Effects of Gamma-Linolenic Acid Adjuvant Therapy in Patients with Atopic Dermatitis:A Survey Study / 대한피부과학회지

Background@#Atopic dermatitis (AD) is a chronic pruritic inflammatory dermatosis. Whether gamma-linolenic acid (GLA) supplementation is beneficial in AD patients remains debatable. @*Objective@#This study investigated whether adjuvant GLA supplementation is associated with clinical improvement in AD patients receiving systemic treatment, as assessed by patient-reported outcome measures. @*Methods@#We enrolled 70 AD patients. Patients who received GLA at a dose of 80∼160 mg/d for over 1 month were included in the GLA group, while others were included in the non-GLA group. Each group was subgrouped into control, immunomodulator, and dupilumab groups based on treatment history. The patients evaluated their symptoms using the Atopic Dermatitis Control Tool (ADCT), Patient Global Assessment of Disease (PGA), and Dermatology Life Quality Index (DLQI). @*Results@#The Mann-Whitney U-test was used to compare differences in ADCT, PGA, and DLQI between both groups. The ADCT scores were significantly lower in the control and immunomodulatory group supplemented with GLA (control U=13.5, p=0.04; immunomodulatory U=28.0, p=0.01), but not in patients taking dupilumab (U=44.5, p=0.70). The PGA and DLQI scores also tended to be lower in the GLA group than those in the non-GLA group. @*Conclusion@#GLA supplementation is a potential adjuvant to systemic therapy may yield additional symptomatic relief in AD patients.

Age-specific variations in hematological and biochemical parameters in middle- and large-sized of dogs

Aging triggers cellular and molecular alterations, including genomic instability and organ dysfunction, which increases the risk of disease in mammals. Recently, due to the markedly growing number of aging dogs in the world, as much as 49% in total number of pet dogs, it is necessary to improve and maintain their quality of life by understanding of the biological effects of aging. Therefore, the aim of this study was to determine specific biomarkers in aging dogs as a means of defining a set of hematological/biochemical biomarkers that influence the aging process. Blood samples were collected from younger (1–3 years) and older (7–10 years) dogs of middle/large size. The hematological/biochemistry analysis was performed to evaluate parameters significantly associated with age. Enzyme-linked immunosorbent assay was used to target growth hormone (GH)/insulin growth factor-1 (IGF-1), one of the main regulators of the aging process. Declining levels of total protein and increased levels of glucose in young dogs was observed regardless of their body size. Notably, a significantly high concentration of GH and IGF-1 in the younger dogs compared to the older dogs was found in middle/large-sized dogs. GH and IGF-1 were also found at significantly high levels in large-sized dogs compared to middle-sized dogs, suggesting a similar trend to that of elderly humans. Consequently, glucose, total protein, GH, and IGF-1 were identified as potential biomarkers for regulating the aging process in large/middle-sized dogs. These findings provide an invaluable insight into the mechanism of aging for the field of aging research.

Age-specific variations in hematological and biochemical parameters in middle- and large-sized of dogs

Aging triggers cellular and molecular alterations, including genomic instability and organ dysfunction, which increases the risk of disease in mammals. Recently, due to the markedly growing number of aging dogs in the world, as much as 49% in total number of pet dogs, it is necessary to improve and maintain their quality of life by understanding of the biological effects of aging. Therefore, the aim of this study was to determine specific biomarkers in aging dogs as a means of defining a set of hematological/biochemical biomarkers that influence the aging process. Blood samples were collected from younger (1–3 years) and older (7–10 years) dogs of middle/large size. The hematological/biochemistry analysis was performed to evaluate parameters significantly associated with age. Enzyme-linked immunosorbent assay was used to target growth hormone (GH)/insulin growth factor-1 (IGF-1), one of the main regulators of the aging process. Declining levels of total protein and increased levels of glucose in young dogs was observed regardless of their body size. Notably, a significantly high concentration of GH and IGF-1 in the younger dogs compared to the older dogs was found in middle/large-sized dogs. GH and IGF-1 were also found at significantly high levels in large-sized dogs compared to middle-sized dogs, suggesting a similar trend to that of elderly humans. Consequently, glucose, total protein, GH, and IGF-1 were identified as potential biomarkers for regulating the aging process in large/middle-sized dogs. These findings provide an invaluable insight into the mechanism of aging for the field of aging research.

Age-specific variations in hematological and biochemical parameters in middle- and large-sized of dogs

Iodixanol supplementation during sperm cryopreservation improves protamine level and reduces reactive oxygen species of canine sperm

The objective of this study was to analyze the protective effects of iodixanol on dog spermatozoa during cryopreservation. The optimal concentration of iodixanol, 1.5%, was determined using fresh spermatozoa and was applied in the following experiments. The 1.5% iodixanol group showed significantly increased sperm motility from that in the control (p < 0.05). Lower mitochondrial reactive oxygen species (ROS) modulator (ROMO1) and pro-apoptotic gene (BAX) expressions, together with higher expressions of protamine-2 (PRM2), protamine-3 (PRM3), anti-apoptotic B-cell lymphoma-2 (BCL2), and sperm acrosome associated-3 (SPACA3) genes were detected in the iodixanol-treated group. In addition, decreased protamine deficiency and cryocapacitation were observed in the treatment group. Our results show that supplementation with 1.5% iodixanol is ideal for reducing production of ROS and preventing detrimental effects during the canine sperm cryopreservation process, effects manifested as increased motility and reduced cryocapacitation in frozen-thawed spermatozoa.

Mechanically Reinforced Extracellular Matrix Scaffold for Application of Cartilage Tissue Engineering

Scaffolds with cartilage-like environment and suitable physical properties are critical for tissue-engineered cartilage repair. In this study, decellularized porcine cartilage-derived extracellular matrix (ECM) was utilized to fabricate ECM scaffolds. Mechanically reinforced ECM scaffolds were developed by combining salt-leaching and crosslinking for cartilage repair. The developed scaffolds were investigated with respect to their physicochemical properties and their cartilage tissue formation ability. The mechanically reinforced ECM scaffold showed similar mechanical strength to that of synthetic PLGA scaffold and expressed higher levels of cartilage-specific markers compared to those expressed by the ECM scaffold prepared by simple freeze-drying. These results demonstrated that the physical properties of ECM-derived scaffolds could be influenced by fabrication method, which provides suitable environments for the growth of chondrocytes. By extension, this study suggests a promising approach of natural biomaterials in cartilage tissue engineering.

Nondestructive Assessment of Glycosaminoglycans in Engineered Cartilages Using Hexabrix-Enhanced Micro-Computed Tomography

It is very useful to evaluate the content and 3D distribution of extracellular matrix non-destructively in tissue engineering. This study evaluated the feasibility of using micro-computed tomography (µCT) with Hexabrix to measure quantitatively sulfated glycosaminoglycans (GAGs) of engineered cartilage. Rabbit chondrocytes at passage 2 were used to produce artificial cartilages in polyglycolic acid scaffolds in vitro. Engineered cartilages were incubated with Hexabrix 320 for 20 min and analyzed via µCT scanning. The number of voxels in the 2D and 3D scanning images were counted to estimate the amount of sulfated GAGs. The optimal threshold value for quantification was determined by regression analysis. The 2D µCT images of an engineered cartilage showed positive correlation with the histological image of Safranin-O staining. Quantitative data obtained with the 3D µCT images of 14 engineered cartilages showed strong correlation with sulfated GAGs contents obtained by biochemical analysis (R² = 0.883, p < 0.001). Repeated exposure of engineered cartilages to Hexabrix 320 and µCT scanning did not significantly affect cell viability, total DNA content, or the total content of sulfated GAGs. We conclude that µCT imaging using Hexabrix 320 provides high spatial resolution and sensitivity to assess the content and 3D distribution of sulfated GAGs in engineered cartilages. It is expected to be a valuable tool to evaluate the quality of engineered cartilage for commercial development in the future.

Health and temperaments of cloned working dogs

Dogs serve human society in various ways by working at tasks that are based on their superior olfactory sensitivity. However, it has been reported that only about half of all trained dogs may qualify as working dogs through conventional breeding management because proper temperament and health are needed in addition to their innate scent detection ability. To overcome this low efficiency of breeding qualified working dogs, and to reduce the enormous costs of maintaining unqualified dogs, somatic cell nuclear transfer has been applied in the propagation of working dogs. Herein, we review the history of cloning working dogs and evaluate the health development, temperaments, and behavioral similarities among the cloned dogs. We also discuss concerns about dog cloning including those related to birth defects, lifespan, and cloning efficiency.

Histomorphometric evaluation of the bone surrounding orthodontic miniscrews according to their adjacent root proximity / 대한치과교정학회지

OBJECTIVE: This study was conducted to perform histomorphometric evaluations of the bone surrounding orthodontic miniscrews according to their proximity to the adjacent tooth roots in the posterior mandible of beagle dogs. METHODS: Four male beagle dogs were used for this study. Six orthodontic miniscrews were placed in the interradicular spaces in the posterior mandible of each dog (n = 24). The implanted miniscrews were classified into no loading, immediate loading, and delayed loading groups according to the loading time. At 6 weeks after screw placement, the animals were sacrificed, and tissue blocks including the miniscrews were harvested for histological examinations. After analysis of the histological sections, the miniscrews were categorized into three additional groups according to the root proximity: high root proximity, low root proximity, and safe distance groups. Differences in the bone–implant contact (BIC, %) among the root proximity groups and loading time groups were determined using statistical analyses. RESULTS: No BIC was observed within the bundle bone invaded by the miniscrew threads. Narrowing of the periodontal ligament space was observed in cases where the miniscrew threads touched the bundle bone. BIC (%) was significantly lower in the high root proximity group than in the low root proximity and safe distance groups. However, BIC (%) showed no significant differences among the loading time groups. CONCLUSIONS: Regardless of the loading time, the stability of an orthodontic miniscrew is decreased if it is in contact with the bundle bone as well as the adjacent tooth root.

The Effects of Spinal Decompression Therapy on Pain and Disability in Patients with Chronic Low Back Pain

PURPOSE: The purpose of this study was to examine the effects of spinal decompression therapy on pain and disability in patients with chronic low back pain. METHODS: Twenty patients with chronic low back pain were divided into an experimental group (spinal decompression therapy, n=10) and a control group (conservative physical therapy, n=10). Both groups were treated three times a week over a four-week period. RESULTS: The comparison of between-group changes post-treatment revealed statistically significant lower levels of pain and disability in the experimental group than the control group. The comparison of within each group changes before and after the treatment showed statistically significant declines in pain and disability indexes of both groups. CONCLUSION: Spinal decompression therapy may be an effective intervention for improving pain and disability in patients with chronic low back pain.

The Effects of High Intensity Laser Therapy on Pain and Function of Patients with Frozen Shoulder

PURPOSE: This study was to identify the effectiveness of high-intensity laser therapy on pain and function of a frozen shoulder. METHODS: Thirty patients were assigned to two groups: the experimental group (n=15) and the control group (n=15). Both groups received traditional therapy for 4 weeks, 3 days a week. The experimental group, however, received an additional high intensity laser therapy. Pain was measured using the visual analogue scale (VAS). The functional ability was measured using the patient specific functional scale (PSFS). A paired t-test was used to determine any differences before and after the treatment, and an independent t-test was used to determine any differences between treatment groups. RESULTS: Both groups showed a statistically significant difference for VAS and PSFS score (p<0.05). In comparison between two groups, more experimental group than control group statistically significant difference (p<0.05). CONCLUSION: There seems to be a positive effect on pain and function of frozen shoulder from using high intensity laser therapy.

Fecal Calprotectin Level Reflects the Severity of Clostridium difficile Infection

Clostridium difficile is a significant nosocomial and community-acquired pathogen, and is the leading cause of antibiotic-induced diarrhea associated with high morbidity and mortality. Given that the treatment outcome depends on the severity of C. difficile infection (CDI), we aimed to establish an efficient method of assessing severity, and focused on the stool biomarker fecal calprotectin (FC). FC directly reflects the intestinal inflammation status of a patient, and can aid in interpreting the current guidelines, which requires the integration of indirect laboratory parameters. The distinction of 80 patients with CDI versus 71 healthy controls and 30 severe infection cases versus 50 mild cases was possible using FC as a marker. The area under the receiver operating characteristic curves were 0.821 and 0.746 with a sensitivity of 75% and 70% and specificity of 79% and 80%, for severe versus mild cases, respectively. We suggest FC as a predictive marker for assessing CDI severity, which is expected to improve the clinical management of CDI.

Learning, memory and exploratory similarities in genetically identical cloned dogs

Somatic cell nuclear transfer allows generation of genetically identical animals using donor cells derived from animals with particular traits. To date, few studies have investigated whether or not these cloned dogs will show identical behavior patterns. To address this question, learning, memory and exploratory patterns were examined using six cloned dogs with identical nuclear genomes. The variance of total incorrect choice number in the Y-maze test among cloned dogs was significantly lower than that of the control dogs. There was also a significant decrease in variance in the level of exploratory activity in the open fields test compared to age-matched control dogs. These results indicate that cloned dogs show similar cognitive and exploratory patterns, suggesting that these behavioral phenotypes are related to the genotypes of the individuals.

Reproductive ability of a cloned male detector dog and behavioral traits of its offspring

In 2007, seven detector dogs were produced by somatic cell nuclear transfer using one nuclear donor dog, then trained and certified as excellent detector dogs, similar to their donor. In 2011, we crossed a cloned male and normal female by natural breeding and produced ten offspring. In this study, we investigated the puppies' temperaments, which we later compared with those of the cloned parent male. The results show that the cloned male had normal reproductive abilities and produced healthy offspring. All puppies completed narcotic detector dog training with a success rate for selection of 60%. Although the litter of cloned males was small in this study, a cloned male dog bred by natural mating produced puppies that later successfully completed the training course for drug detection. In conclusion, cloning an elite dog with superior genetic factors and breeding of the cloned dog was found to be a useful method to efficiently procure detector dogs.

Comparative Results of Trabeculectomy with Mitomycin C in Uveitic Glaucoma versus Primary Open-Angle Glaucoma

PURPOSE: In this study we evaluated the long-term outcomes and prognostic factors of trabeculectomy with mitomycin C (MMC) in eyes with uveitic glaucoma (UG) compared with primary open-angle glaucoma (POAG). METHODS: We performed a retrospective chart review of 60 eyes with UG and 402 eyes with POAG that were followed up for at least 1 year after trabeculectomy with MMC between June 2000 and December 2012. The review included intraocular pressure (IOP), number of anti-glaucoma medications, and postoperative complications. Surgical success was analyzed using the Kaplan-Meier life-table method based on 2 definitions of successful IOP control with topical anti-glaucoma medications: Definition A (IOP < or = 15 mm Hg) and Definition B (IOP < or = 18 mm Hg). Risk factors for surgical failure of trabeculectomy were analyzed using the Cox proportional hazards model. RESULTS: Success rate at 5 years after trabeculectomy was lower in UG than in POAG (65.8% vs. 76.4%, Definition B), but without significant difference. However, UG had a significantly lower cumulative probability of success than POAG based on Kaplan-Meier survival curves (p = 0.049 and 0.044, respectively). Postoperative hypotony and hypotony maculopathy was more frequent in UG (p = 0.044 and 0.044, respectively). In UG, the Cox proportional hazards model showed postoperative shallow anterior chamber was associated with surgical failure in both Definition A and B. CONCLUSIONS: Long-term results of trabeculectomy with MMC in eyes with UG showed successful IOP control similar to POAG. Trabeculectomy with MMC is a reasonable surgical option for the management of UG.

Proposed Motor Scoring System in a Porcine Model of Parkinson's Disease induced by Chronic Subcutaneous Injection of MPTP

Destruction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) is a common pathophysiology of Parkinson's disease (PD). Characteristics of PD patients include bradykinesia, muscle rigidity, tremor at rest and disturbances in balance. For about four decades, PD animal models have been produced by toxin-induced or gene-modified techniques. However, in mice, none of the gene-modified models showed all 4 major criteria of PD. Moreover, distinguishing between PD model pigs and normal pigs has not been well established. Therefore, we planned to produce a pig model for PD by chronic subcutaneous administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), neurotoxin. Changes in behavioral patterns of pigs were thoroughly evaluated and a new motor scoring system was established for this porcine model that was based on the Unified Parkinson's Disease Rating Scale (UPDRS) in human PD patients. In summary, this motor scoring system could be helpful to analyze the porcine PD model and to confirm the pathology prior to further examinations, such as positron emission tomography-computed tomography (PET-CT), which is expensive, and invasive immunohistochemistry (IHC) of the brain.

Comparison of Very Low Fluence and Low Fluence Photodynamic Therapy in Chronic Central Serous Chorioretinopathy

PURPOSE: To investigate the safe, effective light dose for photodynamic therapy (PDT) in the treatment of chronic central serous chorioretinopathy (CSC). METHODS: Thirty-eight eyes of 37 patients with chronic CSC were recruited for this study. From November 2009 to July 2010 and from April 2011 to February 2012, PDT was performed using 50% and 25% of the full light dose in 27 eyes of 27 patients (group I) and 11 eyes of 10 patients (group II), respectively. The minimum follow-up period was 6 months. Mean change in best corrected visual acuity (BCVA) and central retinal thickness, hyperpermeability change from abnormal choriocapillaris, success rate, recurrence rate, and complications were analyzed. RESULTS: Group I showed that BCVA (log MAR) improved significantly from 0.33 +/- 0.17 to 0.14 +/- 0.15 at 6 months (p < 0.001). However, there was no significant improvement of BCVA (p = 0.050) in group II. One eye out of 27 eyes (3.7%) in group I and 5 eyes out of 11 eyes (45.5%) in group II showed recurrence at the 6-month follow-up (p = 0.016). After initial PDT, hyperpermeability from abnormal choriocapillaris reduced or disappeared at 95.5% in group I and 54.5% in group II at month 3 (p = 0.016). No patient in either group experienced severe adverse events. CONCLUSIONS: PDT performed with 50% of the full light dose appears to be a more useful method in the treatment of chronic CSC, with less frequent recurrence, than PDT using 25% of the full light dose.

Macular Edema Following Branch Retinal Vein Occlusion: A Comparison of Natural Course and Treatment with Intravitreal Bevacizumab Injection

PURPOSE: To assess long-term comparisions of intravitreal bevacizumab injection (IVB group) with natural course (Natural course group) in patients with macular edema after branch retinal vein occlusion (BRVO). METHODS: Fifty-seven patients were included in this retrospective study and were followed-up for at least 12 months. Patients in the Natural course group (27 eyes of 27 patients) were enrolled before February 2007, and patients in the IVB group (30 eyes of 30 patients) underwent intravitreal bevacizumab injection as-needed after February 2007. The main efficacy outcome was reported as the mean change from baseline best corrected visual acuity (BCVA), and all patients were measured at the initial visit and after 1, 3, 6, and 12 months. Retreatment criteria included central subfield macular thickness (CSMT) greater than 300 microm or increased CSMT of at least 100 microm between visits. RESULTS: There were no statistically significant differences in age or initial BCVA between the 2 groups. Mean changes of BCVA at initial visit and at 3 and 12 months were 0.61 +/- 0.48, 0.44 +/- 0.46 and 0.34 +/- 0.40 in the Natural course group and 0.67 +/- 0.40, 0.31 +/- 0.26 and 0.27 +/- 0.25 in the IVB group, respectively. Improvement in BCVA was observed in both groups at 12 months, although the IVB group improved significantly more at 3 months and not at 12 months (p = 0.018, p = 0.187, respectively). CONCLUSIONS: More frequent bevacizumab injection schedule appears necessary to achieve better long-term visual outcome for patients with macular edema following BRVO.

Surgical Treatment of Face Turn, and Up and Down Shoot in Duane Retraction Syndrome

PURPOSE: To present the results of patients undergoing surgical treatment and determine clinical guidelines for the face turn, and up and down shoot in Duane retraction syndrome (DRS). METHODS: Thirty-four patients with DRS were treated with single horizontal rectus muscle recession, lateral rectus (LR) recession with Y-splitting, or LR recession with Y-splitting combined with medial rectus (MR) recession. The different treatment approaches were based on the angle of deviation in the primary position, versions, and ductions. In all patients, ocular alignment, face turn and up and down shoot were assessed preoperatively and postoperatively. RESULTS: The average standard deviation reduced from 18.5 +/- 6.5 prism diopters (PD) to 4.6 +/- 5.8 PD in horizontal rectus muscle recession and 14.4 +/- 5.5 PD to 1.6 +/- 2.8 PD in LR recession with Y-splitting. LR recession with Y-splitting combined with MR recession was effective in reducing globe retraction. Postoperative 4-mm LR recession with Y-splitting did not change ocular alignment; 7-mm LR recession with Y-splitting showed an average correction of 12.8 PD. Postoperatively, all patients presented a reduction in face turn; however, there was no statistically significant difference between the 2 procedures (Mann-Whitney U test, p = 0.620). CONCLUSIONS: Decisions regarding surgical approaches in DRS should be based on the amount of deviation in primary eye position, the expression of up and down shoot, and the degree of face turn. Surgeons planning Y-splitting of LR with MR recession must consider modifying the MR recession amount due to the smaller LR recession effect of Y-splitting compared with conventional LR recession.

SRY-positive 78, XY ovotesticular disorder of sex development in a wolf cloned by nuclear transfer

Recently, we reported the three wolves cloning with normal karyotype from somatic cells of endangered male gray wolves (Canis lupus), but one wolf had female external genitalia. In this study, we conducted further clinical, histological, and genetic analyses. This cloned wolf had a normal uterus but developed ovotestis. Through molecular analysis of the SRY gene, a mutation in the coding sequence of SRY gene could be excluded as a cause of intersexuality. This is the first report of a cloned wolf with a 78, XY ovotesticular disorder affecting sexual development characterized by bilateral ovotestes.