Comparison of 1-year effectiveness between phaco-microhook ab-interno trabeculotomy and phaco-iStent trabecular micro-bypass stent in primary open-angle glaucoma with low-teen intraocular pressure.

PURPOSE: To investigate the surgical effectiveness of combined cataract surgery with microhook ab-interno trabeculotomy (phaco-µLOT) or iStent trabecular micro-bypass stent (phaco-iStent) in eyes with primary open-angle glaucoma (POAG) and preoperative intraocular pressure (IOP) controlled below 15 mmHg (low-teen IOP). METHODS: This retrospective cohort study included consecutive patients with POAG and low-teen IOP who underwent phaco-µLOT or phaco-iStent as their initial glaucoma surgery and were followed up for 1 year postoperatively. Surgical failure was defined as the inability to achieve the following criteria twice in a row: (A) IOP of 6-15 mmHg with over 20% IOP reduction; (B) IOP of 6-12 mmHg with over 20% IOP reduction. RESULTS: A total of 75 eyes from 75 subjects were included, with 48 in the phaco-µLOT group and 27 in the phaco-iStent group. The mean preoperative IOP and number of antiglaucoma medications were 13.1 ± 2.1 mmHg and 3.4 ± 0.9 in the phaco-µLOT group, and 12.6 ± 2.0 mmHg and 2.5 ± 1.2 in the phaco-iStent group, respectively. The number of antiglaucoma medications was significantly reduced to 2.5 ± 0.9 (phaco-µLOT) and 2.0 ± 1.1 (phaco-iStent) at 1-year postoperatively (all p < 0.05). For criteria A and B, the survival rates were significantly higher in the phaco-µLOT group than in the phaco-iStent group (all p < 0.01). CONCLUSION: Both phaco-µLOT and phaco-iStent hold promise in reducing the need for antiglaucoma medications in POAG eyes with low-teen IOP. Phaco-µLOT may be more effective than phaco-iStent in controlling IOP. KEY MESSAGES: What is known Minimally invasive glaucoma surgeries (MIGS) procedures target the pressure gradient pathways in patients with higher preoperative intraocular pressure (IOP) levels, however, evidence on their effectiveness in normotensive glaucoma patients remains limited. What is new Combined cataract surgery with microhook ab-interno trabeculotomy (phaco-µLOT) or iStent trabecular micro-bypass stent (phaco-iStent) significantly reduced the number of antiglaucoma medications in primary open-angle glaucoma (POAG) eyes with preoperative IOP controlled below 15 mmHg (low-teen IOP). Phaco-µLOT may be more effective than phaco-iStent in controlling IOP. These procedures should be limited to reducing the number of antiglaucoma medications used, as they did not significantly reduce the postoperative IOP in POAG eyes with low-teen IOP.

Roles of Toric intraocular Lens implantation on visual acuity and astigmatism in glaucomatous eyes treated with iStent and cataract surgery.

BACKGROUND: To assess the efficacy of toric intraocular lenses (IOLs) in combined cataract and minimally invasive glaucoma surgery (MIGS), visual and refractive outcomes were compared between eyes implanted with non-toric and toric IOLs during iStent triple procedures. METHODS: In this retrospective study, open angle glaucoma eyes with preexisting corneal astigmatism of -1.5 diopter (D) or more and implanted with non-toric (n = 9) or toric (n = 9) IOLs were included. The main outcome measures were the intergroup difference in the uncorrected visual acuity (UCVA) and refractive astigmatism at 3 months postoperatively. RESULTS: Preoperatively, the logarithm of the minimum angle of resolution (logMAR) UCVAs and refractive astigmatism were equivalent between the groups. Postoperatively, the logMAR UCVA (non-toric, 0.45 ± 0.31; toric, 0.14 ± 0.15; P = 0.021) was significantly better and the refractive astigmatism (non-toric, -2.03 ± 0.63 D; toric, -0.67 ± 0.53 D; P = 0.0014) significantly less in the toric group. The toric group had postoperative improvements in the logMAR UCVA (-0.21, P = 0.020) and refractive astigmatism (+ 1.72 D, P = 0.0039). Vector analyses showed the postoperative centroid magnitude and confidence eclipses of refractive astigmatism was less in the toric group (0.47 D at 173°±0.73D) than the non-toric group (1.10 D at 2°±1.91D). Postoperatively, 78% of eyes in the toric group had 1.0 D or less refractive astigmatism compared with 11% in the non-toric group. Surgically induced astigmatism (non-toric, 0.18 D at 65°; toric, 0.29 D at 137°) did not differ between groups. CONCLUSION: Use of toric IOLs is a reasonable option for better visual outcomes when the combined cataract and iStent surgery is performed in glaucomatous eyes with corneal astigmatism.

Carteolol hydrochloride reduces visible light-induced retinal damage in vivo and BSO/glutamate-induced oxidative stress in vitro.

The purpose of this study was to determine whether carteolol eye drops, a ß-adrenoceptor antagonist used as an intraocular hypotensive agent, has protective effects against the light-induced oxidative stress in retina. Dark-adapted pigmented rats were pre-treated with topical carteolol ophthalmic solution or saline and then exposed to visible light. The effects on electroretinogram (ERG), morphology, oxidative stress, and expression of mRNAs in the retinas were determined. The l-buthionine-(S,R)-sulfoximine (BSO)/glutamate-induced oxidative stress in 661 W cells, a murine photoreceptor cell line, was evaluated by cell death assays, production of reactive oxygen species (ROS), and activation of caspase. In vivo studies showed that exposure to light caused a decrease in the amplitudes of ERGs and the outer nuclear layer (ONL) thickness and an increase of the 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells in the ONL. These changes were significantly reduced by pre-treatment with carteolol. Carteolol also significantly up-regulated the mRNA levels of thioredoxin 1 and glutathione peroxidase 1 compared to saline-treated group. Moreover, carteolol and timolol, another ß-adrenoceptor antagonist, significantly inhibited BSO/glutamate-induced cell death and reduced caspase-3/7 activity and ROS production in vitro. Therefore, carteolol could protect retina from light-induced damage with multiple effects such as enhancing the antioxidative potential and decreasing the intracellular ROS production.

Effect of Ultraviolet Irradiation of the Implant Surface on Progression of Periimplantitis--A Pilot Study in Dogs.

OBJECTIVE: The objective of this study was to investigate morphologically the progression of periimplantitis around an ultraviolet (UV)-light-irradiated implant in dogs. MATERIALS AND METHODS: Pure titanium implants (3.3 mm in diameter and 8 mm long) were placed into dog jawbone bilaterally. Implants on one side were irradiated with UV light for 15 minutes using a photodevice immediately before placement (UV group), whereas those on the other side were not irradiated (non-UV group). Osseointegration was confirmed 90 days after implant placement by radiography. Experimental periimplantitis was induced by the application of dental floss over 90 days. Clinical and radiographic examination and micro-computed tomography (micro-CT) were performed after 90 and 180 days, and bone resorption was measured. The bone-implant interface in tissue sections was examined by light microscopy. RESULTS: Bone resorption around the UV-irradiated implant was less pronounced than around the non-UV-irradiated implant in the ligature-induced periimplantitis model. Tissue section images revealed no contact and partial destruction at the bone-implant interface. CONCLUSION: Within the limitations of this preliminary investigation, it is suggested that UV-light-irradiated implants suppress spontaneous progression of periimplantitis.

Contribution of nitrergic nerve in canine gingival reactive hyperemia.

Reactive hyperemia reflects a compensatory vasodilation response of the local vasculature in ischemic tissue. The purpose of this study is to clarify the mechanism of regulation of this response in gingival circulation by using pharmacological analysis of reactive hyperemia and histochemical analysis of gingival tissue. Application of pressure to the gingiva was used to create temporary ischemia, and gingival blood flow was measured after pressure release. Reactive hyperemia increased in proportion to the duration of pressure. Systemic hemodynamics remained unaffected by the stimulus; therefore, the gingival reactive hyperemia reflected a local adjustment in circulation. Gingival reactive hyperemia was significantly suppressed by nitric oxide (NO) synthase inhibitors, especially the neural NO synthase-selective antagonist 7-nitroindazole, but not by anticholinergic drugs, ß-blockers, or antihistaminergic drugs. Moreover, immunohistochemical staining for neural NO synthase and histochemical staining for NADPH diaphorase activity were both positive in the gingival perivascular region. These histochemical and pharmacological analyses show that reactive hyperemia following pressure release is mediated by NO-induced vasodilation. Furthermore, histochemical analysis strongly suggests that NO originates from nitrergic nerves. Therefore, NO may play an important role in the neural regulation of local circulation in gingival tissue ischemia.

Bilateral Intraocular Involvement of Recurrent Mantle Cell Lymphoma with Remission of Pseudo-Uveitis and Secondary Glaucoma After Switching Treatment to Ibrutinib: A Case Report.

PURPOSE: We describe a case of bilateral pseudo-uveitis and secondary glaucoma associated with recurrent mantle cell lymphoma (MCL) that was successfully treated with ibrutinib. METHODS: Retrospective case report. RESULTS: A 75-year-old man presented with uveitis masquerade syndrome while undergoing treatment for MCL with rituximab-bendamustine. Initial ophthalmologic examination revealed pseudohypopyon, iris thickening, and considerable vitreous opacity of both eyes. Evaluation via anterior segment optical coherence tomography revealed iris thickening in both eyes. His best-corrected visual acuities were reduced to 20/28 and 20/2000 on the right eye (OD) and left eye (OS), respectively, and his intraocular pressure (IOP) was elevated at 40 (OD) and 52 (OS) mmHg. The patient had findings suggestive of recurrent MCL, such as skin lesions, hyponatremia, elevated blood lactase dehydrogenase, and the results of the skin biopsy were consistent with the pathological diagnosis of MCL in the bone marrow biopsy that had already been performed. He was diagnosed with MCL recurrence and treated by switching to ibrutinib, a Bruton's tyrosine kinase inhibitor. After 1 week of treatment, all anterior ocular and vitreous lesions disappeared. Moreover, the skin lesions also disappeared, and the blood sample findings improved. On day 11 of treatment, BCVA improved to 20/20 in both eyes and IOP decreased to 8 (OD) and 11 (OS) mmHg. During the study course, CD5 and CD20 positive cells were identified in the anterior chamber of the eyes via flow cytometry, which was consistent with the pathological findings of biopsies. CONCLUSION: Ibrutinib may improve recurrent MCL intraocular lesions.

Minimally Invasive Direct Internal Cyclopexy in the Management of Goniotomy-Related Cyclodialysis Cleft with Hypotony Maculopathy.

Introduction: Although ab-interno trabeculotomy-related (goniotomy-related) surgeries has a favorable safety profile, cyclodialysis cleft refractory to conservative management could occur, thereby requiring additional surgical treatment. External and, more recently, internal cycloplexy have been attempted to treat cyclodialysis clefts with hypotony maculopathy, however the traditional methods require conjunctival or scleral incisions and have been inappropriate for glaucoma patients who need to undergo future trabeculectomy. Therefore, we report two cases who underwent a novel reliable technique for suture fixation of the detached ciliary body onto the original scleral bed directly through the intraocular approach without conjunctival or scleral incision, minimally invasive direct internal cyclopexy, in the management of goniotomy-related cyclodialysis cleft with hypotony maculopathy. Case Description: Goniotomy-related cyclodialysis cleft exceeded 45° and vision-threatening hypotony maculopathy was observed in two eyes in two patients with normal tension glaucoma and myopia gravis without a prior history of trauma who had undergone Kahook Dual Blade goniotomy combined with cataract surgery. The patients were followed conservatively for a while, however the cyclodialysis clefts and hypotony maculopathies did not resolve. Therefore, a 72-year-old man underwent minimally invasive direct internal cyclopexy on postoperative day 65 after the goniotomy, and another 67-year-old man underwent minimally invasive direct internal cyclopexy on postoperative day 149. In both cases, topical antibiotic and steroid eye drops were prescribed postoperatively. The cyclodialysis clefts were repaired successfully; however, the latter patient developed delayed-onset acute transient ocular hypertension 33 days after minimally invasive direct internal cyclopexy and required glaucoma medications. The hypotony maculopathies resolved approximately 3 months after suturing, and eventually visual acuity improved from preoperative levels and good intraocular pressure control was achieved in both. No further postoperative complications have been observed to date. Conclusion: We successfully managed two cases of goniotomy-related cyclodialysis cleft with hypotony maculopathy using minimally invasive direct internal cyclopexy.

Regeneration processes of alveolar bone and microvascular changes after the application of platelet-rich fibrin.

OBJECTIVES: Platelet-rich fibrin (PRF) is a promising agent for bone regeneration (BR). Platelets contain several growth factors that promote angiogenesis and BR. In this study, we observed the morphology of alveolar BR. METHODS: PRF (Advanced PRF: A-PRF) was prepared by extracting 10 mL of blood from each dog in a collection tube before tooth extraction. The samples were centrifuged at 200 × g for 8 min and incubated for 10 min to allow clotting. The alveolar socket on the dentition's right side was densely filled with PRF. The opposite side, which did not receive PRF, served as the control group. Different methods were used for specimen preparation and observation. Sections stained with hematoxylin and eosin were observed under a light microscope. Bone specimens were observed using stereoscopic microscopy. The resin cast models were examined using a scanning electron microscope. Moreover, bone formation ratio and height were measured. RESULTS: Fourteen days postoperatively, angiogenesis and bone deposition were more advanced in the PRF group than in the control group. Thirty days postoperatively, both groups developed porous bone. In the PRF group, new bone trabeculae (BT) and a network of blood vessels were formed in the bone marrow. Ninety days postoperatively, the resin cast showed a normal bone structure with BT and bone marrow. Thick BT were observed in the PRF group. CONCLUSIONS: Growth factors in PRF stimulate microcirculation and promote angiogenesis and bone deposition. The benefits of PRF include safety and increased bone formation.

Efficacy and Patient Tolerability of Omidenepag Isopropyl in the Treatment of Glaucoma and Ocular Hypertension.

Current therapeutic approaches for glaucoma aim to reduce intraocular pressure (IOP), which is the only available and reliable strategy proven to control the risk of disease development and progression. Omidenepag isopropyl (OMDI) is a novel topical ocular hypotensive agent that was launched onto the market for the treatment of glaucoma and ocular hypertension (OHT). After topical instillation and during corneal penetration, OMDI is converted into the active metabolite omidenepag (OMD), which behaves as a non-prostaglandin, selective E-prostanoid subtype 2 (EP2) receptor agonist. The topical administration of 0.002% OMDI once-daily (QD) possesses a 20-35% IOP-lowering effect, comparable to that of prostaglandin analogs targeting F-prostanoid (FP) receptor QD, which are the current first-line for pharmaceutical reduction of IOP. However, the mechanism of action and adverse events (AEs) of OMDI are different from those of FP receptor agonists. OMDI reduces IOP by enhancing both conventional trabecular and uveoscleral outflow facilities without complications of prostaglandin-associated periorbitopathy (PAP) seen with FP receptor agonists. Moreover, OMDI was also effective and well-tolerated in non-/poor responders to latanoprost and showed a stable IOP-lowering effect for one year, and its concomitant use with timolol enhanced the IOP-lowering effect. OMDI demonstrated acceptable safety and tolerability with good adherence and can be used in almost every patient. However, OMDI has some AEs such as conjunctival hyperemia, corneal thickening, macular edema/cystoid macular edema and ocular inflammation. Moreover, OMDI is contraindicated in patients who are allergic to the product, in aphakic or pseudophakic eyes, and in combination with tafluprost eye drops. If used appropriately in the right patients, OMDI could be an effective treatment option for glaucoma and OHT as a first-line alternative to FP agonists. Here, we summarize the results of clinical studies of OMDI and discuss its efficacy and patient tolerability in glaucoma and OHT in this review.

Automated Focal Plane Merging From a Stack of Gonioscopic Photographs Using a Focus-Stacking Algorithm.

Purpose: The purpose of this study was to investigate the utility of automated focal plane merging with the collection of gonio-photographs with different depths of field (DOF) using an established focus-stacking algorithm. Methods: A cross-sectional study was conducted at Shimane University Hospital, Izumo, Japan. Sixteen eyes from 16 subjects from the glaucoma clinic were included in this study. Image processing was performed for the images of 16 eyes from 16 angle sector following the successful gonio-photography. The 256 sets of focus-stacked and best-focused images were prepared in random order and were compared for the DOF and informativeness to diagnose angle pathology by masked observers in each set as the subjective assessments. Moreover, the energy of the Laplacian (average |ΔI|), which is an indicator of image sharpness between the photographs with and without the focus-stacking processing was also analyzed with the Laplacian filter as the objective assessment. Results: The automated image processing was successfully performed in all stacks of images. The significant deepening of DOF and improvement of informativeness achieved in 255 (99.6%) and 216 (84.4%) images (P < 0.0001 for both, sign test) and the energy of the Laplacian also significantly increased in 243 (94.9%) images (P < 0.0001, sign test). Conclusions: Focal plane merging by the automated algorithm can make the gonio-images deeper focus compared with the paired best-focused images subjectively and objectively, which would be useful for angle pathological assessment in clinical practice. Translational Relevance: Focal plane merging algorithm for the automated gonio-photography can facilitate the angle assessment by providing informative deep-focus image, which would be useful for glaucoma care.

Application of multi-directionally forged high-strength titanium to dental implants in beagle dogs.

Pure titanium is widely used as a material in dental implants. However, it possesses inferior mechanical strength. This study aimed to elucidate the efficacy of acid treated multi-directionally forged (MDF) pure titanium in vivo. We verified the temporal changes until osseointegration in beagle dogs. Using two types of experimental materials (conventional pure titanium or MDF pure titanium), new bone formation was assessed using morphological examinations, and the bone-to-implant contact (BIC) value was evaluated at each time point (14, 30, and 90 days after the operation). As such, new bone formation was observed around the acid-etched MDF group, in which the BIC value was highest, followed by that in the acid-etched pure titanium group. MDF pure titanium implants showed early promotion of new bone formation compared to conventional titanium implants. The new acid-treated MDF made of pure titanium could be applied to humans in the future to prove its practicality.

Advanced platelet-rich fibrin (A-PRF) has an impact on the initial healing of gingival regeneration after tooth extraction.

OBJECTIVES: Platelet-rich fibrin (PRF) is widely used in wound healing because it contains several growth factors, including vascular endothelial growth factor (VEGF). In this study, we investigated the effects of advanced PRF (A-PRF) in early-stage gingival regeneration after tooth extraction. METHODS: Blood sample was collected from females beagle dogs (age: 12 months) before tooth extraction for A-PRF preparation. All animals were sacrificed by perfusion-fixation on postoperative days 1, 3, and 7. The upper jaws were prepared for hematoxylin and eosin staining and immunostaining (for CD34 and VEGF). The lower jaw samples were prepared for scanning electron microscope observations. Blood flow in the gingiva before and after surgery was measured using laser Doppler flowmetry. RESULTS: In the A-PRF group, a large number of microvessels were observed in the gingival tissue on postoperative day 1. The microvessels in the control group were fewer and sparse. Regarding the vascular resin cast, a large number of new blood vessels were observed on postoperative day 1 in the A-PRF group. A stronger CD34-positive signal was obtained around the blood vessels in the A-PRF group than in the control group. Further, a strong VEGF-positive signal was observed in the perivascular tissue in the A-PRF group. Gingival blood flow was significantly higher in the A-PRF group after surgery. CONCLUSION: A-PRF had a positive impact on angiogenesis in the gingiva through the induction of VEGF expression. Thus, A-PRF may be beneficial for gingival tissue regeneration.

Double superior vena cava and anomaly of cardiovascular system with a review of the literature.

In a student course of gross anatomy dissection at Kanagawa Dental College in 2008, we found an extremely rare case of the double superior vena cava that has a shunt between the right and left atria of a 81-year-old Japanese male cadaver. The left superior vena cava passed through the space between the left cardiac auricle and the left pulmonary vein and entered the coronary sulcus. Then it opened near the opening of the inferior vena cava as the coronary venous sinus to the right atrium. The upper edge of the interatrial septum was located at the site where the right superior vena cava opened to the right atrium. Accordingly, the right atrium connected with left atrium through this site. We discuss the anatomy and etiology of these anomalous structures with a brief review of the literature.

Characterization of Peripheral Anterior Synechiae Formation After Microhook Ab-interno Trabeculotomy Using a 360-Degree Gonio-Camera.

PURPOSE: To investigate the prevalence, locations, and characteristics of peripheral anterior synechiae (PAS) formation after microhook ab-interno trabeculotomy (µLOT), a minimally invasive glaucoma surgery, using a 360-degree gonio-camera, gonioscope GS-1 (NIDEK Co., Gamagori, Japan). SUBJECTS AND METHODS: A total of 105 consecutive eyes of 75 subjects with open-angle glaucoma were analyzed. The eyes had undergone µLOT or combined µLOT and cataract surgery as an initial glaucoma surgery. Postoperative PAS formation was evaluated in 16 iridocorneal angle images with the best focus covering 360 degrees in each eye. RESULTS: Compared to baseline, at 225±226 days postoperatively, the intraocular pressure and number of antiglaucoma medications decreased significantly (p<0.01, respectively). PAS developed in 86% of eyes. The mean number of iridocorneal angle images that showed PAS in all eyes was 4.1 (26%) in the total circumference, 3.1 (39%) within the µLOT incision, and 1.0 (13%) outside of the µLOT incision; the rate was significantly (p<0.0001) higher within the incision than outside of the incision. Moreover, the higher total PAS rate and that within the incision may be associated with later postoperative days (p=0.01 and 0.004, respectively), that outside of the incision with µLOT alone rather than the combined surgery, and with shallower preoperative central anterior chamber depth (p=0.048 and 0.04, respectively), calculated by the mixed-effect model. CONCLUSION: The current results showed the characteristics of PAS formation after µLOT using 360-degree gonio-images, and the formation rate was significantly higher within the µLOT incision. The PAS within and outside of the incision had different causes.

Intraobserver and interobserver agreement among anterior chamber angle evaluations using automated 360-degree gonio-photos.

PURPOSE: To investigate the reproducibility for the iridocorneal angle evaluations using the pictures obtained by a gonioscopic camera, Gonioscope GS-1 (Nidek Co., Gamagori, Japan). METHODS: The pragmatic within-patient comparative diagnostic evaluations for 140 GS-1 gonio-images obtained from 35 eyes of 35 patients at four ocular sectors (superior, temporal, inferior, and nasal angles) were conducted by five independent ophthalmologists including three glaucoma specialists in a masked fashion twice, 1 week apart. We undertook the observer agreement and correlation analyses of Scheie's angle width and pigmentation gradings and detection of peripheral anterior synechia and Sampaolesi line. RESULTS: The respective Fleiss' kappa values for the four elements between manual gonioscopy and automated gonioscope by the glaucoma specialist were 0.22, 0.40, 0.32 and 0.58. Additionally, the respective intraobserver agreements for the four elements by the glaucoma specialist each were 0.32 to 0.65, 0.24 to 0.71, 0.35 to 0.70, and 0.20 to 0.76; the Fleiss' kappa coefficients for the four elements among the three glaucoma specialists were, respectively, 0.31, 0.38, 0.31, and 0.17; the Fleiss' kappa coefficients for the angle width and pigmentation gradings between the two glaucoma specialists each were 0.30 to 0.35, and 0.29 to 0.43, respectively. Overall, the Kendall's tau coefficients for the angle gradings reflected the positive correlations in the evaluations. CONCLUSION: Our findings suggested slight-to-substantial intraobserver agreement and slight-to-fair (among the three) or fair-to-moderate (between the two each) interobserver agreement for the angle assessments using GS-1 gonio-photos even by glaucoma specialists. Sufficient training and a solid consensus should allow us to perform more reliable angle assessments using gonio-photos with high reproducibility.

Aphakic Pupillary Block by an Intact Anterior Vitreous Membrane after Total Lens Extraction by Phacoemulsification.

An 85-year-old Japanese woman with acute primary angle closure in her right eye underwent cataract extraction. Because of the weakness of the Zinn's zonules, all of the lens tissue including the lens capsule was removed by phacoemulsification. Because of the absence of vitreous prolapse into the anterior chamber, vitrectomy was not performed. Nine days postoperatively, acute angle closure due to pupillary block by an anterior vitreous membrane developed. To resolve the pupillary block, anterior vitrectomy was performed on the same day. Postoperatively, her symptoms resolved, the anterior chamber deepened, and the intraocular pressure normalized. Although rare, acute angle closure due to pupillary block by an anterior vitreous membrane can occur after total lens extraction with phacoemulsification. If no vitreous prolapse occurs with total lens extraction, an intentional hyaloidotomy using an anterior vitreous cutter or iridectomy should be considered to avoid secondary angle closure.

Application of deproteinized bovine bone mineral as proangiogenic scaffold for alveolar bone formation in beagle dogs.

Alveolar bone repair after tooth extraction is essential after oral surgeries. Various grafting materials are used to promote the regeneration of lost alveolar bone. This study analysed the morphological features of the tissue regeneration process using deproteinized bovine bone mineral (DBBM). DBBM was used to densely fill the extraction sockets in beagle dogs. Following resin casting of the vasculature, stereomicroscopy and scanning electron microscopy were used to observe blood vessels and hard tissues in haematoxylin and eosin-stained sections on postoperative days 14, 30 and 90 in conjunction with vascular endothelial growth factor (VEGF) immunostaining to evaluate alveolar bone vascularization. On day 14 post-operation, the DBBM granules tightly filled the extraction sockets, maintained alveolar margin height and formed a scaffold for aiding angiogenesis and new bone formation. On day 30, new bone formation was observed around the DBBM granules. By day 90, bone tissue regeneration progressed in both groups but was more pronounced in the DBBM group. Alveolar margin height was maintained in the DBBM group throughout the study. Furthermore, VEGF expression in the DBBM group was detected around newly formed bone. We conclude that DBBM acts as a suitable scaffold for new bone generation, as well as angiogenesis around healing alveolar bone, and that it has the potential to play a key role in vascularization and bone formation.

Changes in the microcirculation in periodontal tissue due to experimental peri-implantitis.

OBJECTIVES: Peri-implantitis causes dislodgement of dental implants due to inflammation in the peri-implant tissue. The microcirculation in the periodontal tissue undergoes morphological and physiological changes due to inflammation. The immune mechanism of peri-implantitis differs from that of periodontitis. In this study, we examined the changes in the microcirculation in the peri-implant tissue with experimentally induced inflammation, using morphological and physiological techniques. METHODS: Six beagle dogs were used in the experiment. After extracting both mandibular premolars, three titanium screw implants were inserted on each side of the mandibular jaw. Dental floss was placed on the right side for 90 days in the study group but not in the control group. Microvascular resin cast models were created, and morphological changes were observed using scanning electron microscopy. Periodontal blood flow was measured using laser Doppler flowmetry. RESULTS: Ninety days after induction of inflammation, bone resorption was observed around the implant body. Osseointegration was impaired, and a gap at the implant-bone interface was observed. The resin cast models showed that inflamed gingival blood vessels had invaded the bone marrow through the resorbed apical margin of the alveolar bone. Analysis of the physiological data obtained using laser Doppler flowmetry showed a significant increase in blood flow around the implants with experimentally induced inflammation. CONCLUSIONS: Significant morphological and physiological changes occur in the gingival microcirculation of peri-implant tissue due to inflammation. Evaluating the vasculature and blood flow in the tissue surrounding the site of peri-implantitis may be helpful for pathologic analysis in clinical settings.

Cognitive Dysfunction in a Mouse Model of Cerebral Ischemia Influences Salivary Metabolomics.

Vascular dementia, caused by cerebrovascular disease, is associated with cognitive impairment and reduced hippocampal metabolite levels. Specifically, cognitive impairment can be induced by decreased hippocampal brain-derived neurotrophic factor (BDNF) expression. The development of low or non-invasive biomarkers to characterize these diseases is an urgent task. Disturbance of metabolic pathways has been frequently observed in cognitive impairment, and salivary molecules also showed the potentials to reflect cognitive impairment. Therefore, we evaluated salivary metabolic profiles associated with altered hippocampal BDNF expression levels in a cerebral ischemia mouse model using metabolomic analyses. The effect of tacrine (a cholinesterase inhibitor) administration was also examined. The arteries of ICR mice were occluded with aneurysm clips to generate the cerebral ischemia model. Learning and memory performance was assessed using the elevated plus maze (EPM) test. Hippocampal and blood BDNF levels were quantified using an enzyme-linked immunosorbent assay. Glutamate decarboxylase 1 (GAD1) mRNA expression, is associated with cognitive impairment, was quantified by a real-time polymerase chain reaction. The EPM test revealed impaired spatial working memory in the cerebral ischemia mouse model; tacrine administration ameliorated this memory impairment. Cerebral ischemia suppressed GAD1 expression by decreasing hippocampal BDNF expression. In total, seven salivary metabolites, such as trimethylamine N-oxide and putrescine, were changed by cognitive impairment and tacrine administration. Our data suggest that salivary metabolite patterns were associated with cognitive function.