Am. J. Trop. Med. Hyg., 75(3), 2006, pp. 556-562
Copyright © 2006 by The American Society of Tropical Medicine and Hygiene
CHINESE HERBAL MEDICINE YIN-CHEN-EXTRACT AS AN ADJUNCT TO ANTHELMINTIC ALBENDAZOLE USED AGAINST ANGIOSTRONGYLUS CANTONENSIS-INDUCED EOSINOPHILIC MENINGITIS OR MENINGOENCEPHALITIS
SHIH-CHAN LAI
Department of Parasitology, Chung Shan Medical University, Taiwan
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ABSTRACT
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The effects of albendazole and Yin-Chen-Extract co-therapy on Angiostrongylus cantonensis-induced eosinophilic meningitis in BALB/c mice were evaluated. Assay indicators for the therapeutic effect include worm recovery, histopathological score of the fourth ventricle, tissue-type plasminogen activator, urokinasetype plasminogen activator, matrix metalloproteinase-9, cerebrospinal fluid total protein, leukocyte counts, and proinflammatory cytokines. As a result, albendazole and Yin-Chen-Extract co-therapy significantly decreased (P < 0.05) these factors. Although Yin-Chen-Extract may possess pharmacologic activities beneficial to the inhibition of parasite-induced inflammation, many of these hypothetical benefits await scientific testing and confirmation before application. This study suggests that the combination of Yin-Chen-Extract and albendazole has synergistic effects in managing eosinophilic meningitis or eosinophilic meningoencephalitis.
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INTRODUCTION
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Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) are serine proteinases that play an important role in the pathogenesis of eosinophilic meningitis caused by Angiostrongylus cantonensis.1 The proinflammatory cytokine tumor necrosis factor (TNF) is a potent activator of neutrophils, mediating adherence, chemo-taxis, and degranulation; it is responsible for the severe cachexia that occurs in chronic infections.2 Matrix metalloproteinase-9 (MMP-9) gene expression by macrophages and polymorphonuclear leukocytes, and hence the release of pro-MMP, can be induced by TNF-
and interleukin (IL)-1 ß.3,4
Albendazole is an effective compound for the management of angiostrongyliasis through its larvicidal activity and facilitation of an improved inflammatory response via the reduction of MMP-9 activity,5 but dead worms in the brain may evoke a severe immune response resulting in brain damage. Recently, albendazole has frequently been used in combination with steroids to prevent the inflammatory reaction due to dead larva. However, the use of steroid therapy is still controversial. To replace steroids, this study considers Chinese herbal medicines, which have been used for thousands of years and are now being manufactured in many countries as quality-controlled drugs with standardized quantities of ingredients. Yin-Chen-Extract (Artemisia capillaries Thunb. extract) has been widely used as an anti-inflammatory agent, especially for diseases of the liver.6,7 This extract is different from anti-malarial artemisinin. Artemisinin is a drug isolated from extracts of leaves of A. annua and has been used in traditional Chinese medicine for the management of fevers for more than 2000 years.8
The present study estimates the efficacy of albendazole and Yin-Chen-Extract co-therapy in a mouse model of parasitic meningitis caused by A. cantonensis infection, and assays the therapeutic indicators of worm recovery, histopathological score of fourth ventricle, tPA, uPA, MMP-9, total protein, and leukocyte counts in parasite-induced eosinophilic meningitis.
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MATERIALS AND METHODS
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Experimental animals.
Five-week-old male BALB/c mice (weighing 20–25 g), were purchased from the National Laboratory Animal Center, Taipei, Taiwan. They were maintained at a 12- hour light/dark cycle photoperiod, provided with Purina Laboratory Chow and water ad libitum. All of the procedures involving animals and their care in this study were approved by the Institutional Animal Care and Use Committee of Chung-Shan Medical University in accordance with institutional guidelines for animal experiments.
Larval preparation.
The infective larvae (L3) of A. cantonensis originally obtained from wild giant African snails (Achatina fulica) that were propagated for several months in our laboratory by cycling through rats and snails (Biomphalaria glabrata). The larvae within tissues were recovered using a modification of the method of Parsons and Grieve.9 Briefly, the shells were crushed, the tissues were homogenized and digested in a pepsin-HCl solution (pH 1-2, 500 I.U. pepsin/g tissue), and incubated with agitation in a 37°C waterbath for 2 hours. Host cellular debris was removed from the digest by centrifugation at 1,400 g for 10 minutes. The larvae in the sediment were collected by serial washing in double-distilled water and counted under a microscope.
Drug.
Albendazole was purchased from Glaxo Smith Kline. Yin-Chen-Extract (Artemisia capillaries Thunb. extract) was purchased from Guanghan Bencao Plant Chemical Co., Ltd (Sichuan, China).
Treatment of animals.
Experiment 1.
To evaluate the effect of the timing of albendazole and Yin-Chen-Extract co-therapy on worm recovery, infected mice were given albendazole (10 mg/kg/d) and Yin-Chen-Extract (100 mg/kg/d) for 7 consecutive days on days 2, 4, 6, 8, 10, 12, and 14 post-inoculation (PI), respectively. Untreated infected mice served as controls. Each group consisted of 6 infected mice. The mice were killed on day 22 PI, and the brains were removed for worm recovery examination.
Experiment 2.
This experiment was conducted to determine the effect of albendazole alone, Yin-Chen-Extract alone, or albendazole and Yin-Chen-Extract co-therapy on worm recovery, histopathological score of the fourth ventricle, tPA, uPA, MMP-9, cerebrospinal fluid total protein, leukocyte counts, and proinflammatory cytokines on day 10 PI. A total of 100 mice were randomly divided into 5 groups; food and water was withheld for 12 hours before infection. The uninfected control mice were inoculated with distilled water by oral inoculation on day 10 PI; the infected-untreated control mice were infected with 50 larvae and treated as previously indicated; the albendazole treated mice were treated with albendazole (10 mg/kg/d) alone for 7 consecutive days starting on day 10 PI; the Yin-Chen-Extract treated mice were treated with Yin-Chen-Extract (100 mg/kg/d) alone for 7 consecutive days starting on day 10 PI; the albendazole and Yin-Chen-Extract co-therapy mice received a treatment combining albendazole (10 mg/kg/d) and Yin-Chen-Extract (100 mg/ kg/d) for 7 consecutive days starting on day 10 PI. All groups were killed on day 22 PI; the brains and CSF-like fluid were collected for histopathological study and biochemical analysis.
Collection of CSF-like fluid.
The mice were killed by cervical dislocation and their brains removed into a 35-mm dish. The cranial cavity and cerebral ventricles (lateral, third, and fourth ventricles) were rinsed with 1 mL 0.15 M phosphate buffered saline (PBS) and CSF was thus harvested with PBS, the washing solution being so-called "CSF-like fluid".
Worm recovery.
Experimental and control mice were killed by cervical dislocation on day 22 PI. Each brain was torn into small pieces and homogenized separately in 15 mL of 0.25% sodium citrate in PBS followed by centrifugation. Larval counts were done under 25 x magnification using a dissecting microscope. The mean number of larvae was compared with the positive control (infected-untreated) group to assess the drug efficacy.
Histopathological examinations.
The mouse brains were fixed separately in 10% neutral buffered formalin for 24 hours. The fixed specimens were dehydrated in a graded ethanol series (50%, 75%, and 100%) and xylene, and then embedded in paraffin at 55°C for 24 hours. Serial sections were cut at 5-µm thickness for each brain from each mouse. Paraffin was removed by heating the sections for 5 minutes at 65°C. These sections were dewaxed by washing 3 times for 5 minutes each in xylene; and then rehydrated through 100%, 95%, and 75% ethanol for 5 minutes each, and finally rinsed with distilled water. After staining with hematoxylin (Muto, Tokyo, Japan) and eosin (Muto, Tokyo, Japan), pathologic changes were examined under a light microscope.
Gelatin and casein substrate zymography.
Activity of MMP-9 was determined by gelatin zymography,10 and tPA and uPA activity by casein zymogyaphy.1 Briefly, the CSF-like fluid was centrifugated at 12,000 g for 10 minutes to remove debris. The protein contents of supernatants were analyzed on SDS-PAGE gels copolymerized with 0.1% gelatin (Sigma, St. Louis, MO, USA) for gelatinase activities, 0.1% casein (Sigma, St. Louis, MO, USA) for plasmin activities, and plasminogen (13 µg/ml, Sigma, St. Louis, MO, USA) for PAs activities. Electrophoresis was performed in running buffer (25 mM Tris, 250 mM glycine, 1% SDS) at room temperature at 120 V for 1 hour. The gel was washed twice at room temperature for 30 minutes each in 2.5% Triton X-100, and then washed twice with double-distilled water for 10 minutes each. The gel was incubated in reaction buffer at 37°C for 18 hours. The gel was then stained with 0.25% Coomassie Brilliant Blue R-250 (Sigma, St. Louis, MO, USA) for 1 hour and destained in 15% methanol/7.5% acetic acid. The final gel had a uniform background except in regions to which MMP-9, tPA, or uPA had migrated and cleaved their respective substrates. Quantitative analysis of the gelatinolytic and caseinolytic enzyme was performed with a computer-assisted imaging densitometer system, UN-SCAN-ITTM gel Version 5.1 (Silk Scientific, Orem, UT, USA).
Measurement of total protein.
The CSF-like fluid was centrifuged at 12,000 g at 4°C for 10 minutes, and the protein contents of the supernatants were determined with protein assay kits (Bio-Rad, Hercules, CA, USA) using bovine serum albumin as the standard. Protein concentration was determined by absorbencies at 595 nm using a HITACHI U1100 spectrophotometer (Tokyo, Japan).
Leukocyte count.
The cranial cavity and cerebral ventricles (lateral, third, and fourth ventricles) were rinsed with 1 mL PBS. The CSF-like fluid was centrifuged at 400 g for 10 minutes. The resultant sediments from each mouse were then resuspended with 30 µL PBS to enumerate the total number of leukocytes. The cell count was assessed with Wright-Giemsa staining (Sigma, Taufkirchen, Germany) in 3 µL/ smear.
Reverse transcriptase polymerase chain reaction (RT-PCR) analysis.
The brain homogenates were centrifugated at 12,000 g for 10 minutes to remove supernatants. Total RNA was isolated using Trizol reagent (Invitrogen, Carslbad, CA, USA) from the brains, according to the manufacturer’s instructions. Five µg of total RNA was used for first strand cDNA synthesis in 20 µL of reaction volume using 50 units of SuperscriptTM II reverse transcriptase (Invitrogen, Carslbad, CA, USA). PCR was performed under standard conditions using Taq DNA polymerase (Invitrogen, Carslbad, CA, USA) and primers. The forward (5'-3') and reverse (5'-3') primers, respectively, were 5'- CCC CTT CAT TGA CCT CAA CTA CAT GG-3' and 5'-GAC ATC AAG AAG GTG GTG AAG CAG GC-3' for glyceraldehyde-3-phosphate de-hydrogenase (GAPDH),11 5'-GCA TCC AGC TAC GAA TCT CCG ACC-3' and 5'-CAC TTG TTG CTC CAT ATC CTG TCC C-3' for IL-1',12 5'- ATG AGC ACA GAA AGC ATG ATC -3' and 5'- TAC AGG CTT GTC ACT CGA ATT -3' for TNF-.13 PCR cycling conditions for GAPDH, IL-1ß, and TNF- were denaturation at 94°C for 45 seconds, annealing at 55°C for 1 minute, primer extension at 72°C for 2 minutes, and then holding at 4°C; this was repeated for 30 cycles for TNF- and IL-1ß; 25 cycles for GAPDH. Ten mi-croliters of the amplified product was then subjected to electrophoresis in 3% agarose gels containing 20 µg/ml ethidium bromide in Tris borate-EDTA buffer. Gels were visualized on a UV transilluminator (Taipei, Taiwan), and digital images were taken using DGIS-5 Digital Gel Image System (Taipei, Taiwan). Quantitative analysis was performed with a computer-assisted imaging densitometer system, UN-SCAN-ITTM gel Version 5.1 (Silk Scientific, Orem, UT, USA).
Statistical analysis.
Results from the different groups of mice were compared using the nonparametric Kruskal-Wallis test, followed by post-testing using Dunn’s multiple comparison of means. All results are presented as mean ± SD (S.D.), and P values of < 0.05 were considered statistically significant.
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RESULTS
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Influence of treatment on larvae recovery.
The timing of albendazole and Yin-Chen-Extract co-therapy is critical for successful treatment of A. cantonensis-infected mice. The highest reductions (100%) were obtained when mice were treated on days 2 or 4 PI. This was followed by treatment on days 6 or 8 PI (96.4–92.8%). Reductions (86.2–80.5%) were observed when mice were medicated on days 10 or 12 PI. Only a slight reduction (62.1%) was observed when mice were medicated on day 14 PI (Table 1
). There were fewer recovered larvae in the treated population, compared with the infected-untreated population. Recovered larvae were virtually absent in the brain tissue of mice treated with al-bendazole alone or albendazole and Yin-Chen-Extract co-therapy. In contrast, no significant difference (P < 0.05) in worm recovery was observed between nontreated group and the group treated by Yin-Chen-Extract alone. The degree of brain inflammation coincided with the larva numbers of stay in CNS. The highest level of worm reduction was observed after co-therapy with albendazole and Yin-Chen-Extract. (Figure 1).
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TABLE 1 Effect of albendazole-Yin-Chen-Extract co-therapy on Angiostrongylus cantonensis larvae in BALB/c mice treated for 7 days at different starting medication
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FIGURE 1. Influence of treatment on larvae recovery. The numbers of recovered larvae were significantly decreased by albendazole (ABZ) alone or by albendazole-Yin-Chen-Extract (ABZ+YCE) co-therapy, compared with infected, untreated mice. There was no significant difference in worm recovery observed between infected-untreated mice and Yin-Chen-Extract (YCE) treated mice (*P < 0.05).
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Histologic observations.
Optical microscopic examination of tissues stained using haematoxylin and eosin revealed that inflammation of the fourth ventricle was induced in BALB/c mice by A. cantonensis infection. Invasion of the fourth ventricle by larvae was evident 22 days after the inoculation of the larvae. Larvae were significantly decreased in number by co-therapy with albendazole and Yin-Chen-Extract, moderately reduced after albendazole treatment, but no reduction after Yin-Chen-Extract treatment alone was observed (Figure 2).
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FIGURE 2. Histologic observations of hematoxylin and eosin staining. (a) The uninfected control present normal structures, including choroids plexus (CP) of the fourth ventricle, granular cells (G) of the cerebellum, molecular layer (ML) of the cerebellum, and medulla oblongata (MO). (b) The choroids plexus (CP) of mice infected with Angiostrongylus cantonensis showing larvae (arrowheads) invasion on day 10 PI. (c) Mice infected with A. cantonensis showing larvae (arrowheads) and leukocytes (L) accumulated in the fourth ventricle on day 22 PI. (d) Treatment with albendazole significantly decreased the larvae and leukocyte numbers (L). (e) Treatment with Yin-Chen-Extract did not kill the larvae (arrowheads) and only mildly decreased the leukocyte numbers (L). (f) Albendazole and Yin-Chen-Extract co-therapy significantly decreased the larvae and leukocyte numbers (L).
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Influence of treatment on the activities of tPA and uPA.
The tPA migrating electrophoretically as a 70 kDa species was significantly increased in CSF-like fluid of BALB/c mice infected with A. cantonensis, compared with control. The lytic area of the 70 kDa band was significantly reduced (P < 0.05) by albendazole or albendazole-Yin-Chen-Extract co-therapy; there was no significantly reduced by Yin-Chen alone. Similarly, the lytic area of the region of 55kDa uPA was significantly reduced (P < 0.05) by albendazole and Yin-Chen-Extract co-therapy or albendazole treatment alone, whereas no significant inhibition was observed by Yin-Chen-Extract alone (Figure 3).
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FIGURE 3. Influence of treatment on the activities of tPA and uPA. (A) The tPA activity was significantly increased in mice infected with Angiostrongylus cantonensis, as compared with control. The lytic area of the 70 kDa tPA band was significantly reduced by albendazole (ABZ) or albendazole-Yin-Chen-Extract (ABZ+YCE) co-therapy. There was no significant reduction by Yin-Chen-Extract (YCE). Similarly, the molecular weight of 55 kDa uPA was significantly reduced by albendazole alone or albendazole-Yin-Chen-Extract co-therapy, whereas no significant inhibition was observed by Yin-Chen-Extract alone. (B) Quantitative analysis of the PA enzymes were performed with a computer-assisted imaging densitometer system (*P < 0.05).
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Influence of treatment on the activity of MMP-9.
This enzyme migrates electrophoretically as a 94 kDa species. This metalloproteinase activity was significantly increased (P < 0.05) in CSF-like fluid of BALB/c mice infected with A. cantonen-sis, compared with control. The lytic area of the MMP-9 band was mildly reduced (P < 0.05) by Yin-Chen-Extract alone. MMP-9 was significantly reduced (P < 0.05) by albendazole alone or albendazole-Yin-Chen-Extract co-therapy. Co-therapy with albendazole-Yin-Chen-Extract was associated with a stronger reduction in MMP-9 activity than anthelminthic albendazole alone (Figure 4).
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FIGURE 4. Influence of treatment on the activity of MMP-9. (A) The MMP-9 activity was significantly increased in mice infected with Angiostrongylus cantonensis, as compared with control. The MMP-9 proteolytic band was significantly reduced by albendazole (ABZ) alone or albendazole-Yin-Chen-Extract (ABZ+YCE) co-therapy, and there was mild inhibition by Yin-Chen-Extract (YCE) alone. (B) Quantitative analysis of the gelatinolytic enzyme was performed with a computer-assisted imaging densitometer system (*P < 0.05).
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Influence of treatment on total protein.
The total protein was significantly increased in the CSF-like fluid of BALB/c mice infected with A. cantonensis, as compared with the control. The concentrations were significantly decreased (P < 0.05) by albendazole or by albendazole-Yin-Chen-Extract co-therapy compared with infected-untreated mice, although there was not a significant decrease by Yin-Chen-Extract treatment alone (Figure 5).
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FIGURE 5. Influence of treatment on total protein. The total protein of CSF-like fluid was significantly increased in mice infected with Angiostrongylus cantonensis, as compared with uninfected control. The concentrations of total protein were significantly less in mice treated by albendazole (ABZ) alone or albendazole-Yin-Chen-Extract (ABZ+YCE) co-therapy mice when compared with concentrations found in untreated infected mice. There was no significant change by Yin-Chen-Extract (YCE) alone (*P < 0.05).
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Influence of treatment on eosinophil counts.
The eosinophils were significantly increased in CSF-like fluid of BALB/c mice infected with A. cantonensis, as compared with control. Eosinophils were significantly reduced (P < 0.05) by albendazole alone or albendazole-Yin-Chen-Extract co-therapy, and there was no significant difference (P < 0.05) by Yin-Chen-Extract alone. Co-therapy with albendazole-Yin-Chen-Extract was more effective than albendazole alone in reducing eosinophilic inflammation (Figure 6).
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FIGURE 6. Influence of treatment on eosinophil counts. The eosinophils were significantly increased in CSF-like fluid of mice infected with Angiostrongylus cantonensis, as compared with uninfected control. Eosinophils were significantly decreased by albendazole or al-bendazole-Yin-Chen-Extract (ABZ+YCE) co-therapy, whereas there was no significant difference between infected-untreated group and Yin-Chen-Extract (YCE) alone.
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Influence of treatment on the mRNA expression of TNF- and IL-1 ß.
Mice infected with A. cantonensis exhibited a significant increase in IL-1ß and TNF-mRNA levels as compared with uninfected mice. Albendazole or albendazole-Yin-Chen-Extract co-therapy significantly lowered (P < 0.05) the mRNA levels of TNF- and IL-1ß compared with A. cantonensis-infected mice. Additionally, the mRNA levels of TNF- were also significantly lowered (P < 0.05) by Yin-Chen-Extract alone (Figure 7).
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DISCUSSION
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One of the most important goals in medicine is to continue searching for newer, more effective treatments. Even in parasite treatment, better and more effective treatment is replacing the older forms of treatment. Traditional medicine has played its role in the past.7,14,15 Advocates of Chinese herbal medicine generally regard this approach as both safe and effective, and there are many patients who report dramatic benefits to their health from treatment. The present study has actually supported the herbalists’ observation of a reduction of inflammation. The number of A. cantonengis larvae was significantly decreased when mice were treated with albendazole and Yin-Chen-Extract co-therapy. The highest reductions (100%) of timing were obtained when mice were treated on days 2 or 4 PI. However, the clinical symptoms were presented 10 days after infection with A. cantonensis. Thus, in the present study, we have found that therapeutic indicators such as worm recovery, tPA, uPA, MMP-9, total protein, and leukocyte counts occur on day 10 PI in mice treated with albendazole and Yin-Chen-Extract co-therapy. Additionally, albendazole and Yin-Chen-Extract co-therapy almost completely inhibited PAs activity and inflammation. Only partial inhibition of PAs and inflammation were produced by Yin-Chen-Extract alone. It can be concluded from these findings that PAs inhibition may promote the process of healing from eosinophilic meningitis and therefore, PAs may make useful diagnostic tools to evaluate healing from meningitis.
In the present study, total protein in CSF-like fluid was significantly decreased when mice were treated with albendazole-Yin-Chen-Extract co-therapy. These results suggest that CSF protein contents might play an important indicator in eosinophilic meningitis. Thus, treatment groups may improve the damage of blood-CSF barrier by reducing activity of PAs and increasing the flow rate of CSF.
The pro-inflammatory cytokines TNF-, and IL-1ß can be induced during A. cantonensis infection, and it is clear that basal levels of TNF- are essential for normal growth and development. Co-therapy with albendazole and Yin-Chen-Extract significantly decreased the mRNA levels of TNF- and IL-1ß, yet the mRNA levels were not completely inhibited. The possibility of co-therapy with albendazole and Yin-Chen-Extract targeting cytokines (TNF- and IL-1ß) may offer an effective management of eosinophilic meningitis or me-ningoencephalitis.
According to in vitro correlates of therapeutic efficacy plus Yin-Chen-Extract is more effective than anthelminthic albendazole alone. Although Yin-Chen-Extract may possess pharmacologic activities that could be beneficial to the inhibition of parasite-induced inflammation in general many of these hypothetical benefits await scientific testing and confirmation before application. The findings of this study suggest that the combination of Yin-Chen-Extract and albendazole may have a synergistic effect in embattling eosinophilic meningitis. A clinical trial is warranted to assess the utility of Yin-Chin extract as an adjunctive tool in treating A. cantonensis-induced eosinophilic meningitis.
Received January 4, 2006.
Accepted for publication April 20, 2006.
Acknowledgments: The author thanks Ke-Min Chen, Shu-Fang Chang, Chiaying Lee, I-Ting Kuan, and Chun-Hsien Wu, Department of Parasitology, Chung Shan Medical University, for assistance in this study.
Address correspondence to Shih-Chan Lai, Department of Parasitology, Chung Shan Medical University, 110, Section 1, Chien-Kuo North Road, Taichung 402, Taiwan. E-mail: shih{at}csmu.edu.tw
Author’s address: Shih-Chan Lai, Department of Parasitology, Chung Shan Medical University, 110, Section 1, Chien-Kuo North Road, Taichung 402, Taiwan. E-mail: shih{at}csmu.edu.tw.
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REFERENCES
|
- Hou RF, Tu WC, Lee HH, Chen KM, Chou HL, Lai SC, 2004. Elevation of plasminogen activators in cerebrospinal fluid of mice with eosinophilic meningitis caused by Angiostrongylus cantonensis. Int J Parasitol 34: 1355–1364.[Web of Science][Medline]
- Beutler B, Cerami A, 1989. The biology of cachectin/TNF: a primary mediator of the host response. Annu Rev Immunol 7: 625–655.[Web of Science][Medline]
- Sarén P, Welgus HG, Kovanen PT, 1996. TNF- and IL-1ß selectively induce expression of 92 kDa gelatinase by human macrophages. J Immunol 157: 4159–4165.[Abstract]
- Pugin J, Widmer MC, Kossodo S, Liang CM, Preas HL, Suffredini AF, 1999. Human neutrophils secrete gelatinase B in vitro and in vivo in response to endotoxin and proinflammatory mediators. Am J Respir Cell Mol Biol 20: 458–464.[Abstract/Free Full Text]
- Lan KP, Wang CJ, Lai SC, Chen KM, Lee SS, Hsu JD, Lee HH, 2004. The efficacy of therapy with albendazole in mice with parasitic meningitis caused by Angiostrongylus cantonensis. Parasitol Res 93: 311–317.[Web of Science][Medline]
- Zhang BZ, Ding F, Tan LW, 1993. Clinical and experimental study on yi-gan-ning granule in treating chronic hepatitis B. Zhongguo Zhong Xi Yi Jie He Za Zhi 13: 597–599.[Medline]
- Hong SH, Seo SH, Lee JH, Choi BT, 2004. The aqueous extract from Artemisia capillaris Thunb. inhibits lipopolysaccharide-induced inflammatory response through preventing NF-kappa B activation in human hepatoma cell line and rat liver. Int J Mol Med 13: 717–720.[Web of Science][Medline]
- Meshnick SR, Taylor TE, Kamchonwongpaisan S, 1996. Artemisinin and the antimalarial endoperoxides: from herbal remedy to targeted chemotherapy. Microbiol Rev 60: 301–315.[Abstract/Free Full Text]
- Parsons JC, Grieve RB, 1990. Effect of egg dosage and host genotype on liver trapping in murine larval toxocariasis. J Parasitol 76: 53–58.[Medline]
- Chen KM, Lee HH, Lu KH, Tseng YK, Hsu LS, Chou HL, Lai SC, 2004. Association of matrix metalloproteinase-9 and Purkinje cell degeneration in mouse cerebellum caused by Angiostrongylus cantonensis. Int J Parasitol 34: 1147–1156.[Web of Science][Medline]
- Betsuyaku T, Fukuda Y, Parks WC, Shipley JM, Senior RM, 2000. Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin. Am J Pathol 157: 525–535.[Abstract/Free Full Text]
- Boven LA, Vergnolle N, Henry SD, Silva C, Imai Y, Holden J, Warren K, Hollenberg MD, Power C, 2003. Up-regulation of proteinase-activated receptor 1 expression in astrocytes during HIV encephalitis. J Immunol 170: 2638–2646.[Abstract/Free Full Text]
- Aris RM, Walsh S, Chalermskulrat W, Hathwar V, Neuringer IP, 2002. Growth factor upregulation during obliterative bronchiolitis in the mouse model. Am J Respir Crit Care Med 166: 417–422.[Abstract/Free Full Text]
- Yeung CY, Leung CS, Chen YZ, 1993. An old traditional herbal remedy for neonatal jaundice with a newly identified risk. J Paediatr Child Health 29: 292–294.[Web of Science][Medline]
- Ho NK, 1996. Traditional Chinese medicine and treatment of neonatal jaundice. Singapore Med J 37: 645–651.[Medline]
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ABSTRACT
INTRODUCTION
