Factors related to hospital-to-home transitional self-monitoring blood glucose behaviour among patients with diabetes-related foot ulcer.

AIMS: To explore the factors related to hospital-to-home transitional self-monitoring blood glucose behaviour among patients with diabetes-related foot ulcer. BACKGROUND: The 30-day readmission rate of patients with diabetes-related foot ulcer can be reduced when good glycaemic control is achieved. The practice of self-monitoring blood glucose promotes optimal glycaemic control. DESIGN: A comparative descriptive study. METHODS: In this study, 200 participants, who had been hospitalized due to diabetes-related foot ulcer, were recruited from August 2017 to July 2018. Before participants were discharged from the hospital, psychosocial factors (family support, threat belief, self-efficacy and knowledge) and pre-hospitalization self-monitoring blood glucose behaviour were collected using a structured questionnaire. Then, after discharge, self-monitoring blood glucose behaviour delivery was collected again. RESULTS: Five variables explained 47% of the variance in the delivery of self-monitoring of blood glucose at home. The delivery of hospital-to-home transitional self-monitoring blood glucose behaviour was more likely for individuals with higher pre-discharge self-efficacy, higher post-discharge self-efficacy, more attention to pre-hospitalization glycaemic status and post-discharge insulin usage and those without an insensitive foot. CONCLUSION: Self-monitoring blood-glucose behaviour should be promoted among post-discharge patients with diabetes-related foot ulcer. The modifiable factors identified in this study can be integrated into the discharge plan.

Factors associated with foot ulcer self-management behaviours among hospitalised patients with diabetes.

AIMS AND OBJECTIVES: To determine prehospitalised diabetes-related foot ulcer (DFU) self-management behaviours and explore the factors associated with these behaviours. BACKGROUND: Although there are many studies that explore DFU prevention and treatment, to our knowledge, there are no quantitative studies of DFU self-management behaviours. DESIGN: Cross-sectional design. METHODS: From June 2015-June 2016, 199 hospitalised patients with DFU were given a survey questionnaire at a medical centre in northern Taiwan. DFU self-management behaviours, diabetes foot self-care behaviours, beliefs in regard to barriers to DFU self-management behaviours, and knowledge regarding warning signs of DFU deterioration were assessed by well-designed measurement tools. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was used to ensure quality reporting during this observational study (see Supporting Information Appendix S1). RESULTS: The results revealed that 62.8% of participants never monitored their blood glucose level when they had foot ulcers, and 63.8% never sought treatment for their wounds when their wounds were not painful. After controlling for demographic and medical variables, stepwise multiple regression analysis revealed that the following eight significant variables were associated with DFU self-management behaviours: two DFU self-management barrier beliefs, foot self-care behaviour, no treatment for diabetes, poor financial status, employment, knowledge regarding the warning signs of DFU deterioration, and number of DFU hospitalisations. CONCLUSIONS: Diabetes-related foot ulcer self-management behaviours were insufficient. Some modifiable factors and high-risk groups for insufficient DFU self-management behaviour were identified. RELEVANCE TO CLINICAL PRACTICE: Diabetes-related foot ulcer self-management behaviours should be promoted. Interventions that modify the risk factors that were identified in this study can be designed to promote the performance of DFU self-management behaviours.

Risk factors for in-hospital mortality in patients with type 2 diabetes complicated by community-acquired Klebsiella pneumoniae bacteremia.

BACKGROUND/PURPOSE: Patients with diabetes are at a high risk of infection-related morbidity and mortality. Klebsiella pneumoniae bacilli are prevalent among diabetic patients, especially in Asian populations. The present study aimed to identify risk factors for in-hospital mortality among diabetic patients complicated by community-acquired K. pneumoniae bacteremia. METHODS: We evaluated the clinical characteristics of 341 Taiwanese type 2 diabetic patients who were treated for community-acquired K. pneumoniae bacteremia. We then analyzed outcome predictors, and in particular comorbidities and the site of infection. RESULTS: The overall in-hospital mortality rate was 14.1%. Comorbid cancer was the leading factor, accounting for 32.1% of all cases of mortality. Pulmonary infection, primary bacteremia, afebrile or shock presentation and low serum albumin level were risk factors for in-hospital mortality. Regardless of comorbidities, pulmonary infection [odds ratio (OR) 10.74, 95% confidence interval (CI) 2.02-57.09] and albumin level (OR 0.15, 95% CI 0.03-0.76) were the main risk predictors. The receiver operating characteristic curve indicated that a serum albumin level lower than 2.4 g/dL (71.1% sensitivity and 77.4% specificity) suggested a poor prognosis in the diabetic patients with K. pneumoniae bacteremia. In patients with pulmonary infection, the capsular serotypes of K. pneumoniae were not related to poor outcomes, and an initial presentation of blunted fever or shock were independent factors for mortality. CONCLUSION: Cancer, pulmonary infection, and low serum albumin levels were independent indicators of in-hospital mortality in the diabetic patients complicated by K. pneumoniae bacteremia. The sites of infection and host characteristics should always elicit medical attention when treating these patients.

Impact of action cues, self-efficacy and perceived barriers on daily foot exam practice in type 2 diabetes mellitus patients with peripheral neuropathy.

AIMS AND OBJECTIVES: To identify the effects of health belief model factors on daily foot-exam practice among diabetes mellitus patients with peripheral neuropathy. BACKGROUND: Daily foot exams are one of the most important self-care behaviours that prevent the occurrence of diabetic foot ulcers and subsequent amputation. Although daily foot exams were under-practiced in patients with peripheral neuropathy, few studies have explored modifiable social-psychological factors related to daily foot exams. DESIGN: A cross-sectional survey was used to collect the data. METHODS: A total of 277 patients with diabetes and peripheral neuropathy were recruited from two hospitals in northern Taiwan. The Family APGAR and Diabetic Foot Ulcer Health Belief Scale (DFUHBS) were used to measure family support and health belief factors respectively. Data on foot-exam practice, perceived self-efficacy and action cues were collected through the use of structured questionnaires. The data were analysed using logistic regression. RESULT: The regression model revealed that select action cues (recommendations from family, friends, or health professionals), perceived self-efficacy and perceived barriers interactively influenced the participants' daily foot-exam practice. CONCLUSION: Factors related to daily foot-exam practice were identified. Specifically, action cues played a significant role in motivating daily foot-exam practice in this group. RELEVANCE TO CLINICAL PRACTICE: This study recognises modifiable factors that influence the daily foot-exam practice of patients with diabetes and peripheral neuropathy. Using the findings of this study, health professionals can design interventions that aim to modify the above factors as a means to promote daily foot-exam practice.

A short-term follow-up of glycemic and body weight changes in diabetic patients who replaced dipeptidyl peptidase-4 inhibitors with the sodium-glucose cotransporter 2.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2is, gliflozins) are associated with lower all-cause mortality than other anti-diabetic agents in patients with type 2 diabetes. In patients who may benefit from SGLT2is, but cannot add them to a dipeptidyl peptidase-4 inhibitor (DPP4i, gliptin) treatment for various reasons, replacement of the DPP4i with a SGLT2i may be considered. OBJECTIVES: Evaluate changes in metabolic parameters in patients with diabetes after replacing a DPP4i with the SGLT2i empagliflozin. DESIGN: Panel study (cross-sectional and cohort hybrid). SETTING: The diabetes outpatient clinics of Chang Gung Memorial Hospital at Linkou, a university hospital in Taiwan. PATIENTS AND METHODS: We reviewed the medical records of patients who had been treated with anti-diabetic agents including a DPP4i between May 2016 and May 2017. Patients who switched from DPP4is to empagliflozin (switched-to-empagliflozin group) without changes to other anti-diabetic agents for at least 6 months were compared patients who continued taking an original antidiabetic agent. The body weight (BW), body mass index (BMI), and glycated hemoglobin (HbA1c) level at baseline and after 3 and 6 months were collected for analysis. MAIN OUTCOME MEASURES: BW, BMI, HbA1c at baseline, 3 and 6 months. SAMPLE SIZE: 236 patients. RESULTS: The HbA1c level and BMI of 110 patients (71%) in the switched-to-empagliflozin group were significantly reduced at 6 months after the switch, and there was a significant negative correlation between baseline HbA1c and change in HbA1c (rho=-0.537, P less than .001). In another 45 patients (29%) who switched to empagliflozin, HbA1c did not have improve, but BW decreased after the switch. No significant change in HbA1c occurred in the group that remained on DPP4is. In addition, BW and BMI decreased regardless of the degree of glucose reduction in the switched-to-empagliflozin group (P less than .001 for both variables at 6 months vs baseline), but not in the patients who remained on DPP4is. CONCLUSIONS: The study demonstrated the metabolic impact of switching from a DPP4i to a well-known SGLT2i, but further large-scale trials are needed to study the long-term effects of replacing a DPP4i with a SGLT2i. LIMITATIONS: Retrospective design, a short observation period, a small number of patients, no evaluations of the quality of life, side effects, or the cost, and data limited to only empagliflozin. CONFLICT OF INTEREST: No any relationship or support from the manufacturer of empagliflozin or other agents.

Antimicrobial resistance and outcomes of community-onset bacterial bloodstream infections in patients with type 2 diabetes.

OBJECTIVES: Antimicrobial resistance of bacterial pathogens in the diabetic population with infection is seldom investigated. This study evaluated the antimicrobial resistance and outcomes of community-onset bloodstream infections (CO-BSIs) in patients with diabetes. METHODS: From 2007-2014, 1271 monomicrobial CO-BSIs and 178 polymicrobial CO-BSIs were identified in patients with type 2 diabetes from three teaching hospitals in Taiwan. Antimicrobial-resistant strains of the ten most prevalent bacterial pathogens in monomicrobial CO-BSIs were recorded and were defined according to individual drug resistance. The 30-day mortality rate and factors associated with outcome were analysed. RESULTS: Antimicrobial-resistant strains were found in 33.7% (379/1125) of monomicrobial CO-BSIs involving the 10 most prevalent pathogens. The leading pathogens in these monomicrobial CO-BSIs were Staphylococcus spp. (33.8%; 430/1271), Escherichia coli (20.9%; 266/1271) and Klebsiella spp. (9.6%; 122/1271); antimicrobial-resistant strains accounted for 61.9%, 18.4% and 10.7% of each, respectively. A higher overall 30-day mortality rate was observed for patients infected by antimicrobial-resistant strains compared with antimicrobial-susceptible strains (9.5% vs. 5.5%; P=0.011, log-rank test). A lower serum albumin level was a predictor of mortality after adjusting for antimicrobial-resistant strains and C-reactive protein level. CONCLUSIONS: Antimicrobial-resistant bacterial pathogens pose a serious threat to diabetic patients with CO-BSIs owing to a higher risk of mortality.

Field Effect Microparticle Generation for Cell Microencapsulation.

The diameter and sphericity of alginate-poly-L-lysine-alginate microcapsules, determined by the size and the shape of calcium alginate microspheres, affect their in vivo durability and biocompatibility and the results of transplantation. The commonly used air-jet spray method generates microspheres with a wider variation in diameter, larger sphere morphology, and evenly distributed encapsulated cells. In order to overcome these drawbacks, we designed a field effect microparticle generator to create a stable electric field to prepare microparticles with a smaller diameter and more uniform morphology. Using this electric field microparticle generator the encapsulated cells will be located at the periphery of the microspheres, and thus the supply of oxygen and nutrients for the encapsulated cells will be improved compared with the centrally located encapsulated cells in the air-jet spray method.

Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive Treatment.

The aim of this study was to investigate whether tolerance-induced protection of islets in the renal subcapsular space can also prevent subcutaneous allogeneic islets from being rejected. We used bone marrow stem cells from C57BL/6 (H2b) mice to construct donor chimerism in conditioned diabetic BALB/c (H2d) mice and investigated the effect of donor chimerism on engraftment and survival of subcutaneously transplanted allogeneic islets in streptozotocin-induced diabetic mice. We also studied the anti-inflammatory effect of mesenchymal stem cell on islet engraftment. Full but not low-grade or no donor chimerism was associated with successful engraftment of allogeneic islets and restoration of normoglycemia in the treated diabetic mice. The temporary hyperglycemia was 11 ± 1 versus 19 ± 5 days (p < 0.05) for the mice with full donor chimerism with transplanted islets in the renal subcapsular space versus the subcutaneous space, respectively. Cotransplantation of mesenchymal stem cell did not enhance alloislet engraftment. Full multilineage donor chimerism was associated with a higher transient expansion of CD11b+ and Gr-1+ myeloid progenitor cells and effector memory CD4 and CD8 T cells. In conclusion, full donor chimerism protected both renal subcapsular and subcutaneous allogeneic islets in this rodent transplantation model.

Effect of limb preservation status and body mass index on the survival of patients with limb-threatening diabetic foot ulcers.

AIMS: To evaluate the effect of limb preservation status and body mass index (BMI) on the survival of patients with diabetic foot ulcers (DFUs). METHODS: A total of 1346 patients treated for limb-threatening DFUs at a major diabetic foot center in Taiwan from 2002 to 2009 were tracked until December 2012. The patients were classified into three groups: limb-preserved (n=858), minor lower-extremity amputation (LEA) (n=249), and major LEA (n=239). Clinical data during treatment were used for survival analysis. RESULTS: With 729 deaths, the median survival time (MST) was 6.14 (95% CI 5.63-6.65) years. Major LEA and BMI were two independent factors associated with mortality after adjusting for age, diabetic duration, HbA1c level, comorbidities and peripheral artery diseases. The mortality hazard ratios for the minor and major LEA groups were 0.92 (95% CI 0.74-1.16) and 1.34 (95% CI 1.07-1.68), respectively, to the reference group (limb-preserved). After stratifying BMI into four categories (underweight, normal weight, overweight and obesity, according to the Taiwanese definition), the MSTs for each category were 2.57, 5.24, 7.47 and 7.85years, respectively (P for trend <0.01). This "obesity paradox" was not observed in the major LEA group (P for trend 0.25). For patients with LEA, the obesity patients had lower MST than those in overweight category (7.97 and 8.84 in minor and 3.25 and 5.42 in major LEA, respectively). CONCLUSIONS: For the patients treated for DFUs, major - but not minor - LEA was associated with poor survival compared with the limb-preserved group. The MST had positive correlation with BMI levels for patients with limb-preserved and minor LEA, but not for those with major LEA.

Enhancing engraftment of islets using perioperative sodium 4-phenylbutyrate.

Primary nonfunction (PNF) adversely impacts islet transplantation. In addition to determining whether sodium 4-phenylbutyrate (4-SPB), an anti-inflammatory agent, reduces PNF, this study investigates how 4-SPB affects PNF. Streptozotocin-induced diabetic C57BL/6 mice, that received 75 syngeneic islets underneath left subrenal space, were fed twice daily of either 4-SPB at 500 mg/kg body weight or isotonic saline (NaCl) from 2 days before through 7 days after transplantation. The graft was removed at days 3, 10 and 84 following transplantation. At 68 h following transplantation, serum levels of interleukin-1beta (IL-1beta) were 2.2+/-0.4 and 0.4+/-0.2 pmol/L (n=6, p<0.005) for NaCl and 4-SPB groups, respectively. Graft genetic expression of IL-1beta was significantly suppressed in 4-SPB group (p<0.01). At day 10, the blood glucose levels were 22.7+/-1.0 and 17.1+/-1.7 mmol/L (n=12, p<0.05) and graft insulin contents (IC) were 35.0+/-8.3 and 107.6+/-29.7 pmol (n=12, p<0.05) for NaCl and 4-SPB groups, respectively. Moreover, the 4-SPB group had a shorter temporary hyperglycemia (15+/-2, n=21 vs. 25+/-2 days, n=19, p=0.001) and a higher cumulative cure rate of diabetes (p<0.001) than the NaCl group. In-vitro studies indicated that 4-SPB did not impact the islets function. These experimental results demonstrated that perioperative administration of 4-SPB decreased serum level and graft genetic expression of IL-1beta and attenuated PNF, which enhanced islet engraftment in a syngeneic transplantation mouse model.

GLP-1 receptor agonist exenatide restores atypical antipsychotic clozapine treatment-associated glucose dysregulation and damage of pancreatic islet beta cells in mice.

BACKGROUND AND AIMS: The aim of this study was to investigate the effect of a glucagon-like peptide-1 receptor agonist (GLP-1RA), exenatide, on clozapine-associated glucose dysregulation in mice. MATERIALS AND METHODS: We randomly separated B6 male mice into four groups (A to D). Mice in groups C and D received a daily oral dose of 13.5 mg/kg body weight of clozapine for 4 months. Mice in groups B and D received 1 µg of exenatide daily. The body weight and blood glucose before and 2 h after clozapine treatment were measured twice a week. Intraperitoneal glucose tolerance test (IPGTT) scores and the amount of daily food intake were recorded. The pancreases of the mice were removed for insulin content (PIC) measurement and histological examination after sacrifice. RESULTS: The mean non-fasting blood glucose levels were not different, and the mean changes in blood glucose 2 h after oral clozapine were 0 ± 4, -40 ± 2, 25 ± 3, and -39 ± 2, in groups A to D, respectively. There was no significant difference in daily calorie intake or area under the curve of IPGTT among the four groups. At sacrifice, the PIC of mice treated with clozapine was significantly lower than that of the control mice, however the PIC was completely restored in the mice treated with exenatide. Histological examination of the pancreas revealed that exenatide treatment reversed the clozapine-induced apoptosis of islet cells. CONCLUSION: Our results provide preclinical evidence of a pharmaceutical role of GLP-1RA in managing glucose dysregulation in schizophrenic patients under long-term atypical antipsychotic treatments.

Pitavastatin improves glycated hemoglobin in patients with poorly controlled type 2 diabetes.

AIMS/INTRODUCTION: To investigate the effect of pitavastatin on glucose control in patients with type 2 diabetes. MATERIALS AND METHODS: Medical records of 340 patients with type 2 diabetes treated with pitavastatin or atorvastatin between 1 August 2013 and 31 May 2014 were reviewed. A total of 96 patients who had not received statins were treated with pitavastatin (N to P group). A total of 100 patients who had previously used atorvastatin were switched to pitavastatin (A to P group). A total of 144 patients continued with atorvastatin treatment. Data were collected at baseline, 3 and 6 months of treatment. Changes in glycated hemoglobin (HbA1c) level were analyzed in 222 patients who did not change their antidiabetic agent during 6 months of treatment. RESULTS: A negative correlation between baseline HbA1c and delta HbA1c at 6 months was found in the pitavastatin-treated patients (N to P group: ρ = -0.329, P = 0.006; A to P group: ρ = -0.480, P < 0.001). The correlation remained similar after adjusting for age, body mass index, dose of pitavastatin, estimated glomerular filtration rate and high-density lipoprotein cholesterol. After 6 months of treatment, the benefit of pitavastatin on HbA1c in the patients with poorly controlled diabetes was significant in both the N to P (8.1 vs 7.4%, P = 0.018) and A to P (9.7 vs 9.0%, P = 0.015) groups. CONCLUSIONS: Pitavastatin decreases HbA1c in patients with type 2 diabetes with a higher baseline HbA1c level. The benefit on HbA1c was also observed in patients with previous use of atorvastatin.

Beneficial effects of hyperbaric oxygen therapy on islet transplantation.

We envisage that hyperbaric oxygen (HBO) would ameliorate islet anoxia, preventing early graft failure. Thus, treatment of HBO to diabetic recipients should improve the outcome of islet transplantation. We tested this hypothesis by syngeneically transplanting insufficient number of islets (150 islets) into streptozotocin-diabetic C57BL/6 mice, each followed by HBO (2.4 ATA, 100% O2) therapy for 1.5 h from day 0 to 28, once daily (group A) or twice daily (group B), or from day 5 to 28, once daily (group C) or twice daily (group D), 6 days/week. Recipients without HBO treatment served as controls. At day 28 after transplantation, groups B, C, and D gained weight and had lower blood glucose compared with their baseline values. In addition, groups B and D had higher insulin content of the graft than the controls. To determine the optimal timing of HBO therapy, groups B and D were compared with recipients treated with HBO twice daily, 6 days/week, from day -14 to 0 (group E) and from day -14 to 28 (group F). At day 28 after transplantation, groups B, D, E, and F had significantly lower blood glucose than their individual baseline values and higher insulin content of the graft than controls. But only group F had more beta-cell mass of the graft than controls. These findings lend credence to the expectation that peritransplant application of adequate frequency of HBO to diabetic recipients would enhance the performance and growth of the islet graft, resulting in an improvement of the outcome of the transplantation.

Loofa sponge as a scaffold for the culture of human hepatocyte cell line.

Loofa sponge was investigated as a three-dimensional scaffold for stationary and perfusion culture of human hepatoblastoma cell line C3A/HepG2. In stationary culture, C3A/HepG2 cells in loofa cubes showed higher alpha-fetoprotein and albumin secretion rates than those in polyurethane foam (PU). To use loofa cylinders in a packed-bed reactor, immobilization of C3A/HepG2 cells by recirculating medium at 26 mL/min (superficial velocity = 51.7 cm/min) resulted in a cell loading density of 5.15 x 10(7) cells/cm(3)-loofa. This cell loading density is higher than values reported in the literature for packed-bed reactor intended for bioartificial liver. During 9 days of perfusion culture in the reactor, immobilized C3A/HepG2 showed steady synthesis of albumin with an average synthesis rate at 42.2 microg/10(6) cells/day. These experimental results and observations by SEM suggested that loofa sponge is a suitable scaffold for high-density culture of human hepatocyte cell line and the immobilized cells could express high levels of liver-specific functions.

The role of foot self-care behavior on developing foot ulcers in diabetic patients with peripheral neuropathy: a prospective study.

BACKGROUND: Although foot self-care behavior is viewed as beneficial for the prevention of diabetic foot ulceration, the effect of foot self-care behavior on the development of diabetic foot ulcer has received little empirical investigation. OBJECTIVE: To explore the relationship between foot self-care practice and the development of diabetic foot ulcers among diabetic neuropathy patients in northern Taiwan. METHODS: A longitudinal study was conducted at one medical center and one teaching hospital in northern Taiwan. PARTICIPANTS: A total of 295 diabetic patients who lacked sensitivity to a monofilament were recruited. Five subjects did not provide follow-up data; thus, only the data of 290 subjects were analyzed. The mean age was 67.0 years, and 72.1% had six or fewer years of education. METHODS: Data were collected by a modified version of the physical assessment portion of the Michigan Neuropathy Screening Instrument and the Diabetes Foot Self-Care Behavior Scale. Cox regression was used to analyze the predictive power of foot self-care behaviors. RESULTS: A total of 29.3% (n=85) of diabetic neuropathy patients developed a diabetic foot ulcer by the one-year follow-up. The total score on the Diabetes Foot Self-Care Behavior Scale was significantly associated with the risk of developing foot ulcers (HR=1.04, 95% CI=1.01-1.07, p=0.004). After controlling for the demographic variables and the number of diabetic foot ulcer hospitalizations, however, the effect was non-significant (HR=1.03, 95% CI=1.00-1.06, p=0.061). Among the foot self-care behaviors, lotion-applying behavior was the only variable that significantly predicted the occurrence of diabetic foot ulcer, even after controlling for demographic variables and diabetic foot ulcer predictors (neuropathy severity, number of diabetic foot ulcer hospitalizations, insulin treatment, and peripheral vascular disease; HR=1.19, 95% CI=1.04-1.36, p=0.012). CONCLUSIONS: Among patients with diabetic neuropathy, foot self-care practice may be insufficient to prevent the occurrence of diabetic foot ulcer. Instead, lotion-applying behavior predicted the occurrence of diabetic foot ulcers in diabetic patients with neuropathy. Further studies are needed to explore the mechanism of lotion-applying behavior as it relates to the occurrence of diabetic foot ulcer.

Down-regulation of matrix metalloproteinase-7 inhibits metastasis of human anaplastic thyroid cancer cell line.

Epigenetic drugs such as histone deacetylase inhibitors (HDACIs) possess anticancer properties due to its ability to regulate genes associated with tumor growth, differentiation, apoptosis and metastasis. In addition to its apoptotic effect, phenylbutyrate (PB), a carboxylic acid HDACI, inhibited an anaplastic (ATC) thyroid cancer cell line ARO from penetrating a matrigel coated transwell with concomitant suppression of a metastasis-associated gene, matrix metalloproteinase-7 (MMP-7) and stimulation of a transformation suppressor protein, reversion-inducing- cysteine-rich protein with Kazal motifs without affecting MMP-2 expression levels. Direct evidence suggesting MMP-7 down-regulated cancer metastasis came from the observation of a decreased pulmonary metastasis in SCID mice xeno-transplanted with MMP-7-knocked-down ARO cells. In addition, H-89, a protein kinase A inhibitor, remarkably restored the down-regulaed MMP-7 level treated by PB. Thus, the suppressive effect of PB on MMP-7 was partially carried out through H3 phosphoacetylation. To conclude, our findings suggest PB inhibits MMP-7 expression epigenetically through phosphoacetylation of histone proteins, and thereby, reduced invasive ability of an ATC thyroid cancer cell line.

High-fat diet aggravates islet beta-cell toxicity in mice treated with clozapine.

BACKGROUND: Clozapine, an atypical antipsychotic drug, induces derangements in glucose homeostasis in certain patients. This study investigated the mechanisms of clozapine-induced beta-cell toxicity. METHODS: Fifty-two healthy C57BL/6 male mice were randomized into 4 groups to study the effects of clozapine (group C, D) and a high-fat diet (group B, D). Three mice from each group were randomly selected to determine the amount of food intake on days 8-10, and their pancreases were removed for histological examination on day 11. The remaining 10 mice in each group were sacrificed at the 8th week to measure pancreatic insulin content (PIC). RESULTS: Mice given clozapine for 8 weeks demonstrated trends of lower PIC. The histological examination of the pancreases retrieved on day 11 already revealed apoptotic changes and suppression of cell proliferation. Although mice fed high-fat chow gained weight, mice given both clozapine and a high-fat diet showed less weight gain and more severe histological deterioration, and had the lowest PIC levels of the 4 groups. CONCLUSION: Pancreatic beta-cell apoptosis, suppression of cell proliferation, and trends of reduction in pancreatic insulin content were observed in mice taking clozapine. The findings of clozapine induced beta-cell toxicity were further aggravated when mice were concomitantly fed a high-fat diet.

Synergistic Effect of Hyperglycemia and p27(kip1) Suppression on Adult Mouse Islet Beta Cell Replication.

The complementary role of hyperglycemia and p27(kip1) suppression on islet beta cell regeneration was investigated in a syngeneic mouse model. p27(kip1) gene silencing was performed by infecting islets of C57BL/6 with shRNA lentiviral particles. At 54 hours after viral infection, p27(kip1) protein content in cultured targeting islets was 22% of that in freshly isolated islets. Six days after transplantation to diabetic mice, targeting islet graft had considerably more cells with Ki67-staining nuclei than nontargeting islets. The mice in the targeting-islet group had a significantly shorter duration of temporary hyperglycaemia than mice in the non-targeting-islet group. The long-term ex vivo beneficial effect of p27(kip1) silencing on graft function was also indicated by the significantly higher cumulative cure rate for diabetes in mice receiving 200 targeting islets than that in mice receiving 200 non-targeting islets. Our data suggest that hyperglycemia and persistent p27(kip1) suppression have a synergistic effect on islet beta cell replication in adult mice.

Risk factors for lower extremity amputation in diabetic foot disease categorized by Wagner classification.

AIMS: To elucidate the risk factors for lower extremity amputation (LEA) in patients of diabetic foot disease with different Wagner gradings. METHODS: This study was conducted in a multidisciplinary diabetic foot care center. Demographic characteristics, laboratory data, disease history, ankle brachial pressure index (ABI) and Wagner classification were considered as independent variables to predict the therapeutic outcome (major LEA, minor LEA, and non-amputation). Risk factors for LEA in different Wagner grades were further analyzed. Multivariate stepwise ordinal logistic regression was performed. RESULTS: Of 789 study subjects, 19.9% received major LEA and 22.9% received minor LEA. Higher Wagner grade, lower ABI, serum albumin and hemoglobin, and elevated white blood cell (WBC) count were significantly associated with an increased risk of LEA. When stratified by Wagner classification, most of the above predictors and estimated glomerular filtration (eGFR) were detected only in grade 3. While in grades 2 and 4, WBC count was identified as primary predictor positively associated with an increased risk of LEA. CONCLUSIONS: Wagner classification remarkably influenced the potential risk factors for LEA, showing different predictors in different grades. The traditionally recognized predictors for diabetic foot amputation such as lower ABI, albumin or eGFR were almost exclusively found in patients with Wagner grade 3.

C-reactive protein as an outcome predictor for percutaneous transluminal angioplasty in diabetic patients with peripheral arterial disease and infected foot ulcers.

AIM: Although percutaneous transluminal angioplasty (PTA) is an effective therapeutic procedure for critical limb ischemia, several clinical factors can influence the outcome of PTA for peripheral arterial disease (PAD). The aim of this study is to identify the outcome predictors of PTA in infected diabetic foot patients with PAD. METHODS: Eighty-five diabetic patients with a total of 90 infected limbs treated by PTA participated in this study. Patients were initially admitted for infected foot ulcers and were later diagnosed with PAD. Even though all patients underwent successful PTA within 15 days of admission, limb salvage was successful in 66 cases while 24 underwent subsequent amputation. The clinical characteristics and laboratory variables of both groups before PTA were compared and analyzed. RESULTS: Significantly higher level of C-reactive protein (CRP) was observed in the major amputation group before PTA. The cutoff value via receiver operating characteristic curve was 50mg/L (81.8% specificity, 70.7% sensitivity). Multivariate logistic regression analysis revealed that CRP levels may serve as valuable marker in determining a successful outcome. CONCLUSION: Reduced CRP levels (<50mg/L), which indicates a low infection severity, may serve as a major predictor of successful PTA outcome in diabetic patients with infected foot ulcers.