Estimating the impact of Trypanosoma evansi infection (surra) on buffalo population dynamics in southern Philippines using data from cross-sectional surveys

Despite the widespread problem with surra (Trypanosoma evansi) in livestock, there are no published studies on its impact on host populations, probably because of the large financial and time cost involved in performing longitudinal studies. During 2002-6, a cross-sectional survey for T. evansi infection involving 1732 buffaloes from 71 villages in southern Philippines was carried out. Other livestock animals (horses, cattle and goats) in every surveyed village were also tested for infection with T. evansi but domestic buffaloes were the primary survey target. Seroprevalence ranged from 6% to 21% and 13% to 100% for buffaloes in low and high risk areas, respectively. Key demographic parameters were estimated from the age structured distributions of the sampled buffalo population for each sex. All areas were dominated by females (69%) and the annual calving rate for areas of 100% and low seroprevalence was 15% and 47%, respectively. Males were removed at a relatively high annual rate of 27% in all areas. In the main reproductive years (4-10) female removal/mortality was <1% and 10% for low and high risk areas, respectively. Older females were removed/died at a rate similar to males regardless of area. In high risk areas there were consistently more 2-year than 1-year old females and the reverse was true for the low risk areas. This implies that females were imported to the high risk areas for breeding. By assuming a stable age structure and similar size populations in each area, it was estimated that 28% of female calves need to be moved from low to high risk areas to maintain the observed age structure. In high risk areas, surra imposes significant financial losses due to reduced fertility, high mortality/removal rate and the necessity to import replacement buffaloes.     

Treatment and reinfection of water buffaloes and cattle infected with Schistosoma japonicum in Yangtze River Valley, Anhui province, China

The aim of the present study was to evaluate the efficacy of praziquantel treatment of Schistosoma japonicum infections in cattle and water buffaloes and to assess the natural rate of reinfection after treatment. The studies were conducted on 2 islands in the Yangtze River, Anhui province, China, from March 2003 to January 2004. The efficacy of praziquantel was 97% when applied orally wrapped in tree leaves at the recommended doses. The efficacy was measured using a miracidium hatching technique on fecal samples collected 20 days after treatment. The treatment did not give rise to any major side effects. Reinfection after treatment was high and occurred throughout the year in both cattle and water buffaloes. Age-related resistance was only observed in water buffaloes. It is concluded that although praziquantel is highly effective against S. japonicum in cattle and water buffaloes, a single annual treatment strategy does not effectively control transmission. New strategies for integrated control of animal schistosomiasis are needed to control schistosomiasis transmission more effectively in farm areas of China.     

The Schistosoma japonicum self-cure phenomenon in water buffaloes: potential impact on the control and elimination of schistosomiasis in China

Schistosomiasis japonica, caused by Schistosoma japonicum, is an important zoonotic disease in China, the Philippines and small pockets of Indonesia. In addition to infecting people, S. japonicum can infect over 40 species of wild and domestic animals which have varying impacts on human infection. It is now generally accepted that bovines, particularly water buffaloes, are the major reservoir for human infection in China as they are naturally infected with schistosomes and deposit more eggs into the environment than humans or any other animal host. This complicates control efforts and the economic burden associated with schistosomiasis morbidity and mortality has taken its toll on both human and livestock populations. Over the last 50 years, the schistosomiasis control program in China has made great strides in reducing prevalence and morbidity, and the Chinese authorities now aim to eliminate the disease nationwide in the next decade. Current Chinese control strategies place particular importance on interventions targeting bovines including: praziquantel treatment, barrier farming to prevent grazing in transmission areas, their replacement with mechanized tractors and possible bovine vaccination. A number of studies have shown that in the period following S. japonicum infection, the worm burden drops sharply in water buffaloes and some other animal hosts such as pigs. This is due to a self-cure phenomenon whereby there is parasite clearance by both immune and non-immune factors. Here we review studies investigating the self-cure effect, paying particular attention to S. japonicum infection in water buffaloes, and discuss its potential impact on the future schistosomiasis control and elimination efforts in China. Further understanding of the mechanism of self-cure in water buffaloes could be important for future schistosome vaccine design and delivery.     

Trypanosomiasis of domestic animals in China

Trypanosomiasis caused by Trypanosoma evansi (surra) is a problem of great economic importance in livestock in China because it affects important working animals: buffaloes in the south and east, and horses and cattle in the north and west. In addition, buffaloes are an important source of meat and leather for the Chinese population. In the north and west, T. evansi is found mainly in camels, whereas in the east, the south and the southwest, it is primarily buffaloes, cattle and horses that are affected by this parasitic flagellate. Although trypanosomiasis is one of the most important parasitic diseases of domestic animals in China, little information on this disease has been published. In this article Zhao-Rong Lun, Yuang Fang, Chang-Ji Wang and Reto Brun evaluate trypanosomiasis of domestic animals in China and review epidemiological studies of the past 40 years.     

Estimating sensitivity and specificity of a faecal examination method for Schistosoma japonicum infection in cats, dogs, water buffaloes, pigs, and rats in Western Samar and Sorsogon Provinces, The Philippines

Schistosoma japonicum causes a chronic parasitic disease, which persists as a major public health concern in The Philippines, the People's Republic of China and Indonesia. This infection is unique among helminthic zoonoses because it can infect humans and more than 40 other mammals. The objective of this study was to estimate the sensitivity and specificity of the Danish Bilharziasis Laboratory technique in cats, dogs, pigs, water buffaloes and rats in the Philippines. Faecal samples from each animal were collected on up to five occasions on five consecutive days in four villages of Sorsogon and Western Samar Provinces between January and July 2003. The faecal samples were analysed with the filtration and sedimentation Danish Bilharziasis Laboratory technique. Sensitivity and specificity of one, two, three, four, and five faecal samples were estimated using a Bayesian latent class approach. A total of 59, 43, 74, and 80% of the censored cats, dogs, pigs, and water buffaloes in the four villages were sampled, respectively. For all species, the sensitivity estimates when using the results of only 1 day of sampling were less than 80%. However, the sensitivity improved to at least 96% in all species when three or more faecal samples were collected on three separate days. The specificity was estimated to be above 92% across all species, even if just a single sample is used. The prevalences and 95% credible intervals of S. japonicum, adjusted for imperfect sensitivity and specificity, in cats, dogs, pigs, rats, and water buffaloes were 11.9% (6.8–18.3%), 19.9% (15.1–25.2%), 2.9% (1.1–5.2%), 31.3% (18.3–45.6%) and 6.3% (2.1–12.6%), respectively. Our results suggest that the Danish Bilharziasis Laboratory technique is valid for the detection of infection with S. japonicum in animals, and that sensitivity estimates are excellent when faecal samples are collected on at least three different days. Monitoring S. japonicum infection in animal reservoirs with a valid test could contribute to more effective public health control programmes.     

Point prevalence of bovine fascioliasis and the influence of chemotherapy on the milk yield in a lactating bovine population from the district of Toba Tek Singh, Pakistan

This paper provides an estimation of the point prevalence of fascioliasis and its economic impact in terms of increased milk yield after chemotherapy of a bovine population from the district of Toba Tek Singh, Punjab, Pakistan. A total of 2400 cattle and buffaloes were examined quantitatively using the McMaster egg-counting technique. Infected cattle and buffaloes (50 of each) were randomly selected and each divided into two groups of 25 animals. Groups A (buffaloes) and C (cattle) were treated with oxyclozanide (orally, 16.6?mg?kg-?1 body weight). Groups B and D served as negative controls for buffaloes and cattle, respectively. Pre- and post-treatment milk yield was recorded to determine if there were any changes in milk yield after treatment. Of 2400 faecal samples analysed, 654 (27.25%) were positive for Fasciola spp. with a mean number of eggs per gram (EPG) of 503.2. The point prevalence and worm burden of fascioliasis was significantly higher (OR?=?2.13; P?相似文献   

High Prevalence of Schistosoma japonicum Infection in Carabao from Samar Province,the Philippines: Implications for Transmission and Control

Schistosoma japonicum is endemic in the Philippines, China and Indonesia, and infects more than 40 mammalian host species, all of which can act as reservoirs of infection. In China, water buffaloes have been shown to be major reservoirs of human infection. However, in the Philippines, carabao have not been considered important reservoir hosts for S. japonicum due to the low prevalence and infection intensities reported, the only exception being a qPCR-based study indicating 51% of carabao were S. japonicum-positive. However, the low prevalence found for the same animals when using conventional copro-parasitological techniques means that there is still confusion about the role of carabao in the transmission of schistosomiasis japonicum. To address this inconsistency, and to shed light on the potential role of carabao in the transmission of S. japonicum in the Philippines, we undertook a pilot survey, collecting fecal samples from animals in Western Samar Province and we used a combination of molecular and copro-parasitological techniques to determine the prevalence and intensity of S. japonicum. We found a high prevalence of S. japonicum in the carabao using a validated real-time PCR (qPCR) and a copro-parasitological tool, the formalin-ethyl acetate sedimentation (FEA-SD) technique. A much lower prevalence of S. japonicum was recorded for the same fecal samples using conventional PCR, the Kato-Katz technique and miracidial hatching. These results suggest that, due to their low diagnostic sensitivity, traditional copro-parasitological techniques underestimate infection in carabao. The use of FEA-SD and qPCR provides a more accurate diagnosis. Based on these findings, the role of bovines in the transmission of S. japonicum appears to be more important in the Philippines than previously recognized, and this may have significant implications for the future control of schistosomiasis there, particularly as, in contrast with previous surveys, we found an unprecedented high prevalence of S. japonicum in humans.     

Serum prolactin levels of non-cycling murrah buffaloes (Bubalus bubalis )

Prolactin levels were quantified by double antibody radio-immunoassay in the blood sampled daily for 24 days, from 9 non-cyclic Murrah buffaloes during hot months (ambient temp.41 to 43 degrees C). All buffaloes were kept in open loose housing. Three buffaloes were sprinkled with water for half an hour twice daily between 1200 and 1430 h to overcome partly the effect of heat during the period of investigation. Mean prolactin levels of 6 unsprinkled buffaloes ranged on different days from 249 to 739 ng/ml serum. The range of averages in case of 3 sprinkled animals was from 152 to 342 ng/ml serum. Buffaloes subjected to sprinkling had significantly (P / 0.01) lower prolactin levels than control buffalo.     

Experimental treatment of summer anoestrous — Buffaloes with norgestomet and prid

Two experiments were undertaken to treat summer anoestrous buffaloes drawn from two distinct levels of total management, i.e., village vs. farm. At both locations, animals were randomly divided into three groups. One group was treated with norgestomet implants^a plus 700 I.U. PMSG at implant removal; the second group was treated with progesterone releasing intravaginal devices (PRID)^b and the third group was retained as untreated control. Serum samples were collected immediately before the commencement of treatments, before the withdrawal of treatments and on day 10 post-insemination (Artificial Insemination done 48 and 72 hours after the withdrawal of treatments). The samples were analysed for progesterone by radioimmunoassay. The ovulation and conception rates of norgestomet-treated animals were 58.33% vs. 77.79% and 40.16% vs. 60.11%, respectively, at village vs. farm. Similarly, the ovulation and conception rates of PRID-treated animals were 33.33% vs. 38.33% and 8.33% vs. 27.77%, respectively, at village vs. farm. None of the control animals exhibited oestrus during the course of the study.     

High prevalence of Schistosoma japonicum by perfusion in naturally exposed water buffalo in a region of the Philippines endemic for human schistosomiasis

In the past decade, ecological surveys emphasized rats and dogs as the most significant animal reservoirs for Schistosoma japonicum (S.j) in the Philippines. However, recent studies demonstrated 51–91% prevalence of schistosomiasis among water buffalo using qPCR in the Sj endemic regions in the Philippines. In order to resolve the inconsistency of reported surveys regarding Sj endemicity among carabao, a domestic water buffalo that is the most important draught animal, we introduced 42 schistosome negative water buffalo to Macanip, Jaro municipality, Leyte, the Philippines, a subsistence rice-farming village that has been the focus of schistosomiasis japonica studies of our group for the past 20 years. We conducted perfusion to the remaining 34 buffalo that survived 10 months of nature exposure and Typhoon Haiyan. Thirty-three water buffalo were found to be positive with at least 1 pair of worms from the mesenteric vein. The infection rate is 97%, with the worm burden of 94 (95% confidence interval, 49–138 worms) worms. To our knowledge, this is the first report about S. japonicum worm burden in naturally infected water buffalo in the Philippines. The fact that with less than one-year of exposure, in this human schistosomiasis endemic area, only 1 out of 34 water buffalo was uninfected is striking. Urgent attention is needed for a cost-effective technique for monitoring Sj infection in animals and humans. Meanwhile, intervention implementation, including water buffalo treatment and vaccination, should be taken into consideration.     

Identification of crossbred buffalo genotypes and their chromosome segregation patterns

Chromosome analysis on different breed types of water buffaloes (Bubalus bubalis) was undertaken to identify their karyotypes and to determine the pattern of chromosome segregation in crossbred water buffaloes. Altogether, 75 purebred and 198 crossbred buffaloes including 118 from Malaysia and 80 from the Philippines, were analyzed in this study. The diploid chromosome number of the swamp buffalo from both countries was 48 and that of the river buffalo was 50, while all F1 hybrids exhibited 49 chromosomes. The F2 hybrids consisted of three different karyotype categories (2n = 48, 2n = 49, and 2n = 50), whereas the backcrosses included two different karyotype categories each, with 2n = 48 and 2n = 49 in the three quarters swamp types and 2n = 49 and 2n = 50 in the three quarters river types. Chi-square tests on pooled data from Malaysia and the Philippines indicated that the distribution of different karyotype categories of F2 animals did not deviate significantly from the 1:2:1 ratio expected if only balanced gametes with 24 and 25 chromosomes were produced by the F1 hybrids. In the three quarters swamp and three quarters river types, the respective karyotypic categories were in ratios approximating 1:1. The distribution of chromosome categories among the F2 hybrids and backcrosses suggests that only genetically balanced gametes of the F1 hybrids are capable of producing viable F2 and backcross generations.     

Attenuation of luteolytic response following fish meal supplementation in dairy buffaloes (Bubalus bubalis)

Luteolysis of corpus luteum, due to un-inhibited PGF(2α) secretion, has been reported to be a cause of early embryonic mortality in dairy animals. The objective of this study was to determine the effects of fish meal (FM) supplementation on the uterine secretion of PGF(2α) and hence establish its supplementation as an antiluteolytic strategy in dairy buffaloes. Five cycling Murrah buffaloes were supplemented with 250g FM daily for 55 days in addition to their routine feed and seven buffaloes were kept as non-supplemented control. After 30 days of FM supplementation, the oestrus was synchronized in all the buffaloes using Ovsynch protocol. On day 15 of synchronized cycle, animals were challenged with oxytocin (OT; 100IU) intravenously and blood samples were collected at 15min interval, 1h before to 4h after OT challenge. The PGF(2α) response was measured as the venous concentration of 13,14-dihydro-15-keto PGF(2α) (PGFM). The mean hourly concentration of PGFM in FM supplemented buffaloes was lower than in the control buffaloes at all the occasions. During peak response (1h post-OT challenge), PGFM concentration was significantly lower (P<0.05) in FM supplemented buffaloes than in the control (197.4±41.7pg/ml versus 326.3±33.5pg/ml, respectively). Also the percent rise in PGFM after OT-challenge in FM supplemented buffaloes was less than the control (11.73% versus 22.47%). The dietary supplementation did not affect the size of corpus luteum (CL) and plasma progesterone concentration. Plasma glucose and total protein concentrations remained within the normal physiological limits during FM supplementation. The present study indicated that supplementing FM decreased the concentrations of PGF(2α) without alterations in the size of CL and plasma progesterone concentrations in dairy buffaloes.     

Bio-histopathological studies of endometrium in repeat breeding buffaloes (Bubalus bubalis)

A total of 24 uterine biopsies were successfully obtained from 40 repeat-breeding buffaloes. The endometrium of 15 buffaloes showed marked neutrophilic infiltration in the epithelium, stroma and uterine glands. In some cases, lymphocyte and plasma cell infiltration, cystic dilatation of the glands and periglandular fibrosis indicated chronicity of the endometritis. Most of the animals (85.0%) had uterine cultures positive for Streptococci, Staphylococci, Gram positive variable cocci, Gram negative bacilli, Anthracoids, and Gram positive bacilli with a predominance of Corynebacteria. With the treatment based on in vitro drug sensitivity tests, 57.1% repeat-breeding buffaloes conceived.     

Characteristics of the estrous cycle of the swamp buffalo under temperate conditions

Estrous cycle, duration of estrus and time of ovulation of eight cyclic buffaloes were examined during a period of one year. Animals were kept under loose-housing conditions and fed according to the Japanese Feeding Standards for dairy cattle. All the animals were observed for the occurrence of estrus twice daily by using a vasectomized bull, and ovarian cycles of each animal were monitored by weekly rectal palpation. Duration of estrus and time of ovulation were determined in 32 estrous periods from eight animals. Animals came in estrus throughout the year. The estrous cycles corresponding to single ovarian cycles ranged from 11 to 38 days with a mode interval of 20 days, averaged 21.5 +/- 4.7 days. Percentage of the cycles within a range of a mean +/- 1 SD (17-26 days) was 79.2 %, whereas that of cycles shorter or longer than the expected range was 9.4 % and 11.4 %, respectively. Estrus took place regardless of the time of day and lasted 9 to 27 hr (19.9 +/- 4.4 hr). Ovulation occurred 6 to 21 hr (13.9 +/- 3.4 hr) after the end of estrus, with a mode interval of 12 hr. There were no significant seasonal variations in the estrus characteristics studied.     

Effect of CGP 20376 on Brugia malayi and parasite antigenemia in jirds

This study was designed to investigate the activity of CGP 20376, a benzothiazole derivative, against Brugia malayi in jirds and to illustrate the utility of parasite antigen detection as a means of monitoring drug efficacy in filariasis. Drug treatment was 100% effective in jirds treated 3 or 24 days after infection. Microfilaria and adult worm counts were reduced (relative to counts in sham-treated control animals) by 96% and 95%, respectively, in animals treated 153 days after infection. Four of 6 animals in this treatment group cleared their microfilaremias and were free of adult worms 5 mo after treatment. Thus, CGP 20376 was effective against all life cycle stages of B. malayi in jirds. Parasite antigen levels in jird sera were consistent with parasitological results in all treatment groups, but antigen clearance was incomplete in some cases after apparently successful treatment of mature and immature infections.     

A comparison of experimental visceral leishmaniasis in the opossum, armadillo and ferret

Visceral leishmaniasis is a severe, chronic protozoal disease of humans and animals. Although chemotherapeutic agents are available for the treatment of this disease, problems such as drug toxicity, drug ineffectiveness and drug resistance of the parasite are responsible for treatment failures. To determine whether a drug is a potential antileishmanial agent, screening tests are performed using in vitro and in vivo models. Subsequently, a study using an appropriate animal model is performed to clearly determine the efficacy of a drug against Leishmania. Due to current public concerns regarding the use of companion animals in addition to the high costs of obtaining and maintaining these animals for research use, conventional animal models used in these chemotherapy studies, notably the dog and monkey, are becoming less acceptable. Therefore, new, less expensive and more accessible animal models are needed for the study of antileishmanial compounds. In this study, the armadillo, ferret and opossum were evaluated as possible new animal models for visceral leishmaniasis. The marked body weight loss, hepatomegaly, splenomegaly, large amastigote densities and the microscopic lesions observed in the infected opossums indicated that the opossum was more susceptible to visceral leishmaniasis than the armadillo or ferret.     

Evaluating alternative mowing regimes for conservation management of Central European mesic hay meadows: A field experiment

Conservation status of hay meadows highly depends on their management. The main goal of this study was to assess the efficiency of different mowing regimes in maintenance of plant species richness and diversity of mesic hay meadows. The field experiment was carried out on a species rich, mesic hay meadow in Western Hungary. We evaluated the effects of four alternative types of management on the plant community after 7 years of continuous treatment: (1) mowing twice a year, typical traditional management, (2) mowing once a year in May, most practised currently by local farmers, (3) mowing once a year in September, often proposed for conservation management and (4) abandonment of mowing. Traditional mowing resulted in significantly higher number and higher diversity of vascular plant species than other mowing regimes. Mowing twice a year was the only efficient way to control the spread of the invasive Solidago gigantea, and mowing in September was more successful in it than mowing in May. We conclude that the traditional mowing regime is the most suitable to maintain botanical diversity of mesic hay meadows; however, other regimes should also be considered if certain priority species are targeted by conservation.     

Resistance to Protease Inhibitors in a Model of HIV-1 Infection with Impulsive Drug Effects

Background

The emergence of drug resistance is one of the most prevalent reasons for treatment failure in HIV therapy. This has severe implications for the cost of treatment, survival and quality of life.

Methods

We use mathematical modelling to describe the interaction between T cells, HIV-1 and protease inhibitors. We use impulsive differential equations to examine the effects of different levels of protease inhibitors in a T cell. We classify three different regimes according to whether the drug efficacy is low, intermediate or high. The model includes two strains: the wild-type strain, which initially dominates in the absence of drugs, and the mutant strain, which is the less efficient competitor, but has more resistance to the drugs.

Results

Drug regimes may take trajectories through one, two or all three regimes, depending on the dosage and the dosing schedule. Stability analysis shows that resistance does not emerge at low drug levels. At intermediate drug levels, drug resistance is guaranteed to emerge. At high drug levels, either the drug-resistant strain will dominate or, in the absence of longer-lived reservoirs of infected cells, a region exists where viral elimination could theoretically occur. We provide estimates of a range of dosages and dosing schedules where the trajectories lie either solely within a region or cross multiple regions.

Conclusion

Under specific circumstances, if the drug level is physiologically tolerable, elimination of free virus is theoretically possible. This forms the basis for theoretical control using combination therapy and for understanding the effects of partial adherence.     

Topical Treatment of Dermatophytic Lesion on Mice (<Emphasis Type="Italic">Mus musculus</Emphasis>) Model

Antidermatophytic potential of three weed plants viz. Tridax procumbens L., Capparis decidua (forsk) Edgew and Lantana camara L. were explored and experimentally induced dermatophytic lesion was topically treated in mice. Microbroth dilution method was carried out for determination of MIC and MFC of different extracts of selected plants. In animal studies, mice were experimentally inoculated with Trichophyton mentagrophytes and infected animals were topically treated with 5 mg/g terbinafine and two concentrations, i.e., 5 and 10 mg/g of test extract ointment. Complete recovery from the infection was observed on 12th day of treatment for reference drug terbinafine (5 mg/g) and 10 mg/g concentration of test extract ointment whereas 5 mg/g concentration of test extract ointment showed complete cure on 16th day of treatment. Fungal burden was also calculated by culturing skin scrapings from infected animals of different groups. Test extract ointment successfully treated induced dermatophytosis in mice without any disease recurrence incidences, thereby indicating efficacy of test extract as an excellent topical antifungal agent for the cure of dermatophytosis.     

Zhi-fuzi, a cardiotonic Chinese herb, a new medical treatment choice for portal hypertension?

Zhi-Fuzi (Radix Aconiti lateralis preparata) is prescribed fairly frequently in Chinese medicine clinical practice for treating the complications of cirrhosis. However, scientific evidence regarding its efficacy and safety has not been available until now; in addition, its treatment efficacy has not yet been evaluated in well-designed clinical trials. Hence, we investigated the hemodynamic effects of Zhi-Fuzi in conscious rats with portal vein ligation (PVL) and the safety in normal rats. Our study included 3 parts: (i) early administration during which the hemodynamic effects of low and high doses of Zhi-Fuzi (0.4 and 0.8 g/kg twice daily) and propranolol (15 and 30 mg/kg twice daily) administered for 14 days after PVL on male Sprague-Dawley rats were evaluated; (ii) late administration during which the other group of PVL rats received 2.4 g/kg of Zhi-Fuzi twice daily from the 15th to 28th postoperative day; hemodynamic effects were measured when the Zhi-Fuzi treatment was finished; and (iii) safety evaluation during which 2 groups of normal rats were administered Zhi-Fuzi (0.4 and 0.8 g/kg twice daily) for 14 days; biochemical and histopathologic studies were completed after hemodynamic measurement. In early administration the portal pressures in rats receiving low and high doses of Zhi-Fuzi, low and high doses of propranolol, and distilled water were 13.81 +/- 0.11, 11.59 +/- 0.07, 17.09 +/- 0.06, 14.52 +/- 0.29, and 20.11 +/- 0.22 mm Hg, respectively. The high dose of Zhi-Fuzi exerted more portal hypotensive effects than propranolol and simultaneously ameliorated the systemic arterial hypotension in PVL rats. The late administration of Zhi-Fuzi also significantly reduced the elevated portal pressure (14.56 +/- 0.19 vs. 19.50 +/- 0.31 mm Hg in control, P < 0.05). There were no adverse effects seen in normal rats receiving Zhi-Fuzi. The results suggest that Zhi-Fuzi is a potential drug for the prophylaxis and treatment of portal hypertension.