Temporal change in the diagnosis and treatment rates of osteoporosis: results from the Korea National Health and Nutrition Examination Survey.

To compare the diagnosis andtreatment rates of osteoporosis and diabetes in Korea, a nationwide database was used. The results showed that although osteoporosis management is improving, it is still lower compared with that of diabetes; thus, further efforts are needed in this regard. INTRODUCTION: This study aimed to re-evaluate the diagnosis and treatment of osteoporosis from the KNHANES 2016-2017 and compare the temporal change of the rate with those of diabetes as another prevalent chronic disease in South Korea. METHODS: The prevalence of osteoporosis in 2016 was estimated using the previous data classified by age groups (50-59,60-69, and ≥70years) and the 2016 Korean census data. The physician diagnosis and treatment rates of osteoporosis in adults aged ≥50years were estimated using the 2016-2017 KNHANES data. The physician diagnosis and treatment rates of diabetes were evaluated using the KNHANES 2008-2009 and 2016-2017 data. RESULTS: The estimated physician diagnosisrate of osteoporosis increased from 29.9% in females and 5.8% in males in 2008-2009 to 62.8% in females and 22.8% in males in 2016-2017. The treatment rate for the estimated total number of patients with osteoporosis increased from 14.4% in females and 3.8% in males in 2008-2009 to 32.2% in females and 9.0% in males in 2016-2017. An increasing trend in the estimated treatment rateof physician-diagnosed osteoporosis patients was not observed (48.3% [2008-2009] vs 51.5% [2016-2017] in females; 42.6% [2008-2009] vs 42.2% [2016-2017] in males). The physician diagnosis and treatment rates of diabetes were considerably better and more stable than those of osteoporosis. CONCLUSION: Osteoporosis management in South Korea is improving but is insufficient compared with diabetes management. More extensive efforts are needed to improve the diagnosis and treatment rates of osteoporosis.

Clinical implication of novel drug resistance-conferring mutations in resistant tuberculosis.

Evolving novel and/or unfamiliar mutations are revolutionizing the pathways of antibiotic resistance of clinical tuberculosis. The accumulation and interaction of these poorly characterized mutations augment the complexity of resistant pathogenic strains and raise public health concerns. This article reviews our current understanding of the genetic changes that characterize drug resistance in tuberculosis and highlights the imperative for further investigations focusing on the effects of an individual mutation and interacting mutations with detailed strain epidemiology, particularly as these pertain to technology-limited countries with high tuberculosis incidence rates. Concomitantly, there is a need for the development, testing, and uptake of new tools for studying the effects of these mutations in drug resistance and fitness cost of the pathogen. Such genetic data are critical for effective localized and global tuberculosis control interventions and for accurate epidemiological predictions.

White matter abnormalities in drug-naïve patients with obsessive-compulsive disorder: a diffusion tensor study before and after citalopram treatment.

OBJECTIVE: The aim was to investigate the white matter abnormalities of drug-naïve patients with obsessive-compulsive disorder (OCD) using diffusion tensor-imaging and the white matter changes in the patients after pharmacotherapy. METHOD: Thirteen drug-naïve OCD patients and 13 age- and sex-matched healthy comparison subjects were examined using diffusion tensor-imaging and structural magnetic resonance imaging. Measurements were made in OCD patients before and after 12 weeks of citalopram treatment. RESULTS: Compared with controls, the drug-naïve OCD patients showed significant increases in fractional anisotropy (FA) in the corpus callosum, the internal capsule and white matter in the area superolateral to the right caudate. The increases in FA were mostly no longer observed in patients after 12 weeks of treatment compared with controls. CONCLUSION: Our findings suggest that white matter alterations are associated with the pathophysiology of OCD, and the abnormalities may be partly reversible with pharmacotherapy.

Structure determination of new analogues of vardenafil and sildenafil in dietary supplements.

New analogues of vardenafil and sildenafil illegally added to dietary supplements were detected by high-performance liquid chromatography (HPLC) analysis with a photodiode array detector (PDA). These compounds were isolated and their structures elucidated by mass spectrometry (MS), infrared (IR) spectroscopy, one- and two-dimensional nuclear magnetic resonance (NMR). One of the new analogues given the trivial name pseudovardenafil (compound 1) was structurally elucidated and shown to be 1-[[3-(1,4-dihydro-5-methyl-4-oxo-7-propylimidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxyphenyl]sulfonyl]-piperidine. It was a vardenafil analogue isolated from a dietary supplement capsule. Compared with vardenafil, the piperidine ring was substituted for the ethylpiperazine group. The second new analogue, trivially named hydroxyhongdenafil (compound 2), was separated from bulk powder used as a raw material for a dietary supplement. The piperazine and phenyl groups were connected through an acetyl group instead of a sulfonyl group, and hydroxyethylpiperazine was substituted for the methylpiperazine of sildenafil. It was structurally elucidated as 5-[2-ethoxy-5-[[4-(2-hydroxyethyl)-1-piperazinyl]acetyl]phenyl]-1,4-dihydro-1-methyl-3-propyl-7H-pyrazolo[4,3-d]pyrimidin-7-one.

Natural killer cell activity and quality of life were improved by consumption of a mushroom extract, Agaricus blazei Murill Kyowa, in gynecological cancer patients undergoing chemotherapy.

A mushroom extract, Agaricus blazei Murill Kyowa (ABMK), has been reported to possess antimutagenic and antitumor effects. Here, we investigate the beneficial effects of ABMK consumption on immunological status and qualities of life in cancer patients undergoing chemotherapy. One hundred cervical, ovarian, and endometrial cancer patients were treated either with carboplatin (300 mg / m(2)) plus VP16 (etoposide, 100 mg / m(2)) or with carboplatin (300 mg / m(2)) plus taxol (175 mg / m(2)) every 3 weeks for at least three cycles with or without oral consumption of ABMK. We observed that natural killer cell activity was significantly higher in ABMK-treated group (ANOVA, n = 39, P < 0.002) as compared with nontreated placebo group (n = 61). However, no significant difference in lymphokine-activated killer and monocyte activities was observed in a manner similar to the count of specific immune cell populations between ABMK-treated and nontreated groups. However, chemotherapy-associated side effects such as appetite, alopecia, emotional stability, and general weakness were all improved by ABMK treatment. Taken together, this suggests that ABMK treatment might be beneficial for gynecological cancer patients undergoing chemotherapy.

Nutritive and economic values of high oil corn in layer diet.

Two layer feeding trials were conducted to demonstrate the nutritive and economic values of recently developed high oil corn (HOC) in Korea. A corn-soybean meal-based commercial layer diet was chosen as the control diet. The yellow dent corn in the control diet was replaced with HOC to give an isocaloric diet, or replaced with HOC on a 1:1 basis to give a high energy diet. In Trial 1, 510 23-wk-old ISA Brown layers were allotted to three dietary treatments with five replicates per treatment. In Trial 2, 600 38-wk-old Hy-Line Brown layers were allotted to three dietary treatments, again with five replicates per treatment. Both trials were conducted for 15 wk. To measure the ME values of typical corn and HOC, two metabolism trials were performed with layers and adult roosters. The HOC used in this trial contained approximately 94% higher crude fat (6.60% as-fed basis) compared with typical corns. The gross energy, AMEn, and TME values of HOC, are 5.7 to 7.7% higher than those of typical corns, indicating that the energy use of each corn were similar. Oil from the HOC contains 6.5 to 8.3% more oleic acid and 6 to 7% less linoleic acid than oil from typical corns. HOC feeding, on an isocaloric basis or on 1:1 replacement with typical corn, did not exert any effect on various laying performances, including the physical quality of egg. This result reflects the quality of the commercial diet chosen as the control diet, which was already fairly good, such that the performance was already maximal. The polyunsaturated fatty acid content in yolk from hens fed HOC was higher than that from hens fed typical corns, reflecting higher linoleic acid content in the HOC. HOC feeding decreased the saturated fatty acid content in the yolk, due primarily to decreased palmitic acid. If used alone replacing typical corn completely in a layer diet, the acceptance price of HOC was estimated to be 154 won/kg when the price of typical corn was 131 won/kg (118:100). When both corns were allowed to be used, the acceptance price of HOC increased to 184 won/kg (140:100), indicating that a lot cheaper layer diet can be formulated when both HOC and typical corn are used in laying hen diet formulation.

Synthesis and biological properties of new 1beta-methylcarbapenems containing heteroaromatic thioether moiety.

The synthesis and biological activities of a series of new 1beta-methylcarbapenems 1a-h having heteroaromatic thioether moiety at C-5 position of pyrrolidine were described. Among these compounds, 1,2,3-thiadiazole derivative 1h showed the most potent antibacterial activity and advanced pharmacokinetics in comparison with meropenem.

Spatio-temporal pattern of EEG in young brain respiration-training children.

We have evaluated the effect of 'Brain Respiration' training on brain activity using Karhunen-Loeve (KL) decomposition as a method for spatio-temporal analysis of the electroencephalogram (EEG). BR training is a form of breath-work to optimize the function of the brain by concentrating Qi energy in the brain. Recently, BR-training has been reported to improve emotional maturity (i.e., EQ), short-term memory and intuition (Yoo et al., 1998). EEG data were taken during BR-training from 12 young BR-trainees (average age: 9.4 years) who had trained for 4 to 14 months, and during relaxation from age matched non-trained children. Spatio-temporal analysis showed a significant difference of EEG dynamics in right prefrontal, right inferior frontal, posterior temporal, parietal and occipital areas between BR-trainees and the control group. Amplitude of eigenvector components of BR-trainees in the areas of frontal, temporal and occipital cortex was larger than that of non-trained children (values were smaller in parietal cortex), with remarkably high amplitude alpha coherence all over the scalp. These results suggest that BR-training possibly activates brain function through changes in the activity of the frontal association area where higher mental integration and creative activities are mediated.

A comparison of mechanical properties of all-ceramic alumina dental crowns prepared from aqueous- and non-aqueous-based tape casting.

Alumina-glass dental composites were prepared by aqueous- and non-aqueous-based tape casting and sintering at 1120 degrees C, followed by glass infiltration at 1100 degrees C. Flexural strength and fracture toughness of the composites were investigated in terms of influence of tape constituents, namely, alumina powder, binder, and plasticizer on the mechanical properties. For the alumina-glass composites prepared from the aqueous-based tapes, both strength and toughness increased with increasing alumina fraction ratio in tape constituents including organic substances, a/a+o, and binder content ratio in binder/binder + plasticizer mixture, b/b+p. For the composites prepared from the non-aqueous-based tapes, on the other hand, both strength and toughness increased with increasing the a/a+o ratio but decreased with increasing the b/b+p ratio. These observations were consistent with influence of the constituents on mean alumina particle distance in tapes, suggesting that high strength of the glass infiltrated alumina composites is related to toughening by crack bowing. The optimized strength of the aqueous and nonaqueous tape cast composites was 559 and 508 MPa, and the fracture toughness was 3.3 and 3.1 MPam(1/2), respectively.

Mechanical properties, phase stability, and biocompatibility of (Y, Nb)-TZP/Al(2)O(3) composite abutments for dental implant.

ZrO(2)/Al(2)O(3) composites were prepared by mixing a tetragonal ZrO(2), stabilized by 5.31 mol% Y(2)O(3) and 4.45 mol% Nb(2)O(5), and various amounts of Al(2)O(3). Influence of the amount of Al(2)O(3) on strength and toughness and tetragonal phase stability in the composites under autoclave conditions was investigated. In addition, in vitro and in vivo biocompatibility of the composites was examined. The composite, prepared with addition of 20 vol% Al(2)O(3), exhibited the highest strength of 700 MPa and toughness of 8.1 MPa. m(1/2) and showed no hydrothermal degradation while aging in an autoclave. The biocompatibility of the composite exhibited no cytotoxicity and no significant adverse soft-tissue response for up to 3 months implant period in guinea pigs.

Enhanced quinone reductase (QR) activity correlates with promotion potential of diethyl maleate (DEM) in rat forestomach and glandular stomach carcinogenesis initiated with N-methyl-N'-nitrosoguanidine (MNNG).

The modifying effect of diethyl maleate (DEM) on gastric tumor development was studied in rats initially given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and hypertonic sodium chloride (H-NaCl 10% or 5%). Groups of animals were maintained with or without a 0.2% DEM dietary supplement after treatment with MNNG and H-NaCl and sacrificed at week 20. Forestomachs and livers cytosolic NAD(P)H:quinone-acceptor oxidoreductase (QR) activity was also analyzed. The incidences of forestomach severe hyperplasias in the MNNG + H-NaCl --> DEM groups were also significantly higher than in the MNNG + H-NaCl alone group (P < 0.01 and P < 0.05 for 5% and 10% groups, respectively). Similarly, in the glandular stomach, the numbers of preneoplastic pepsinogen 1 altered pyloric glands (PAPGs) in the MNNG + H-NaCl --> DEM groups were significantly increased (P < 0.01 for both concentrations). The QR activities in the groups treated with DEM showed 2- to 3-fold increases as compared with the control level. The results indicate that treatment with 0.2% DEM after MNNG initiation exerts enhancing effects on both forestomach and glandular stomach carcinogenesis. Induction of QR, a Phase II enzyme, activity in the rat stomach by DEM may be associated with promotion of stomach carcinogenesis rather than inhibition.

Osteoblastic phenotype of rat marrow stromal cells cultured in the presence of dexamethasone, beta-glycerolphosphate, and L-ascorbic acid.

We investigated the effects of the time course of addition of osteogenic supplements dexamethasone, beta-glycerolphosphate, and L-ascorbic acid to rat marrow stromal cells, and the exposure time on the proliferation and differentiation of the cells. It was the goal of these experiments to determine the time point for supplement addition to optimize marrow stromal cell proliferation and osteoblastic differentiation. To determine this, two studies were performed; one study was based on the age of the cells from harvest, and the other study was based on the duration of exposure to supplemented medium. Cells were seen to proliferate rapidly at early time points in the presence and absence of osteogenic supplements as determined by 3H-thymidine incorporation into the DNA of replicating cells. These results were supported by cell counts ascertained through total DNA analysis. Alkaline phosphatase (ALP) activity and osteocalcin production at 21 days were highest for both experimental designs when the cells were exposed to supplemented medium immediately upon harvest. The ALP levels at 21 days were six times greater for cells maintained in supplements throughout than for control cells cultured in the absence of supplements for both studies, reaching an absolute value of 75 x 10(-7) micromole/min/cell. Osteocalcin production reached 20 x 10(-6) ng/cell at 21 days in both studies for cells maintained in supplemented medium throughout the study, whereas the control cells produced an insignificant amount of osteocalcin. These results suggest that the addition of osteogenic supplements to marrow-derived cells early in the culture period did not inhibit proliferation and greatly enhanced the osteoblastic phenotype of cells in a rat model.

Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1,2-dimethylhydrazine initiation.

The present study was carried out to examine the chemopreventive effects of carotenoids such as fucoxanthin, lycopene and lutein as well as curcumin and its derivative, tetrahydrocurcumin (THC), on development of putative preneoplastic aberrant crypt foci (ACF) in colons of mice initiated with 1,2-dimethylhydrazine dihydrochloride (DMH). Influence on proliferation of colonic crypt epithelial cells was also assessed in terms of 5-bromo-2'-deoxyuridine (BrdU) incorporation. Five-week-old B6C3F1 male mice were divided into three groups, groups 1 and 2 being given DMH (20 mg/kg body wt, s.c.) twice a week for 3 weeks. Animals of group 1 were then treated with one of the test compounds, lycopene (0.005% and 0.0025%) or fucoxanthin (0.01%) in the drinking water and lutein (0.05%), curcumin (0.5%) or THC (0.5% and 0.2%) in the diet from weeks 5-12. Group 2 served as a carcinogen alone control and group 3 mice were given test compounds alone. All animals were killed at week 12. Numbers of ACF/mouse in the group 1 treated with fucoxanthin (47.1 +/- 13.7), lutein (42.6 +/- 19.6) or 0.5% THC (46.6 +/- 17.7) were significantly decreased as compared to the control group 2 value (63.3 +/- 19.4) (P < 0.01). Numbers of aberrant crypts (ACs)/mouse were also significantly lower after treatment with lutein (79.9 +/- 34.7) or 0.5% THC (81.8 +/- 32.5) than in the control group (115.1 +/- 37.1) (P < 0.01). BrdU labeling indices (LI) in mice treated with lutein and 0.5% THC were significantly decreased in both upper and lower half compartments of colonic crypts as compared to the controls (P < 0.05 and 0.01, respectively), especially the upper half data corresponding to reduction of ACs/mouse. The results thus suggest that fucoxanthin, lutein, and THC may have potential as chemopreventive agents against colon carcinogenesis.

Potential preventive effects of Chelidonium majis L. (Papaveraceae) herb extract on glandular stomach tumor development in rats treated with N-methyl-N'-nitro-N nitrosoguanidine (MNNG) and hypertonic sodium chloride.

The modifying effects of Chelidonium majis L. (Papaveraceae) herb extract (CH), an analgesic traditionally prescribed for gastric and duodenal ulcer patients, on gastric tumor development were studied in rats given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Sixty-four male 6-week-old Wistar rats were used. Group 1 rats were initially given MNNG (200 mg/kg b.w.) by gavage at days 0 and 14 as well as saturated sodium chloride solution (S-NaCl, 1 ml per rat) every 3 days during weeks 0-3 (six times), and then placed on basal diet containing 0.1 or 0.2% CH for 16 weeks from week 4. Rats of Group 2 and 3 were treated with MNNG together with S-NaCl or saline (0.9% NaCl, 1 ml per rat), respectively, timed as in Group 1 but without further treatment. All surviving animals were killed at week 20 and histopathologically investigated. In the glandular stomach, the number of preneoplastic pepsinogen 1 altered pyloric glands (PAPGs) in the MNNG + S-NaCl-->CH (0.1%) group (Group 1) was significantly smaller than in the MNNG + S-NaCl group (Group 2) (P < 0.02). The incidences of forestomach neoplastic lesions (papillomas and squamous cell carcinomas) also showed a tendency to decrease with the CH treatment. The results thus indicate that CH exerts inhibitory effects on glandular stomach carcinogenesis in the rat, so that it may have potential as a chemopreventive agent for stomach cancer in man.

Characterization of recombinant human coagulation factor XFriuli.

Naturally occurring plasma factor XFriuli (pFXFr) is marginally activated by both the extrinsic and intrinsic coagulation pathways and has impaired catalytic potential. These studies were initiated to obtain confirmation that this molecule is multi-functionally defective due to the substitution of Ser for Pro at position 343 in the catalytic domain. By the Nelson-Long site-directed mutagenesis procedure a construct of cDNA in pRc/CMV was derived for recombinant factor XFriuli (rFXFr) produced in human embryonic (293) kidney cells. The rFXFr was purified and shown to have a molecular size identical to that of normal plasma factor X (pFX) by gel electrophoretic, and amino-terminal sequencing revealed normal processing cleavages. Using recombinant normal plasma factor X (rFXN) as a reference, the post-translational gamma-carboxy-glutamic acid (Gla) and beta-hydroxy aspartic acid (beta-OH-Asp) content of rFXFr was over 85% and close to 100%, respectively, of expected levels. The specific activities of rFXFr in activation and catalytic assays were the same as those of pFXFr. Molecular modeling suggested the involvement of a new H-bond between the side-chains of Ser-343 and Thr-318 as they occur in anti-parallel beta-pleated sheets near the substrate-binding pocket of pFXFr. These results support the conclusion that the observed mutation in pFXFr is responsible for its dysfunctional activation and catalytic potentials, and that it accounts for the moderate bleeding tendency in the homozygous individuals who possess this variant procoagulant.

Effect of nicotine, lobeline, and mecamylamine on sensory gating in the rat.

In normal subjects, if an acoustic startle stimulus is immediately preceded by a small brief change in background noise intensity, the magnitude of the subsequent startle response is decreased. This prepulse inhibition (PPI) of an acoustic startle response has been shown to be associated with sensorimotor gating. PPI is disrupted in schizophrenic patients and has been linked to attentional disorders characteristic of this disease. We tested the effects of (-)-nicotine, (0.19, 0.62, and 1.9 mumol/kg IP) (equivalent to 0.03, 0.1, and 0.3 mg/kg base) and the nicotinic cholinergic receptor (nAChR) channel blocker, mecamylamine (5.0 and 50 mumol/kg IP) (equivalent to 1.0 and 10.0 mg/kg) on PPI of the acoustic startle response in the rat. Nicotine increased the PPI at the lowest prepulse signal levels but not at the stronger levels. Mecamylamine was without effect at 5.0 mumol/kg, but the 50 mumol/kg dose decreased the inhibition at both weak and strong prepulse (PP) levels. Mecamylamine (5.0 mumol/kg) pretreatment did not block the (-)-nicotine-induced increase in PPI. Lobeline (0.19, 0.62, 1.9, and 6.2 mumol/kg IP) (equivalent to 0.071, 0.23, 0.71, and 2.3 mg/kg) was without effect. These results are consistent with a mecamylamine-insensitive effect of nicotine to improve gating in normal rats. The nAChR subtype involved in producing nicotine's increase of PPI needs further investigation.

Shikonin production by extractive cultivation in transformed-suspension and hairy root cultures of Lithospermum erythrorhizon.

Effects of in situ extraction, fungal elicitation, a permeabilizing agent, and the oxygen transfer rate on shikonin production in transformed suspension and hairy root cultures of Lithospermum erythrorhizon were studied. Shikonin production with in situ extraction in transformed cell and hairy root cultures by n-hexadecane was 7.6 and 3 times higher than those of the control culture. Shikonin production of transformed L. erythrohizon increased with the enhanced gas exchange, and in situ extraction also increased sucrose consumption and shikonin production. The optimal volume of n-hexadecane in the hairy root culture was similar to that in the transformed cell cultures. In situ extraction at an earlier stage significantly enhanced shikonin production both in transformed cell and hairy root cultures. Dimethylsulfoxide used as a permeabilizing agent was harmful to cell growth and shikonin production, and permeabilizing was unnecessary when in situ extraction was applied. This occurred because with the solvent addition, most shikonin was spontaneously released from the cells and was dissolved in the solvent layer. The combined addition of n-hexadecane of the extract of the fungus Penicillium as an elicitor seemed to result in a higher production of shikonin both in cell suspensions and transformed root cultures. However, an increase of shikonin induction by fungal elicitation in a hairy root culture was not significant in comparison with that of normal cell cultures.

Effects of pyrimidine salvage inhibitors on uracil incorporation of Toxoplasma gondii.

Metabolic inhibitors which act in the process of pyrimidine salvage influenced on the uracil incorporation into nucleic acids of Toxoplasma. Inhibitors of dihydrofolate reductase, pyrimethamine and methotrexate, and inhibitors of thymidylate synthase, fluoro-uridine, fluoro-dUMP and fluoro-uracil, diminished isotopic uracil uptake in dose-dependent manners. Azauridine which suppresses de novo pyrimidine biosynthesis did not affect the salvage even in a relatively high dose. These results suggested that the activation of uracil salvage should be closely related with the function of TMP biosynthetic enzymes. The pattern of thymidine uptake had no differences between control HL-60 cells and Toxoplasma infected cells, which did not reflect the specific proliferation of Toxoplasma. It can be exploited to characterize the effects of various compounds related with the proliferation of Toxoplasma, especially its DNA synthesis.

Multivesicular liposomes containing 1-beta-D-arabinofuranosylcytosine for slow-release intrathecal therapy.

Optimal anticancer treatment with cell cycle-specific antimetabolites requires maintenance of a cytotoxic drug level for a prolonged period of time. We explored the use of multivesicular liposomes as a slow-release depot of 1-beta-D-arabinofuranosylcytosine for intrathecal administration. The intrathecal half-life of the liposome-encapsulated drug was 148 h, in contrast to the half-life of 2.7 h for the unencapsulated free drug, in a Sprague-Dawley rat model. The prolonged maintenance of a therapeutic drug level may increase efficacy, and the elimination of the very high peak level may decrease toxicity.