Effect of Denosumab on the Change of Osteoclast Precursors Compared to Zoledronate Treatment in Postmenopausal Women with Osteoporosis

Background@#A rapid increase in bone turnover and bone loss has been observed in response to the discontinuation of denosumab. It led to an acute increase in the fracture risk, similar to that observed in the untreated patients. We aimed to investigate the effect of denosumab on osteoclast (OC) precursor cells compared to that of zoledronate. @*Methods@#The study compared the effects of denosumab (60 mg/24-week) and zoledronate (5 mg/48-week) over 48 weeks in postmenopausal women with osteoporosis. From patients’ peripheral mononuclear cells, CD14+/CD11b+/vitronectin receptor (VNR)- and CD14+/CD11b+/VNR+ cells were isolated using fluorescent-activated cell sorting, representing early and late OC precursors, respectively. The primary endpoint was the changes in OC precursors after 48 weeks of treatment. @*Results@#Among the 23 patients, 11 were assigned to the denosumab group and 12 to the zoledronate group (mean age, 69 years). After 48 weeks, the changes in OC precursors were similar between and within the groups. Serum C-terminal telopeptide of type I collagen levels were inversely correlated with OC precursor levels after denosumab treatment (r=-0.72, P<0.001). Lumbar spine, femur neck, and total hip bone mineral density (BMD) increased in both groups. Lumbar spine BMD increased more significantly in the denosumab group than in the zoledronate group. @*Conclusions@#Denosumab and zoledronate treatments induced similar changes in OC precursors. During denosumab treatment, old age and suppressed bone turnover were associated with increased OC precursor cell populations. Further validation studies with prospective designs are required.

Molecular Markers for Detecting a Wide Range of Trichoderma spp. that Might Potentially Cause Green Mold in Pleurotus eryngii

In Pleurotus sp., green mold, which is considered a major epidemic, is caused by several Trichoderma species. To develop a rapid molecular marker specific for Trichoderma spp. that potentially cause green mold, eleven Trichoderma species were collected from mushroom farms and the Korean Agricultural Culture Collection (KACC). A dominant fungal isolate from a green mold-infected substrate was identified as Trichoderma pleuroticola based on the sequences of its internal transcribed spacer (ITS) and translation elongation factor 1-a (tef1) genes. In artificial inoculation tests, all Trichoderma spp., including T. atroviride, T. cf. virens, T.citrinoviride, T. harzianum, T. koningii, T. longibrachiatum, T. pleurotum, and T. pleuroticola, showed pathogenicity to some extent, and the observed symptoms were soaked mycelia with a red-brown pigment and retarded mycelium regeneration. A molecular marker was developed for the rapid detection of wide range ofTrichoderma spp. based on the DNA sequence alignment of the ITS1 and ITS2 regions ofTrichoderma spp. The developed primer set detected only Trichoderma spp., and no cross reactivity with edible mushrooms was observed. The detection limits for the PCR assay of T. harzianum (KACC40558), T. pleurotum (KACC44537), and T. pleuroticola (CAF-TP3) were found to be 500, 50, and 5 fg, respectively, and the detection limit for the pathogen-to-host ratio was approximately 1:10,000 (wt/wt).

Changes in plasma lipoxin A4, resolvins and CD59 levels after ischemic and traumatic brain injuries in rats

Ischemic and traumatic brain injuries are the major acute central nervous system disorders that need to be adequately diagnosed and treated. To find biomarkers for these acute brain injuries, plasma levels of some specialized pro-resolving mediators (SPMs, i.e., lipoxin A4 [LXA4], resolvin [Rv] E1, RvE2, RvD1 and RvD2), CD59 and interleukin (IL)-6 were measured at 0, 6, 24, 72, and 168 h after global cerebral ischemic (GCI) and traumatic brain injuries (TBI) in rats. Plasma LXA4 levels tended to increase at 24 and 72 h after GCI. Plasma RvE1, RvE2, RvD1, and RvD2 levels showed a biphasic response to GCI; a significant decrease at 6 h with a return to the levels of the sham group at 24 h, and again a decrease at 72 h. Plasma CD59 levels increased at 6 and 24 h post-GCI, and returned to basal levels at 72 h post-GCI. For TBI, plasma LXA4 levels tended to decrease, while RvE1, RvE2, RvD1, and RvD2 showed barely significant changes. Plasma IL-6 levels were significantly increased after GCI and TBI, but with different time courses. These results show that plasma LXA4, RvE1, RvE2, RvD1, RvD2, and CD59 levels display differential responses to GCI and TBI, and need to be evaluated for their usefulness as biomarkers.

Changes in plasma lipoxin A4, resolvins and CD59 levels after ischemic and traumatic brain injuries in rats

Ischemic and traumatic brain injuries are the major acute central nervous system disorders that need to be adequately diagnosed and treated. To find biomarkers for these acute brain injuries, plasma levels of some specialized pro-resolving mediators (SPMs, i.e., lipoxin A4 [LXA4], resolvin [Rv] E1, RvE2, RvD1 and RvD2), CD59 and interleukin (IL)-6 were measured at 0, 6, 24, 72, and 168 h after global cerebral ischemic (GCI) and traumatic brain injuries (TBI) in rats. Plasma LXA4 levels tended to increase at 24 and 72 h after GCI. Plasma RvE1, RvE2, RvD1, and RvD2 levels showed a biphasic response to GCI; a significant decrease at 6 h with a return to the levels of the sham group at 24 h, and again a decrease at 72 h. Plasma CD59 levels increased at 6 and 24 h post-GCI, and returned to basal levels at 72 h post-GCI. For TBI, plasma LXA4 levels tended to decrease, while RvE1, RvE2, RvD1, and RvD2 showed barely significant changes. Plasma IL-6 levels were significantly increased after GCI and TBI, but with different time courses. These results show that plasma LXA4, RvE1, RvE2, RvD1, RvD2, and CD59 levels display differential responses to GCI and TBI, and need to be evaluated for their usefulness as biomarkers.

Development of a Molecular Marker Linked to the A4 Locus and the Structure of HD Genes in Pleurotus eryngii

Allelic differences in A and B mating-type loci are a prerequisite for the progression of mating in the genus Pleurotus eryngii; thus, the crossing is hampered by this biological barrier in inbreeding. Molecular markers linked to mating types of P. eryngii KNR2312 were investigated with randomly amplified polymorphic DNA to enhance crossing efficiency. An A4-linked sequence was identified and used to find the adjacent genomic region with the entire motif of the A locus from a contig sequenced by PacBio. The sequence-characterized amplified region marker 7-2299 distinguished A4 mating-type monokaryons from KNR2312 and other strains. A BLAST search of flanked sequences revealed that the A4 locus had a general feature consisting of the putative HD1 and HD2 genes. Both putative HD transcription factors contain a homeodomain sequence and a nuclear localization sequence; however, valid dimerization motifs were found only in the HD1 protein. The ACAAT motif, which was reported to have relevance to sex determination, was found in the intergenic region. The SCAR marker could be applicable in the classification of mating types in the P. eryngii breeding program, and the A4 locus could be the basis for a multi-allele detection marker.

T Cell-Specific Knockout of STAT3 Ameliorates Dextran Sulfate Sodium-Induced Colitis by Reducing the Inflammatory Response

Signal transducer and activator of transcription 3 (STAT3) has a crucial role in various autoimmune disorders including, inflammatory bowel disease (IBD). Our previous study demonstrated that STAT3 activation by IL-6 in colonic epithelial cells exacerbates experimental ulcerative colitis. Activated T lymphocytes are also found in ulcerative colitis patients with intestinal inflammation, but the role of STAT3 in T cells remains elusive. To determine the STAT3 function of T cells in intestinal inflammation, we generated T cell-specific STAT3 knockout (KO) mice and used dextran sulfate sodium (DSS) to induce colitis. In this study, we demonstrated that T cell-specific STAT3 deletion alleviated DSS-induced colitis in mice, resulting in reduced histological scores and myeloperoxidase (MPO) activity. Importantly, the population of T cells in the spleen and lymph nodes was significantly decreased in the control and DSS-induced groups of STAT3 KO mice. In addition, STAT3 deficiency in T cells markedly reduced the production of interferon (IFN)-γ, IL-6, and IL-17A, whereas IL-10 secretion was increased. Collectively, the results suggest that STAT3 in T cells may be a therapeutic target in ulcerative colitis by balancing the immune response through T cell homeostasis.

The Clinical Results of 6-mm Iris-Fixated Phakic IOL

PURPOSE: To evaluate the clinical results of 6 mm iris-fixated phakic intraocular lens (Artisan(R) lens) implantation in myopic patients. METHODS: Forty eyes of 23 myopic patients underwent 6-mm Artisan(R) phakic IOL implantation and were followed-up for over 6 months. We prospectively analyzed the efficacy, stability, predictability, change of astigmatism, endothelial cell count, pupil diameter, degree of decentration, subjective satisfaction and complications. RESULTS: The preoperative mean spherical equivalent was -9.46 D, and postoperative spherical equivalent was -0.70D at 1 month, -0.55D at 3 months, -0.54D at 6 months, -0.78D at 12 months and remained stable during the follow-up period. The preoperative mean astigmatism was -1.88D and postoperative astigmatism was -0.87D at 6 months. Postoperative uncorrected visual acuity (UCVA) was more than 0.8 in 85% of the eyes at 1 month, 91% at 3 months, 95% at 6 months, and 89% at 12 months. The spherical equivalent refraction after surgery was within 1.0D of emmetropia in 78% of eyes at 1 month, 80% at 3 months, 88% at 6 months, and 64% at 12 months. There was no significant decrease in the endothelial cell count during the follow-up period. Preoperative scotopic pupil diameters were significantly decreased at 1 month and the mean decentration of the lens was 0.38 mm. Patient satisfaction was generally high. Complications included the transient elevation of intraocular pressure in 1 eye, corneal edema in 4 eyes, iritis in 1 eye, traumatic dislocation in 1 eye and iris atrophy in 2 eyes. CONCLUSIONS: The 6-mm Artisan(R)phakic IOL implantation may be an effective surgical procedure for myopic patients who cannot undergo corneal refractive surgery, as it provided good visual results, predictability, patient satisfaction, and short-term safety.

Study on the interface between light-cured glass ionomer base and indirect composite resin inlay and dentin / 대한치과보존학회지

This study was done to evaluate the shear bond strength between light-cured glass ionomer cement (GIC) base and resin cement for luting indirect resin inlay and to observe bonding aspects which is produced at the interface between them by SEM. Two types of light cured GIC (Fuji II LC Improved, GC Co. Tokyo, Japan and Vitrebond(TM), 3M, Paul, Minnesota, U.S.A) were used in this study. For shear bond test, GIC specimens were made and immersed in 37degrees C distilled water for 1 hour, 24 hours, 1 week and 2 weeks. Eighty resin inlays were prepared with Artglass(R) (Heraeus Kultzer, Germany) and luted with Variolink(R) II (Ivoclar Vivadent, Liechtenstein). Shear bond strength of each specimen was measured and fractured surface were examined. Statistical analysis was done with one-way ANOVA. Twenty four extracted human third molars were selected and Class II cavities were prepared and GIC based at axiopulpal lineangle. The specimens were immersed in 37degrees C distilled water for 1 hour, 24 hours, 1 week and 2 weeks. And then the resin inlays were luted to prepared teeth. The specimens were sectioned vertically with low speed saw. The bonding aspect of the specimens were observed by SEM (JSM-5400(R), Jeol, Tokyo, Japan). There was no significant difference between the shear bond strength according to storage periods of light cured GIC base. And cohesive failure was mostly appeared in GIC. On scanning electron micrograph, about 30 - 120 microm of the gaps were observed on the interface between GIC base and dentin. No gaps were observed on the interface between GIC and resin inlay.

A Case of Steroid Treatment on Haze after LASIK Retreatment in eye with previous PRK

PURPOSE: A corneal haze after LASIK retreatment in eye with previous PRK has not been reported in Korea. We experienced a case of myopic regression and haze after LASIK retreatment and treated it with fortified steroid eye solution. Herein we will present it. METHODS: A 38-year-old woman underwent the PRK for the correction of myopia in 1994 and the bilateral LASIK retreatment of myopic regression in January 2000. One year later, the left eye showed myopic regression and severe corneal haze but right eye was nearly emmetropia. PredForte(R) was dropped 4 times daily for 3 months, tapered, substituted with Flumetholon(R) for the next 3 months. We observed for 6 months. RESULTS: Three months later, refraction became nearly emmetropic and uncorrected visual acuity was 0.6. Corneal haze, central keratometric and pachymetric value were much decreased. It remained stable for 6 months.

The Study of Normal Visual Fields Using Normal Strategy and Dynamic Strategy in Octopus 101 Automated Perimetery in Korean

Automated static perimeters, which are commonly used for early diagnosis and follow-up of glaucoma patients in Korea, are manufactured overseas, and their basic data were obtained from foreigners and normal values were set to meet them. Therefore, verification of validity of those data should precede their application to Koreans. We compared the mean normal values of standard indices of OCTOPUS 101 automated static perimeter with the values obtained from 140 eyes of 70 healthy Koreans using normal strategy(NS)and dynamic strategy(DS). Mean navlues of mean defect(MD), loss variance(LV), corrected loss variance(CLV), and short-term fluctuation(SF)were: 2.84+/-0.85dB, 2.15+/-0.54dB, 1.22+/-0.42dB, 1.43+/-0.22dBwith NS, and 2.05+/-0.81dB, 1.98 +/-0.58dB, 0.97+/-0.49dB, 1.43+/-0.24dB, repectively with DS. With NS, 114 of 140 eyes (81. 4%)were out of the normal range of MD. With DS, 67 of 140 eyes(47. 9%)were out of normal range of MD, and 2 of 140 eyes(1. 4%)were out of the normal range of SF. Values of the other indices were within normal range of both strategies. Statistical analysis of global indices showed that age was significantly correlated with LV, CLV and SF in NS(P<0.05), and that it was also correlated with LV and CLV in DS(P<0.05). These results suggest that both race and age should be taken into acoount in interpretation of visual fields on automated static perimetry.

Migration of Photoreceptor Cells Into the Subretinal Space in Rabbit Retina

The migration of photoreceptors into the subretinal space has been reported to occur in developing and aged rat retina, in aged human retina, in detached owl monkey, and in detached cat retina. Subretinal photoreceptor cells have been observed in aphakic-vitrectomized rabbit eyes with or without intravitreal saline or antibiotic injection. Variety of photoreceptor cell nuclei can be distinguished. The nuclei of photoreceptor cells change their shape so as to pass easily through the juncition and thereafter they returned to their original shape in sub retinal space. The mechanisms and biological significance of this phenomenon are not yet certain, but it may by one of the important factors contributing to decreased vision with aging.

Effect of Fibrin Glue(Tissel(R))in Experimental Corneal Perforation

Fibrinogen is converted into fibrin by the action of thrombin under presence of calcium. In addition to its hemostatic effect, fibrin coagulum has tissue adhesive effect and fibroblast stimulating effect in the healing process. Perforating wounds about 1mm X 3mm in size were made in the center of rabbit corneas, and then were treated with fibrin glue. Simple full-thickness lacerations were also made in the central cornea of the other eye without any treatment as a control group. These eyes were enucleated after various periods of interval and the wound sites were studied with light and electron microscope. Tissue defect of perforated cornea was closed well by fibrin glue and active proliferation of the fibroblasts was seen near the glue. From these results, fibrin glue may be useful in the treatment of human corneal perforation and it will be used for the other ocular surgery.

Effect of Fibrin Glue(Tissel(R))in Experimental Corneal Perforation

Fibrinogen is converted into fibrin by the action of thrombin under presence of calcium. In addition to its hemostatic effect, fibrin coagulum has tissue adhesive effect and fibroblast stimulating effect in the healing process. Perforating wounds about 1mm X 3mm in size were made in the center of rabbit corneas, and then were treated with fibrin glue. Simple full-thickness lacerations were also made in the central cornea of the other eye without any treatment as a control group. These eyes were enucleated after various periods of interval and the wound sites were studied with light and electron microscope. Tissue defect of perforated cornea was closed well by fibrin glue and active proliferation of the fibroblasts was seen near the glue. From these results, fibrin glue may be useful in the treatment of human corneal perforation and it will be used for the other ocular surgery.

A Case of Inverse Duane's Retraction Syndrome

The retraction syndrome in its classic form is characterized that severe limitation of abduction, slightly limitation of adduction, globe retraction and narrowing of the palpebral fissure on adduction, frequently associated elevation or depression in adduction, and convergency insufficiency. While many authors reported this type, there were few reports about inverse Duane's retraction syndrome, as exotropia in primary position, severe limitation of adduction. globe retraction and narrowing palpebral fissure on abduction. So the authors present a case of inversed Duane's retraction syndrome.

A Case of Osteopetrosis with Optic Atrophy

The authors experienced a case of osteopetrosis with optic atrophies and nystagmoid movements, exceedingly rare disease, in 12 year-old girl for 5 years without fracture in long bone. On the X-ray studies: 1. The skull bone showed moderately increased osteosclerotic changes in base of the skull and narrowings in optic foramina. 2. The findings of the extremities showed flask shaped deformities and cortical thickness in both femurs. and transverse line and epiphyseal separations in mid-tibia.

A Case of Wasp Sting of the Eye

We presented a case of wasp sting of 42 year old, farmer who got stung on the cornea directly. At the time of first examination, the patient had visual acuity of 0.02 in the right eye. Slit lamp examination revealed corneal epithelial desquamation and vesicle, striate keratitis, diffuse stromal edema and fine keratic precipitates on the corneal endothelium. The iris was depigmented and atrophic, and pupil was mydriatic and nonreactive. The lens was opaque at the center of anterior caspsule and fundus was not visualized. 4 months later, the corneal lesion was slightly improved. Clinical findings of iris and lens still unchanged.

Retinal Vascular Patterns Part III: Endophthalmitis following by perforating injury and corneal ulcer

The authors studied the retinal vascular patterns of human eye suffered from complicated endophthalmitis following by perforating injury and corneal ulcer. The technique of preparing slides to study the retinal vascular patterns were same as previously noted Part I report. A lot of microorganisms, such as cocci, bacilli and fungi are found in the inflamed foci(with or without filaments) around the retinal vessels unless the vessels were completely occluded. Focal and diffuse exudative vasculitis is related to the species of microorganisms and cbserved stage but almost all retinal vessel waIls show diffuse loss of perivascular argyrophilic fibers, socalled "moth eaten" appearance. In the later stage of vasculitis microorganisms are not found in the inflamed focus("punched out" lesion) of the occluded vessels which show as "bark-stripped-dead tree" appearance in reticulin stain.

Ultrasonograms in the Ocular and Orbital Diseases

Ultrasonograms were obtained from 27 cases of intraocular and 10 cases of orbital diseases with S.K.L containing a general transducer(A-mode), 1~3 MHz in its frequency and 15mm in its diameter. The authors summerized that these ultrasonograms would provide some benefits in supplementary clinical diagnosis, especially in confirming the presence of intraocular tumors, differential diagnosis of primary and secondary retinal detachment and deciding the location and surgical procedure preoperatively in the orbital tumors.

Follow-up Study of Trabeculectomy

In 1968, Cairns introduced the trabeculectomy operation and reported it to be a highly succesful form of surgery for the reduction of intraocular pressure in primary open-angle glaucoma. At the present time trabeculectomy is the treatment of choice for patients with primary open-angle glaucoma requiring surgery. In the period January, 1975. to March, 1978, 72 eyes of chronic simple, chronic angle-closure, secondary, and developmental glaucoma were operated by trabeculectomy and/or trabeculotomy in Busan National University Hospital. Follow-up study was achieved in 28 eyes(chronic simple glaucoms 17, chronic angle-closure glaucoma 4, secondary glaucoma 3, and developmental 4) of 72 eyes, and the duration of follow-up ranged from 1 year to 2 and 1/2 years(average 18 months). Our operative procedure, which was different from others, was made with 1/3 thickness of scleral flap, and made 2 knots with 8-0 nylon placed in free edge of scleral flap and 1/3 of all cases was not placed scleral flap sutures. We achieved success in 23 eyes (82.1% )of 28 eyes of all types of glaucoma and 14 eyes (82.4%) of 17 eyes of openangle glaucoma. The control of intraocular pressure in interrelationship to formation of filtering bleb was statistically significance(x2(0.05, 1)=3.84>5.46), and to scleral flap suture was not significance(x2(0,05, 1)=3.84>0.39). The complications during and after operation were delayed formation of anterior chamber, hyphema, posterior synechia, vitreous prolapse, choroidal detachment, and lens and vitreous opacity in order.

Retinal Vascular Patterns-Part II: Primary, secondary and absolute glaucoma

The authors observed retinal vascular patterns of the blind eyes surgically removed on account of pain, high intraocular pressure and global rupture by injury. Material for the study was 10 eyes which were 4 eyes of long standing absolute glaucoma, late stage of chronic simple glaucoma (3 eyes) and chronic angle closure glaucoma (1 eye). aphakic glaucoma (1 eye) and an eye of chronic simple glaucoma with traumatic global rupture. The technique of preparation of the slides was made of flat preparations of retinal vessels that all nonvascular components were digested with tris-buffered 3% trypsin solution and stained with PAS-hematoxylin and Wilder's reticulin stain. RESULTS OBTAINED AS FOLLOWS; 1. it is possible that diffuse acellularity (predominant loss of endothelium) in the capillaries of the equatorial and posterior portion of retina results from the arterial occlusion. 2. Solitary microaneurysm in the peripheral retinal capillary was found in the early stage and numerous saccular and fusiform aneurysms (rows of bead-like aneurysms) on the venules, and arteriolar and venular capillaries are related to the degree and duration of the venous occlusion. 3. The majority have had venous occlusion initially, on which distal venule there are found rows of bead-like outpouchings, and the occlusive arterioles show fibrinous appearence, accllularity and increasing PAS staining. 4. It is possible that abnormal A-V shunts and venous collaterals result from the venous occlusion and rows of bead-like microaneuysms in the capillaries will be switched over to shunts and collaterals.