Seroepidemiology and genotypes of hepatitis C virus in Thailand

HCV can be classified into 6 major genotypes based on the phylogenetic analysis of the genomic sequences. The 3 major genotypes found in Thailand are 3, 1 and 6, respectively. In 2004, an epidemiological survey was carried out to evaluate the seroprevalence of HCV infections among populations aged 2-60 years in four provinces of Thailand, representing the North, Northeast, Center and South of the country, respectively. One hundred and twenty five out of 5,825 serum samples (2.15%) were positive for anti-HCV by ELISA. Fifty eight out of 100 anti-HCV positive samples (58.0%) were positive by RT-PCR of the 5'UTR. The core region of 45 representative samples was sequenced allowing classification into genotype variants 1a (6.7%), 1b (26.7%), 2a (2.2%), 2c (2.2%), 3a (51.1%), 3b (2.2%) and 6 (8.9%). This information might be crucial for public health surveillance and prevention of HCV infection.     

Alginate-based pellets prepared by extrusion/spheronization: a preliminary study on the effect of additive in granulating liquid.

The aim of this study was to investigate the possibility of producing alginate-based pellets by extrusion/spheronization and also to improve the formation of spherical alginate-based pellets by investigating the effect of additive in granulating liquid on characteristics and drug release from resulting pellets. Two types of sodium alginate (30%) were evaluated in combination with theophylline (20%), microcrystalline cellulose (50%) and different granulation liquids. The pellets were then prepared in a basket extruder, then spheronized and dried. The final products were characterized by morphological examination and drug release study. Different additives in the granulating liquid influenced the ability of the extruded mass to form pellets (the processability) with this technique. However, different sodium alginate types responded to shape modifications to a different extent. Long, dumbbell-shaped pellets were obtained with viscous granulating liquids. However, short, nearly spherical pellets were obtained with watery granulation liquid with calcium chloride that reduced the swelling ability of sodium alginate. Improvements in the pellet characteristics were also dependent on the sodium alginate type employed. Most of pellet formulations released about 75-85% drug within 60min and showed a good fit into both Higuchi and Korsmeyer-Peppas equations. Higher amount of 3% calcium chloride, as a granulating liquid, in the formulation showed higher mean dissolution time resulting from the cross-linking properties of calcium ions to the negative charges of alginate molecules.     

Swelling, erosion and release behavior of alginate-based matrix tablets.

Hydrophilic matrix tablets based on the alginate system have been used in relation to their possible function in modified drug delivery formulations using metronidazole as a model drug. The matrix tablets were prepared by direct compression using different grades of alginate. The effect of some factors (i.e. particle size of drug, additive used, and pH of medium) on drug release from alginate-based matrix tablets was also investigated. Swelling, erosion, and in vitro release studies of the matrix tablets were carried out in 0.1N HCl or phosphate buffer (pH 6.8). The alginate-based matrix tablets swelled or eroded while in contact with the aqueous medium and formed a continuous gel layer or underwent combination of swelling and erosion. The swelling action of alginate matrices is controlled by the rate of its hydration in the medium. Different grades of alginate insignificantly influenced the matrix swelling in acidic medium but significantly influenced in neutral medium. The presence of ammonium or calcium salts induced tablet disintegration in acidic medium. However, incorporation of calcium acetate and sodium bicarbonate can alter the tablet swelling in acidic medium. Release studies showed that all investigated factors influence the drug release. The extent of matrix swelling, erosion, and diffusion of drug determined the kinetics as well as mechanism of drug release from alginate-based matrix tablets. Most of the release data in acidic medium showed a good fit into Korsmeyer-Peppas equation but fitted well with zero-order release model, in neutral medium.     

Development of polysaccharide gel-coated pellets for oral administration. 2. Calcium alginate.

Calcium alginate gel-coated pellets were developed by forming an insoluble gel coat on extruded-spheronized pellets by interfacial complexation. Experiments were designed to investigate the effect of pellet size, alginate type, alginate concentration, and dissolution medium on swelling and drug release behavior. Low swelling in acidic media was related to proton-calcium ion exchange forming insoluble acid gels. In contrast, partial formation of soluble sodium alginate in 0.1M NaCl induced water uptake, resulting in greater swelling. Drug release from coated pellets showed a lag time when the gel coat hydrated and swelled, followed by a zero-order release. Significantly slower release was observed when either the pellet size or the alginate concentration was increased. Alginate with high guluronic acid content gave the slowest release. Different types of alginate with high mannuronic acid content showed different release behaviors that are probably due to the different monomer sequences and botanical sources. The faster drug release in acidic media and 0.1M NaCl compared to water is probably due to reduced calcium cross-linking in the gel. These results suggest that the pellet size, alginate type and concentration and dissolution medium influenced the swelling and drug release behavior of calcium alginate gel-coated pellets.     

Morphology and buoyancy of oil-entrapped calcium pectinate gel beads

A new emulsion-gelation method to prepare oil-entrapped calcium pectinate gel (CaPG) beads capable of floating in the gastric condition was designed and tested. The gel beads containing edible oil were prepared by either being gently mixed or homogenized an oil phase and a water phase containing pectin, and then extruded into calcium chloride solution with gentle agitation at room temperature. The gel beads formed were then separated, washed with distilled water, and dried at 37 degrees C for 12 hours. A model of the emulsion-gelation process to illustrate the formation of oil-entrapped CaPG beads was proposed. The effect of selected factors, such as type of oil, percentage of oil, and type of pectin on morphology and floating properties was investigated. The oil-entrapped calcium pectinate gel beads floated if a sufficient amount of oil was used. Scanning electron photomicrographs demonstrated very small pores, ranging between 5 and 40 microm, dispersed all over the beads. The type and percentage of oil play an important role in controlling the floating of oil-entrapped CaPG beads. The results suggested that oil-entrapped CaPG beads were promising as a carrier for intragastric floating drug delivery.     

Use of back-scattered electron imaging as a tool for examining matrix structure of calcium pectinate

The internal structure of pharmaceutical solid dosage forms is commonly revealed by secondary electron imaging using standard scanning electron microscopy (SEM) technique. In this work we propose a back-scattered electron imaging (BEI) as a new tool for examining the matrix structure of calcium pectinate beads. Imaging samples with back-scattered electrons in the SEM is based on material or atomic number contrast. High atomic number elements, such as calcium, reflect more electrons and appear bright on electron micrographs. The BEI-SEM images of calcium pectinate matrix beads clearly showed net-like structure of calcium pectinate and uniform distribution of drug particles. The matrix compositions were confirmed by energy dispersive analyzer. The result demonstrates the advantageous of BEI for examining the matrix structure of calcium pectinate.     

Alginate-based pellets prepared by extrusion/spheronization: Effect of the amount and type of sodium alginate and calcium salts

Pellets containing microcrystalline cellulose (MCC), a model drug (theophylline) and a range of levels of sodium alginate (i.e., 10–50% w/w) were prepared by extrusion/spheronization. Two types of sodium alginate were evaluated with and without the addition of either calcium acetate or calcium carbonate (0, 0.3, 3 and 10% w/w). The effects of amount and type of sodium alginate and calcium salts on pellet properties, e.g., size, shape, morphology and drug release behavior, were investigated. Most pellet formulations resulted in pellets of a sufficient quality with respect to size, size distribution and shape. The results showed that the amounts of sodium alginate and calcium salts influenced the size and shape of the obtained pellets. However, different types of sodium alginate and calcium salt responded to modifications to a different extent. A cavity was observed in the pellet structure, as seen in the scanning electron micrographs, resulting from the forces involved in the spheronization process. Most of pellet formulations released about 75–85% drug within 60 min. Incorporation of calcium salts in the pellet formulations altered the drug release, depending on the solubility of the calcium salts used. The drug release data showed a good fit into both Higuchi and Korsmeyer–Peppas equations.     

Primary vesicoureteral reflux mediated renal scarring after urinary tract infection in Thai children

AIM: To evaluate the association between primary vesicoureteral reflux (VUR) and renal scarring in children using 99 m Technetium-labelled dimercaptosuccinic acid (DMSA). METHODS: Children attending at Songklanagarind Hospital from 1987 to 2002 were evaluated. RESULTS: Ages at diagnosis of VUR in 46 boys and 52 girls were 1.1+/-1.6 and 2.9+/-2.5 years, median 0.6 and 2.3 years, respectively (P<0.001). DMSA scans were performed at 4.1+/-3.6 years. Renal parenchymal damage was detected in 34 kidneys (22%) of 154 demonstrated refluxing ureters, and one kidney (2%) of 42 non-refluxing ureters (P=0.002). Of 79 refluxing ureters in boys and 75 refluxing ureters in girls, there were 25 and nine renal scars, respectively (32% and 12%, P=0.003). Renal scars in VUR grades I-V were 11%, 7%, 12%, 44% and 64%, respectively (P<0.001). Multivariate analysis revealed that high grade VUR (P<0.001), age of diagnosis of VUR greater than 5 years (P=0.001), and male gender (P=0.002) were the most significant risk factors for renal scarring. CONCLUSION: High-grade VUR, age of diagnosis of VUR greater than 5 years and male gender were the most significant risk factors for renal scarring.     

Declining trend in the seroprevalence of infection with hepatitis A virus in Thailand

Since the mid 1970s, infection with hepatitis A virus (HAV) in Thailand has shifted from hyper-endemic to mesoendemic. In 2004, to explore this trend in prevalence further, 3997 subjects from four geographically distinct provinces of Thailand were tested, in a commercial ELISA, for antibodies to HAV. The results indicate that the seroprevalence of HAV continues to fall, almost certainly because the profound socio-economic development that has occurred over the last few decades in Thailand has brought with it significant improvements in sanitation and personal hygiene. As exposure to HAV declines, however, the risks of symptomatic and potentially severe infection in adulthood (rather than asymptomatic infection during childhood) and of epidemics of such infection, which would lead to profound economic loss, increases. Improvements in hygiene and sanitation to reduce exposure to the virus and measures to reduce the incidence of symptomatic disease in those infected, such as vaccination (which may only be cost-effective when targeted at high-risk groups), need to be carefully considered.