Biomedical subjects

B J Lee

Publications and source records attributed to B J Lee.

At least 73 records · Page 4Linked to original sources

PubMed2000

Detection of porcine epidemic diarrhea virus by immunohistochemistry with recombinant antibody produced in phages.

Several diagnostic methods including immunofluorescence, enzyme-linked immunosorbent assay, polymerase chain reaction and immunohistochemistry have been developed for the detection of porcine epidemic diarrhea virus (PEDV). An immunohistochemical method using a new recombinant antibody produced by a phage antibody system (PAS16) kit was investigated and compared with that using a monoclonal antibody for PEDV detection in PEDV-infected piglets. In both the immunohistochemical methods, PEDV antigens were detected in the cytoplasm of villous enterocytes and in the macrophages infiltrated in the lamina propria at 18 to 110 hr post inoculation. The positive signals with the recombinant PAS16 antibody were similar to those with the monoclonal antibody. This result suggests that the recombinant PAS16 antibody can be applicable for the rapid immunohistochemical diagnosis of PEDV infection.

Animals↗

PubMed2000

Association of tightly spiraled bacterial infection and gastritis in pigs.

Tightly spiral bacteria were observed only in the pyloric mucosa of 4 (8.0%) of 50 swine stomachs, mainly in the surface of epithelia, the gastric pits and the lumen of gastric glands. The presence of the spiral bacteria was significantly associated with chronic pyloric gastritis (p<0.05). Mean gastritis score of the bacteria-positive pyloric mucosa was 3.25 +/- 0.25, whereas that of the bacteria-negative pyloric mucosa was 2.37 +/- 0.12. Parakeratosis and hyperkeratosis were spontaneously seen in the mucosa layer of pars oesophagea, regardless of the bacterial infection. Marked infiltration of mononuclear cells and granulocytes were seen in the cardiac mucosa, regardless of the bacterial infection. Mean gastritis score of the bacteria-positive cardiac mucosa was 3.27 +/- 0.32, whereas that of the bacteria-negative cardiac mucosa was 2.84 +/- 0.13. There was no significant difference between the bacteria-positive and negative cardiac mucosa (p>0.05). Inflammatory response in the fundic mucosa was rare (gastritis score=0.75 +/- 0.08). The tightly spiraled bactera were not cultured with various culture media. These results suggest that the presence of tightly spiraled bacteria is associated with only the pyloric gastritis in pigs.

Animals↗

PubMed2000

Neurovirulence of glycoprotein C(gC)-deleted bovine herpesvirus type-5 (BHV-5) and BHV-5 expressing BHV-1 gC in a rabbit seizure model.

Herpesvirus glycoprotein C (gC) is one of the major virus attachment proteins. Bovine herpesvirus type 1 (BHV-1) causes respiratory and genital diseases in cattle, whereas BHV-5 causes acute meningoencephalitis in calves. The gC gene sequence of these two viruses are substantially different. To determine the contribution of the BHV-5 glycoprotein gC (gC5) to the neuropathogenesis of BHV-5, we have constructed two BHV-5 recombinants: gC-deleted BHV-5 (BHV-5gCDelta) and BHV-5 expressing BHV1 gC (BHV-5gC1). Neurovirulence properties of these viruses were analyzed using a rabbit seizure model that distinguishes BHV-1 and -5 based on their differential neuropathogeneses. Intranasal inoculations of BHV-5gCDelta and BHV-5gC1 viruses produced neurological signs in 30% and 40% of the infected rabbits, respectively. Immuno-histochemistry results showed that the number of infected neurons was 2 - 4-fold less with the gC-deleted BHV-5 than with the wild-type BHV-5. The gC-deleted BHV-5 did not invade the hippocampus but invaded additional sites not invaded by wild-type BHV-5. Similarly, the BHV-5gC1 virus failed to invade the hippocampus, but it did not invade the additional sites. Virus isolation results suggest that these recombinants replicate less efficiently in the brain than the wild-type and gC-revertant viruses. However, compared to the gC-deleted BHV-5, the gC-exchanged BHV-5gC1 replicated better within the CNS. These results indicate that gC regulates BHV-5 neurotropism in some areas of the olfactory pathway. Additionally, gC is important for BHV-5 neurovirulence in the olfactory pathway but it is not essential.

Animals↗

PubMed2000

Glia-to-neuron signaling and the neuroendocrine control of female puberty.

It is becoming increasingly clear that astroglial cells are active participants in the process by which information is generated and disseminated within the central nervous system (CNS). In the hypothalamus, astrocytes regulate the secretory activity of neuroendocrine neurons. They contribute to facilitating sexual development by stimulating the release of luteinizing hormone-releasing hormone (LHRH), the neuropeptide that controls sexual development, from LHRH neurons. Astrocytes secrete several growth factors able to stimulate LHRH secretion. Two members of the epidermal growth factor (EGF) family--transforming growth factor alpha (TGFalpha) and the neuregulins (NRGs)-are produced in hypothalamic astrocytes and elicit LHRH secretion indirectly, via activation of receptor complexes formed by three members of the EGF receptor family, also located on astrocytes. Activation of these receptors results in the production of at least one neuroactive substance, prostaglandin E2 (PGE2), which stimulates LHRH secretion upon binding to specific receptors on LHRH neurons. Overexpression of TGFalpha in the hypothalamus accelerates puberty, whereas blockade of either TGFalpha or NRG actions delays the process, indicating that both peptides are physiological components of the neuroendocrine mechanism that controls sexual maturation. An increase in hypothalamic expression of at least two of the erbB receptors is initiated before the pubertal augmentation of gonadal steroid secretion and is completed on the day of the first preovulatory surge of gonadotropins. This secondary increase is brought about by gonadal steroids. Estrogen and progesterone facilitate erbB-mediated glia-to-LHRH neuron communication by enhancing astrocytic gene expression of at least one of the EGF-related ligands (TGFalpha) and two of the receptors (erbB-2 and erbB-4). They also facilitate the LHRH response to PGE2 via induction of PGE2 receptors in LHRH neurons. A search for genes that may act as upstream regulators of the pubertal process resulted in the identification of two potential candidates: Oct-2, a POU domain gene originally described in cells of the immune system, and TTF-1, a member of the Nkx family of homeodomain transcriptional regulators required for diencephalic morphogenesis. The hypothalamic expression of both genes increases during juvenile development before the first hormonal manifestations of puberty take place. Their mRNA transcripts are localized to specific hypothalamic cellular subsets, where they appear to regulate different, but interactive, components of the neuronal-glial complex controlling LHRH secretion. While Oct-2 transactivates the TGFalpha promoter, TTF-1 does so to the erbB-2 and LHRH genes but inhibits preproenkephalin promoter activity, suggesting that both transcriptional regulators may act coordinately in the normal hypothalamus to activate genes involved in facilitating the advent of puberty and repress those restraining sexual development. Altogether, these observations indicate that the central activation of the pubertal process involves the participation of both neuronal and astroglial networks and the contribution of upstream transcriptional regulators acting on both the neuronal and glial components of the system.

Animals↗

PubMed1999

Association between apolipoprotein E polymorphism and Alzheimer's disease in Koreans.

We analyzed the aplolipoprotein E (APOE) genotypes of 110 probable AD patients and 226 cognitively normal controls in Koreans. The APOE epsilon4 allele was more prevalent in both early- and late-onset AD patients (P < 0.01) than in controls. The odds for the APOE epsilon4-heterozygous subjects were 2.7 (95% CI = 1.6-4.5), and those for the APOE epsilon4-homozygous subjects were 17.4 (95% CI = 2.0-147.3). But the odds were not uniform across age groups, and were higher in women than in men. Although the APOE epsilon2 allele frequency did not differ by diagnosis, the patients carrying an APOE epsilon2 allele showed delayed age-at-onset (P = 0.02). In conclusion, the APOE e4 allele increased the risk for AD in dose-dependent manner, and the APOE epsilon4-conferred AD risk was age- and sex-dependent in Koreans.

Age of Onset↗

PubMed1999

Effects of dopamine and melatonin on the regulation of the PIT-1 isotype, placental growth hormone and lactogen gene expressions in the rat placenta.

Rat placenta produces several members of the placental prolactin-growth hormone (PRL-GH), including placental lactogen (PL) and placental prolactin like protein (PLP), during pregnancy. It is important to study placental local regulators that control the expression of PRL-GH genes. We have previously reported that dopamine (DA) can regulate Pit-1 and PL-II gene expressions. In this study we aimed to investigate the local expression of melatonin receptor 1a (Mel1a) and the effects of DA and melatonin on the expressions of PL-Iv, PL-II, PLP-C genes and Pit-1 gene that are involved in the expression of PRL-GH genes in the rat pituitary and placenta. According to the Northern blot analysis, DA receptor 2 (D2) was expressed in the rat placenta. We also report on the local expression of Mel1a in the rat placenta for the first time. Injected DA agonist, bromocriptine (in vivo) decreased PL-Iv, PLP-C and Pit-1 mRNA levels in the rat placenta. The melatonin agonist, chloromelatonin in culture media also decreased the levels of PL-Iv, PL-II and PLP-C mRNA. However, melatonin does not affect the Pit-1 mRNA level. These data suggest that D2 and Mel1a may control the expression of PRL-GH genes in the rat placenta and its response to the extracellular changes of DA and melatonin secreted from the maternal organ. However, Pit-1 may not be involved in the Mel1a induced inhibition of PRL-GH gene expressions in the rat placenta.

Animals↗

PubMed1999

Analysis of selenocysteine (Sec) tRNA([Ser]Sec) genes in Chinese hamsters.

Several recent observations have indicated that the primary structure of the Chinese hamster selenocysteine tRNA([Ser]sec) is different than those of other mammalian species. These reports prompted us to investigate the gene sequence for this tRNA in Chinese hamsters. Southern blotting of Chinese hamster ovary (CHO) genomic DNA derived from cultured cells with a tRNA([Ser]sec) probe indicated several hybridizing bands, and each of the corresponding genetic loci was isolated from a recombinant CHO library by molecular cloning. Sequence analysis of these regions indicated three likely pseudogenes and a single functional gene whose sequence differed from those of other mammals. Of these, only one pseudogene and the putative functional gene are actively transcribed following their microinjection into Xenopus oocytes. The possibility that the functional CHO tRNA([Ser]sec) evolved from an edited transcript is discussed.

Animals↗

PubMed1999

Controlled release of dual drug-loaded hydroxypropyl methylcellulose matrix tablet using drug-containing polymeric coatings.

A dual drug-loaded hydroxypropylmethylcellulose (HPMC) matrix tablet simultaneously containing drug in inner tablet core and outer coated layer was formulated using drug-containing aqueous-based polymeric Eudragit RS30D dispersions. Effects of coating levels, drug loadings in outer layers, amount and type of five plasticizers and talc concentration on the release characteristics were evaluated on the characteristics in simulated gastric fluid for 2 h followed by a study in intestinal fluids. Melatonin (MT) was selected as a model drug. The surface morphology of dual drug-loaded HPMC tablets using scanning electron microscope (SEM) was smooth, showing the distinct coated layer with about 75-microm coating thickness at the 15% coating level. Unlike the uncoated and conventionally coated HPMC tablet, the dual drug-loaded HPMC matrix tablet gave a biphasic linear release, showing a zero-order for 4 h (first) followed by another zero-order release when fitted using linear regression (r(2) = 0.99). As the coating levels (15, 25%) increased, the release rate was further decreased. The biphasic release profiles of dual drug-loaded HPMC matrix tablet was unchanged except when 25% coating level containing 0.5% drug concentration was applied. As the drug concentration in polymeric coating dispersion increased (0.25-1.0%), the amount of drug released increased. The time for the first linear release was also advanced. However, the biphasic release pattern was not changed. The biphasic release profiles of dual drug-loaded HPMC matrix tablet were highly modified, depending on the amount and type of five plasticizers. Talc (10-30%) in coating dispersion as an anti-sticking material did not affect the release profiles. The current dual drug-loaded HPMC matrix tablet, showing biphasic release profiles may provide an alternative to deliver drugs with circadian rhythmic behaviors in the body but needs to be further validated in future in human studies. The dual drug-loaded coating method is also interesting for the modified release of poorly water-soluble drugs because solubilizers and other additives can be added in drug-containing polymeric coating dispersions.

Anticonvulsants↗

PubMed1999

Redox regulation of cell signaling by selenocysteine in mammalian thioredoxin reductases.

The intracellular generation of reactive oxygen species, together with the thioredoxin and glutathione systems, is thought to participate in redox signaling in mammalian cells. The activity of thioredoxin is dependent on the redox status of thioredoxin reductase (TR), the activity of which in turn is dependent on a selenocysteine residue. Two mammalian TR isozymes (TR2 and TR3), in addition to that previously characterized (TR1), have now been identified in humans and mice. All three TR isozymes contain a selenocysteine residue that is located in the penultimate position at the carboxyl terminus and which is encoded by a UGA codon. The generation of reactive oxygen species in a human carcinoma cell line was shown to result in both the oxidation of the selenocysteine in TR1 and a subsequent increase in the expression of this enzyme. These observations identify the carboxyl-terminal selenocysteine of TR1 as a cellular redox sensor and support an essential role for mammalian TR isozymes in redox-regulated cell signaling.

Amino Acid Sequence↗

PubMed1999

The zebrafish genome contains two distinct selenocysteine tRNA[Ser]sec genes.

The zebrafish is widely used as a model system for studying mammalian developmental genetics and more recently, as a model system for carcinogenesis. Since there is mounting evidence that selenium can prevent cancer in mammals, including humans, we characterized the selenocysteine tRNA[Ser]sec gene and its product in zebrafish. Two genes for this tRNA were isolated and sequenced and were found to map at different loci within the zebrafish genome. The encoding sequences of both are identical and their flanking sequences are highly homologous for several hundred bases in both directions. The two genes likely arose from gene duplication which is a common phenomenon among many genes in this species. In addition, zebrafish tRNA[Ser]sec was isolated from the total tRNA population and shown to decode UGA in a ribosomal binding assay.

Animals↗

PubMed1999

Selenium metabolism in Drosophila. Characterization of the selenocysteine tRNA population.

The selenocysteine (Sec) tRNA population in Drosophila melanogaster is aminoacylated with serine, forms selenocysteyl-tRNA, and decodes UGA. The Km of Sec tRNA and serine tRNA for seryl-tRNA synthetase is 6.67 and 9.45 nM, respectively. Two major bands of Sec tRNA were resolved by gel electrophoresis. Both tRNAs were sequenced, and their primary structures were indistinguishable and colinear with that of the corresponding single copy gene. They are 90 nucleotides in length and contain three modified nucleosides, 5-methylcarboxymethyluridine, N6-isopentenyladenosine, and pseudouridine, at positions 34, 37, and 55, respectively. Neither form contains 1-methyladenosine at position 58 or 5-methylcarboxymethyl-2'-O-methyluridine, which are characteristically found in Sec tRNA of higher animals. We conclude that the primary structures of the two bands of Sec tRNA resolved by electrophoresis are indistinguishable by the techniques employed and that Sec tRNAs in Drosophila may exist in different conformational forms. The Sec tRNA gene maps to a single locus on chromosome 2 at position 47E or F. To our knowledge, Drosophila is the lowest eukaryote in which the Sec tRNA population has been characterized to date.

Animals↗

PubMed1999

Selenocysteine-containing thioredoxin reductase in C. elegans.

Mammalian thioredoxin reductases contain a TGA-encoded C-terminal penultimate selenocysteine (Sec) residue, and show little homology to bacterial, yeast, and plant thioredoxin reductases. Here we show that the nematode, Caenorhabditis elegans, contains two homologs related to the mammalian thioredoxin reductase family. The gene for one of these homologs contains a cysteine codon in place of TGA, and its product, designated TR-S, was previously suggested to function as thioredoxin reductase. The other gene contains TGA and its product is designated TR-Se. This Sec-containing thioredoxin reductase lacks a canonical Sec insertion sequence element in the 3'-untranslated area of the gene. TR-Se shows greater sequence similarity to mammalian thioredoxin reductase isozymes TR1 and TR2, whereas TR-S is more similar to TR3. TR-Se was identified as a thioredoxin reductase selenoprotein by labeling C. elegans with 75Se and characterizing the resulting 75Se-labeled protein by affinity and other column chromatography and gel-electrophoresis. TR-Se was expressed in Escherichia coli as a selenoprotein when a bacterial SECIS element was introduced downstream of the Sec TGA codon. The data show that TR-Se is the major naturally occurring selenoprotein in C. elegans, and suggest an important role for selenium and the thioredoxin system in this organism.

3' Untranslated Regions↗

PubMed1999

Recruitment of TBP or TFIIB to a promoter proximal position leads to stimulation of RNA polymerase II transcription without activator proteins both in vivo and in vitro.

Eukaryotic transcriptional activators may function, at least in part, to facilitate the assembly of the RNA polymerase II (pol II) preinitiation complex at the core promoter region through their interaction with a subset of components of the basal transcription machinery. Previous studies have shown that artificial tethering of TATA-binding protein (TBP) to the promoter region is sufficient to stimulate pol II transcription in yeast. To test whether this phenomenon is a general one in eukaryotic pol II transcription, the DNA-binding domain of yeast GAL4 was fused to either Xenopus laevis TBP or TFIIB in order to enable these factors to be efficiently positioned near the transcription start site in a GAL4-binding site-dependent manner. We found that GAL4-xTBP as well as GAL4-xTFIIB directed an increased level of transcription without involvement of the transcriptional activator, suggesting that incorporation of these basal factors into a preinitiation complex (PIC) is a major rate-limiting step accelerated by activator proteins in metazoans. These results show that transcription activation by artificial recruitment of basal transcription machinery can be observed in general among eukaryotic transcription both in vivo and in vitro. Furthermore, failure of recovery of transcription by adding GAL4-xTFIIB after depletion of endogenous TBP with TATA oligo competitor suggests that recruitment of TBP cannot be bypassed for Pol II transcription.

Animals↗

PubMed1999

Transfer RNA modification status influences retroviral ribosomal frameshifting.

The possibility of whether tRNAs with and without a highly modified base in their anticodon loop may influence the level of retroviral ribosomal frameshifting was examined. Rabbit reticulocyte lysates were programmed with mRNA encoding UUU or AAC at the frameshift site and the corresponding Phe tRNA with or without the highly modified wyebutoxine (Y) base on the 3' side of its anticodon or Asn tRNA with or without the highly modified queuine (Q) base in the wobble position of its anticodon added. Phe and Asn tRNAs without the Y or Q base, respectively, stimulated the level of frameshifting, suggesting that the frameshift event is influenced by tRNA modification status. In addition, when AAU occurred immediately upstream of UUU as the penultimate frameshift site codon, addition of tRNAAsn without the Q base reduced the stimulatory effect of tRNAPhe without the Y base, whereas addition of tRNAAsn with the Q base did not alter the stimulatory effect. The addition of tRNAAsn without the Q base and tRNAPhe with the Y base inhibited frameshifting. The latter studies suggest an interplay between the tRNAs decoded at the penulimate frameshift and frameshift site codons that is also influenced by tRNA modification status. These data may be intrepreted as indicating that a hypomodified isoacceptor modulates frameshifting in an upward manner when utilized at the frameshift site codon, but modulates frameshifting in a downward manner when utilized at the penultimate frameshift site codon.

Animals↗

PubMed1999

Purification and characterization of Moran 20K from Morus alba.

A new glycoprotein was purified from the aqueous methanolic extract of the root bark of Morus alba which has been used as a component of antidiabetic remedy in Oriental Medicine. SDS-PAGE result shows that the molecular weight of the glycoprotein was approximately 20 kDa. This new glycoprotein was named as Moran 20K. The protein lowered blood glucose level in streptozotocin-induced hyperglycemic mice model and it also increased the glucose transport in cultured epididymis fat cells. The amino acid composition of the protein was analyzed, and the protein contained above 20% serine and cysteine such as insulin. The actual molecular weight of the protein was determined as 21,858 Da by MALDI-TOF mass spectroscopy.

Adipose Tissue↗

PubMed1999

Spider mite allergy in apple-cultivating farmers: European red mite (Panonychus ulmi) and two-spotted spider mite (Tetranychus urticae) may be important allergens in the development of work-related asthma and rhinitis symptoms.

BACKGROUND: Recent investigations have suggested that the citrus red mite (Panonychus citri) is the most important allergen affecting citrus-cultivating farmers with asthma, allergic rhinitis, or both. OBJECTIVE: We sought to evaluate type I hypersensitivity to spider mites, particularly the European red mite (Panonychus ulmi) and the two-spotted spider mite (Tetranychus urticae), and to determine the relationship between hypersensitivity to spider mites and respiratory dysfunction. METHODS: We performed a cross-sectional survey. Questionnaires were given, and skin prick tests for 11 inhalant allergens common in Korea and 2 species of spider mites (European red mite and two-spotted spider mite) were performed in 725 apple-cultivating farmers in Korea. RESULTS: Results of skin prick tests in the apple farmers indicated that European red mite (23.2%) was the most common sensitizing allergen, followed by Tyrophagus putrescentiae (21.2%), two-spotted spider mite (16.6%), Dermatophagoides farinae (16.3%), D pteronyssinus (14.4%), cockroach (13.1%), and Hop Japanese (Humulus Japonicus) pollen (12.0%). Positive skin responses (mean wheal size >/=3 mm) to one or more of 13 inhalant allergens were found in 48.2% of farmers tested, whereas 40 subjects (8.6%) had an isolated skin response to the spider mites. Among 119 farmers with work-related asthmatic symptoms, the positive skin response rates to European red mite and two-spotted spider mite were 40.4% and 27.0%, respectively. These figures were significantly higher than those found among farmers without work-related symptoms (19.1% and 14.1%, respectively; P <.01). The prevalence of work-related asthma symptoms was higher in farmers with positive skin responses to spider mites than in those with negative skin responses to spider mites and those with positive skin responses to any allergen tested (31.4% vs 15.0% vs 21.0%, respectively; P <.05). CONCLUSION: Spider mites, particularly European red mite and 2-spotted spider mite, are common sensitizing allergens in apple-cultivating farmers. These spider mites may be important causative allergens in the development of work-related respiratory symptoms in these workers.

Administration, Inhalation↗

PubMed1999

Linkage between IgE receptor-mediated histamine releasability from basophils and gene marker of chromosome 11q13.

BACKGROUND: The genetics of the regulation of the release of mediators involving the interaction of IgE with cells and their ability to release mediators have not been extensively investigated. With use of the candidate gene approach, it was reported that the gene regulating the beta chain of the high-affinity receptor for IgE is on chromosome 11q13. OBJECTIVE: To determine whether gene(s) in chromosome 11q13 may control the expression of maximal histamine release from basophil to anti-IgE stimuli, linkage analysis between this phenotype and the gene marker of chromosome 11q13 was performed. METHODS: Maximal histamine release to anti-IgE and calcium ionophore A23187 and genotyping chromosome 11q13 with use of microsatellite marker (D11S97) were performed in 56 probands with asthma and 59 of their siblings. The linkage was analyzed by affected sib-pair analysis and the quantitative trait locus approach. RESULTS: Maximal histamine release (mean +/- SE) to anti-IgE and A23187 was 43.3% +/- 3.5% and 30.9 +/- 3.4% in probands and 29.5% +/- 2.6% and 22.2% +/- 2.7 in siblings, respectively. Of 20 sib-pairs with the maximal histamine release to anti-IgE more than 33% (mean plus 1 SD of nonasthmatic controls), 11 (55%) shared 2 D11S97 alleles, 9 (45%) shared 1 allele, and neither sib-pair shared identical alleles, which indicates a significant linkage of maximal histamine to anti-IgE and gene marker of chromosome 11q13 (P =.02). The difference (mean +/- SE) of the maximal histamine release to anti-IgE between each proband and sibling was smaller in sib-pairs with 2 identical alleles than in those with 1 identical allele and with no identical allele (14.1% +/- 2.6% vs 25.8% +/- 3.1% vs 41.0% +/- 4.9%). However, the difference (mean +/- SE) to A23187 between each proband and sibling was not different among the 3 groups (9.7% +/- 1.8% vs 17.9% +/- 3.6% vs 10.4% +/- 4.8%). CONCLUSION: Maximal histamine release from basophils to anti-IgE stimuli was linked to the gene marker of chromosome 11q13.

Adolescent↗

PubMed1999

Formulation and release characteristics of hydroxypropyl methylcellulose matrix tablet containing melatonin.

A hydroxypropyl methylcellulose (HPMC) matrix tablet containing melatonin (MT) was formulated as a function of HPMC viscosity, drug loading, type and amount of disintegrant, lubricant and glidant, and aqueous polymeric coating level and was compared with two commercial products. The release characteristics of the HPMC matrix tablet were investigated in the gastric fluid for 2 hr followed by study in intestinal fluid. The surface morphology of an uncoated HPMC matrix tablet using scanning electron microscopy (SEM) was crude, showing aggregated particles and rough crystals or pores, but it became smoother as the coating levels increased. As the HPMC polymer viscosity increased, the release rate had a tendency to decrease. As the drug loadings increased, the release rate slightly decreased. When Polyplasdone XL, Primojel, and Ac-Di-Sol, except Avicel, were incorporated in the HPMC matrix tablet, the release rate was markedly increased. There was no significant difference in release profiles when a mixture of lubricants and glidants (magnesium stearate, talc, and Cab-O-Sil), except for magnesium stearate alone, was incorporated into low and high viscosity grade HPMC matrix tablets. As the coating level increased, the release rate gradually decreased, giving an increased lag time. The sustained-release HPMC matrix tablet with optimizing formulations may provide an alternative for oral controlled delivery of MT and be helpful in the future treatment of circadian rhythmic disorders.

Chemistry, Pharmaceutical↗