Factors Related to Blood Intact Incretin Levels in Patients with Type 2 Diabetes Mellitus

BACKGROUND: We performed this study to identify factors related to intact incretin levels in patients with type 2 diabetes mellitus (T2DM). METHODS: We cross-sectionally analyzed 336 patients with T2DM. Intact glucagon-like peptide 1 (iGLP-1) and intact glucose-dependent insulinotropic polypeptide (iGIP) levels were measured in a fasted state and 30 minutes after ingestion of a standard mixed meal. The differences between 30 and 0 minute iGLP-1 and iGIP levels were indicated as ΔiGLP-1 and ΔiGIP. RESULTS: In simple correlation analyses, fasting iGLP-1 was positively correlated with glucose, C-peptide, creatinine, and triglyceride levels, and negatively correlated with estimated glomerular filtration rate. ΔiGLP-1 was positively correlated only with ΔC-peptide levels. Fasting iGIP showed positive correlations with glycosylated hemoglobin (HbA1c) and fasting glucose levels, and negative correlations with ΔC-peptide levels. ΔiGIP was negatively correlated with diabetes duration and HbA1c levels, and positively correlated with Δglucose and ΔC-peptide levels. In multivariate analyses adjusting for age, sex, and covariates, fasting iGLP-1 levels were significantly related to fasting glucose levels, ΔiGLP-1 levels were positively related to ΔC-peptide levels, fasting iGIP levels were related to fasting C-peptide levels, and ΔiGIP levels were positively related to ΔC-peptide and Δglucose levels. CONCLUSION: Taken together, intact incretin levels are primarily related to C-peptide and glucose levels. This result suggests that glycemia and insulin secretion are the main factors associated with intact incretin levels in T2DM patients.

Jeju seaweeds suppress lipopolysaccharide-stimulated proinflammatory response in RAW 264.7 murine macrophages

<p><b>OBJECTIVE</b>To investigate the anti-inflammatory effects of Jeju seaweeds on macrophage RAW 264.7 cells under lipopolysaccharide (LPS) stimulation.</p><p><b>METHODS</b>Ethyl acetate fractions were prepared from five different types of Jeju seaweeds, Dictyopteris divaricata (D. divaricata), Dictyopteris prolifera (D. prolifera), Prionitis cornea (P. cornea), Grateloupia lanceolata (G. lanceolata), and Grateloupia filicina (G. filicina). They were screened for inhibitory effects on proinflammatory mediators and cytokines such as nitric oxide (NO), prostaglandin E2, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6).</p><p><b>RESULTS</b>Our results revealed that D. divaricata, D. prolifera, P. cornea, G. lanceolata, and G. filicina potently inhibited LPS-stimulated NO production (IC50 values were 18.0, 38.36, 38.43, 32.81 and 37.14 µg/mL, respectively). Consistent with these findings, D. divaricata, D. prolifera, P. cornea, and G. filicina also reduced the LPS-induced and prostaglandin E2 production in a concentration-dependent manner. Expectedly, they suppressed the expression of inducible NO synthase and cyclooxygenase-2 at the protein level in a dose-dependent manner in the RAW 264.7 cells, as determined by western blotting. In addition, the levels of TNF-α and IL-6, released into the medium, were also reduced by D. divaricata, D. prolifera, P. cornea, G. lanceolata, and G. filicina in a dose-dependent manner (IC50 values for TNF-α were 16.11, 28.21, 84.27, 45.52 and 74.75 µg/mL, respectively; IC50 values for IL-6 were 37.35, 80.08, 103.28, 62.53 and 84.28 µg/mL, respectively). The total phlorotannin content was measured by the Folin-Ciocalteu method and expressed as phloroglucinol equivalents. The content was 92.0 µg/mg for D. divaricata, 151.8 µg/mg for D. prolifera, 57.2 µg/mg for P. cornea, 53.0 µg/mg for G. lanceolata, and 40.2 µg/mg for G. filicina.</p><p><b>CONCLUSIONS</b>Thus, these findings suggest that Jeju seaweed extracts have potential therapeutic applications for inflammatory responses.</p>

Jeju seaweeds suppress lipopolysaccharide-stimulated proinflammatory response in RAW 264.7 murine macrophages

Objective: To investigate the anti-inflammatory effects of Jeju seaweeds on macrophage RAW 264.7 cells under lipopolysaccharide (LPS) stimulation. Methods: Ethyl acetate fractions were prepared from five different types of Jeju seaweeds, Dictyopteris divaricata (D. divaricata), Dictyopteris prolifera (D. prolifera), Prionitis cornea (P. cornea), Grateloupia lanceolata (G. lanceolata), and Grateloupia filicina (G. filicina). They were screened for inhibitory effects on proinflammatory mediators and cytokines such as nitric oxide (NO), prostaglandin E

Melittin Ameliorates the Inflammation of Organs in an Amyotrophic Lateral Sclerosis Animal Model

Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disorder characterized by a selective loss of motor neurons in the spinal cord, brainstem, and motor cortex, leading to weakness of the limb and bulbar muscles. Although the immediate cause of death in ALS is the destruction of motor neurons, ALS is a multi-organ disease that also affects the lungs, spleen, and liver. Melittin is one of components of bee venom and has anti-neuroinflammatory effects in the spinal cord, as shown in an ALS animal model. To investigate the effects of melittin on inflammation in the lungs and spleen, we used hSOD1(G93A) transgenic mice that are mimic for ALS. Melittin treatment reduced the expression of inflammatory proteins, including Iba-1 and CD14 by 1.9- and 1.3-fold (p<0.05), respectively, in the lungs of symptomatic hSOD1(G93A) transgenic mice. In the spleen, the expression of CD14 and COX2 that are related to inflammation were decreased by 1.4 fold (p<0.05) and cell survival proteins such as pERK and Bcl2 were increased by 1.3- and 1.5-fold (p<0.05) in the melittin-treated hSOD1G93A transgenic mice. These findings suggest that melittin could be a candidate to regulate the immune system in organs affected by ALS.

Antiallodynic Effects of Electroacupuncture Combined with MK-801 Treatment through the Regulation of p35/p25 in Experimental Diabetic Neuropathy

The anti-allodynic effect of NMDA receptor antagonist and acupuncture treatments were explored through spinal p35 regulation of diabetic neuropathic rat. We evaluated the change over time of p35/p25 protein levels in the spinal cord compared with behavioral responses to thermal and mechanical stimulation in streptozotocin (STZ)-induced diabetic rats. Additionally, we studied p35 expression when electroacupuncture (EA) and a sub-effective dose of NMDA (N-methyl-D-aspartate) receptor antagonist (MK-801) were used to treat hyperalgesia in the diabetic neuropathic pain (DNP). Thermal paw withdrawal latency (PWL) and mechanical paw withdrawal threshold (PWT) were significantly decreased in the early stage of diabetes in rats. p35 expression after STZ injection gradually decreased from 1 week to 4 weeks compared to normal controls. p25 expression in 4-week diabetic rats was significantly higher than that of 2-week diabetic rats, and thermal PWL in 4-week diabetic rats showed delayed responses to painful thermal stimulation compared with those at 2 weeks. EA applied to the SP-9 point (2 Hz frequency) significantly prevented the thermal and mechanical hyperalgesia in the DNP rat. Additionally, EA combined with MK-801 prolonged anti-hyperalgesia, increased p35 expression, and decreased the cleavage of p35 to p25 during diabetic neuropathic pain. In this study we show EA combined with a sub-effective dose of MK-801 treatment in DNP induced by STZ that is related to p35/p25 expression in spinal cord.

Quantitative and Qualitative Estimation of Bacteria Contaminating Human Hairs

Human hairs have been known to be easily contaminated with microorganisms. This study was performed in order to measure what bacterial species and how much microorganisms contaminate human hairs in specific place. Virgin human hairs were left at 6 positions in inside corner and beside window in a laboratory for 7 days. The number of viable bacterial cells, which were determined by most probable number method, contaminating the human hairs was measured at a maximum of 10(6)/g hair and a minimum of 10(3)/g hair in inside corner and maximum of 10(6)/g hair and a minimum of 10(3)/g hair beside window. The bacterial cells-contaminating human hairs were observed via fluorescence light microscopy after 4',6-diamino-2-phenylindole (DAPI) staining. The bacterial community contaminating human hairs was analyzed via the thermal gradient gel electrophoresis (TGGE) technique, based on the diversity of the 16S-rDNA variable region. In total, approximately 20 bacterial species were detected from 12 groups of hair samples. In this study, general experimental methods-fluorescence staining, TGGE and MPN-were combined to develop new method for observation and estimation of bacteria contaminating human hairs.

Quantitative and Qualitative Estimation of Bacteria Contaminating Human Hairs

Human hairs have been known to be easily contaminated with microorganisms. This study was performed in order to measure what bacterial species and how much microorganisms contaminate human hairs in specific place. Virgin human hairs were left at 6 positions in inside corner and beside window in a laboratory for 7 days. The number of viable bacterial cells, which were determined by most probable number method, contaminating the human hairs was measured at a maximum of 10(6)/g hair and a minimum of 10(3)/g hair in inside corner and maximum of 10(6)/g hair and a minimum of 10(3)/g hair beside window. The bacterial cells-contaminating human hairs were observed via fluorescence light microscopy after 4',6-diamino-2-phenylindole (DAPI) staining. The bacterial community contaminating human hairs was analyzed via the thermal gradient gel electrophoresis (TGGE) technique, based on the diversity of the 16S-rDNA variable region. In total, approximately 20 bacterial species were detected from 12 groups of hair samples. In this study, general experimental methods-fluorescence staining, TGGE and MPN-were combined to develop new method for observation and estimation of bacteria contaminating human hairs.

Mastoid Foramen and Superficial Mastoid Canals of Korean Men / 체질인류학회지

The mastoid foramina and the superficial mastoid canals at the mastoid area are well known to have much clinical and anthropological significances. However, few sutdies on these structures were reported. Authors performed this study to analyze those structures of the Korean men, and compared with other populations. The existence, number, location of matoid foramen, distance from the posterior border of the opening of external acoustic meatus were measured. In addition, the existence, shape and the direction of the superficial mastoid canals were investigated. The results were as follows; 1. Among the 67 skulls of Korean men, there was no mastoid foramen on both sides in 1 case. In 10 cases, there was mastoid foramen on right side only, and in 4 cases left side only. In 52 cases (77.6%), there was mastoid foramen on both sides. 2. In the incidence of mastoid foramen, 1 in 27 cases, 2 in 23 cases and 3 in 11 cases on the right side, and 1 in 25 cases, 2 in 22 cases and 3 in 17 cases on the left side were found. 3. 64.0% of mastoid foramina located on the temporal bone, 28.5% were on the occipitomastoid suture, 5.2% were on the occipital bone, 1.9% were on parietomastoid suture, and 1 case on the parietal bone. 4. In the sidedness of mastoid foramen, 1-1 foramen on each side was 15 cases, 2-2 foramina on each side was 10 cases, 1-2 foramina on right-left side was 8 cases, and 0-0 on each side, 2-4 on right-left side, and 4-3 on right-left side were 1 case respectively. 5. The average diameter of mastoid foramen was 2.0+/-0.69 mm, and the distance from the posterior margin of the external acoustic meatus was 33.6+/-3.69 mm. There was no significant differences between right and left sides. 6. The superficial mastoid canals appeared in 23 cases (34.3%), among which 12 cases were on right side and 11 cases were on left side. 14 canals were straight in shape, 2 were grooved, and others were arched, sigmoid or bridged. 21 canals directed toward parietal bone and others directed occipital bone. According to the above results, the existence, number, size and the distance from external acoustic meatus of mastoid foramina, and the incidence, shapes and directions of superficial mastoid canals were much variable. Of course, these variations would have great clinical significances during the neurosurgical and otolaryngeal surgery. These data would contribute to study epigenetic study of minor variations of skull and anthropological study.

Histological and Biochemical Study on the Effect of Cadmium Chloride on the Rat Testis / 대한해부학회지

Although cadmium is a well known heavy metal which has an influence testis and brings about male infertility, the mechanism of action in the testis is still fully unknown. In these experiment, cadmium chloride 4 mg/kg of body weight administered intraperitoneally to the rat (Sprague-Dawley) and sacrificed after 1 week, and morphological changes were observed by LM and TEM. In addition, electrophoresis, immunoprecipitation and Western blotting and N-terminal analysis performed to reveal the protein changes. 1. Major findings under light microscope were hemorrhagic necrosis and death of all the spermatogenic cells and supporting cells within the seminiferous tubules, and decreased volume of ECM, many apoptotic bodies, and death of interstitial cells and fibroblasts within interstitium. 2. The EM findings were disruption of nuclear membrane and disappearance of cell organelles of spermatogenic cells and supporting cells within seminiferous tubules, and decreased filopodia, increased inclusion bodies, vacuolation and apoptotic changes of the interstitial cells and fibroblastic cells, many short electron-dense collagen fibers in the extracellular matrix of interstitium. 3. Two proteins of molecular weight 42 kDa and 21 kDa which disappeared after cadmium treatment were rat collagen type I alpha 2. According to the above results, it is considered that cadmium degrades the collagen of the wall of small blood vessels within seminiferous tubules and interstitium and disrupts vascular walls, which results hemorrhagic necrosis, death of all the spermatogenic cells, and the death of interstitial cells and fibroblastic cells.

A Study on the Congenital Anomalies induced by Cadmium Chloride / 체질인류학회지

The purpose of this study is to observe the optimium effects of cadmium chloride on the rat fetus. Cadmium chloride 5 mg/kg was administered intraperitoneally once to the pregnant rats on GD10.5, and the rats were sacrificed on GD 17.5 followed by formalin fixation for bone-cartilage counterstaining, Bowin fixation for palate observation and fixation with 5% glutaraldehyde solution for SEM. The results were as follows; 1. In the cadmium chloride treated group, the survival rate of rat embryos was 65.7% and the average body weight was 589+/-77.5 mg. Both were significantly lower statistically than those of the control group. 2. In the cadmium chloride treated group, craniofacial anomalies such as hydrocephalus, hemorrhagic bullae and cleft palates, and anomalies of the limbs such as polydactyly and oligodactyly were observed. 3. In the cadmium chloride treated group, no primary ossification centers were found in all fetuses. In the vertebral column and the ribs, congenital anomalies such as fusion of vertebral laminae, short tail, fused ribs, division of ribs, accessary rib and loss of rib were observed. 4. In the cadmium chloride treated group, congenital anormalies of the ribs were predominently on the right side and that of the feet were predominently on the left side. 5. In the cadmium chloride treated group, a protein with molecular weight of 14.1 kDa was disappeared in the forelimbs and hindlimbs of GD12.5, and proteins with molecular weight of 14.1 kDa and 30.2 kDa were decreased in the forelimbs of GD13.5, and a protein with molecular weight of 14.1 kDa was disappeared in the hindlimbs of GD13.5, and a protein with molecular weight of 14.1 kDa was decreased in the hindlimbs of GD13.5. With the above results, it is considered that cadmium chloride causes death in utero due to direct acute poisoning of the rat fetuses, inhibits development of skeletal system, and induces various congenital anomalies. And the action mechanisms of cadmium chloride may be the cause of the destruction of capillaries in CNS as well as the inhibition of carbonic anhydrase. But this is still not confirmed.

5-Fluorouracil-Induced Apoptosis in the Rat Thymus / 체질인류학회지

Thymocyte death has been recognized as one of the best characterized experimental models of apoptosis that can be induced by a variety of stimuli such as glucocorticoids, ionizing radiation, anticancer drugs and toxins. The aim of this study was to investigate 5-fluorouracil (5-FU)-induced apoptosis in the rat thymus morphologically. Sprague Dawley rats were injected intramuscularly with 5-FU 100mg/kg body weight and 200mg/kg body weight, and were then sacrificed on day 1, 3, 6, 9 and 12 after treatment. H-E stain and the TUNEL method using the ApopTag kit were used. The results were as follows: 1. On day 1 and 3 after 5-FU treatment, thin cortex and prominent reduction of thymocytes in the cortex were detected. The degree of change was more extensive in the 5-FU 200 mg/kg-treated group than in the 5-FU 100 mg/kg-treated group. Pleomorphic apoptotic cells detected in the cortex were increased in the 5-FU 200mg/kgtreated group and on day 3 after treament. 2. In the 5-FU 100mg/kg-treated group, germinal centers appeared in the cortex on day 6 after treatment starting recovery. Formation of germinal centers continued to day 9 after treatment. In the germinal centers, there were large numbers of typical round apoptotic cells. The thymus exhibited normal architecture on day 12 after treatment. In the 5-FU 200 mg/kg-treated group, however, there were some that did not recover from involution of the thymus on day 6 after treatment and showed fibrosis with decrease of thymocytes and increase of connective tissue to day 9 after treatment. Others recovered and occurred similar changes to the 5-FU 100mg/kgtreated group. 3. 5-FU-induced pleomorphic apoptosis appeared mainly in the cortex and increased gradually depending on dose up to day 1, 3 after treatment. Apoptosis in the germinal centers first occurred from day 6 after treatment and revealed typical large round apoptotic cells. According to the above results, it is thought that 5-FU has an inhibitory effect on DNA synthesis, cell death and involution on surrounding tissue by direct action on thymocytes. The effect continues upto day 3~4 after treatment. Meanwhile, along with the recovery of the thymus from day 6 after treatment, new germinal centers appeared and active lymphocytes production occurred in the germinal centers, which was considered as compensatory reaction. To eliminate enormous B cells newly produced in the germinal center, active apoptosis would occur.

Morphogenesis of the Hindlimb Digits and 5-FU induced Apoptotic Changes / 체질인류학회지

During the morphogenesis of the hindlimb and the digits of the rat, apoptosis has a crucial role to make their normal shape. In this study, apoptotic changes of the hindlimb from GD 13.5 to GD 17.5 were observed and compared with 5 -FU treated group to reveal the mechanism of teratogenic action of 5 -FU. The results were as follows; 1. The mean body weight of rat fetuses was decreased significantly in the 5 -FU treated group. 2. Congenital anomalies of the hindlimb digits were cleft foot, syndactyly and short digits, and the occurance rate of congenital anomalies was 58.1%, in which right -sided anomalies was 49.1% and left -sided anomalies was 18.9%. 3. Normal morphogenesis of the hindlimb digits was as follows; initially, hindlimb bud appeared at the lateral wall of lumbar somite on GD 10.5, grown as an elliptical mass proximodistally on GD 13.5, flattening and digital rays formation on GD 14.5, interdigital notches appeared on GD 15.5, interdigital spaces formation and interphalageal joints formation on GD 16.5, and deepening of interdigital spaces and elongation of digits on GD 17.5. 4. 5 -FU inhibited differentiation and growth of hindlimb bud initially, but its effect on development of hindlimb was disappeared after GD 15.5. According to the above results, it is considered that 5 -FU has an inhibitory effect on differentiation and growth of hindlimb of rat fetuses, and the TUNEL immunohistochemical method is much available to detect normal morphogenesis of an organ and to detect the mechanism of action of various teratogens.

Analysis of FUDR --induced Congenital Anomalies in the Rat / 체질인류학회지

For the study on the teratogenic effects and its mechanism of FUDR on the developing rat fetuses, Sprague -Dawley rats as experimental animal and 5 -fluoro -2 '-deoxyuridine (Sigma chemicals) as FUDR were used respectively. On the day of gestation 10.5, 60 mg/kg, 65 mg/kg and 70 mg/kg of FUDR was injected intraperitoneally, and sacrificed under ether anesthesia on the day of gestation 17.5. External congenital malformations such as hydrocephalus, lens defect, cleft palate, short tail, forelimb and hindlimb malformations were observed under stereoscope, and compared each other with control group. The results were as follows; 1. Congenital anomalies induced by FUDR were hydrocephalus, lens defect, cleft palate, short tail, and defects of extremities such as phocomelia, loss of first and second digits, undergrowth of digits, and syndactyly. 2. There is close relation between the rate of occurance of congenital anomalies and doses of FUDR in some organs. 3. There is significant differences between forelimbs and hindlimbs and between right forelimb and left forelimb in the rate of occurance of congenital anomalies of the extremities. According to the above results, it is considered that there is significant differences between the types and occurance rates of congenital anomalies induced by FUDR and the doses of FUDR. But distinct mechanism of action during teratogenesis of FUDR still remains unclear.

Two Cases of Sternalis of Korean / 체질인류학회지

No abstract available.