Use of cutting-edge RNA-sequencing technology to identify biomarkers and potential therapeutic targets in canine and feline cancers and other diseases

With the growing interest in companion animals and the rapidly expanding animal healthcare and pharmaceuticals market worldwide. With the advancements in RNAsequencing (RNA-seq) technology, it has become a valuable tool for understanding biological processes in companion animals and has multiple applications in animal healthcare.Historically, veterinary diagnoses and treatments relied solely on clinical symptoms and drugs used in human diseases. However, RNA-seq has emerged as an effective technology for studying companion animals, providing insights into their genetic information. The sequencing technology has revealed that not only messenger RNAs (mRNAs) but also noncoding RNAs (ncRNAs) such as long ncRNAs and microRNAs can serve as biomarkers. Based on the examination of RNA-seq applications in veterinary medicine, particularly in dogs and cats, this review concludes that RNA-seq has significant potential as a diagnostic and research tool. It has enabled the identification of potential biomarkers for cancer and other diseases in companion animals. Further research and development are required to maximize the utilization of RNA-seq for improved disease diagnosis and therapeutic targeting in companion animals.

Gallic Acid Hindered Lung Cancer Progression by Inducing Cell Cycle Arrest and Apoptosis in A549 Lung Cancer Cells via PI3K/Akt Pathway

This study elucidates the anti-cancer potential of gallic acid (GA) as a promising therapeutic agent that exerts its effect by regulating the PI3K/Akt pathway. To prove our research rationale, we used diverse experimental methods such as cell viability assay, colony formation assay, tumor spheroid formation assay, cell cycle analysis, TUNEL assay, Western blot analysis, xenograft mouse model and histological analysis. Treatment with GA inhibited cell proliferation in dose-dependent manner as measured by cell viability assay at 48 h. GA and cisplatin (CDDP) also inhibited colony formation and tumor spheroid formation. In addition, GA and CDDP induced apoptosis, as determined by the distribution of early and late apoptotic cells and DNA fragmentation. Western blot analysis revealed that inhibition of the PI3K/Akt pathway induced upregulation of p53 (tumor suppressor protein), which in turn regulated cell cycle related proteins such as p21, p27, Cyclin D1 and E1, and intrinsic apoptotic proteins such as Bax, Bcl-2 and cleaved caspase-3. The anti-cancer effect of GA was further confirmed in an in vivo mouse model. Intraperitoneal injection with GA for 4 weeks in an A549-derived tumor xenograft model reduced the size of tumor mass. Injection of them downregulated the expression of proliferating cell nuclear antigen and p-Akt, but upregulated the expression of cleaved caspase-3 in tumor tissues. Taken together, these results indicated that GA hindered lung cancer progression by inducing cell cycle arrest and apoptosis, suggesting that GA would be a potential therapeutic agent against non-small cell lung cancer.

A Case of Fulminant Type 1 Diabetes Mellitus after Recovery from COVID-19 Infection / 임상당뇨병

testing revealed that the patient was positive for HLA-DRB1*04, HLA-DRB1*12, HLA-DQB1*03, andHLA-DQB1*04. To the best of our knowledge, this is the first case of fulminant T1DM reported to occurimmediately after COVID-19 infection.

High Serum-Induced AhRL Is Associated with Prevalent Metabolic Syndrome and Future Impairment of Glucose Tolerance in the Elderly

Background@#High circulating levels of dioxins and dioxin-like chemicals, acting via the aryl hydrocarbon receptor (AhR), have previously been linked to diabetes. We now investigated whether the serum AhR ligands (AhRL) were higher in subjects with metabolic syndrome (MetS) and in subjects who had developed a worsened glucose tolerance over time. @*Methods@#Serum AhRL at baseline was measured by a cell-based AhRL activity assay in 70-year-old subjects (n=911) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The main outcome measures were prevalent MetS and worsening of glucose tolerance over 5 years of follow-up. @*Results@#AhRL was significantly elevated in subjects with prevalent MetS as compared to those without MetS, following adjustment for sex, smoking, exercise habits, alcohol intake and educational level (P=0.009). AhRL at baseline was higher in subjects who developed impaired fasting glucose or diabetes at age 75 years than in those who remained normoglycemic (P=0.0081). The odds ratio (OR) of AhRL for worsening glucose tolerance over 5 years was 1.43 (95% confidence interval [CI], 1.13 to 1.81; P=0.003, continuous variables) and 2.81 (95% CI, 1.31 to 6.02; P=0.008, in the highest quartile) adjusted for sex, life style factors, body mass index, and glucose. @*Conclusion@#These findings support a large body of epidemiologic evidence that exposure to AhR transactivating substances, such as dioxins and dioxin-like chemicals, might be involved in the pathogenesis of MetS and diabetes development. Measurement of serum AhRL in humans can be a useful tool in predicting the onset of metabolic disorders.

Clinical Value of Serum Mitochondria-Inhibiting Substances in Assessing Renal Hazards: A Community-Based Prospective Study in Korea

Background@#Mitochondrial dysfunction is strongly associated with several kidney diseases. However, no studies have evaluated the potential renal hazards of serum mitochondria-inhibiting substance (MIS) and aryl hydrocarbon receptor ligand (AhRL) levels. @*Methods@#We used serum level of MIS and AhRL and clinical renal outcomes from 1,511 participants of a prospective community-based cohort in Ansung. MIS was evaluated based on intracellular adenosine triphosphate (MIS-ATP) or reactive oxygen species (MIS-ROS) generation measured using cell-based assays. @*Results@#During a mean 6.9-year follow-up, 84 participants (5.6%) developed a rapid decline in kidney function. In the lowest quartile group of MIS-ATP, patients were older and had metabolically deleterious parameters. In multivariate logistic regression analysis, higher MIS-ATP was associated with decreased odds for rapid decline: the odds ratio (OR) of 1% increase was 0.977 (95% confidence interval [CI], 0.957 to 0.998; P=0.031), while higher MIS-ROS was marginally associated with increased odds for rapid decline (OR, 1.014; 95% CI, 0.999 to 1.028; P=0.055). However, serum AhRL was not associated with the rapid decline in kidney function. In subgroup analysis, the renal hazard of MIS was particularly evident in people with hypertension and low baseline kidney function. @*Conclusion@#Serum MIS was independently associated with a rapid decline in kidney function, while serum AhRL was not. The clinical implication of renal hazard on serum MIS requires further evaluation in future studies.

High Serum-Induced AhRL Is Associated with Prevalent Metabolic Syndrome and Future Impairment of Glucose Tolerance in the Elderly

Background@#High circulating levels of dioxins and dioxin-like chemicals, acting via the aryl hydrocarbon receptor (AhR), have previously been linked to diabetes. We now investigated whether the serum AhR ligands (AhRL) were higher in subjects with metabolic syndrome (MetS) and in subjects who had developed a worsened glucose tolerance over time. @*Methods@#Serum AhRL at baseline was measured by a cell-based AhRL activity assay in 70-year-old subjects (n=911) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The main outcome measures were prevalent MetS and worsening of glucose tolerance over 5 years of follow-up. @*Results@#AhRL was significantly elevated in subjects with prevalent MetS as compared to those without MetS, following adjustment for sex, smoking, exercise habits, alcohol intake and educational level (P=0.009). AhRL at baseline was higher in subjects who developed impaired fasting glucose or diabetes at age 75 years than in those who remained normoglycemic (P=0.0081). The odds ratio (OR) of AhRL for worsening glucose tolerance over 5 years was 1.43 (95% confidence interval [CI], 1.13 to 1.81; P=0.003, continuous variables) and 2.81 (95% CI, 1.31 to 6.02; P=0.008, in the highest quartile) adjusted for sex, life style factors, body mass index, and glucose. @*Conclusion@#These findings support a large body of epidemiologic evidence that exposure to AhR transactivating substances, such as dioxins and dioxin-like chemicals, might be involved in the pathogenesis of MetS and diabetes development. Measurement of serum AhRL in humans can be a useful tool in predicting the onset of metabolic disorders.

Effect of Dialysis on Aryl Hydrocarbon Receptor Transactivating Activity in Patients with Chronic Kidney Disease

Protective Effect of Rice Bran Oil against β-Amyloid Protein-Induced Memory Impairment and Neuronal Death in Mice

This study was undertaken to investigate the protective effect of rice bran oil (RBO) on amyloid β protein (Aβ) (25-35)-induced memory impairment and brain damage in an ICR mouse model. Memory impairment was produced by intracerebroventricular microinjection of 15 nmol Aβ (25-35) and assessed using the passive avoidance test. Treatment with RBO at 0.1, 0.5, or 1 mL/kg (p.o. daily for 8 days) protected against Aβ (25-35)-induced memory impairment. Furthermore, Aβ (25-35)-induced decreases in glutathione and increases in lipid peroxidation and cholinesterase activity in brain tissue were inhibited by RBO, and Aβ (25-35)-induced increases of phosphorylated mitogen-activated protein kinases (MAPKs) and inflammatory factors, and changes in the levels of apoptosis-related proteins were significantly inhibited by RBO. Furthermore, Aβ (25-35) suppressed the PI3K/Akt pathway and the phosphorylation of CREB, but increased phosphorylation of tau (ptau) in mice brain; these effects were significantly inhibited by administration of RBO. These results suggest that RBO inhibits Aβ (25-35)-induced memory impairment by inducing anti-apoptotic and anti-inflammatory effects, promoting PI3K/Akt/CREB signaling, and thus, inhibiting p-tau formation.

Surgical Outcomes for Native Valve Endocarditis

Background@#The aim of this study was to evaluate the short-term and long-term results of surgical treatment for native valve endocarditis (NVE) and to investigate the risk factors associated with mortality. @*Methods@#Data including patients’ characteristics, operative findings, postoperative results, and survival indices were retrospectively obtained from Hallym University Sacred Heart Hospital. @*Results@#A total of 29 patients underwent surgery for NVE (affecting the mitral valve in 20 patients and the aortic valve in 9) between 2003 and 2017. During the follow-up period (median, 46.9 months; interquartile range, 19.1–107.0 months), the 5-year survival rate was 77.2%. In logistic regression analysis, body mass index (p=0.031; odds ratio [OR], 0.574; 95% confidence interval [CI], 0.346–0.951), end-stage renal disease (ESRD) (p=0.026; OR, 24.0; 95% CI, 1.459–394.8), and urgent surgery (p=0.010; OR, 34.5; 95% CI, 2.353–505.7) were significantly associated with in-hospital mortality. Based on Cox proportional hazard regression analysis, the statistically significant predictors of long-term outcomes were hypertension, ESRD, and urgent surgery. @*Conclusion@#Surgical treatment for NVE is associated with considerable mortality. The in-hospital mortality and 5-year survival rates of this study were 13.8% and 77.2%, respectively. Underlying conditions, including hypertension and ESRD, and urgent surgery were independent risk factors for unfavorable outcomes.

The Association between Pulmonary Functions and Incident Diabetes: Longitudinal Analysis from the Ansung Cohort in Korea

Background@#We sought to explore whether reduced pulmonary function is an independent risk factor for incident diabetes in Koreans. @*Methods@#We conducted a prospective cohort study of pulmonary function as a risk factor for incident diabetes using 10-year follow-up data from 3,864 middle-aged adults from the Ansung cohort study in Korea. The incidence of diabetes was assessed using both oral glucose tolerance tests and glycosylated hemoglobin levels. @*Results@#During 37,118 person-years of follow-up, 583 participants developed diabetes (incidence rate: 15.7 per 1,000 personyears). The mean follow-up period was 8.0±3.7 years. Forced vital capacity (FVC; % predicted) and forced expiratory volume in 1 second (FEV1; % predicted) were significantly correlated with incident diabetes in a graded manner after adjustment for sex, age, smoking, exercise, and metabolic parameters. The adjusted hazard ratio (HR) and confidence interval (CI) for diabetes were 1.408 (1.106 to 1.792) and 1.469 (1.137 to 1.897) in the first quartiles of FVC and FEV1, respectively, when compared with the highest quartile. Furthermore, the FVC of the lowest first and second quartiles showed a significantly higher 10-year panel homeostasis model assessment of insulin resistance index, with differences of 0.095 (95% CI, 0.010 to 0.018; P=0.028) and 0.127 (95% CI, 0.044 to 0.210; P=0.003), respectively, when compared to the highest quartiles. @*Conclusion@#FVC and FEV1 are independent risk factors for developing diabetes in Koreans. Pulmonary factors are possible risk factors for insulin resistance and diabetes.

Anti-nociceptive and Anti-inflammatory Properties of Ilex latifolia and its Active Component, 3,5-Di-caffeoyl Quinic Acid Methyl Ester

The present study was conducted to investigate anti-nociceptive and anti-inflammatory effects of the leaves of Ilex latifolia Thunb (I. latifolia) in in vivo and in vitro. Writhing responses induced by acetic acid and formalin- and thermal stimuli (tail flick and hot plate tests)-induced pain responses for nociception were evaluated in mice. I. latifolia (50 – 200 mg/kg, p.o.) and ibuprofen (100 mg/kg, p.o.), a positive non-steroidal anti-inflammatory drug (NSAID), inhibited the acetic acid-induced writhing response and the second phase response (peripheral inflammatory response) in the formalin test, but did not protect against thermal nociception and the first phase response (central response) in the formalin test. These results show that I. latifolia has a significant anti-nociceptive effect that appears to be peripheral, but not central. Additionally, I. latifolia (50 and 100 µg/mL) and 3,5-di-caffeoyl quinic acid methyl ester (5 µM) isolated from I. latifolia as an active compound significantly inhibited LPS-induced NO production and mRNA expression of the pro-inflammatory mediators, iNOS and COX-2, and the pro-inflammatory cytokines, IL-6 and IL-1β, in RAW 264.7 macrophages. These results suggest that I. latifolia can produce antinociceptive effects peripherally, but not centrally, via anti-inflammatory activity and supports a possible use of I. latifolia to treat pain and inflammation.

Childhood obesity and endocrine disrupting chemicals

The prevalence of obesity around the world has increased sharply. Strong evidence has emerged over the last decades that human exposure to numerous endocrine disrupting chemicals (EDCs) is the cause of obesity and obesity-related metabolic diseases. Many EDCs are manmade chemicals that are released into the environment. EDCs are exogenous compounds that interfere with hormonal regulation and normal endocrine systems, thereby affecting the health of animals and humans. The number of chemicals belonging to EDCs is increasing and some of them are very stable; they persist in the environment (persistent organic pollutants). Although they are banned, their concentrations have been continuously increasing over time. This review gives a brief introduction to common EDCs, and evidence of harmful effects of EDCs on obesity-related diseases; we focus in particular on EDCs' role in causing mitochondrial dysfunction.

Plasma Glucose Regulation and Mortality in Korea: A Pooled Analysis of Three Community-Based Cohort Studies

BACKGROUND: Although diabetes is a well-known risk factor for death, its impact on cancer death is not clearly understood. Furthermore, it remains controversial whether impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are associated with increased risk of mortality. We investigated the impact of diabetes or glucose tolerance categories on all cause and cause-specific mortality. METHODS: Mortality analysis was conducted in three population-based cohort studies of 3,801 participants, divided according to fasting plasma glucose (FPG) (normal; stage 1 IFG [5.6< or =FPG<6.1 mmol/L]; stage 2 IFG [6.1< or =FPG<7.0 mmol/L]; diabetes mellitus [DM]-FPG); or 2-hour glucose after 75 g glucose loading (2hPG) (normal; IGT; DM-2hPG), or a combination of FPG and 2hPG criteria. RESULTS: During a median follow-up of 11.0 years, 474 subjects died from all causes. Hazard ratios (HRs) for all cause death were higher in those with diabetes as defined by either FPG or 2hPG criteria than their normal counterparts (HR, 2.2, 95% confidence interval [CI], 1.6 to 2.9 for DM-FPG; HR, 2.0, 95% CI, 1.5 to 2.7 for DM-2hPG). Similarly, diabetes defined by either FPG or 2hPG was associated with cancer death (HR, 2.9, 95% CI, 1.7 to 5.0; and HR, 2.1, 95% CI, 1.2 to 3.9, respectively). Although neither IFG nor IGT conferred higher risk for death, when combining stage 2 IFG and/or IGT, the risk of all cause death was higher than in subjects with normal glucose regulation (HR, 1.3; 95% CI, 1.0 to 1.6). CONCLUSION: Diabetes is associated with higher risk of death from all causes and cancer. In subjects without diabetes, stage 2 IFG and/or IGT confers increased risk for mortality.

Identification of a genetic locus on chromosome 4q34-35 for type 2 diabetes with overweight

The incidence of type 2 diabetes is rising rapidly because of an increase in the incidence of being overweight and obesity. Identification of genetic determinants for complex diseases, such as type 2 diabetes, may provide insight into disease pathogenesis. The aim of the study was to investigate the shared genetic factors that predispose individuals to being overweight and developing type 2 diabetes. We conducted genome-wide linkage analyses for type 2 diabetes in 386 affected individuals (269 sibpairs) from 171 Korean families and association analyses with single-nucleotide polymorphisms of candidate genes within linkage regions to identify genetic variants that predispose individuals to being overweight and developing type 2 diabetes. Through fine-mapping analysis of chromosome 4q34-35, we detected a locus potentially linked (nonparametric linkage 2.81, logarithm of odds 2.27, P=6 x 10-4) to type 2 diabetes in overweight or obese individuals (body mass index, BMI> or =23 kg m-2). Multiple regression analysis with type 2 diabetes-related phenotypes revealed a significant association (false discovery rate (FDR) P=0.006 for rs13144140; FDR P=0.002 for rs6830266) between GPM6A (rs13144140) and BMI and waist-hip ratio, and between NEIL3 (rs6830266) and insulin level from 1314 normal individuals. Our systematic search of genome-wide linkage and association studies, demonstrate that a linkage peak for type 2 diabetes on chromosome 4q34-35 contains two type 2 diabetes-related genes, GPM6A and NEIL3.

Comparison of the Outcomes between Axillary and Femoral Artery Cannulation for Acute Type A Aortic Dissection

BACKGROUND: At present, many surgeons prefer axillary artery cannulation because it facilitates antegrade cerebral perfusion and may diminish the risk of cerebral embolization. However, axillary artery cannulation has not been established as a routine procedure because there is controversy about its clinical advantage. MATERIALS AND METHODS: We examined 111 patients diagnosed with acute type A aortic dissection between January 2000 and December 2009. The right axillary artery was cannulated in 58 patients (group A) and the femoral artery was cannulated in 53 (group F). The postoperative outcomes were retrospectively reviewed and compared between the two groups. RESULTS: There were 46 male and 65 female patients with a mean age of 58.9+/-13.1 years (range, 26 to 84 years). The extent of aortic replacement in both groups did not differ. There were 8 early deaths (7.2%) and 2 late deaths (1.8%). The mean follow-up duration was 46.0+/-32.6 months (range, 1 month to 10 years). Transient neurologic dysfunction was observed in 11 patients (19.0%) in group A and 14 patients (26.4%) in group F. A total of 11 patients (9.9%) suffered from a permanent neurologic dysfunction. Early and delayed stroke were observed in 6 patients (10.3%) and 2 patients (3.4%), respectively, in group A as well as 2 patients (3.8%) and 1 patient (1.9%), respectively, in group F. There were no statistical differences in the cannulation-related complications between both groups (3 in group A vs. 0 in group F). CONCLUSION: There were no differences in postoperative neurologic outcomes and cannulation-related complications according to the cannulation sites. The cannulation site in an aortic dissection should be carefully chosen on a case-by-case basis. It is important to also pay attention to the possibility of intraoperative malperfusion syndrome occurring and the subsequent need to change the cannulation site.

Descending Thoracic Aorta to Bilateral Femoral Artery Bypass in a Hostile Abdomen

Descending thoracic aorta to femoral artery bypass has been used as a remedial operation after aortic or axillofemoral graft failure or graft infection and other intra-abdominal pathologies not amenable to standard aortofemoral revascularization. It can avoid abdomen approach and has been known as a durable procedure with excellent long-term patency. We reported descending thoracic aorta to femoral artery bypass grafting for primary revascularization in a 55-year-old male with hostile abdominal conditions.

Comparing 18F-Fluorodeoxyglucose Positron Emission Tomography and Video-assisted Thoracoscopic Surgery in the Evaluation of Small Pulmonary Nodules in Patients with a History of Malignancy

BACKGROUND: The aims of the study were to determine the accuracy of fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting pulmonary metastasis through video-assisted thoracoscopic surgery (VATS), a technique that allows the excisional biopsy of small pulmonary nodules in patients with known malignancies. MATERIALS AND METHODS: Between October 2007 and April 2010, 28 patients with known malignancies and small pulmonary nodules underwent VATS excisional biopsies. All patients were in follow-up for a previously treated malignancy. The malignancies included the following: colorectum (9), breast (6), head and neck (5), stomach (3), lymph (1), ovary (1), uterus (1), bladder (1), and liver (1). RESULTS: There were 16 men and 12 women whose mean age was 56.7 years old (range, 38 to 77 years). The sizes of the mean nodules removed were 11.3 mm (range, 7 to 21 mm). Diagnoses included metastatic (11), bronchioloalveolar carcinoma (1), primary adenocarcinoma (1), pulmonary tuberculosis (6), fibrosis (5), organizing pneumonia (3), lymphoid hyperplasia (1). Among these lesions, 46.4% were malignant. CONCLUSION: True positive FDG-PET was 39.2%. FDG-PET is not a sensitive test in the evaluation of patients with a history of an extrathoracic malignancy and newly diagnosed small pulmonary nodules. VATS excision allows the early diagnosis of small pulmonary nodules, with low morbidity, in patients with known malignancies.

Prevalence and Clinical Characteristics of Recently Diagnosed Type 2 Diabetes Patients with Positive Anti-Glutamic Acid Decarboxylase Antibody

BACKGROUND: Latent autoimmune diabetes in adults (LADA) refers to a specific type of diabetes characterized by adult onset, presence of islet auto-antibodies, insulin independence at the time of diagnosis, and rapid decline in beta-cell function. The prevalence of LADA among patients with type 2 diabetes varies from 2% to 20% according to the study population. Since most studies on the prevalence of LADA performed in Korea were conducted in patients who had been tested for anti-glutamic acid decarboxylase antibody (GADAb), a selection bias could not be excluded. In this study, we examined the prevalence and clinical characteristics of LADA among adult patients recently diagnosed with type 2 diabetes. METHODS: We included 462 patients who were diagnosed with type 2 diabetes within 5 years from the time this study was performed. We measured GADAb, fasting insulin level, fasting C-peptide level, fasting plasma glucose level, HbA1c, and serum lipid profiles and collected data on clinical characteristics. RESULTS: The prevalence of LADA was 4.3% (20/462) among adult patients with newly diagnosed type 2 diabetes. Compared with the GADAb-negative patients, the GADAb-positive patients had lower fasting C-peptide levels (1.2+/-0.8 ng/mL vs. 2.0+/-1.2 ng/mL, P=0.004). Other metabolic features were not significantly different between the two groups. CONCLUSION: The prevalence of LADA is 4.3% among Korean adult patients with recently diagnosed type 2 diabetes. The Korean LADA patients exhibited decreased insulin secretory capacity as reflected by lower C-peptide levels.

Fracture Incidence and Risk of Osteoporosis in Female Type 2 Diabetic Patients in Korea

BACKGROUND: There are no published data regarding fracture risk in type 2 diabetic patients in Korea. In this study, we compared the fracture incidence and risk of osteoporosis of type 2 diabetic female patients with those in a non-diabetic hypertensive cohort. METHODS: The incidence of fracture in a type 2 diabetic cohort was compared with that in a non-diabetic hypertensive cohort over the course of 7 years. Female type 2 diabetic and non-diabetic hypertensive patients who visited Eulji General Hospital outpatient clinic from January 2004 to April 2004 were assigned to the diabetic cohort and the non-diabetic hypertensive cohort, respectively. Surveys on fracture event, use of anti-osteoporosis medications, and bone mineral density were performed. RESULTS: The number of fractures was 88 in the female diabetic cohort (n=1,268, 60.6+/-11.5 years) and 57 in the female non-diabetic hypertensive cohort (n=1,014, 61.4+/-11.7 years). The RR in the diabetic cohort was 1.38 (P=0.064; 95% confidence interval [CI], 0.98 to 1.94) when adjusted for age. Diabetic patients with microvascular complications (61.0%) showed a higher RR of 1.81 (P=0.014; 95% CI, 1.13 to 2.92) compared with those without these complications. The prevalence of osteoporosis was comparable between the groups, while use of anti-osteoporosis medication was more common in the diabetic cohort (12.8%) than in the hypertensive cohort (4.5%) (P<0.001). CONCLUSION: In our study, a higher fracture risk was observed in female type 2 diabetics with microvascular complications. Special concern for this risk group is warranted.

Mitochondrial Dysfunction and Insulin Resistance: The Contribution of Dioxin-Like Substances

Persistent organic pollutants (POPs) are known to cause mitochondrial dysfunction and this in turn is linked to insulin resistance, a key biochemical abnormality underlying the metabolic syndrome. To establish the cause and effect relationship between exposure to POPs and the development of the metabolic syndrome, Koch's postulates were considered. Problems arising from this approach were discussed and possible solutions were suggested. In particular, the difficulty of establishing a cause and effect relationship due to the vagueness of the metabolic syndrome as a disease entity was discussed. Recently a bioassay, aryl-hydrocarbon receptor (AhR) trans-activation activity using a cell line expressing AhR-luciferase, showed that its activity is linearly related with the parameters of the metabolic syndrome in a population. This finding suggests the possible role of bioassays in the analysis of multiple pollutants of similar kinds in the pathogenesis of several closely related diseases, such as type 2 diabetes and the metabolic syndrome. Understanding the effects of POPs on mitochondrial function will be very useful in understanding the integration of various factors involved in this process, such as genes, fetal malnutrition and environmental toxins and their protectors, as mitochondria act as a unit according to the metabolic scaling law.