Rapid development in molecular biology and recent advancement in recombinant technology increase identification and commercialization of potential protein drugs. Traditional forms of administrations for the peptide and protein drugs often rely on their parenteral injection, since the bioavailability of these therapeutic agents is poor when administered nonparenterally. Tremendous efforts by numerous investigators in the world have been put to improve protein formulations and as a result, a few successful formulations have been developed including sustained-release human growth hormone. For a promising protein delivery technology, efficacy and safety are the first requirement to meet. However, these systems still require periodic injection and increase the incidence of patient compliance. The development of an oral dosage form that improves the absorption of peptide and especially protein drugs is the most desirable formulation but one of the greatest challenges in the pharmaceutical field. The major barriers to developing oral formulations for peptides and proteins are metabolic enzymes and impermeable mucosal tissues in the intestine. Furthermore, chemical and conformational instability of protein drugs is not a small issue in protein pharmaceuticals. Conventional pharmaceutical approaches to address these barriers, which have been successful with traditional organic drug molecules, have not been effective for peptide and protein formulations. It is likely that effective oral formulations for peptides and proteins will remain highly compound specific. A number of innovative oral drug delivery approaches have been recently developed, including the drug entrapment within small vesicles or their passage through the intestinal paracellular pathway. This review provides a summary of the novel approaches currently in progress in the protein oral delivery followed by factors affecting protein oral absorption.
Journal of Physiology & Pathology in Korean Medicine
/
v.21
no.4
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pp.815-821
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2007
Concept of Cho was used both etiologically and symptomatically at the same time. Hwa was the main cause of diseases derived from Cho, and its damage is on Jin-Eum. Cho is one of the members of Euk-Eum, which belongs to Whae-In, but it is also recognized as pathogen of internal dysfunction, therefore symptoms can be classified into two groups. Whae-cho-zheung and Nae-cho-zheung. Organs related to Cho are lung, stomach, intestine, kidney, liver and gall Bladder. Symptoms of Whae-cho usually combines Pyo-zheung, manifesting on lung and skin, whereas symptoms of Nae-cho combines Rhee-zheung, manifesting on internal organs and tissues. In treating of Cho, Ja-eum-yang-hyul-chung-yeolis the main principle. Chung-Yun-Pe-Weis used in Whae-cho-zheung and Sang-cho-byung, while Yu-Yang-Gan-Shin is used in Nae-cho-zheung and Ha-cho-byung.
BACKGROUND/OBJECTIVES: Mulberry leaf (ML) has been shown to have an inhibitory effect on ${\alpha}$-glucosidase, and suppresses postprandial hyperglycemia, which may be related to its deoxynojirimycin (DNJ) content. This study was conducted to investigate the hypoglycemic and dyslipidemic effects of rice coated with ML rich in DNJ in a type 2 diabetes mouse model. MATERIALS/METHODS: The mice were divided into four groups (n = 8 each): non-diabetic normal control (NC); diabetic control (DM-C), fed with 10% polished rice powder (DM-R); and fed with 10% polished rice powder coated with DNJ-rich ML (DM-DNJR). RESULTS: Supplementation with DNJR for six weeks decreased levels of fasting blood glucose, plasma insulin, triglyceride, total cholesterol, and blood glycosylated hemoglobin; conversely, levels of glucagon-like peptide-1 and high-density lipoprotein-cholesterol showed an increase in the same treatment. In addition, weights of mesenteric, epididymal, and total adipose tissues decreased with DNJR supplementation, when compared with diabetic control db/db mice, while maltase, lactase, and sucrase activity in the small intestine were inhibited. The anti-diabetic effects were marginally greater in the DM-DNJR group than in the DM-R group. CONCLUSIONS: These results suggest that rice coated with ML rich in DNJ can reduce hyperglycemia and hyperlipidemia in db/db mice, and may prove useful for individuals with diabetes.
Doo Sik Park;Eun Hyun Cho;Kyung Hoon Park;Soo Min Jo;Bumjung Park;Sun Huh
Parasites, Hosts and Diseases
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v.61
no.3
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pp.298-303
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2023
This study aimed to describe a rare case of gnathostomiasis in the vocal cord. A 54-yearold Chinese woman living in Korea visited with a chief complaint of voice change at the outpatient department of otorhinolaryngology in Hallym Sacred Heart Hospital, Hallym University on August 2, 2021. She had eaten raw conger a few weeks before the voice change developed, but her medical history and physical examinations demonstrated neither gastrointestinal symptoms nor other health problems. A round and red cystic lesion, recognized in the anterior part of the right vocal cord, was removed using forceps and scissors through laryngeal microsurgery. The histopathological specimen of the cyst revealed 3 cross-sections of a nematode larva in the lumen of the cyst wall composed of inflammatory cells and fibrotic tissues. They differ in diameter, from 190 ㎛ to 235 ㎛. They showed characteristic cuticular layers with tegumental spines, somatic muscle layers, and gastrointestinal tracts such as the esophagus and intestine. Notably, intestinal sections consisted of 27-28 lining cells containing 0-4 nuclei per cell. We tentatively identified the nematode larva recovered from the vocal cord cystic lesion as the thirdstage larva of Gnathostoma, probably G. nipponicum or G. hispidum, based on the sectional morphologies.
A 1 : 1 mixture of acriflavine (ACF; CAS 8063-24-9) and guanosine is currently being evaluated as a possible antitumor agent in preclinical studies. Guanosine is known to potentiate the anticancer activity of some compounds. However, the distributions of trypaflavine (TRF) or proflavine (PRF) have not been investigated in mammals. We, therefore, investigated the distribution of TRF and PRF after i.m. administration of the combination mixture (ACF and guanosine) at a dose of 30 mg/kg ACF in rats. to analyze TRF and PRF levels in biological samples, we used an HPLC-based method. The calibration curves for TRF and PRF in the samples were linear over the concenration range of $0.05{\sim}200\;{\mu}g/ml$. The intra- and inter-day assay accuracies of this method were within ${\pm}15\%$ of norminal values and the precision did not exceed $15\%$ of relative standard diviation. The lower limits of quantitation were 50 ng/ml for both TRF and PRF. The distribution of TRF or PRF was determined by 48 h after i.m. administration of the combination mixture at a dose of 30 mg/kg ACF. TRF and PRF were distributed as the following order; kidney>lung>liver>small intestine>muscle. Of the various tissues, TRF and PRF were mainly distributed to the kidney and lung. The concentrations of TRF or PRF in the tissues 24 h after i.m. administration decreased to undetectable levels. The concentrations of TRF or PRF in the blood cells were comparable to those for the plasma. However, the concentrations of TRF or PRF in the both plasma and blood cells 12 h after i.m. administration were not detected. The number of the platelets in the 1 ml of the blood was calculated to be $0.183{\times}10^8/ml$ of blood. The PRF concentration in platelets was higher than that of TRF at initial times after i.m. administration of the combination mixture. However, both the TRF and PRF concentrations in the plateles 24 h after i.m. administration of the combination mixture were below the quantifiable limit. In conclusion, the concentrations of TRF or PRF in the various tissues, plasma, blood cells, and plateles decreased to undetectable levels 24 h after i.m. administration of the combination mixture at a dose of 30 mg/kg ACF.
Park, Kwon-moo;Park, Jln-bong;Li, Long-hua;Han, Seong-kyu;Lee, Hye-sook;Park, Jong-myung;Chang, Byoung-sun;Lee, Mun-han;Ryu, Pan-dong
Korean Journal of Veterinary Research
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v.39
no.2
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pp.257-266
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1999
Ivermectin is a widely used broad spectrum antiparasitic agent in veterinary medicine. In this work, we examined the pharmacokinetic parameters and the tissue residue profile of a new injectable formulation of ivermectin developed for pigs. The plasma ivermectin levels reached the peak at about 9 and 2 hours after the administrations in young and adult pigs, respectively. But the elimination half-life (3-3.5 days) and the $C_{max}$ values (24~28 ng/ml) were not significantly different between young and adult pig groups. When compared to the reference formulation, the $C_{max}$ of test formulation was higher and $T_{1/2}$ values were shorter than those of the reference formulation, respectively. The tissue residue levels were dose- and time-dependent and were higher in the liver and fat, than in the other tissues such as the injection sites, the kidney, intestine, muscle, plasma (4~74 ng/g) at the 7th day after the administration of both formulations of ivermectin. Then, the mean tissue ivermectin levels at the 21st day after the administration in all the tissues decreased to 7.4 and 25% of the 7th day levels in the test and reference formulations, respectively. In general, the tissue levels of ivermectin in the animals treated with the test formulation decreased more rapidly than those with the reference formulation. The tissue to plasma distribution ratio (T/P ratio) of ivermectin was higher in the liver and fat than other tissues. The T/P ratio in the liver of animals treated with the test formulation was somewhat higher than that in the animals treated with the reference formulation. Taken together, the results of pharmacokinetic and tissue residue studies indicate that the test formulation of ivermectin for subcutaneous injection is comparable to the reference formulation, but unique in that it has higher peak plasma concentrations, shorter elimination half-life and higher T/P ratio in the liver than the reference formulation.
Rama Rao, S.V.;Raju, M.V.L.N.;Reddy, M.R.;Panda, A.K.
Asian-Australasian Journal of Animal Sciences
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v.18
no.1
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pp.80-84
/
2005
An experiment was conducted to study the performance, carcass traits, serum lipid profile and immune competence in commercial broilers (2 to 42 d of age) fed graded levels (25, 50, 75 and 100%) of finger millet (FM) (Elusine coracana) in place (w/w) of yellow maize (YM). Each diet was fed to eight replicates (five female Vencobb broilers/replicate) housed in stainless steel battery brooders. The estimated metabolizable energy content of FM was about 540 kcal less than the YM. FM contained more protein (10.42 vs. 9.05%) and fibre (9.52 vs. 2.24%) compared to YM. Body weight gain, ready to cook yield, relative weights of giblet, liver, intestine and length of intestine at 42 d of age was not affected due to replacing YM with FM. But, the feed efficiency decreased in broilers fed diets containing 75 and 100% FM in place of YM at both 21 and 42 d of age. The amount of fat deposited in abdominal area decreased and the relative weight of gizzard increased with increase in level of FM in the diet. The serum HDL cholesterol at 21 and 42 d of age and serum triglycerides at 42 d of age decreased with increase in level of FM in diet. The relative weight of spleen and antibody titers against sheep red blood cells (SRBC) at 5 d post inoculation (PI) decreased in broilers fed FM at 100% of YM. However, the relative weight of bursa, SRBC titers at 10 d PI, antibody titers against ND virus and mortality were not affected due to incorporation of FM in place of YM in diet. The fat content in thigh muscle and liver decreased, while the protein content in these tissues increased with increase in the level of FM in broiler diet. Based on the results, it may be concluded that YM can be replaced with FM up to 25% on weight basis without affecting weight gain, carcass yields and immunity in commercial broiler diet (up to 42 d of age). Further, inclusion of finger millet reduced the fat deposition in thigh muscle, liver and in abdominal area compared to those fed maize as the principal source of energy.
The growth rate of the young pig is generally much less than it's potential and may be constrained by endocrine status as well as nutrient intake. Growth factors are present in relatively high quantities in colostrum and play an important part in gut development. It is possible that supplementation of colostrum protein isolate may stimulate gut and whole body growth in the pig. Eight male and 8 female (Large Whitex${\times}$Landrace) piglets were weaned at 1 d of age after each pig had obtained colostrum from their dam, and were trained to consume one of two liquid diets. The two diets were based on either a colostrum protein isolate (n = 4 males and 4 females) or whey protein concentrate (n = 4 males and 4 females) and were formulated to contain equal levels of crude protein and amino acids. Pigs were fed their diets ad libitum for 28 days after which time 12 pigs were euthanised and various tissues and organs weighed. Pigs were bled for IGF-I analyses at 21 and 28 days of age. Daily gain was higher in pigs consuming the colostrum isolate (171 vs. 216 g/d, p = 0.010), particularly between 2 and 4 weeks of age (212 vs. 298 g/d, p = 0.010). Pigs tended to consume more of the liquid feed containing colostrum isolate (25.5 vs. 29.1 kg, p = 0.074) and gained more live weight per unit of liquid feed (0.203 vs. 0.223 g/g, p = 0.056). There were no effects of sex on growth performance. Pigs consuming the diet supplemented with colostrum isolate had higher (p<0.05) full gut weight (445 vs. 554 g, p = 0.026), empty gut weight (356 vs. 463 g, p = 0.008), stomach weight (42.2 vs. 54.4 g, p = 0.001), small intestine weight (222 vs. 275 g, p = 0.025) and large intestine weight (63.7 vs. 98.0 g, p = 0.005). Plasma IGF-I (99 vs. 150 ng/ml, p<0.001) and IGF-II (265 vs. 406 ng/ml, p<0.001) were higher in pigs fed colostrum isolate. Pigs consuming colostrum protein isolate ate more, grew faster and had higher plasma IGF-I concentrations than pigs consuming a diet with similar macronutrient content but devoid of growth factors.
Lipins play dual function in lipid metabolism by serving as phosphatidate phosphatase and transcriptional co-regulators of gene expression. Mammalian lipin proteins consist of lipin1, lipin2, and lipin3 and are encoded by their respective genes Lpin1, Lpin2, and Lpin3. To date, most studies are concerned with Lpin1, only a few have addressed Lpin2 and Lpin3. Ontogenetic expression of Lpin2 and Lpin3 and their associations with traits would help to explore their molecular and physiological functions in sheep. In this study, 48 animals with an equal number of males and females each for both breeds of fat-tailed sheep such as Guangling Large Tailed (GLT) and Small Tailed Han (STH) were chosen to evaluate the ontogenetic expression of Lpin2 and Lpin3 from eight different tissues and months of age by quantitative real-time polymerase chain reaction (PCR). Associations between gene expression and slaughter and tail traits were also analyzed. The results showed that Lpin2 mRNA was highly expressed in perirenal and tail fats, and was also substantially expressed in liver, kidney, reproductive organs (testis and ovary), with the lowest levels in small intestine and femoral biceps. Lpin3 mRNA was prominently expressed in liver and small intestine, and was also expressed at high levels in kidney, perirenal and tail fats as well as reproductive organs (testis and ovary), with the lowest level in femoral biceps. Global expression of Lpin2 and Lpin3 in GLT both were significantly higher than those in STH. Spatiotemporal expression showed that the highest levels of Lpin2 expression occurred at 10 months of age in two breeds of sheep, with the lowest expression at 2 months of age in STH and at 8 months of age in GLT. The greatest levels of Lpin3 expression occurred at 4 months of age in STH and at 10 months of age in GLT, with the lowest expression at 12 months of age in STH and at 8 months of age in GLT. Breed and age significantly influenced the tissue expression patterns of Lpin2 and Lpin3, respectively, and sex significantly influenced the spatiotemporal expression patterns of Lpin3. Meanwhile, Lpin2 and Lpin3 mRNA expression both showed significant correlations with slaughter and tail traits, and the associations appear to be related with the ontogenetic expression as well as the potential functions of lipin2 and lipin3 in sheep.
Gong, W.H.;Tang, Z.L.;Han, J.L.;Yang, S.L.;Wang, H.;Li, Y.;Li, K.
Asian-Australasian Journal of Animal Sciences
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v.21
no.11
/
pp.1544-1550
/
2008
The retinoids (vitamin A and its derivatives) play a critical role in vision, growth, reproduction, cell differentiation and embryonic development. Using the IMpRH panel, porcine cellular retinol binding protein genes 5 and 7 (RBP5 and RBP7) were assigned to porcine chromosomes 5 and 6, respectively. The complete coding sequences (CDS) of the RBP5 and RBP7 genes were amplified using the reverse transcriptase polymerase chain reaction (RT-PCR) method, and the deduced amino acid sequences of both genes were compared to human corresponding proteins. The mRNA distributions of the two genes in adult Wuzhishan pig tissues (lung, skeletal muscle, spleen, heart, stomach, large intestine, lymph node, small intestine, liver, brain, kidney and fat) were examined. A total of nine single nucleotide polymorphisms (SNPs) were identified in two genes. Three of these SNPs were analyzed using the polymerase chain reaction-restriction-fragment length polymorphism (PCR-RFLP) method in Laiwu, Wuzhishan, Guizhou, Bama, Tongcheng, Yorkshire and Landrace pig breeds. Association analysis of genotypes of these SNP loci with economic traits was done in our experimental populations. Significant associations of different genotypes of $RBP5-A/G^{63}$, $RBP5-A/G^{517}$ and $RPB5-T/C^{intron1-90}$ loci with traits including maximum carcass length (LM), minimum carcass length (LN), marbling score (MS), back fat thickness at shoulder (SBF), meat color score (MCS) and hematocrit (HCT) were detected. These SNPs may be useful as genetic markers in genetic improvement for porcine production.
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