The relationship between masticatory performance and intakes of foods and nutrients in Japanese male workers: A cross-sectional study.

BACKGROUND: Although many studies have been conducted on the relationship between masticatory performance and nutrient ingestion in the elderly, few large-scale studies have been carried out using relatively young individuals. OBJECTIVES: The objective of this study was to clarify the association between the masticatory performance evaluated by the gummy-jelly test, not by visual examination, and nutrient ingestion state based on the brief self-administered diet history questionnaire (BDHQ). METHODS: This was a cross-sectional survey of 540 male workers. Somatometry, blood pressure measurement, blood test and medical interview were performed as a periodic health check-up. In the dental check-up, an oral examination, gummy-jelly test (glucosensor) and survey of ingested food and nutrients using BDHQ were performed. The participants were classified into two groups with low and normal values of masticatory performance. Participants with a score on the gummy-jelly test below 150 mg/dL or 150 mg/dL or higher were included in the low and normal groups, respectively. RESULTS: Two hundred and forty-eight participants (45.8%) had low masticatory performance, and 292 (53.2%) had normal masticatory performance. The intakes of some minerals and vitamins, such as calcium, vitamin D, vitamin B2 , small fish with bones and non-oily fish, were significantly lower in the low masticatory group than in the normal group. In contrast, the intake of sugar for coffee and tea and that of chicken were significantly higher in the low masticatory group than in the normal group. CONCLUSION: This study suggested that low masticatory performance can affect nutrient intake, which may cause non-communicable diseases.

Serum microRNA levels in patients with Crohn's disease during induction therapy by infliximab.

BACKGROUND AND AIM: microRNAs (miRNAs) have been suggested to be candidates for biomarkers in various diseases including Crohn's disease (CD). To identify possible biomarkers predictive of the therapeutic effect of infliximab in CD, we investigated serum miRNA levels during the induction therapy by the medication. METHODS: Nineteen CD patients who were applied to the induction therapy by infliximab were enrolled. Serum samples for miRNA analyses were obtained at weeks 0 and 6, and the therapeutic efficacy by infliximab was assessed according to the Crohn's disease activity index value at week 14. Exploratory miRNA profiling by low-density array was initially performed in three patients. The levels of candidate miRNA were subsequently determined by real-time polymerase chain reaction (PCR) assays in the remaining 16 patients. The miRNA levels during the induction therapy were compared between the two groups classified by the clinical response to infliximab at week 14. RESULTS: Low-density array analysis identified 14 miRNAs that showed twofold or more altered expression during the induction therapy by infliximab. Subsequent analysis by real-time PCR demonstrated significantly increased levels of five miRNAs (let-7d, let-7e, miR-28-5p, miR-221, and miR-224) at week 6 when compared with those at week 0 (P < 0.05 each). In addition, miRNA levels of let-7d and let-7e were significantly increased in the group of patients who achieved clinical remission by infliximab (P = 0.001 and P = 0.002, respectively). CONCLUSION: let-7d and let-7e might be possible therapeutic biomarkers in patients with CD, who are treated by infliximab.

Decreased serum creatinine to cystatin C ratio is associated with low tongue pressure.

AIM: Tongue strength plays an important role in the process of food intake, and low tongue pressure has been associated with aspiration pneumonia, cognitive decline, and mortality. However, special equipment for tongue pressure measurement is uncommon in general practice. Recently, the serum creatinine-to-cystatin C (Cr/CysC) ratio has been validated as a marker of muscle volume mass. Thus, we aimed to investigate the association of the serum Cr/CysC ratio with tongue pressure in a cross-sectional study. METHODS: This single-center, cross-sectional study enrolled 73 participants (mean age, 71.7 years; men, 49.3%) who regularly attended the hospital for treatment of chronic disease. A tongue pressure of <30 kPa was defined as low tongue pressure. We evaluated the relationships between the serum Cr/CysC ratio and tongue pressure using multiple regression analysis. RESULTS: The serum Cr/CysC ratio was correlated with tongue pressure (R2 = 0.25, P < 0.0001). In multiple regression analyses adjusted for confounders including age, sex, body mass index, and serum albumin, the association remained significant (P = 0.0001). In logistic analyses, the multivariable-adjusted odds ratios of the Cr/CysC ratio for tertiles 1 and 2 compared with tertile 3 for low tongue pressure were 7.81 (95% confidence interval, 1.45-51.73) and 2.71 (95% confidence interval, 0.60-13.19), respectively. CONCLUSIONS: We demonstrated that a decreased serum Cr/CysC ratio was associated with a higher risk of low tongue pressure. Our findings suggest that this simple serum surrogate marker may be a first step toward an intervention for oral function by general practitioners. Geriatr Gerontol Int 2024; 24: 102-108.

Activities of daily living dependency and disease-specific mortality during 12-year follow-up in an 80-year-old population.

BACKGROUND AND AIMS: Although total mortality is likely to be higher in elderly individuals with frailty or impaired activities of daily living (ADL), little is known about the relationships between disease-specific mortality and ADL dependency in the elderly. Therefore, we examined whether 12-year disease-specific mortality may be associated with ADL dependency in an 80-year-old population. METHODS: In 1998, of 1,282 community-dwelling residents of Japan's Fukuoka Prefecture, 824 (64.3 %) (309 males and 515 females) participated, the remaining 458 subjects did not participate, and their deaths and causes of death were followed up for 12 years after the baseline examination. ADL dependency was determined according to the guidelines for disabled elderly from the Health, Labor, and Welfare Ministry of Japan, and ADL dependency was measured only at baseline. RESULTS: During the 12-year follow-up, 506 died, 276 did not die, and 42 were lost. Of the 506 who died, 128 died due to cardiovascular disease, 96 to respiratory tract disease, 87 to cancer, and 51 to senility. The subjects were classified into three groups as follows: ADL-1 (independent group, n = 600), ADL-2 (almost-independent group, n = 113), and ADL-3 (dependent group, n = 93).Total-cause mortality was 2.8 times higher in ADL-3 subjects, respiratory disease mortality was 4.1 times higher in ADL-3 subjects, and senility mortality was 5.7 times higher in ADL-3 subjects than in ADL-1 subjects, after adjusting for various confounding factors. There was no association between mortality due to cancer or cardiovascular disease and ADL dependency. CONCLUSIONS: We found an independent association between ADL dependency and mortality due to all causes, respiratory disease or senility, but no association with mortality due to cancer or cardiovascular disease. These findings suggest that improving ADL dependency may reduce all mortality and mortality due to respiratory disease or senility.

Role of heme oxygenase-1 in inflammatory response induced by mechanical stretch in synovial cells.

OBJECTIVE: The purpose of this study was to investigate the mechanism by which heme oxygenase-1 (HO-1) regulates inflammatory responses induced by mechanical stretch in human fibroblast-like synoviocyte (HFLS) cells. MATERIALS AND METHODS: HFLS cells were cultured in the presence of hemin and seeded into fibronectin-coated silicon chambers. The chambers were attached to a stretching apparatus which applied a uniaxial sinusoidal stretching force. The genetic expressions of cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß) and HO-1 were analyzed using real-time RT-PCR. The expression and localization of HO-1 protein were detected by immunofluorescence staining. The amounts of prostaglandin E(2) (PGE(2)) released into the culture medium were determined using ELISA. RESULTS: Mechanical stretch enhanced the expressions of COX-2 and IL-1ß, and the amount of PGE(2) synthesis in HFLS cells, whereas that of HO-1 was slightly increased. In contrast, treatment with hemin enhanced HO-1 gene expression and mechanical stretch enhanced this expression in hemin-pretreated cells. In addition, hemin pretreatment suppressed PGE(2) synthesis induced by mechanical stretch. CONCLUSION: We found that constitutive HO-1 expression in hemin-pretreated HFLS cells suppressed mechanical stretch-induced inflammatory responses, suggesting that HO-1 may play a role as a regulation factor in synovial tissue inflammation.

Low-level laser irradiation enhances BMP-induced osteoblast differentiation by stimulating the BMP/Smad signaling pathway.

Low-level laser irradiation (LLLI) has been shown to induce bone formation and osteoblast differentiation both in vivo and in vitro. However, the molecular mechanism by which LLLI stimulates osteoblast differentiation is still unclear. The aim of the present study was to examine whether Ga-Al-As laser irradiation could enhance BMP2-induced alkaline phosphatase (ALP) activity in C2C12 cells. Laser irradiation at 0.5 W for 20 min enhanced BMP2-induced ALP activity. Laser treatment alone did not affect ALP activity. To exclude the effect of pH or temperature changes during irradiation, we shortened the exposure time to 2 min, with various levels of laser power. At 2.5 W, irradiation stimulated BMP2-induced ALP activity but not cell proliferation, whereas 1 or 5 W laser power did not induce any significant effects. Irradiation stimulated BMP2-induced phosphorylation of Smad1/5/8 and BMP2 expression, but had no effect on the expression of inhibitory Smads 6 and 7, BMP4, or insulin-like growth factor 1. Laser irradiation enhanced Smad-induced Id1 reporter activity as well as expression of bone morphogenetic protein (BMP)-induced transcription factors such as Id1, Osterix, and Runx2. Laser irradiation also stimulated BMP-induced expressions of type I collagen, osteonectin, and osteocalcin mRNA, markers of osteoblasts. This enhancement of BMP2-induced ALP activity and Smad phosphorylation by laser irradiation was also observed in primary osteoblasts. These results suggest that LLLI accelerates the differentiation of BMP-induced osteoblasts by stimulating the BMP/Smad signaling pathway.

Keratin 8 overexpression promotes mouse Mallory body formation.

Keratins 8 and 18 (K8/18) are major constituents of Mallory bodies (MBs), which are hepatocyte cytoplasmic inclusions seen in several liver diseases. K18-null but not K8-null or heterozygous mice form MBs, which indicates that K8 is important for MB formation. Early stages in MB genesis include K8/18 hyperphosphorylation and overexpression. We used transgenic mice that overexpress K8, K18, or K8/18 to test the importance of K8 and/or K18 in MB formation. MBs were induced by feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Livers of young K8 or K8/K18 overexpressors had no histological abnormalities despite increased keratin protein and phosphorylation. In aging mice, only K8-overexpressing livers spontaneously developed small "pre-MB" aggregates. Only K8-overexpressing young mice are highly susceptible to MB formation after short-term DDC feeding. Thus, the K8 to K18 ratio, rather than K8/18 overexpression by itself, plays an essential role in MB formation. K8 overexpression is sufficient to form pre-MB and primes animals to accumulate MBs upon DDC challenge, which may help explain MB formation in human liver diseases.

IgA level is associated with risk for mortality in an eighty-year-old population.

BACKGROUND: Immunoglobulin levels are elevated in the older people. However, it is unknown whether these levels are related to mortality. OBJECT: To evaluate the association between immunoglobulin levels and mortality. METHODS: The study population included 697 individuals (277 males and 420 females) of 1,282 eighty-year-old individuals residing in the Fukuoka prefecture, Japan. The participants were followed for 4 years after the baseline examination. RESULTS: The hyper-IgA group, defined as a serum IgA level >400 mg/dl, had high mortality using Kaplan-Meier analysis (log rank, p=0.037). Multivariate Cox regression analyses revealed a high risk of mortality (hazard rate=1.233, 95% confidence interval 1.109-1.491, p=0.031) after adjusting for covariates. The high risk of mortality in the hyper-IgA group was significant in males, but not in females. Moreover, Kaplan-Meier analysis revealed that IgA was related to cancer mortality in males (log rank, p=0.031), but not to pneumonia or cardiovascular disease. IgM and IgG levels were not related to high risk of mortality. CONCLUSION: Serum IgA levels appear to be a predictor of mortality, especially cancer mortality in males.

Does decreased diastolic blood pressure associate with increased mortality in 80-year-old Japanese?

Hypertension is one of the greatest risk factors for cardiovascular disease, but its contribution to cardiovascular mortality weakens with aging. We have previously demonstrated that at the age of 80, higher systolic blood pressure (SBP) is not correlated with increased mortality in Japan. However, we did not examine in detail whether diastolic blood pressure (DBP) independently affects mortality. In the present study, 639 participants, who were 80 years old in 1997, were enrolled. The subjects were divided by their DBP [below 70 mmHg (group 1, n = 136), from 70 mmHg to 80 mmHg (group 2, n = 200), from 80 mmHg to 90 mmHg (group 3, n = 194), over 90 mmHg (group 4, n = 109)]. During the 4-year follow-up period, 90 individuals died. Cox multivariate regression analysis revealed that group 1 showed a significantly higher mortality rate than group 4 [relative risk (RR) 2.47, confidence interval (CI) 1.07-5.70, p = 0.03)]. The relative risks of deaths from cardiovascular diseases, pneumonia, and cancer tended to be higher in group 1 than in group 4, but the difference did not reach statistical significance. These results suggest that decreased DBP is associated with higher mortality in the Japanese elderly.

Hemin-activated macrophages home to the pancreas and protect from acute pancreatitis via heme oxygenase-1 induction.

Hemin upregulates heme oxygenase-1 (HO-1), a stress-induced enzyme implicated in protection from a variety of injuries while its related isoform HO-2 is constitutively expressed. The role of hemin or HO-1 in the pancreas and their potential modulation of pancreatic injury are unknown. We show that HO-1 is induced in pancreatitis caused by caerulein and more prominently in severe pancreatitis caused by feeding a choline-deficient diet (CDD). Intraperitoneal hemin administration dramatically increases peritoneal and pancreas macrophages that overexpress HO-1 in association with pancreatic induction of the chemoattractants monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha but not RANTES or macrophage inflammatory protein-2. Hemin administration before CDD feeding protected 8 of 8 mice from lethality while 7 of 16 controls died. Protection is mediated by HO-1-overexpressing macrophages since hemin-primed macrophages home to the pancreas after transfer to naive mice and protect from CDD-induced pancreatitis. Suppression of hemin-primed peritoneal cell HO-1 using HO-1-specific small interfering RNA prior to cell transfer abolishes protection from CDD-induced pancreatitis. Similarly, hemin pretreatment in caerulein-induced pancreatitis reduces serum amylase and lipase, decreases pancreatic trypsin generation, and protects from lung injury. Therefore, hemin-like compounds or hemin-activated macrophages may offer novel therapeutic approaches for preventing acute pancreatitis and its pulmonary complication via upregulation of HO-1.

Atrophic gastritis, but not antibody to Helicobacter pylori, is associated with body mass index in a Japanese population.

BACKGROUND: The relationship between Helicobacter pylori (HP) infection and body mass index (BMI) is controversial. Several reports have indicated that eradication of HP infection induces an increase in BMI. In contrast, epidemiological case-control studies have failed to show an association between HP infection and BMI. Therefore, we investigated whether HP and atrophic gastritis (AG) were associated with BMI. METHODS: A total of 617 individuals were recruited for the measurements of BMI, serum leptin, pepsinogens (PGs) I and II, and IgG antibody to HP (HP-IgG). BMI and leptin of the subjects were compared when the subjects were stratified by HP-IgG and PGs. RESULTS: The subjects were divided into AG-positive and AG-negative groups according to PGs (AG-positive: PG I < or = 70 ng/ml and PG I/II ratio < or =3.0). BMI after adjusting for sex and age was significantly lower in the AG-positive group than in the AG-negative group (23.47 +/- 3.05 vs. 24.18 +/- 3.25, P = 0.010). When the subjects were divided into two groups according to HP-IgG, BMI tended to be lower in the HP-IgG-positive group, though the difference was not large. When the subjects were divided into four groups for different combinations of AG and HP-IgG, BMI was the lowest in the AG-positive and HP-IgG-negative group. CONCLUSIONS: BMI was associated with AG, as diagnosed by PGs, but not with HP infection status. These results mean that HP infection affects BMI via atrophic gastritis.

Recombinant human granulocyte colony-stimulating factor reduces colonic epithelial cell apoptosis and ameliorates murine dextran sulfate sodium-induced colitis.

OBJECTIVE: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a potentially effective therapy for Crohn's disease. The purpose of this study was to test the rhG-CSF in murine dextran sulfate sodium-induced colitis (DSS colitis). MATERIAL AND METHODS: Murine colitis was induced by feeding with water containing 3% DSS for 9 days. Six to 7-week-old female BALB/c mice were given rhG-CSF (100 microg/kg) or phosphate-buffered saline (PBS) subcutaneously once a day from day 0 to day 8, and the mice were sacrificed at days 3, 5, 7 and 9. Tissue specimens from the transverse colon, descending colon and rectum were obtained and stained with hematoxylin and eosin. Inflammation was scored for severity, extent, epithelial damage and crypt loss. TUNEL staining was performed to assess epithelial cell apoptosis. RESULTS: Treatment with rhG-CSF significantly attenuated body-weight loss, stool score and shortening of the colon length in comparison with treatment with PBS (p<0.01,<0.05,<0.01, respectively). Histological scores for inflammation, epithelial cell damage and crypt loss of the rectum were less severe at day 9 in the rhG-CSF group than in the PBS group (p<0.01, 0.05, 0.01, respectively). The number of TUNEL-positive cells in the rectum was smaller in the rhG-CSF group than in the PBS group (p<0.001). CONCLUSIONS: Treatment with rhG-CSF ameliorates murine DSS colitis by suppressing mucosal inflammation and epithelial damage in the rectum. The prevention of epithelial cell apoptosis seems to precede the anti-inflammatory action of rhG-CSF.

Association between body mass index and mortality in an 80-year-old population.

OBJECTIVES: To evaluate the association between body mass index (BMI) and all-cause mortality and cardiovascular disease (CVD) in an 80-year-old population. DESIGN: Cohort study. SETTING: Community-based. PARTICIPANTS: Six hundred ninety-seven of 1,282 (54.4%) 80-year-old candidate individuals. MEASUREMENTS: The dates and causes of all deaths were followed up for 4 years. RESULTS: The relative hazard ratios (HRs) for all-cause mortality were lower in overweight subjects (BMI > or= 25.0) than in underweight (BMI<18.5) or normal-weight (BMI 18.5-24.9) subjects. Similarly, the HRs for mortality due to CVD in overweight subjects were 78% less (HR=0.22, 95% confidence interval (CI)=0.06-0.77) than those in underweight subjects, and those in normal weight subjects were 78% less (HR=0.22, 95% CI=0.08-0.60) than those in underweight subjects. Mortality due to CVD was 4.6 times (HR 4.64, 95% CI=1.68-12.80) as high in underweight subjects as in normal-weight subjects, and mortality due to cancers was 88% lower (HR=0.12, 95% CI=0.02-0.78) in the overweight group than in the underweight group. There were no differences in mortality due to pneumonia. CONCLUSION: Overweight status was associated with longevity and underweight with short life, due to lower and higher mortality, respectively, from CVD and cancer.

Physical fitness and 4-year mortality in an 80-year-old population.

BACKGROUND: Because little is known about the relationship between physical fitness and mortality among very elderly people, we evaluated this association in a Japanese population of 80-year-old community residents. METHODS: Among 1282 80-year-old residents of Fukuoka Prefecture, Japan, 697 individuals (277 men and 420 women) underwent physical fitness tests of handgrip strength, isometric leg extensor strength, isokinetic leg extensor power, stepping rate, and one-leg standing time. Four years later, the dates and causes of death among the participants during those years were analyzed based on data from resident registration cards and from official death certificates. RESULTS: During the 4-year follow-up period, 107 individuals (58 men and 49 women) died. Of these deaths, 27 were due to cardiovascular disease (CVD), 27 to cancer, 22 to pneumonia, and the rest to other causes. The relative hazard ratios (HR) for all-cause mortality, adjusted for various confounding factors, fell with increases in stepping rate, and the HR for pneumonia mortality fell with increases in leg extensor strength. In contrast, there was no association between cardiovascular or cancer mortality and physical fitness. CONCLUSIONS: A partial association was found between impaired physical fitness at the age of 80 years and increased mortality in the 4 years thereafter. Mortality due to all causes was related only to stepping rate, and mortality due to pneumonia was related to leg extensor strength. Mortality due to CVDs or cancers was not associated with physical fitness.

Formation of Mallory body-like inclusions and cell death induced by deregulated expression of keratin 18.

Mallory bodies (MBs) are cytoplasmic inclusions that contain keratin 8 (K8) and K18 and are present in hepatocytes of individuals with alcoholic liver disease, nonalcoholic steatohepatitis, or benign or malignant hepatocellular neoplasia. Mice fed long term with griseofulvin are an animal model of MB formation. However, the lack of a cellular model has impeded understanding of the molecular mechanism of this process. Culture of HepG2 cells with griseofulvin has now been shown to induce both the formation of intracellular aggregates containing K18 as well as an increase in the abundance of K18 mRNA. Overexpression of K18 in HepG2, HeLa, or COS-7 cells also induced the formation of intracellular aggregates that stained with antibodies to ubiquitin and with rhodamine B (characteristics of MBs formed in vivo), eventually leading to cell death. The MB-like aggregates were deposited around centrosomes and disrupted the microtubular array. Coexpression of K8 with K18 restored the normal fibrous pattern of keratin distribution and reduced the toxicity of K18. In contrast, an NH(2)-terminal deletion mutant of K8 promoted the formation of intracellular aggregates even in the absence of K18 overexpression. Deregulated expression of K18, or an imbalance between K8 and K18, may thus be an important determinant of MB formation, which compromises the function of centrosomes and the microtubule network and leads to cell death.

Cognitive function and 10 year mortality in an 85 year-old community-dwelling population.

The relationship between mortality and impaired cognitive function has not been thoroughly investigated in a very elderly community-dwelling population, and little is known about the association of disease-specific mortality with Mini-Mental State Examination (MMSE) subscale scores. Here we evaluated these data in Japanese community-dwelling elderly. In 2003, 85 year-olds (n=207) were enrolled; 205 completed the MMSE for cognitive function and were followed-up for 10 years, during which time 120 participants died, 70 survived, and 17 were lost to follow-up. Thirty-eight deaths were due to cardiovascular disease, 22 to senility, 21 to respiratory disease, and 16 to cancer. All-cause mortality decreased by 4.3% with a 1-point increase in the global MMSE score without adjustment, and it decreased by 6.3% with adjustment for both sex and length of education. Cardiovascular mortality decreased by 7.6% and senility mortality decreased by 9.2% with a 1-point increase in the global MMSE score with adjustment for sex and education. No association was found between respiratory diseases or cancer mortality and global MMSE score. All-cause mortality also decreased with increases in MMSE subscale scores for time orientation, place orientation, delayed recall, naming objects, and listening and obeying. Cardiovascular mortality was also associated with the MMSE subscale of naming objects, and senility mortality was associated with the subscales of time orientation and place orientation. Thus, we found that impaired cognitive function determined by global MMSE score and some MMSE subscale scores were independent predictors of all-cause mortality or mortality due to cardiovascular disease or senility in 85 year-olds.

Serum total cholesterol concentration and 10-year mortality in an 85-year-old population.

Little is known about the association between total cholesterol (TC) and all-cause mortality in the elderly (especially the very elderly). Here we examined the association between TC and all-cause mortality in 207 very elderly (85-year-old) participants. In 2003, we performed a baseline laboratory blood examination, and blood pressure (BP) and body mass index (BMI) measurements, and lifestyle questionnaires were completed by the participants. The participants were followed for the subsequent 10 years. As of 2013, of the 207 participants in 2003, 70 participants had survived, 120 individuals had died, and 17 were lost to follow up. The TC values were divided into high-TC (≥209 mg/dL), intermediate-TC (176-208 mg/dL), and low-TC (≤175 mg/dL) categories. With the Kaplan-Meier method, we found that both the high-TC and intermediate-TC participants survived longer than the low-TC participants. The men with high TC survived longer than those with low TC, but no corresponding difference was found for the women. A multivariate Cox proportional hazards regression model, with adjustment for gender, smoking, alcohol intake, history of stroke or heart disease, serum albumin concentration, BMI, and systolic BP, revealed that the total mortality in the low-TC group was 1.7-fold higher than that in the high-TC group. Mortality, adjusted for the same factors, decreased 0.9% with each 1 mg/dL increase in the serum TC concentration and decreased 0.8% with each 1 mg/dL increase in the serum (low-density lipoprotein) LDL-cholesterol (LDL-C) concentration. Our results indicate an association between lower serum TC concentrations and increased all-cause mortality in a community-dwelling, very elderly population. Mortality decreased with the increases in both TC and LDL-C concentrations, after adjustment for various confounding factors. These findings suggest that low TC and low LDL-C may be independent predictors of high mortality in the very elderly.

Prognosis factors in the treatment of bisphosphonate-related osteonecrosis of the jaw - Prognostic factors in the treatment of BRONJ.

OBJECTIVES: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a relatively rare but serious side effect of bisphosphonate (BP)-based treatments. This retrospective study aimed to investigate the risk factors and predictive markers in cases where patients were refractory to a recommended conservative treatment offered in our hospital. PATIENTS AND METHODS: This single-center study collated the medical records of all patients treated for BRONJ between 2004 and 2011. A complete medical history, including detailed questionnaires, was collected for all patients, focusing on identifying underlying risk factors, clinical features, location and bone marker levels of BRONJ. RESULTS: The mean BRONJ remission rate was 57.6%, and the median duration of remission was seven months. Eighteen patients (34.6%) had persistent or progressive disease with a recommended conservative treatment for BRONJ. Notably, urinary cross-linked N-terminal telopeptide of type 1 collagen (NTX) levels in those resistant to conservative treatment tended to be lower than in patients that healed well. CONCLUSIONS: We confirm that a significant proportion of BRONJ sufferers are refractory to a recommended conservative treatment and find that anticancer drugs, periodontal disease, the level of bone exposure and the dosage of intravenous BPs (e.g. zoledronate) represent specific risk factors in BRONJ that may determine the success of a recommended conservative treatment. Additionally, the NTX levels might be able to be a prognostic factor for the conservative treatment of BRONJ; additional research is necessary. Key words:Bisphosphonate, osteonecrosis, jaw, prognostic, retrospective.

Effects of heme oxygenase-1 on bacterial antigen-induced articular chondrocyte catabolism in vitro.

This study tested the hypothesis that heme oxygenase-1 (HO-1) expression counteracts bacterial antigen-induced catabolic metabolism in human articular chondrocytes. HO-1 expression was induced in chondrocytes by the iron-containing porphoryin, hemin. Anti-catabolic and anti-apoptotic effects of HO-1 expression were evaluated following bacterial antigen (lipopolysaccharides, LPS) activation of chondrocytes by quantification of cytokine and cartilage matrix protein expression. Effects of HO-1 over-expression on chondrocyte matrix metabolism were evaluated using plasmid-driven protein synthesis. Hemin increased HO-1 expression and LPS increased interleukin-1beta and interleukin-6 gene and protein expression in chondrocytes. Hemin-induced HO-1 decreased LPS-induced interleukin-1beta and interleukin-6 gene and protein expression. Increased HO-1 expression partially reversed LPS-suppression of aggrecan and type II collagen gene expression and suppressed LPS-induced gene expression of IL-6, inducible nitric oxide synthase (iNOS), matrix metalloproteinases (MMPs), and IL-1beta. HO-1 induction was inversely correlated with LPS-induced chondrocyte apoptosis. HO-1 over-expression in chondrocytes decreased matrix protein gene expression. With LPS activation, increased HO-1 expression decreased chondrocyte catabolism, partially reversed LPS-dependent inhibition of cartilage matrix protein expression and protected against apoptosis. Without LPS, hemin-induced HO-1 and plasmid-based over-expression of HO-1 inhibited cartilage matrix gene expression. The results suggest that elevated HO-1 expression in chondrocytes is protective of cartilage in inflamed joints but may otherwise suppress matrix turn over.

Body mass index and disease-specific mortality in an 80-year-old population at the 12-year follow-up.

Although many investigations examined the relationship between body mass index (BMI) and mortality, little is known about the possible associations between BMI and disease-specific mortality in very elderly people. Here we evaluated this association in an 80-year-old population. In 1998, 675 residents in Japan's Fukuoka Prefecture participated. They were followed up for 12 years after the baseline examination; 37 subjects (5.5%) were lost to follow-up. The subjects were divided into six groups by their BMI values: <19.5 (most-thin), 19.5 to <21.1 (relatively thin), 21.1 to <22.5 (thin/normal), 22.5 to <23.8 (normal/overweight), 23.8 to <26.0 (relatively obese), ≥26.0 (most-obese). The most-thin group had the highest mortality from all-causes, and from respiratory disease. The normal/overweight group had the lowest overall mortality among the six BMI groups. These associations were found in the men, but not in the women. The most-obese group did not have higher mortality from all-causes or cardiovascular disease compared to the normal/overweight group. Respiratory disease-related mortality was lowest in the most-obese group. No association was found between BMI group and mortality from cancer. In conclusion, in an 80-year-old Japanese population, mortality from all-causes or respiratory disease was highest in the most-lean group (BMI <19.5), and mortality from all-causes or cardiovascular disease was lowest in the group with BMI 22.5 to <23.8.