Titanium Nanosurface with a Biomimetic Physical Microenvironment to Induce Endogenous Regeneration of the Periodontium.

The periodontium supports the teeth by dentoalveolar fibrous joints that serve unique oral functions. Endogenous regeneration of the periodontium around artificial teeth (dental implants) provides a cost-effective solution for the extension of healthy life expectancy but remains a challenge in regenerative medicine. Biomimetics can create smart biomaterials that tune endogenous cells at a tissue-material interface. Here, we created a smart titanium nanosurface mimicking the surface nanotopography and micromechanical properties of the tooth root cementum (TRC), which is essential for the induction of dentoalveolar fibrous joints to regenerate the periodontium. After transplantation into the rat renal capsule, only the titanium artificial tooth with the TRC-mimetic nanosurface formed a complex dentoalveolar fibrous joint structure, with bone tissue, periodontal ligament (PDL), and TRC, in the decellularized jawbone matrix. TRC-mimetic titanium implants induce the formation of functional periodontium, even in a jawbone implantation model, which generally causes osseointegration (ankyloses). In human PDL cells, TRC analogousness in the surface mechanical microenvironment regulates matrix mineralization through bone sialoprotein expression and phosphorus metabolism, which are critical for cementogenesis. Therefore, the titanium nanosurfaces with nanotopographical and mechanical microenvironments mimicking the TRC surface induce dentoalveolar fibrous joints for periodontal regeneration by interfacial tuning of endogenous cells.

Real-Time Monitoring of Key Gene Products Involved in Rice Photoperiodic Flowering.

Flowering is an important biological process through which plants determine the timing of reproduction. In rice, florigen mRNA is induced more strongly when the day length is shorter than the critical day length through recognition of 30-min differences in the photoperiod. Grain number, plant height, and heading date 7 (Ghd7), which encodes a CCT-domain protein unique to monocots, has been identified as a key floral repressor in rice, and Heading date 1 (Hd1), a rice ortholog of the Arabidopsis floral activator CONSTANS (CO), is another key floral regulator gene. The Hd1 gene product has been shown to interact with the Ghd7 gene product to form a strong floral repressor complex under long-day conditions. However, the mRNA dynamics of these genes cannot explain the day-length responses of their downstream genes. Thus, a real-time monitoring system of these key gene products is needed to elucidate the molecular mechanisms underlying accurate photoperiod recognition in rice. Here, we developed a monitoring system using luciferase (LUC) fusion protein lines derived from the Ghd7-LUC and Hd1-LUC genes. We successfully obtained a functionally complemented gene-targeted line for Ghd7-LUC. Using this system, we found that the Ghd7-LUC protein begins to accumulate rapidly after dawn and reaches its peak more rapidly under a short-day condition than under a long-day condition. Our system provides a powerful tool for revealing the accurate time-keeping regulation system incorporating these key gene products involved in rice photoperiodic flowering.

Paravertebral compartment syndrome after exercise: a case report.

BACKGROUND: Paravertebral compartment syndrome occurring without trauma is quite rare. We report a case of compartment syndrome that occurred after spinal exercises. CASE PRESENTATION: A 23-year-old Japanese rower developed severe back pain and was unable to move 1 day after performing exercises for the spinal muscles. Initial evaluation at a nearby hospital revealed hematuria and elevated creatine phosphokinase levels. He was transferred to our hospital, where magnetic resonance imaging revealed no hematoma but confirmed edema in the paravertebral muscles. The compartment pressure measurements were elevated bilaterally. Despite his pain being severe, his creatine phosphokinase levels were expected to peak and decline; his urine output was normal; and surgery was undesirable. Therefore, we opted for conservative management. The next day, the patient's compartment pressure diminished, and his pain levels decreased to 2/10. After 5 days, he was able to walk without medication. CONCLUSIONS: We present a rare case of compartment syndrome of the paravertebral muscles with good resolution following conservative management. We hope our case findings will help avoid unnecessary surgery in cases of paravertebral compartment syndrome.

Disseminated Varicella zoster infection with abdominal pain and periarterial fat stranding in a patient taking pomalidomide.

BACKGROUND: Disseminated Varicella zoster virus infection (DVI) is a severe infection associated with severe abdominal pain of unknown cause. We report a case in which periarterial (the celiac artery and superior mesenteric artery) fat stranding (PFS) on computed tomography (CT) was the presumed cause of abdominal pain in a patient taking pomalidomide. CASE PRESENTATION: A 62-year-old woman was admitted to our hospital with abdominal pain. Her medical history was multiple myeloma treated with pomalidomide. Computed tomography showed no remarkable findings on admission, but 1 day later, a contrast-enhanced CT showed PFS. A skin eruption appeared on day 4 and we started acyclovir. On day 10, Varicella zoster virus antigen and antibody tests were positive, confirming the diagnosis of DVI. The abdominal pain subsequently improved, together with the PFS, and she was discharged. CONCLUSION: When patients present with severe abdominal pain and PFS, DVI and acyclovir must be considered.

Initial inferior vena cava diameter predicts massive transfusion requirements in blunt trauma patients: A retrospective cohort study.

OBJECTIVES: The inferior vena cava (IVC) diameter is associated with shock and increased mortality in trauma patients. However, there are no reports examining the association between the IVC diameter and massive transfusion (MT) requirements in trauma patients. The aim of this study was to evaluate the association between IVC diameter and MT requirements in patients with blunt trauma. METHODS: We retrospectively reviewed all patients who were consecutively hospitalized with blunt trauma (Injury Severity Score [ISS] ≥16) between from November 1, 2011 to March 30, 2016. Univariate and multivariate analyzes were performed to identify the independent predictors of MT (defined as >10units of red cell concentrate transfusions within 24h of admission). Receiver operating characteristic curve and the area under the curve (AUC) were estimated. RESULTS: Of the 222 patients included in this study, MT occurred in 22.5% patients. On multiple regression analysis, IVC diameter [Odds ratio (OR), 0.88; 95% confidence interval (CI), 0.80-0.96; p<0.01], fibrin degradation product (FDP; OR, 1.01; 95% CI, 1.00-1.01; p<0.01), and fibrinogen level (OR, 0.99; 95% CI, 0.98-1.00; p<0.01) were strong predictors of MT. IVC diameter demonstrated moderate accuracy (AUC, 0.74; cutoff level, 13.0mm; sensitivity, 67%; specificity, 73%). Combined cutoff levels of FDP <80.5µg/ml, fibrinogen ≥165mg/dl, and IVC diameter ≥13mm could also determine how unnecessary a MT was with 100% accuracy. CONCLUSIONS: Initial IVC diameter is a predictor of MT in blunt trauma patients.

Linezolid versus vancomycin for nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus in the elderly: A retrospective cohort analysis: Effectiveness of linezolid in the elderly.

OBJECTIVES: Several reports have compared the efficacy of linezolid (LZD) in Methicillin-resistant Staphylococcus aureus (MRSA) infections with that of vancomycin (VCM); however, these two antibiotics for the treatment of nosocomial MRSA pneumonia in elderly patients has not been well evaluated. The purpose of this study is to evaluate the efficacy and safety of LZD compared with VCM for the treatment of elderly patients with nosocomial MRSA pneumonia in a retrospective chart review of a cohort. METHODS: We included 28 consecutive patients aged ≥65years hospitalized with a confirmed diagnosis of MRSA pneumonia and treated with LZD (n=11) or VCM (n=17) between November 2010 and May 2015. We collected patient, disease, and laboratory data. The primary outcome was 30-day mortality. The secondary outcomes were the sequential organ failure assessment (SOFA) total, respiratory, renal, coagulation, hepatic, cardiovascular, and central nervous system scores on days 1, 3, 7, and 14. RESULTS: There were no significant differences between the two groups with regard to baseline characteristics. The 30-day mortality rate was significantly lower in the LZD group than in the VCM group (0% vs. 41%, P=.02). The SOFA total score on days 3, 7, and 14 were significantly lower those at baseline in the LZD group (P<.05). The SOFA respiratory score on days 14 was also significantly lower than baseline in the LZD group (P<.05). CONCLUSION: LZD may be more efficacious than VCM for treating elderly patients with nosocomial MRSA pneumonia.

[Case of alkaline esophagitis due to sodium hypochlorite ingestion].

The severity of alkaline esophagitis due to sodium hypochlorite ingestion is variable and the findings of endoscope within 48 hours of ingestion are reported to be associated with its prognosis. We report a good recovery case of grade 2B of alkaline esophagitis, which was treated with close observation. The patient was 59-year old man. He was found lying on the bed by his wife, after drinking bactericidal agents (Jianok) and kitchen cleaner (Magiclean) for suicide attempt. After his trachea was intubated, he underwent upper gastrointestinal scope, which displayed circumferential ulcers at the lower esophagus. He was diagnosed as having a Grade 2B alkaline esophagitis, which was associated with a higher probability of stricture or perforation. On the 14th day of the admission, the 2nd endoscope was performed and no esophageal strictures were detected. He was extubated and started oral feeding on the 15th day. After that, his hospital course was uneventful and was discharged on the 18th day. 6 months have passed since he left hospital. No esophageal strictures were detected so far.

Geonotoxicity study of illegal drug MDMA and its nitroso derivative N-MDMA by micronucleus and chromosomal aberration tests using Chinese hamsger lung fibroblast cell line.

OBJECTIVES: An increase in incidence of the illegal use of tablets containing 3,4-methylenedioxymethamphetamine hydrochloride (MDMA) has recently become a widespread social problem. MDMA ingested orally reacts with nitrite in the stomach and is synthesized intoN-nitroso-3,4-methylenedioxymethamphetamine (N-MDMA). The aim of this study is to investigate the genotoxic effects of MDMA and N-MDMA on the basis of the results of an in vitro micronucleus (MN) test and an in vitro chromosomal aberration (CA) test using a Chinese hamster lung fibroblast cell line (CHL/IU). METHODS: Tablets containing MDMA obtained from the Regional Bureau of the Ministry of Health, Labor and Welfare were purified, and N-MDMA was synthesized from MDMA in our laboratory. To evaluate the effects of MDMA and N-MDMA, the MN test established by our laboratory and the CA test in accordance with the guidelines for toxicity studies of drugs recommended by the Ministry of Health, Labor and Welfare were performed. RESULTS: In the MN test, no increased frequency of MNs was not found for MDMA. On the other hand, an apparently increased frequency of MNs was observed for N-MDMA. In the CA test, no CA was found for MDMA, but CA was observed for N-MDMA apparently. CONCLUSION: N-MDMA genotoxicity was observed in the MN and CA tests. However, no MDMA genotoxicity was observed.

Effect of static magnetic field on the induction of micronuclei by some mutagens.

OBJECTIVES: It is important to assess the risk of static magnetic fields (SMFs) on human health, because epidemiological studies have indicated that SMFs play a role in the development of diseases such as leukemia and brain tumor. In our environment, we have numerous chances to be exposed to not only SMFs but also many chemicals containing mutagens. The aim of this study is to investigate the effect of SMFs on the induction of micronuclei induced by some mutagens. METHODS: BALB/c mice were exposed to 4.7 tesla (T) SMF for 24 hr immediately after the injection of carboquone (alkylating agent), colcemid (spindle poison), mitomycin C (cross-linking agent), vincristine (spindle poison), sodium fluoride (a byproduct of aluminum plants under strong SMF) or 1-ethyl-1-nitrosourea (brain tumor-, gliomas- and thymic lymphoma-inducing chemical). RESULTS: The frequency of micronuclei induced by six mutagens increased after co-exposure to SMF. CONCLUSIONS: An additive/synergistic effect of SMF and chemicals was observed from the results of increased frequency of micronuclei induced by mutagens in mouse bone marrow erythrocytes.

Genotoxic effects of N-nitrosoketamine and ketamine as assessed by in vitro micronucleus test in Chinese hamster lung fibroblast cell line.

OBJECTIVES: Ketamine hydrochloride (KT) is a secondary amine that has been safely used as an injectable anesthetic and analgesic to avoid the production of nitroso compounds in the stomach. However, ketamine in the tablet form has recently become an abused, recreational drug. The aim of this study was to investigate the genotoxic effects of N-nitrosoketamine (NKT) and KT on the basis of an in vitro micronucleus (MN) test using a Chinese hamster lung fibroblast cell line (CHL/IU). METHODS: NKT was synthesized from KT in our laboratory. In the MN tests, CHL/IU cells were continuously treated with either NKT or KT for 24, 48, or 72 hours without the S9 mix. The cells were also treated with NKT or KT with or without the S9 mix for 6 hours, followed by a recovery period of 18, 42, or 66 hours (short-term treatment). The results were considered to be statistically significant when the p-values of both Fisher's exact test and the trend test were less than 0.05. RESULTS: After the short-term treatment with either NKT or KT with and without the S9 mix, the frequency of micronuclei significantly increased. However, the frequency of micronuclei did not significantly increase after the continuous treatment with either NKT or KT. Both NKT and KT were determined to be genotoxic in the short-term treatment with or without the S9 mix, but they were determined to be nongenotoxic in continuous treatment. CONCLUSION: Our findings suggest that NKT has a stronger genotoxic effect than KT.

The frequencies of micronuclei induced by cisplatin in newborn rat astrocytes are increased by 50-Hz, 7.5- and 10-mT electromagnetic fields.

OBJECTIVES: Epidemiological studies have suggested that exposure to environmental and occupational electromagnetic fields (EMFs) contribute to the induction of brain tumors, leukemia, and other neoplasms. The aim of this study was to investigate the genotoxic effects of exposure to 50-Hz EMFs. and of co-exposure to cisplatin, a mutagen and carcinogen, and 50-Hz EMFs, using an in vivo newborn rat astrocyte micronucleus assay. METHODS: Three day-old male Sprague-Dawley rats were co-exposed to 50-Hz EMFs and 1.25 or 2.5 mg/kg of cisplatin. Brain cells were dissociated into single cells and cultured for 96 hours, then stained with acridine orange and an antibody against glial fibrillary acidic protein. The frequency of micronucleated astrocytes was counted with a fluorescent microscope. RESULTS: The frequency of micronuclei was not increased in rat astrocytes exposed to EMFs alone. However, the frequencies of micronuclei in co-exposure to 2.5 mg/kg cisplatin and EMFs (7.5- and 10-mT) were significantly increased, compared with those in exposure to 2.5 mg/kg cisplatin alone (sham-exposure, 0-mT EMFs) for 72 hours (p<0.01). CONCLUSION: Exposure to EMFs alone did not have a genotoxic effect but co-exposure to EMFs increased the genotoxic activity induced by cisplatin. Our findings suggest that EMFs enhance the genotoxic effects of cisplatin.