Key factors to establish the ovalbumininduced atopic dermatitis minipig model: age and body weight / 한국실험동물학회지

Background@#Given its similar structure and immune response to the human skin, porcine is a good model for dermal studies. Here, we sensitized ovalbumin (Ova) on minipig back skin for 2–4 weeks to induce chronic atopic dermatitis (AD). @*Results@#Gross observation, serum cytokine level, epidermal thickness, and epidermal integrity did not change after 4 weeks of Ova induction compared with the control, indicating AD modeling failure. Only the neutrophils in the blood and macrophages in bronchoalveolar lavage fluid changed slightly until 3 or 2 weeks after Ova sensitization, respectively. The successful and failed Ova-induced AD minipig models only differ in age and body weight of the minipigs. The minipigs, 12 months old with a 30-kg median weight, had a two-fold thicker dermis than minipigs 8–10 months old, with an 18.97-kg median weight, resulting in impaired Ova permeability and immune response. @*Conclusion@#Age and body weight are key factors that should be considered when developing an Ova-induced AD minipig model.

Precision Capsular Infarct Modeling to Produce Hand Motor Deficits in Cynomolgus Macaques

Stroke research in non-human primates (NHPs) with gyrencephalic brains is a critical step in overcoming the translational barrier that limits the development of new pharmaceutical and rehabilitative strategies for stroke. White-matter stroke (WMS) has a unique pathophysiology from graymatter stroke and is not well understood because of a lack of pertinent animal models. To create a precise capsular infarct model in the cynomolgus macaque, we first used electrical stimulation to map hand movements, followed by viral tracing of the hand motor fibers (hMFs). This enabled us to identify stereotactic targets in the posterior limb of the internal capsule (PLIC). Neural tracing showed that hMFs occupy the full width of the PLIC, owing to overlap with the motor fibers for the leg. Furthermore, the hMFs were distributed in an oblique shape, requiring coronal tilting of the target probe. We used the photothrombotic infarct lesioning technique to precisely destroy the hMFs within the internal capsule. Double-point infarct lesioning that fully compromised the hMFs resulted in persistent hand motor and walking deficits whereas single-point lesioning did not. Minor deviations in targeting failed to produce persistent motor deficits. Accurate stereotactic targeting with thorough involvement of motor fibers is critical for the production of a capsular infarct model with persistent motor deficits. In conclusion, the precision capsular infarct model can be translated to the NHP system to show persistent motor deficits and may be useful to investigate the mechanism of post-stroke recovery as well as to develop new therapeutic strategies for the WMS.

Comparative analysis of immune related genes between domestic pig and germ-free minipig / 한국실험동물학회지

Recently, minipig has been considered as an animal model that is appropriate for human disease model to study toxicology, pharmacology, and xenotransplantation. Nevertheless, minipigs are bred in various environment according to their use. Here, we suggest that minipigs used for research should be bred in well-controlled facility, comparing immune status of pigs raised in different breeding environment. DNA microarray was performed with ear skin and placenta of Landrace domestic pigs (DPs) and Minnesota germ-free minipigs (GPs). Their immune transcriptome was analyzed by gene ontology (GO) annotation database, based on criteria of |log2 fold change| ≥1 with P ≤ 0.05. As a result, we found that immune related genes in the ear skin of DPs were highly activated, compared to GPs. On the other hand, no significant s were found in the placenta. Quantitative real-time PCR (qRT-PCR) was performed in five candidate immune genes. Their fold changes were consistent with the results from DNA microarray (P ≤ 0.05). In conclusion, we experimentally proved that porcine immune system was affected by different breeding environment, suggesting the importance of controlling microbes in animal room for the qualified research.

Comparative analysis of immune related genes between domestic pig and germ-free minipig / 한국실험동물학회지

Recently, minipig has been considered as an animal model that is appropriate for human disease model to study toxicology, pharmacology, and xenotransplantation. Nevertheless, minipigs are bred in various environment according to their use. Here, we suggest that minipigs used for research should be bred in well-controlled facility, comparing immune status of pigs raised in different breeding environment. DNA microarray was performed with ear skin and placenta of Landrace domestic pigs (DPs) and Minnesota germ-free minipigs (GPs). Their immune transcriptome was analyzed by gene ontology (GO) annotation database, based on criteria of |log2 fold change| ≥1 with P ≤ 0.05. As a result, we found that immune related genes in the ear skin of DPs were highly activated, compared to GPs. On the other hand, no significant s were found in the placenta. Quantitative real-time PCR (qRT-PCR) was performed in five candidate immune genes. Their fold changes were consistent with the results from DNA microarray (P ≤ 0.05). In conclusion, we experimentally proved that porcine immune system was affected by different breeding environment, suggesting the importance of controlling microbes in animal room for the qualified research.

Three-axis Modification of Coordinates Enables Accurate Stereotactic Targeting in Non-human Primate Brains of Different Sizes

The brain grows with age in non-human primates (NHPs). Therefore, atlas-based stereotactic coordinates cannot be used directly to target subcortical structures if the size of the animal's brain differs from that used in the stereotactic atlas. Furthermore, growth is non-uniform across different cortical regions, making it difficult to simply apply a single brain-expansion ratio. We determined the skull reference lines that best reflect changes in brain size along the X, Y, and Z axes and plotted the changes in reference-line length against the changes in body weight. The skull reference lines had a linear relationship with body weight. However, comparison of skull reference lines with body weight confirmed the non-uniform skull growth during postnatal development, with skull growth more prominent in the X and Y axes than the Z axis. Comparing the differences between the atlas-based lengths and those calculated empirically from plot-based linear fits, we created craniometric indices that can be used to modify stereotactic coordinates along all axes. We verified the accuracy of the corrected stereotactic targeting by infusing dye into internal capsule in euthanized and preserved NHP brains. Our axis-specific, craniometric-index-adjusted stereotactic targeting enabled us to correct for targeting errors arising from differences in brain size. Histological verification showed that the method was accurate to within 1 mm. Craniometric index-adjusted targeting is a simple and relatively accurate method that can be used for NHP stereotactic surgery in the general laboratory, without the need for high-resolution imaging.

Comparison of Approaches for the Removal of Metallic Intraocular Foreign Bodies

PURPOSE: To review the management of posterior segment metallic intraocular foreign bodies (IOFB) and to compare the use of an external approach using a large electromagnet and an internal approach using vitrectomy and its tools for their removal. METHODS: A retrospective review was performed on 49 eyes of 49 patients who underwent surgical removal of metallic IOFBs with either an internal or an external approach at a single institution between January 2003 and December 2006. We divided 49 eyes into two groups based on the type of approach: 26 external (n=26) and 23 internal (n=23). Visual acuity and the presence of any complications occurring with the two approaches were the main outcome measures studied. RESULTS: Thirty of 49 eyes (61%) showed improvements in visual acuity. When we compared patients treated with an external versus an internal approach, we found no statistically significant difference in regard to visual outcome. Preoperative vitreous hemorrhage and endophthalmitis were more common in the internal approach group. A trend toward a higher rate of reoperation was more common in the external approach group, but they were not statistically significant. Postoperative complications found to be significantly different between the two groups were the rate of postoperative endophthalmitis and retinal detachment, which were more common in the external approach group. CONCLUSIONS: Surgical removal of metallic IOFBs results in significant visual improvement regardless of the approach method. The internal approach by vitrectomy is recommended as the first choice in preoperative conditions such as severe cataracts, vitreous hemorrhage and endophthalmitis, as well as in groups at high risk for postoperative endophalmitis and retinal detachment.

A Case of Corneal Ulcer by Alcaligenes Faecalis

PURPOSE: To report a case of corneal ulcer due to Alcaligenes faecalis in a patient with a preexisting corneal ulcer. CASE SUMMARY: A 58-year-old male patient presented with a corneal ulcer without a history of any trauma. The patient had a history of corneal ulcer 9 months earlier. The patient had previously been diagnosed with diabetic retinopathy and neovascular glaucoma, and his visual acuity was no light perception. Corneal scraping and culture yielded Alcaligenes faecalis susceptible to most antibiotics in the antibiotic susceptibility test. After treatment with empirical systemic antibiotics and eyedrops, his eye improved with a remaining corneal scar. CONCLUSIONS: Alcaligenes faecalis should be considered as a causal pathogen of corneal ulcer in patients with suspicious compromised ocular surface, such as previous corneal ulcer.

Prognostic Factors in Patients With Endogenous Endophthalmitis

PURPOSE: We evaluated the causative microorganisms, dispositions, and visual prognosis of endogenous endophthalmitis. METHODS: The records of 12 eyes of 10 patients who were diagnosed with endogenous endophthalmitis were retrospectively reviewed with respect to the causative microorganisms, dispositions, visual prognosis, initial visual acuity, time interval between onset of symptom, and the course of treatment. RESULTS: Three of the four eyes infected with a candida species recovered a visual acuity of 0.1 or better; none of the other infected eyes reached higher than 0.1 (p=0.024). Initial visual acuity of less than hand movement reached globe loss in three eyes, while 5 eyes with initial visual acuity of better than hand movement of seven eyes did not lose the globe (p=0.045). Three out of patients with a time interval between onset of symptoms and treatment of more than five days did not lose the globe, while those with a time interval of less than five days of eight eyes did not lose the globe. CONCLUSIONS: Visual prognosis and globe survival depends mainly on the underlying microorganism, initial visual acuity, the time interval between the onset of symptom, and treatment. Patients with candida endophthalmitis had good visual outcome compared with the others, and thus microbial culture identification is a useful predictor of visual acuity and treatment.