Action mechanisms of complementary and alternative medicine therapies for rheumatoid arthritis / 中国结合医学杂志

Rheumatoid arthritis (RA) is characterized as a chronic inflammatory disease in joints and concomitant destruction of cartilage and bone. Cartilage extracellular matrix components, such as type II collagen and aggrecan are enzymatically degraded by matrix metalloproteinases (MMPs) and aggrecanases in RA. Currently, treatments targeting cytokines, including anti-tumor necrosis factor (TNF) α antibodies, soluble TNF receptor, anti-interleukin (IL)-6 receptor antibody, and IL-1 receptor antagonist, are widely used for treating RA in addition to antiantiinflammatory agents and disease-modifying antirheumatic drugs (DMARDs), such as inflmethotrexate, but these treatments have some problems, especially in terms of cost and the increased susceptibility of patients to infection in addition to the existence of low-responders to these treatments. Therefore, therapeutics that can be safely used for an extended period of time would be preferable. Complementary and alternative medicines including traditional Chinese medicines (TCM) have been used for the arthritic diseases through the ages. Recently, there are many reports concerning the anti-arthritic action mechanisms of TCM-based herbal formulas and crude herbal extracts or isolated ingredients. These natural herbal medicines are thought to moderately improve RA, but they exert various actions for the treatment of RA. In this review, the current status of the mechanism exploration of natural compounds and TCM-based herbal formulas are summarized, focusing on the protection of cartilage destruction in arthritic diseases including RA and osteoarthritis.

Risk factors for epilepsy in rural Lao PDR: a case-control study.

The objective of this study was to assess the major etiologic categories of epilepsy in a rural district of the Lao PDR. Thirty-one newly identified patients with confirmed active epilepsy were compared with 124 controls, matched for gender, age and village residence. Risk factors for epilepsy were investigated with particular focus on cysticercosis serology. A history of head trauma (OR=4.7, p=0.05), family history of epilepsy (OR=12.8, p=0.03), and the use of human feces to fertilize domestic vegetable gardens (OR=4.9, p=0.04) were significantly associated with epilepsy. The study did not confirm any direct relation between epilepsy and cysticercosis serology. The cysticercosis seroprevalence was nil in the epilepsy group. This is the first study in the Lao PDR on epilepsy risk factors representing important data for the subregion. Parasitic, environmental, and behavioral factors of this traditional population deserve further studies to explain the missing link between epilepsy and cysticercosis.

Neurocysticercosis: clinical manifestation, neuroimaging, serology and molecular confirmation of histopathologic specimens.

Diagnosis of neurocysticercosis (NCC) is usually based on neuroimaging and/or immunological analysis of cerebrospinal fluid (CSF) and/or serum samples for detection of specific antibodies against T. solium antigens. Additional confirmative diagnosis may be possible by morphological and molecular confirmation of resected histopathologic specimens. The majority of NCC cases do not always show typical neuroimaging figures with invaginated scolex. So, serology using highly specific antigens of T. solium, either semi-purified native or recombinant antigens, is essential for confirming NCC cases. There is some debate about the usefulness of CSF and serum for immunodiagnosis. When NCC cases with a solitary cyst or with calcified lesions are examined, serology is not always sensitive to differentiating such cases. Malignant brain tumor is most commonly suspected in Japan and is often treated surgically as an urgent task, if the clinicians have no experience of NCC cases. Only histopathological specimens are expected to show direct evidence of T. solium cysticercosis. Morphology is not always sufficient for identification of the Taenia species, even if the majority of cysticerci in the human brain are expected to be T. solium. Crucial confirmation is based on molecular identification. In this review, these four issues are briefly summarized.

Towards the international collaboration for detection, surveillance and control of taeniasis/ cysticercosis and echinococcosis in Asia and the Pacific.

Both cysticercosis and echinococcosis are potentially among the most serious helminth zoonoses threatening human health worldwide. However, due to the lack of reliable tools for confirmation or identification of patients or infected animals, epidemiological data are expected to be underestimated. Conversely, sometimes, such data are over estimated due to the lack of specificity. The most important issue for doing field surveys is that they use evidence based science. In this communication, advanced immunological and molecular tools for detection of individuals infected with either metacestodes or adult tapeworms are briefly overviewed, and the applications of such tools for epidemiological surveys in Indonesia, China and other countries are introduced. As immunological tools are based on antigen-antibody responses, there may exist some cross-reactions. Therefore, immunodiagnostic tools are expected to be useful for primary screening, and should be combined with confirmation of direct parasitological evidence (morphology or DNA), and imaging techniques for cysts. As a risk factor for human cysticercosis is the presence of tapeworm carriers, detection of taeniasis cases and differentiation of the three human Taenia species (Taenia solium, T. saginata and T. asiatica) in Asia and the Pacific requires consideration. Similarly, in northwest China, Echinococcus granulosus and E. multilocularis are coendemic and differentiation of these species is required in humans and definitive hosts. It is stressed that combination of several tools for identification of the parasite and for confirmation of diseases is important for obtaining highly reliable data before consideration of control of these zoonoses. Recent projects coordinated by Asahikawa Medical College have concentrated on immunological and molecular diagnostic techniques transferable to colleagues from endemic regions of Asia and the Pacific, and on organization of two international symposia to establish a platform for further collaboration in the future.

Taeniasis and cysticercosis in Asia and the Pacific: present state of knowledge and perspectives.

Several topics on taeniasis and cysticercosis in Asia and the Pacific are overviewed. In Asia and the Pacific, three human taeniid species have been recognized: Taenia solium, Taenia saginata and Taenia asiatica. The first topic is on evolution of T. solium. Mitochondrial DNA polymorphisms of T. solium worldwide are discussed with emphasis of two specific genotypes: American-African and Asian. The second topic is recent major advances in sero- and molecular-diagnosis of T. solium cysticercosis in humans, pigs and dogs. The third is the present situation of T. solium taeniasis/cysticercosis in Papua (Irian Jaya), Indonesia. The forth is the present situation of T. solium cysticercosis and T. saginata taeniasis in Bali, Indonesia. The fifth is the present situation of T. asiatica taeniasis in Asia and the Pacific and in North Sumatra, Indonesia. The sixth is on the debate of the exact definition of T. asiatica. Because T. asiatica can not be differentiated from T. saginata morphologically, it is time to re-evaluate T. saginata in Asia and the Pacific. New and broad-based surveys across this region are necessary from epidemiological and public health perspectives, based on evidence.

Fundamental study of expression-library immunization against Taenia taeniaeformis in rats.

Expression-library immunization has been proposed as an effective means to screen a large number of genes of the pathogen as candidate protective molecules. In this study, we examined the efficacy of expression-library immunization using a T. taeniaeformis rat model system. Total RNAs were isolated from the last 15 segments of adult T. taeniaeformis and poly A RNA was purified. cDNA library was produced using SuperScript Plasmid System, which contains a mammalian expression vector, pCMV*SPORT6. From about 3,500 clones examined, more than 800 clones were found to contain DNA fragments. About 200 clones were sequenced and the homology search was carried out. The blast search revealed that 29% of the expression genes were mitochondrial genes (rRNA; 17%, protein; 12%). Nuclear rRNA genes (10%), nuclear protein (9%) and genes from Escherichia coli were also detected. Forty-two percent of sequences did not show a significant similarity to any genes deposited in the public database. Rats were immunized with expression-library and injected orally with 1,000 T. taeniaeformis eggs. However the protective effect of expression-library vaccine was not confirmed.

Molecular identification of Taenia solium cysticercus genotype in the histopathological specimens.

PCR-based molecular diagnosis was done for identification of causative agents found in paraffin-embedded specimens that were resected from two suspected neurocysticercosis patients. DNA samples were extracted from tissues or sections and cytochrome c oxidase subunit 1 gene and cytochrome b gene were amplified for the detection of taeniid DNA. Two different genes were successfully amplified in both specimens, but the sizes of amplified products seemed to depend on the quality of DNA. Based on the nucleotide sequences of the PCR-amplified genes, the causative agents from two cases were identified as T. solium Asian genotype. When infection with T. solium is not confirmed by histopathological examination, molecular diagnosis will be more useful for definitive diagnosis.

Treatment of taeniasis and cysticercosis with praziquantel and albendazole.

Recent methods, doses and results of medical treatment on taeniasis/cysticercosis, a zoo-notic parasitic disease caused by Taenia solium and Taenia saginata are discussed. In cases of cysticercosis T. solium, especially neurocysticercosis the optimal length and dose of albendazole is a course of 8 days with doses of 15 mg/kg/day divided in two times added by 50 mg/day of prednisone in the morning. The drug is effective in almost any location of the parasites for 80-90% of macroscopic cysts seen by imaging studies. For taeniasis a single dose of praziquantel, 10-15 mg/kg achieves cure rates of more than 90%. Side effects such as nausea, headache and abdominal pain are mild. Evaluation of drug treatment is done by clinical, radiological and serological evaluation. In Papua (=Irian Jaya) nine cases with suspected neurocysticercosis, serologically positive, were treated with 1200 mg single dose albendazole for 15 days. Prednisone tablets, three times daily one tablet, 5 mg during 7 days were added. After one year 6 cases were still serologic positive. At the same time praziquantel, 1200 mg, single dose was given to ten cases during 15 days and prednisone tablets, 3 times daily one tablet, 5 mg during 7 days. After one year 5 sero-positive cases were still found. Albendazole and praziquantel are both effective drugs for taeniasis and cysticercosis, with minor side effects. In addition symptomatic treatment should be given if necessary.

Cysticercosis: IgG-ELISA evaluations of peak1 antigen and <30 kDa antigen of delipidized extract of Taenia solium metacestodes.

The antigenicity of ether-delipidized Taenia solium metacestode extract (DLPAg) was investigated by IgG-ELISA. The antigen showed higher antigenicity than that of non-delipidized antigen (NDLPAg). Then the DLPAg was subjected to Sephacryl S-200 gel chromatography and a partially purified antigen (DLPP1Ag) was identified as the promised antigen by IgG-ELISA using 25 sera from cysticercosis cases, 177 cases of 24 heterologous infections, and healthy controls. Sensitivity was 52% and specificity was 91.8% at the cut-off value (X + 7SD), 0.399. Cross-reactivity occurred with 17 cases of eight diseases: cystic echinococcosis (7/11), taeniasis (1/16), gnathostomiasis (2/8), strongyloidiasis (1/12), angiostrongyliasis (1/12), paragonimiasis heterotremus (2/15), opisthorchiasis (1/9) and fascioliasis (2/7). When DLPP1Ag was fractionated through Ultra free centrifugal tube (retained 30 kDa) and Amicon (PM10), MWCOP1Ag (<30-10> kDa) was obtained; the antigen showed better results than DLPP1Ag with 88% sensitivity and 95.6% specificity at the cut-off value (X + 4SD), 0.264. Nine cases of six diseases cross-reacted with this antigen: cystic echinococcosis (2/11), gnathostomiasis (2/8), trichinellosis (2/12), toxocariasis (1/5), schistosomiasis (1/6), and fascioliasis (1/7). MWCOP1Ag gave higher sensitivity than that of DLPP1Ag but some cross-reactivity occurred.

Echinococcosis and cysticercosis in Asia: evaluation of the modern technology for epidemiological study.

The recent emergence of zoonotic parasitic diseases of public health importance represents a growing global concern. Among zoonotic helminthic diseases, both echinococcosis and cysticercosis are the most serious diseases threatening human life. Neurocysticercosis (NCC) caused by ingestion of eggs of the pork tapeworm, Taenia solium, is spreading worldwide and not rare even in Muslim or Jewish communities. Alveolar echinococcosis (AE) caused by the proliferation of metacestodes of the fox tapeworm, Echinococcus multilocularis, is the most potentially lethal parasitic infection of the non-tropical northern hemisphere, whereas cystic echinococcosis (CE) caused by the proliferation of metacestodes of the dog tapeworm, E. granulosus, has rather a cosmopolitan distribution. As the life cycles of T. solium, E. multilocularis and E. granulosus are completed through predator-prey interactions, including humans, it is crucial to interrupt the cycle for control of these zoonotic cestodiases. Both NCC and CE are expected to be eradicable, since the principal life cycles of T. solium and E. granulosus are maintained between humans and pigs and between dogs and herbivorous domestic animals, respectively. In contrast, AE is perhaps not eradicable, since the life cycle of E. multilocularis is maintained between wild foxes and rodents. Modern technologies, including imaging, immunology and molecular biology, have been applied for epidemiological surveys. In the present review, we introduce such technologies applied in Japan, China and Indonesia, and point out the problems that need to be solved for control of these three zoonotic cestodiases.

Multiple cysticercus nodules in skin and brain in a Balinese woman: A case report.

A case of multiple subcutaneous and cerebral cysticercosis in a 33-year-old Balinese female, is reported. The patient suffered from seizures since adolescence, which was not treated. Since three years before admission she started developing multiple nodules in the skin, starting from her forehead and since a year ago also in other parts of the head and body such as shoulders, chest and back. Serum sample tested against cysticercus antigen by immunoblot assay against antigen of Taenia solium was positive. The copro-antigen test was also positive, indicating the presence of the adult worm in the intestines. The patient was treated with praziquantel for the adult T. solium infection and thereafter with albendazole for the larval stages, which resulted in obvious reduction of the cerebral cysts and most of the subcutaneous nodules disappeared. However the adult worm was not recovered in the 24 hours stool specimen and after one year the immunoblot test was still positive.

Collaboration for the control of cysticercosis/echinococcosis in Vietnam.

A collaborative international project to control cysticercosis and cystic echinococcosis in Vietnam began in 2000. The project has drawn together the National Institute of Malariology, Parasitology and Entomology (NIMPE), Vietnam, and the WHO (Hanoi). Other contributors are the Prince Leopold Institute of Tropical Medicine (PLITM) in Belgium, the University of Salford, England, and the Asahikawa Medical College (AMC). Based on my experience of similar collaborations on cysticercosis in Indonesia, I offer a brief explanation of what my group at AMC has been doing and what we can do. The most important proposals are; 1) how to transfer up-to-date technology for differential sero- and molecular diagnosis that will be of use in an epidemiological survey of cysticercosis and echinococcosis as well in the identification of patients; 2) how to collaborate with the NIMPE for the control of these diseases; 3) how to encourage the young generation of researchers in the NIMPE to participate in the project.

The problem of Taeniasis and Cysticercosis in Irian Jaya, Indonesia.

The disease, caused by the adult and larva of Taenia solium, spread to the western part of Irian Jaya crossing the border of Indonesian to Papua New Guinea. Twenty local health centers reported 638 and 945 new cases with epileptic seizures in 1994 and 1995 respectively. Questionnaires were distributed to 31 respondents with results as follows: 83.9% were illiterate, 93.6% farmers and all of them sometimes ate not well-cooked pork; no other meat was consumed. In this area no healthy drinking water was available; also there was no sanitary facilities. Pigs were roaming around the houses, rarely the pigs were put behind fences. After international collaboration with several institutions, e.g with Asahikawa Medical College, Japan, 29 serum samples were examined by immunoblot with positive results for 67% of the cases suffering from epileptic seizures and 65% with subcutaneous nodules. Moving of people to other areas personal and environmental hygiene, the importance of pigs in the daily life of the community were important issues in maintaning the disease being caused by T.Solium in this area.