Peri-implantitis, in which inflammation caused by plaque and biofilm on the implant surface spreads to the hard tissue, can be treated by decontamination of the implant surface and reconstruction of the lost hard tissue through surgical methods. We have described the management of 3 peri-implantitis cases by decontamination of the implant surface using a round titanium brush and regenerative therapy. All cases showed clinical improvements, and no further radiographic bone loss was observed during a 2-year follow-up. This treatment method can be effective for clinical improvement and bone regeneration. However, a longer follow-up period is necessary to support these outcomes.

We investigated whether β-carotene (β-CA) or ellagic acid (EA), originating from various fruits and vegetables, has a preventive effect against male infertility induced by exogenous scrotal hyperthermia. ICR adult mice were intraperitoneally treated with 10 mg/kg of β-CA or EA daily for 13 days consecutively. During this time, mice were subjected to transient scrotal heat stress in a water bath at 43℃ for 20 min on day 7, and their testes and blood were obtained on day 14 for histopathologic and biochemical analyses. Heat stress induced significant testicular weight reduction, germ cell loss and degeneration, as well as abnormal localization of phospholipid hydroperoxide glutathione peroxidase (PHGPx) and manganese superoxide dismutase (MnSOD) in spermatogenic and Leydig cells. Heat stress also altered the levels of oxidative stress (lipid peroxidation, SOD activity, and PHGPx, MnSOD, and HIF-1α mRNAs), apoptosis (Bax, Bcl-xL, caspase 3, NF-κB, and TGF-β1 mRNAs), and androgen biosynthesis (serological testosterone concentration and 3β-hydroxysteroid dehydrogenase mRNA) in testes. These changes were all improved significantly by β-CA treatment, but only slightly improved by EA treatment. These findings indicate that β-CA, through modulations of oxidative stress, apoptosis, and androgen biosynthesis, is a potent preventive agent against testicular injuries induced by scrotal hyperthermia.
Adult ; Animals ; Apoptosis ; Baths ; beta Carotene ; Caspase 3 ; Ellagic Acid ; Fever ; Fruit ; Germ Cells ; Glutathione Peroxidase ; Hot Temperature ; Humans ; Hydrogen Peroxide ; Infertility, Male ; Leydig Cells ; Male ; Mice ; Oxidative Stress ; Oxidoreductases ; Superoxide Dismutase ; Testis ; Testosterone ; Vegetables ; Water ; Weight Loss

We investigated whether β-carotene (β-CA) or ellagic acid (EA), originating from various fruits and vegetables, has a preventive effect against male infertility induced by exogenous scrotal hyperthermia. ICR adult mice were intraperitoneally treated with 10 mg/kg of β-CA or EA daily for 13 days consecutively. During this time, mice were subjected to transient scrotal heat stress in a water bath at 43℃ for 20 min on day 7, and their testes and blood were obtained on day 14 for histopathologic and biochemical analyses. Heat stress induced significant testicular weight reduction, germ cell loss and degeneration, as well as abnormal localization of phospholipid hydroperoxide glutathione peroxidase (PHGPx) and manganese superoxide dismutase (MnSOD) in spermatogenic and Leydig cells. Heat stress also altered the levels of oxidative stress (lipid peroxidation, SOD activity, and PHGPx, MnSOD, and HIF-1α mRNAs), apoptosis (Bax, Bcl-xL, caspase 3, NF-κB, and TGF-β1 mRNAs), and androgen biosynthesis (serological testosterone concentration and 3β-hydroxysteroid dehydrogenase mRNA) in testes. These changes were all improved significantly by β-CA treatment, but only slightly improved by EA treatment. These findings indicate that β-CA, through modulations of oxidative stress, apoptosis, and androgen biosynthesis, is a potent preventive agent against testicular injuries induced by scrotal hyperthermia.

Although hyaluronic acid (HA) has been developed as a nanoparticle (NP; 320–400 nm) for a drug delivery system, the tissue targeting efficacy and the pharmacokinetics of HA-NPs are not yet fully understood. After a dose of 5 mg/kg of cyanine 5.5-labeled HA-NPs or HA-polymers was intravenously administrated into mice, the fluorescence was measured from 0.5 h to 28 days. The HA-NPs fluorescence was generally stronger than that of HA-polymers, which was maintained at a high level over 7 days in vivo, after which it gradually decreased. Upon ex vivo imaging, liver, spleen, kidney, lung, testis and sublingual gland fluorescences were much higher than that of other organs. The fluorescence of HA-NPs in the liver, spleen and kidney was highest at 30 min, where it was generally maintained until 4 h, while it drastically decreased at 1 day. However, the fluorescence in the liver and spleen increased sharply at 7 days relative to 3 days, then decreased drastically at 14 days. Conversely, the fluorescence of HA-polymers in the lymph node was higher than that of HA-NPs. The results presented herein may have important clinical implications regarding the safety of as self-assembled HA-NPs, which can be widely used in biomedical applications.
Animals ; Drug Delivery Systems ; Fluorescence ; Hyaluronic Acid ; Kidney ; Liver ; Lung ; Lymph Nodes ; Mice ; Nanoparticles ; Pharmacokinetics ; Spleen ; Sublingual Gland ; Testis ; Tissue Distribution ; Toxicokinetics

Although hyaluronic acid (HA) has been developed as a nanoparticle (NP; 320–400 nm) for a drug delivery system, the tissue targeting efficacy and the pharmacokinetics of HA-NPs are not yet fully understood. After a dose of 5 mg/kg of cyanine 5.5-labeled HA-NPs or HA-polymers was intravenously administrated into mice, the fluorescence was measured from 0.5 h to 28 days. The HA-NPs fluorescence was generally stronger than that of HA-polymers, which was maintained at a high level over 7 days in vivo, after which it gradually decreased. Upon ex vivo imaging, liver, spleen, kidney, lung, testis and sublingual gland fluorescences were much higher than that of other organs. The fluorescence of HA-NPs in the liver, spleen and kidney was highest at 30 min, where it was generally maintained until 4 h, while it drastically decreased at 1 day. However, the fluorescence in the liver and spleen increased sharply at 7 days relative to 3 days, then decreased drastically at 14 days. Conversely, the fluorescence of HA-polymers in the lymph node was higher than that of HA-NPs. The results presented herein may have important clinical implications regarding the safety of as self-assembled HA-NPs, which can be widely used in biomedical applications.

Hyaluronic acid (HA) has been investigated for biomedical and pharmaceutical applications. This study was conducted to determine the distributions of HA nanoparticles (NPs; size 350–400 nm) and larger HA polymers in mice at intervals after application. ¹⁷⁷Lutetium (Lu)-labeled HA-NPs or HA polymers were intravenously injected (5 mg/kg) into male ICR mice, and radioactivity levels in blood and target organs were measured from 0.25 h to 28 days post-injection. In blood, the radioactivities of HA-NPs and HA polymer peaked at 0.5 h after injection but were remarkably decreased at 2 h; subsequently, they maintained a constant level until 6 days post-injection. HA-NPs and HA polymers were observed in the liver, spleen, lung, kidney, and heart (in ascending order) but were seldom observed in other organs. After 3 days, both the HA-NP and HA polymer levels showed similar steady decreases in lung, kidney, and heart. However, in liver and spleen, the HA-NP levels tended to decrease gradually after 1 day and both were very low after 14 days, whereas the HA polymer level accumulated for 28 days. The results indicate that HA-NPs, with their faster clearance pattern, may act as a better drug delivery system than HA polymers, especially in the liver and spleen.
Animals ; Drug Delivery Systems ; Heart ; Humans ; Hyaluronic Acid* ; Kidney ; Liver ; Lung ; Male ; Mice* ; Mice, Inbred ICR ; Nanoparticles* ; Polymers* ; Radioactivity ; Spleen

Temporal and subcellular distributions of hyaluronic acid (HA) as a degradable nanoparticle (NP) in animals were investigated to determine if HA-NP could be utilized as an appropriate drug delivery system. After mice were intravenously injected with 5 mg/kg of Cy5.5-labeled HA-NP sized 350–400 nm or larger HA-polymers, the fluorescence intensity was measured in all homogenized organs from 0.5 h to 28 days. HA-NP was greatly detected in spleen, liver and kidney until day 28, while it was maintained at low levels in other organs. HA-polymer was observed at low levels in all organs. HA-NP quantities in spleen and liver were reduced until day 3, but increased sharply between days 3 and 7, then decreased again, while their HA-polymers were maintained at low levels until day 28. In kidneys, both HA-NP and HA-polymer showed high levels after 0.5 h of administration, but steadily decreased until day 28. According to ultrastructural analyses, HA-NP was engulfed in Kupffer cells of liver and macrophages of spleen and kidney at day 1 and was accumulated in the cytoplasm of kidney tubular cells at day 7. Overall, these findings suggest that HA-NP could be considered a desirable drug carrier in the liver, kidney, or spleen.
Animals ; Cytoplasm ; Drug Carriers* ; Drug Delivery Systems ; Fluorescence ; Hyaluronic Acid* ; Kidney ; Kupffer Cells ; Liver ; Macrophages ; Mice* ; Nanoparticles* ; Pharmacokinetics ; Spleen

Emodin is an anthraquinone derivative from the roots of Rheum officinale Baill that possesses a variety of biological activities, including inhibition of 5α-reductase and prostaglandin D2. In this study, we investigated whether emodin promotes hair growth. After emodin was topically applied to the shaved dorsal skin of telogenic C57BL/6 N mice, the hair growth rate and morphological analysis were evaluated in dorsal skin for 15 days. After 13 days of treatment, minoxidil or emodin (0.01% or 0.1%)-treated groups showed remarkable regrowth of hairs relative to the vehicle control group. Scoring of the hair growth and rate of hair growth area for 15 days revealed that groups treated with minoxidil and 0.1% emodin were significantly higher than the vehicle control group. Histological examination revealed the emodin and minoxidil groups markedly recovered the number and morphology of hair follicles, including the subcutis depth, relative to the vehicle group. These results suggest that emodin has an excellent promoting effect in hair growth similar to that of minoxidil and might be useful for treatment of baldness or alopecia.
Alopecia ; Animals ; Emodin* ; Hair Follicle ; Hair* ; Mice* ; Minoxidil ; Prostaglandin D2 ; Rheum ; Skin

Diffuse refractory vascular spasms associated with coronary bypass artery grafting (CABG) are rare but devastating. A 42-year-old male patient with a past history of stent insertion was referred for the surgical treatment of a recurrent left main coronary artery disease. A hemodynamic derangement developed during graft harvesting, necessitating a hurried initiation of cardiopulmonary bypass (CPB). Although CABG was carried out as planned, the patient could not be weaned from the bypass. An emergency coronary angiography demonstrated a diffuse spasm of both native coronary arteries and grafts. CPB was switched to the femorofemoral extracorporeal membrane oxygenator (ECMO). Although he managed to recover from heart failure, his discharge was delayed due to the ischemic injury of the lower limb secondary to cannulation for ECMO. We reviewed the case and literature, placing emphasis on the predisposing factors and appropriate management.
Adult ; Arteries ; Cardiopulmonary Bypass ; Catheterization ; Causality ; Coronary Angiography ; Coronary Artery Bypass ; Coronary Artery Disease ; Coronary Vasospasm ; Coronary Vessels ; Emergencies ; Extracorporeal Membrane Oxygenation ; Heart Failure ; Hemodynamics ; Humans ; Lower Extremity ; Male ; Oxygenators, Membrane ; Spasm* ; Stents ; Transplants*

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays an important role in vascular functions, including vasorelaxation. We here investigated the pharmacological effect of the natural product syringaresinol on vascular relaxation and eNOS-mediated NO production as well as its underlying biochemical mechanism in endothelial cells. Treatment of aortic rings from wild type, but not eNOS-/- mice, with syringaresinol induced endothelium-dependent relaxation, which was abolished by addition of the NOS inhibitor NG-monomethyl-L-arginine. Treatment of human endothelial cells and mouse aortic rings with syringaresinol increased NO production, which was correlated with eNOS phosphorylation via the activation of Akt and AMP kinase (AMPK) as well as elevation of intracellular Ca2+ levels. A phospholipase C (PLC) inhibitor blocked the increases in intracellular Ca2+ levels, AMPK-dependent eNOS phosphorylation, and NO production, but not Akt activation, in syringaresinol-treated endothelial cells. Syringaresinol-induced AMPK activation was inhibited by co-treatment with PLC inhibitor, Ca2+ chelator, calmodulin antagonist, and CaMKKbeta siRNA. This compound also increased eNOS dimerization, which was inhibited by a PLC inhibitor and a Ca2+-chelator. The chemicals that inhibit eNOS phosphorylation and dimerization attenuated vasorelaxation and cGMP production. These results suggest that syringaresinol induces vasorelaxation by enhancing NO production in endothelial cells via two distinct mechanisms, phosphatidylinositol 3-kinase/Akt- and PLC/Ca2+/CaMKKbeta-dependent eNOS phosphorylation and Ca2+-dependent eNOS dimerization.
Animals ; Aorta/*drug effects/physiology ; Enzyme Activation/drug effects ; Furans/*pharmacology ; Gene Deletion ; Human Umbilical Vein Endothelial Cells/drug effects/metabolism ; Humans ; Lignans/*pharmacology ; Mice ; Mice, Inbred C57BL ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/genetics/*metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide Phospholipase C/metabolism ; Phosphorylation/drug effects ; Protein Multimerization/*drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; Vasodilation/*drug effects