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Biomedical subjects

Shuhua Xiao

Publications and source records attributed to Shuhua Xiao.

13 recordsLinked to original sources
PubMed2005

Simultaneous determination of ZT-1 and its metabolite Huperzine A in plasma by high-performance liquid chromatography with ultraviolet detection.

ZT-1 is a novel acetylcholinesterase (AChE) inhibitor. It is rapidly transformed to Huperzine A (Hup A) in vitro. A simple and rapid HPLC-UV method for the simultaneous determination of ZT-1 and its metabolite Hup A in plasma is described. The chromatographic separations were achieved on a C(18) ODS column (250 mm x 4.6 mm ID) using methanol-1 mmol/L ammonium acetate (70:30,v/v) as mobile phase. The flow rate was 0.7 mL/min, the detection wavelength was 313 nm and the column temperature was kept at 35 degrees C. Plasma samples were prepared as rapidly as possible and extracted immediately with 5 mL of chloroform:iso-propyl alcohol mixture (v/v, 9:1). The retention times of ZT-1 and Huperzine A (Hup A) were 18.7 and 14.4 min, respectively. The mean absolute recoveries of two analytes were >90%. Quantification limits were all 0.02 nmol/mL for ZT-1 and Hup A. This analytical method was reliable and convenient procedure that meets the criteria for the pharmacokinetic evaluation of ZT-1 on experimental animals.

Alkaloids↗
PubMed2005

Antibodies against a secreted protein from hookworm larvae reduce the intensity of hookworm infection in humans and vaccinated laboratory animals.

The development of a vaccine would provide an important new tool for the control of human hookworm infection. On the basis of successful vaccination of laboratory animals with living irradiated, third-stage hookworm larvae (L3), we examined the antibody responses of individuals from hookworm endemic areas of Brazil and China against the most abundant L3 secreted antigens, the ancylostoma secreted proteins, ASP-1 and ASP-2. Logistic regression was used to investigate the effects of antibody isotype responses to ASPs on the risk of an individual harboring heavy hookworm infection. A significant protective association was observed between increasing anti-ASP-2 IgE levels and the risk of heavy hookworm infection. To confirm that ASP-2 is a protective antigen, laboratory dogs were immunized with recombinant ASP-2 formulated with the GlaxoSmithKline Adjuvant, AS03. Sera obtained from the immunized dogs exhibited high geometric mean antibody titers, immunoprecipitated native ASP-2 from L3 extracts and localized the site of ASP-2 expression to the glandular esophagus and body channels exiting to the cuticle. The sera also exhibited an increased ability to inhibit migration of L3 through tissue in vitro relative to sera from AS03-injected controls. Upon L3 challenge, the ASP-2 vaccinated dogs exhibited significant reductions in fecal egg counts and intestinal hookworm burden. These findings provide strong support for the development of an effective recombinant vaccine against hookworm infection in humans.

Adolescent↗
PubMed2005

Biochemical characterization and vaccine potential of a heme-binding glutathione transferase from the adult hookworm Ancylostoma caninum.

We report the cloning and expression of Ac-GST-1, a novel glutathione S-transferase from the adult hookworm Ancylostoma caninum, and its possible role in parasite blood feeding and as a vaccine target. The predicted Ac-GST-1 open reading frame contains 207 amino acids (mass, 24 kDa) and exhibited up to 65% amino acid identity with other nematode GSTs. mRNA encoding Ac-GST-1 was detected in adults, eggs, and larval stages, but the protein was detected only in adult hookworm somatic extracts and excretory/secretory products. Using antiserum to the recombinant protein, Ac-GST-1 was immunolocalized to the parasite hypodermis and muscle tissue and weakly to the intestine. Recombinant Ac-GST-1 was enzymatically active, as determined by conjugation of glutathione to a model substrate, and exhibited a novel high-affinity binding site for hematin. The possible role of Ac-GST-1 in parasite heme detoxification during hemoglobin digestion or heme uptake prompted interest in evaluating it as a potential vaccine antigen. Vaccination of dogs with Ac-GST-1 resulted in a 39.4% reduction in the mean worm burden and 32.3% reduction in egg counts compared to control dogs following larval challenge, although the reductions were not statistically significant. However, hamsters vaccinated with Ac-GST-1 exhibited statistically significant worm reduction (53.7%) following challenge with heterologous Necator americanus larvae. These studies suggest that Ac-GST-1 is a possible drug and vaccine target for hookworm infection.

Amino Acid Sequence↗
PubMed2003

Determination of vertilmicin in rat serum by high-performance liquid chromatography using 1-fluoro-2,4-dinitrobenzene derivatization.

A procedure for the high-performance liquid chromatographic determination of vertilmicin in rat serum was described using pre-column derivatization. The serum proteins were precipitated with acetonitrile and vertilmicin in the supernatant was derivatized with 1-fluoro-2,4-dinitrobenzene. Etimicin was selected as the internal standard. The mobile phase consisted of methanol--20mM ammonium acetate (80:20, v/v), and flow-rate was 0.9 ml/min. Ultraviolet detection was set at 365 nm. The reaction products were chromatographed on a C(18) column kept at 40 degrees C. A good linearity was found in the range of 0.5-250 microg/ml. Both intra- and inter-day precisions of vertilmicin, expressed as the relative standard deviation, were less than 7.4%. Accuracy, expressed as the relative error, ranged from -0.1 to 3.6%. The mean absolute recovery of vertilmicin at three different concentrations was 92.5%. Serum volumes of 50 microl were sufficient for the determination of vertilmicin. The method was proved suitable for the pharmacokinetic study of vertilmicin in rats.

Aminoglycosides↗
PubMed2003

Progress in the development of a recombinant vaccine for human hookworm disease: the Human Hookworm Vaccine Initiative.

Hookworm infection is one of the most important parasitic infections of humans, possibly outranked only by malaria as a cause of misery and suffering. An estimated 1.2 billion people are infected with hookworm in areas of rural poverty in the tropics and subtropics. Epidemiological data collected in China, Southeast Asia and Brazil indicate that, unlike other soil-transmitted helminth infections, the highest hookworm burdens typically occur in adult populations, including the elderly. Emerging data on the host cellular immune responses of chronically infected populations suggest that hookworms induce a state of host anergy and immune hyporesponsiveness. These features account for the high rates of hookworm reinfection following treatment with anthelminthic drugs and therefore, the failure of anthelminthics to control hookworm. Despite the inability of the human host to develop naturally acquired immune responses to hookworm, there is evidence for the feasibility of developing a vaccine based on the successes of immunising laboratory animals with either attenuated larval vaccines or antigens extracted from the alimentary canal of adult blood-feeding stages. The major antigens associated with each of these larval and adult hookworm vaccines have been cloned and expressed in prokaryotic and eukaryotic systems. However, only eukaryotic expression systems (e.g., yeast, baculovirus, and insect cells) produce recombinant proteins that immunologically resemble the corresponding native antigens. A challenge for vaccinologists is to formulate selected eukaryotic antigens with appropriate adjuvants in order to elicit high antibody titres. In some cases, antigen-specific IgE responses are required to mediate protection. Another challenge will be to produce anti-hookworm vaccine antigens at high yield low cost suitable for immunising large impoverished populations living in the developing nations of the tropics.

Adolescent↗
PubMed2002

Emerging patterns of hookworm infection: influence of aging on the intensity of Necator infection in Hainan Province, People's Republic of China.

We examined risk factors associated with Necator americanus infection among persons aged > or =50 years in Hainan Province, People's Republic of China. Age and sex made the most important contributions to the variation in infection intensity (28%-30%), with age alone responsible for 27% of this variation. When stratified by 20-year age intervals, the influence of shared residence was 23% for persons aged > or =50 years and 27% for those aged <20 years, who had the highest and lowest levels of infection intensity, respectively. This points to shared residence as a means of capturing the complex relationship between aging and shared socioeconomic, environmental, and behavioral factors that influence transmission of Necator infection. None of the other 26 personal or 32 household risk factors were found to be significant. The importance of aging in Necator infection reveals an emerging public health problem among the elderly population of developing countries.

Adolescent↗
PubMed2002

Ultrastructural alterations in adult Schistosoma mansoni caused by artemether.

Progress has been made over the last decade with the development and clinical use of artemether as an agent against major human schistosome parasites. The tegument has been identified as a key target of artemether, implying detailed studies on ultrastructural damage induced by this compound. We performed a temporal examination, employing a transmission electron microscope to assess the pattern and extent of ultrastructural alterations in adult Schistosoma mansoni harboured in mice treated with a single dose of 400 mg/kg artemether. Eight hours post-treatment, damage to the tegument and subtegumental structures was seen. Tegumental alterations reached a peak 3 days after treatment and were characterized by swelling, fusion of distal cytoplasma, focal lysis of the tegumental matrix and vacuolisation. Tubercles and sensory organelles frequently degenerated or collapsed. Typical features of subtegumental alterations, including muscle fibres, syncytium and parenchyma tissues, were focal or extensive lysis, vacuolisation and degeneration of mitochondria. Severe alterations were also observed in gut epithelial cells and vitelline cells of female worms. Our findings of artemether-induced ultrastructural alterations in adult S. mansoni confirm previous results obtained with juvenile S. mansoni and S. japonicum of different ages.

Animals↗
PubMed2002

Transmission electron microscopic observations on ultrastructural damage in juvenile Schistosoma mansoni caused by artemether.

Artemether, a derivative of the antimalarial artemisinin, has been shown to induce rapid and extensive alteration to the tegument of juvenile Schistosoma japonicum, S. mansoni and S. haematobium. Less is known with regard to ultrastructural damage caused by artemether; therefore, the present work was designed to assess the damage in juvenile S. mansoni. Mice infected with S. mansoni were treated intragastrically with a single dose of 400 mg/kg artemether 21 days post-infection. Between 8 h and 14 days after treatment groups of two mice were sacrificed, and schistosomula recovered for transmission electron microscopic observations. Ultrastructural damage was seen in the tegument, subtegumental musculature, parenchymal tissues and gastrodermis. It was already apparent 8 h after drug administration and increased gradually to reach a peak, 7 days post-treatment. Tegumental alterations were characterised by swelling, vesiculation and degeneration of sensory structures. Damage in subtegumental musculature, parenchymal tissues and gastrodermis included swelling, focal or extensive lysis, and decrease in granular endoplasmatic reticulum. Fourteen days after treatment ultrastructural damage was still seen in most schistosomula, however, there was partial repair in some specimens. The ability of artemether to cause extensive ultrastructural damage to juvenile S. mansoni correlates with its schistosomicidal effects and confirms earlier findings with S. japonicum.

Animals↗
PubMed2002

Recent investigations of artemether, a novel agent for the prevention of schistosomiasis japonica, mansoni and haematobia.

Two decades ago, a group of Chinese scientists discovered the antischistosomal properties of artemether, a derivative of the antimalarial drug artemisinin. However, it was only recently that the importance of this finding was recognized internationally, following a collaborative effort between Chinese, European and African scientists, who investigated the effects of artemether against the major human schistosome species. Laboratory studies revealed that artemether exhibits the highest activity against juvenile stages of the parasites, while adult worms are significantly less susceptible. There was no indication of neurotoxicity following repeated high doses of artemether given fortnightly for up to 5 months. Randomized controlled clinical trials confirmed that artemether, orally administered at a dose of 6 mg/kg once every 2-3 weeks, results in no drug-related adverse effects, and significantly reduces the incidence and intensity of schistosome infections. The risk that these treatment regimens might select for resistance, particularly for resistant-plasmodia, appears to be low. Combined treatment with artemether and praziquantel, given to animals harbouring juvenile and adult schistosome worms, resulted in significantly higher worm burden reductions than each drug administered singly. In conclusion, artemether-integrated with other control strategies-has considerable potential for reducing the current burden of schistosomiasis in different epidemiological settings.

Administration, Oral↗
PubMed2002

Potential long-term toxicity of repeated orally administered doses of artemether in rats.

Artemether, an efficacious antimalarial drug, effectively prevents patent schistosome infections and morbidity, as established in laboratory models and in clinical trials. In view of concern about the potential long-term toxicity, rats were treated orally with 80 mg/kg artemether once every 2 weeks for 5 months. After the final treatment, routine blood test results were normal except for reversible reductions of reticulocyte counts and reversible increases in hemoglobin levels. Liver and kidney function and histopathological examination showed no differences between treated and untreated rats. Administration of 400 mg/kg artemether resulted in transient focal vesicle degeneration of the liver or slight damage to the proprius layer lamina of intestinal villi. No damage to the central nervous system tissues, including cerebrum, cerebellum, midbrain, thalamus, pons, medulla oblongata, and spinal cord, was seen at either concentration. There were no alterations in electrocardiograms during the 6-month treatment period. We conclude that 80 mg/kg artemether administered once every 2 weeks is safe, and doses of 400 mg/kg do not result in evidence of neurotoxicology.

Administration, Oral↗
PubMed2002

Clinical efficacy of albendazole emulsion in treatment of 212 cases of liver cystic hydatidosis.

OBJECTIVE: To evaluate the clinical efficacy of a new formulation of albendazole emulsion (AbzE) in cases of liver cystic hydatidosis. METHODS: Two regimens of AbzE (10 mg.kg(-1).d(-1) and 12.5 mg.kg(-1).d(-1)) were given to 212 patients with liver cystic hydatidosis in courses ranging from 3 months to more than one year. Assessment of drug efficacy was essentially based on imaging signs with ultrasonography as the main tool. Assessments were performed at the end of different courses and in the follow-up study of 1 - 4 years after the cessation of therapy. RESULTS: At the end of therapeutic courses, the overall cure rate of the 212 cases was 74.5%, with a 99.1% effective rate. In the follow-up study, the cure rate was 83.1%, effective rate was 89.3%, ineffective rate was 0.6%, and recurrence rate was 10.2%. The highest cure rate was observed in cases receiving AbzE 12.5 mg.kg(-1).d(-1) for 9 months. Retreatment of recurrent cases with AbzE obtained satisfactory results. CONCLUSIONS: AbzE surpassed other currently used antihydatidosis drugs or formulations with its promising efficacy and mild side effects, and could be recommended as a drug of choice in the treatment of cystic hydatidosis.

Adolescent↗
PubMedDate not supplied

Comparative study of the effects of artemether and artesunate on juvenile and adult Schistosoma mansoni in experimentally infected mice.

Artemether and artesunate, derivatives of the antimalarial artemisinin, also exhibit antischistosomal properties. There is a need to assess comparatively the activity of both compounds against different developmental stages of schistosome parasites. Since artemisinin derivatives will be increasingly used to treat malaria, it is important to study the effects of 7-day monotherapy regimens on schistosome infections. We carried out experiments with mice, infected with juvenile or adult Schistosoma mansoni, and treated with artemether or artesunate at various doses and regimens including those currently used for monotherapy of malaria. Three doses of artemether, at concentrations of 150 or 300 mg/kg, administered to mice with juvenile S. mansoni resulted in worm reductions of 88-97%, which were significantly higher than the 67-77% obtained with artesunate (P < 0.05). Total concentrations of 600 or 800 mg/kg artemether, administered over 2 or 4 consecutive days to mice with adult S. mansoni, reduced the worm burden significantly by 46-51% (P < 0.05). The reduction of the worm burden observed with artesunate was considerably lower, 24-33%, and not significant when compared with untreated control mice. Seven-day monotherapy regimens of artemether or artesunate given at different concentrations to mice with adult S. mansoni showed total worm reductions of 53-61% or 34-49%, respectively. We conclude that artemether and artesunate are efficacious antischistosomal agents, with artemether displaying consistently higher activities. Our findings may contribute to the current strategic discussions on the effect and use of artemisinin derivatives against schistosomes when they are used in malaria chemotherapy in areas of co-endemicity of both parasites.

Animals↗