患者の流れの傾向を検討した。つぎに「地区間移動率」による階層的クラスター分析を実施し,千葉県における実態医療圏を求め,計画医療圏のあり方について検討した。2)一般入院の市町村内受診率は全県で57.8%であり,人口当たりの病院数等の医療供給指標と強い相関を認めた。市町村間の相互依存を示す地区間移動率は,鉄道路線と関連を認めた。隣接する市町村間の移動を検討した結果,「辺縁効果」「勾配効果」の存在が示唆された。移動指数は,男性・生産年齢・入院医療・悪性腫瘍と精神疾患で大きい傾向を認めた。地区別でも格差を認め特に印旛郡,山武郡等で大きかった。3)患者の相互移動で表した地区間の結び付きの指標である地区間移動率を用いた階層的クラスター分析によって実態医療圏を求めた。4)求めた実態医療圏を計画医療圏として用いる上では地域特性はほぼ均質であるが,行政圏域や商圏とは一部で違いを認めた。圏域間の変動については近郊医療圏での人口集中や郡部での広域化が問題と思われた。5)医療圏間で医療需給の指標は地域特性を示す社会経済的指標よりも変動係数が大きく,潜在的医療需要を示すと思われる老年人口割合や粗死亡率よりも顕在化した需要である入院患者数の方が変動が大きかった。また医療圏内受診率は千葉市圏を除いて70%以下にとどまった。医療の質的量的充実が医療計画上の課題と思われた。6)地区間移動率およびそれを用いた階層的クラスター分析は実態医療圏解析の有効な方法と考えられる。To determine the regions for health plann

Scalable Preparation and Differential Pharmacologic and Toxicologic Profiles of Primaquine Enantiomers

Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the only antimalarial drug in clinical use for treatment of relapsing Plasmodium vivax malaria. PQ is currently clinically used in its racemic form. A scalable procedure was developed to resolve racemic PQ, thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. These enantiomers were compared for antiparasitic activity using several mouse models and also for general and hematological toxicities in mice and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity than (−)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ was a more potent suppressive agent than (−)-(R)-PQ in a mouse model of Pneumocystis carinii pneumonia. However, at higher doses, (+)-(S)-PQ also showed more systemic toxicity for mice. In beagle dogs, (+)-(S)-PQ caused more methemoglobinemia and was toxic at 5 mg/kg of body weight/day given orally for 3 days, while (−)-(R)-PQ was well tolerated. In a novel mouse model of hemolytic anemia associated with human G6PD deficiency, it was also demonstrated that (−)-(R)-PQ was less hemolytic than (+)-(S)-PQ for the G6PD-deficient human red cells engrafted in the NOD-SCID mice. All these data suggest that while (+)-(S)-PQ shows greater potency in terms of antiparasitic efficacy in rodents, it is also more hematotoxic than (−)-(R)-PQ in mice and dogs. Activity and toxicity differences of PQ enantiomers in different species can be attributed to their different pharmacokinetic and metabolic profiles. Taken together, these studies suggest that (−)-(R)-PQ may have a better safety margin than the racemate in human

Supplementary data for article: Opsenica, I.; Burnett, J. C.; Gussio, R.; Opsenica, D. M.; Todorović, N.; Lanteri, C. A.; Sciotti, R. J.; Gettayacamin, M.; Basilico, N.; Taramelli, D.; et al. A Chemotype That Inhibits Three Unrelated Pathogenic Targets: The Botulinum Neurotoxin Serotype A Light Chain, P. Falciparum Malaria, and the Ebola Filovirus. Journal of Medicinal Chemistry 2011, 54 (5), 1157–1169. https://doi.org/10.1021/jm100938u

Supporting information for: [https://doi.org/10.1021/jm100938u]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1157

KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment, and prevention of disease transmission

Renewed global efforts toward malaria eradication have highlighted the need for novel antimalarial agents with activity against multiple stages of the parasite life cycle. We have previously reported the discovery of a novel class of antimalarial compounds in the imidazolopiperazine series that have activity in the prevention and treatment of blood stage infection in a mouse model of malaria. Consistent with the previously reported activity profile of this series, the clinical candidate KAF156 shows blood schizonticidal activity with 50% inhibitory concentrations of 6 to 17.4 nM against P. falciparum drug-sensitive and drug-resistant strains, as well as potent therapeutic activity in a mouse models of malaria with 50, 90, and 99% effective doses of 0.6, 0.9, and 1.4 mg/kg, respectively. When administered prophylactically in a sporozoite challenge mouse model, KAF156 is completely protective as a single oral dose of 10 mg/kg. Finally, KAF156 displays potent Plasmodium transmission blocking activities both in vitro and in vivo. Collectively, our data suggest that KAF156, currently under evaluation in clinical trials, has the potential to treat, prevent, and block the transmission of malaria