Association of sodium-glucose cotransporter 2 inhibitor use with risk of osteoporotic fracture among older women: A nationwide, population-based cohort study.

INTRODUCTION: We investigated the relationship between sodium-glucose cotransporter-2 inhibitor (SGLT2i) and fracture in elderly women diagnosed with type 2 diabetes mellitus (T2DM) and newly prescribed antidiabetic medications (ADMs). MATERIAL AND METHODS: We used the population-based cohort study data from the National Health Insurance Service of Korea (2013-2020). Women ≥65 years old with T2DM, who were newly prescribed ADMs other than glucagon-like peptide-1 receptor agonists and thiazolidinedione, and who had comprehensive health check-up data were included. RESULTS: A total of 1,333 SGLT2i users were matched in a 1:2 ratio with 2,626 non-SGLT2i users. After propensity score matching, mean age, body mass index, number of ADMs, and other covariates were well-balanced between SGLT2i users and non-SGLT2i users. During the follow-up period, a higher incidence of vertebral fractures in SGLT2i users than in non-SGLT2i users (incidence rate 19.2 vs. 13.8 per 1,000 person-years; hazard ratio 1.40, 95 % confidence interval 1.00-1.96, p = 0.049). No significant difference was noted in other types of fracture. CONCLUSION: SGLT2i use showed an increased risk of vertebral fracture than non-SGLT2i use in elderly women. Although further validation is required, SGLT2i should be cautiously prescribed in older women due to the potential association with fracture risk.

Association of Muscle Mass Loss with Diabetes Development in Liver Transplantation Recipients.

BACKGRUOUND: Post-transplant diabetes mellitus (PTDM) is one of the most significant complications after transplantation. Patients with end-stage liver diseases requiring transplantation are prone to sarcopenia, but the association between sarcopenia and PTDM remains to be elucidated. We aimed to investigate the effect of postoperative muscle mass loss on PTDM development. METHODS: A total of 500 patients who underwent liver transplantation at a tertiary care hospital between 2005 and 2020 were included. Skeletal muscle area at the level of the L3-L5 vertebrae was measured using computed tomography scans performed before and 1 year after the transplantation. The associations between the change in the muscle area after the transplantation and the incidence of PTDM was investigated using a Cox proportional hazard model. RESULTS: During the follow-up period (median, 4.9 years), PTDM occurred in 165 patients (33%). The muscle mass loss was greater in patients who developed PTDM than in those without PTDM. Muscle depletion significantly increased risk of developing PTDM after adjustment for other confounding factors (hazard ratio, 1.50; 95% confidence interval, 1.23 to 1.84; P=0.001). Of the 357 subjects who had muscle mass loss, 124 (34.7%) developed PTDM, whereas of the 143 patients in the muscle mass maintenance group, 41 (28.7%) developed PTDM. The cumulative incidence of PTDM was significantly higher in patients with muscle loss than in patients without muscle loss (P=0.034). CONCLUSION: Muscle depletion after liver transplantation is associated with increased risk of PTDM development.

A post hoc comparative real-world analysis of HEAD-US score for joint health assessment of patients with severe haemophilia A and B in Spain.

AIM: Joint damage due to haemarthrosis can be effectively monitored with point-of care ultrasound using the Haemophilia Early Arthropathy Detection with US (HEAD-US) scoring system. A post hoc comparative analysis of the joint status of patients with severe haemophilia A (HA) or B (HB) was performed. METHODS: The databases of two observational, cross-sectional studies that recruited patients with HA or HB from 12 Spanish centres were analysed to compare the status of the elbows, knees and ankles in patients with severe disease according to treatment modality. The HEAD-US score was calculated in both studies by the same trained operators. RESULTS: Overall, 95 HA and 41 HB severe patients were included, with a mean age of 35.2 ± 11.8 and 32.7 ± 14.2 years, respectively. The percentage of patients who received prophylaxis, over on-demand (OD) treatment, was much higher in HA (91.6%) than in HB (65.8%) patients. With a similar number of target joints, the HEAD-US score was zero in 6.3% HA and 22.0% HB patients (p < .01), respectively. The HA population showed significantly worse HEAD-US scores. Whilst osteochondral damage occurred more frequently in patients OD or tertiary prophylaxis, our data suggest that articular damage is less prominent in primary/secondary prophylaxis, regardless of the type of haemophilia. These latter treatment modalities were also associated with a lower prevalence of synovial hypertrophy, particularly in HB patients. CONCLUSION: This post hoc analysis indicates that joint status seems to be significantly influenced by haemophilia type (HA or HB) and treatment modality in these severe Spanish populations with severe disease. Continuing HEAD-US monitoring for the early detection and management of intra-articular abnormalities, as well as more efficiently tailored therapies should be warranted.

Renal Tubular Damage Marker, Urinary N-acetyl-ß-D-Glucosaminidase, as a Predictive Marker of Hepatic Fibrosis in Type 2 Diabetes Mellitus.

BACKGROUND: Non-alcoholic steatohepatitis is closely associated with the progression of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). We investigated whether urinary N-acetyl-ß-D-glucosaminidase (u-NAG), an early renal tubular damage biomarker in DKD, could be related to the degree of hepatic fibrosis in patients with T2DM. METHODS: A total of 300 patients with T2DM were enrolled in this study. Hepatic steatosis and fibrosis were determined using transient elastography. The levels of urinary biomarkers, including u-NAG, albumin, protein, and creatinine, and glucometabolic parameters were measured. RESULTS: Based on the median value of the u-NAG to creatinine ratio (u-NCR), subjects were divided into low and high u-NCR groups. The high u-NCR group showed a significantly longer duration of diabetes, worsened hyperglycemia, and a more enhanced hepatic fibrosis index. A higher u-NCR was associated with a greater odds ratio for the risk of higher hepatic fibrosis stage (F2: odds ratio, 1.99; 95% confidence interval [CI], 1.04 to 3.82). Also, u-NCR was an independent predictive marker for more advanced hepatic fibrosis, even after adjusting for several confounding factors (ß=1.58, P<0.01). CONCLUSION: The elevation of u-NAG was independently associated with a higher degree of hepatic fibrosis in patients with T2DM. Considering the common metabolic milieu of renal and hepatic fibrosis in T2DM, the potential use of u-NAG as an effective urinary biomarker reflecting hepatic fibrosis in T2DM needs to be validated in the future.

Uric Acid Variability as a Predictive Marker of Newly Developed Cardiovascular Events in Type 2 Diabetes.

Background: Cardiovascular disease (CVD) is associated with morbidity and mortality in patients with type 2 diabetes mellitus (T2D). However, the role of serum uric acid as a risk factor for developing cardiovascular disease is controversial. This study investigated whether uric acid variability was associated with new-onset symptomatic CVD in patients with T2D, requiring percutaneous coronary intervention. Methods: A total of 1,071 patients were enrolled in this retrospective cross-sectional study after propensity score matching. Patients with T2D and new-onset symptomatic CVD who received percutaneous coronary intervention for the first time, and with at least three consecutive 6-monthly measurements of serum uric acid were recruited from Severance Hospital between January 2015 and December 2019. Uric acid variability was measured by average successive variability (ASV) and analyzed to evaluate a possible correlation with the risk of developing CVD. Results: The patients were divided into quartiles based on the uric acid variability. Patients in the highest quartile were older and presented lower renal function and a higher mortality from CVD. There was a linear association between a high uric acid variability and the development of CVD. Compared to the lowest quartile, patients in the higher quartiles had a higher risk of CVD [quartile 3: adjusted odds ratio (aOR) = 1.76; 95% confidence interval (CI), 1.20-2.82; P = 0.019; quartile 4 aOR = 2.89; 95% CI, 1.74-4.80; P < 0.001]. Conclusion: High uric acid variability is independently associated with an increased risk of new-onset symptomatic CVD requiring percutaneous coronary intervention in patients with T2D. Thus, maintaining serum uric acid in a narrow range by prescribing effective medications is essential to prevent new-onset CVD in patients with T2D. Nonetheless, the potential use of uric acid variability as a predictive marker of CVD in patients with T2D needs further validation.

Efficacy and Cerebrospinal Fluid Rhinorrhea after Cabergoline Treatment in Patients with Bioactive Macroprolactinoma.

Predicting dopamine agonist resistance in patients with macroprolactinoma is essential for clinicians to prevent treatment failure and subsequent complications such as medication-induced cerebrospinal fluid (CSF) rhinorrhea. We evaluated the features of patients with cabergoline resistance and CSF rhinorrhea in patients with prolactinomas with prolactin levels ≥1000 ng/mL. A total of 140 patients who were newly diagnosed with prolactinoma secreting only prolactin ≥1000 ng/mL and treated with cabergoline for the first time were included in this study. Based on the hormonal and radiologic response of the prolactinoma, the patients were divided into responders and non-responders. Non-responders (36/140, 25.8%) included a higher number of patients receiving hormone replacement than responders (responders, n (%) = 12(11.5) vs. non-responders = 13(36.1), p = 0.001). In propensity score matching analysis, patients who developed CSF rhinorrhea presented more frequent hormone deficiency than responders regardless of initial cabergoline dose. Hormone deficiency was associated with a greater odds ratio for the risk of non-responders (adjusted odds ratio = 5.13, 95% CI 1.96-13.46, p = 0.001). Cabergoline was effective in bioactive macroprolactinoma. Furthermore, initial cabergoline dose was not significantly associated with long-term responsiveness and development of CSF rhinorrhea but the hypopituitarism was independently associated with an increased risk of cabergoline resistance and CSF rhinorrhea.

Effects of social prescribing pilot project for the elderly in rural area of South Korea during COVID-19 pandemic.

BACKGROUND: Older adults-classified as a high-risk group-are highly likely to experience increased loneliness due to the implementation of various policies designed to prevent the spread of COVID-19. Accordingly, this study aims to examine the effects of a pilot social prescribing project for elderly people in rural area of South Korea during the COVID-19 pandemic. METHODS: Using the PRECEDE-PROCEED model, the effectiveness of the pilot project was verified through pre- and post-impact and outcome evaluation. RESULTS: According to the results of the impact evaluation, loneliness reduced significantly, while the social participation attitude score increased. Although the average score of self-efficacy increased, it was not statistically significant. Moreover, it was found that self-esteem increased significantly. In the outcome evaluation, depression reduced considerably. CONCLUSION: To conclude, the pilot social prescribing project was effective in reducing depression and loneliness for the elderly in rural areas of Korea. It was also confirmed that there is potential to develop a new health promotion project that can improve the self-esteem of the elderly, and expand their social activities. Second, the pilot project was carried out in an integrated manner by utilizing resources in communities with good accessibility. Therefore, it is expected to be used as a new "Integrated community care model" to improve the mental health of the elderly in rural areas. Third, during the COVID-19 pandemic, the elderly tend to experience increasing feelings of depression, isolation, and loneliness due to "social distancing." Therefore, it is expected that social prescribing programs for the elderly in rural areas would become a new alternative for relieve mental disorder of the seniors.

Ultrasound evaluation of joint damage and disease activity in adult patients with severe haemophilia A using the HEAD-US system.

INTRODUCTION: The Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) system and scoring scale has proven to be an accurate and time-efficient imaging method for identifying joint damage in patients with haemophilia. AIM: Observational, multicentre, cross-sectional study conducted in 8 centres in Spain that assessed the joint status of adult patients with severe haemophilia A (SHA) using HEAD-US. METHODS: Joint status of the elbow, knee and ankle was evaluated in adults with SHA receiving on-demand (OD) treatment, or primary (PP), secondary (SP), tertiary (TP) or intermittent (IP) prophylaxis. RESULTS: Of the 95 patients enrolled, 87 received prophylaxis (6.3% PP, 38.9% SP, 43.2% TP and 3.2% IP). Mean age was 35.2 years, and 59% of patients had not undergone image testing in the last year. The HEAD-US score was 0 in all joints in 6.3% of patients. The ankle was the most affected joint, regardless of treatment regimen. Patients receiving OD treatment, TP or IP had the overall worst scores, mainly in the ankles and elbows; a similar but milder profile was observed in patients on SP; and patients on PP had the best score in all joints. CONCLUSION: Joint function may be effectively preserved in patients with SHA on PP, but OD treatment or later initiation of prophylaxis does not seem to prevent progression of arthropathy. Disease worsening was observed in patients OD, TP or IP, most often affecting ankles and elbows. Closer ultrasound imaging monitoring may improve management of these patients.

Cost of patients with hemophilia A treated with standard half-life or extended half-life FVIII in Spain.

BACKGROUND: In a real-world analysis (RWA) conducted in the United States (US), median international units (IUs) of extended half-life (EHL) recombinant coagulation factor VIII (rFVIII) dispensed were 10% to 45% greater than standard half-life (SHL) rFVIII. The mean IUs of each rFVIII dispensed quarterly were obtained from two databases (N = 776). METHODS: A probabilistic model in a 1-year time horizon was used in order to analyze the cost comparison of SHL and EHL rFVIII products in Spain. In this analysis, mean IUs were those of the RWA, and frequency of use and prices for each rFVIII were obtained from sales estimates based on Spanish sources (IQVIA; €, 2019). RESULTS: Data showed an average annual savings per patient of €11,227 for SHL rFVIII versus EHL rFVIII products, with a savings probability of 75.5%. The results were stable in the sensitivity analyses. Not switching treatment from SHL to EHL rFVIII resulted in greater savings per patient (€53,078), with a savings probability of 99.9%. Considering the frequency of rFVIII dispensation in the US, annual savings per patient would increase to €16,350 in Spain, with a savings probability of 79.9%. CONCLUSIONS: According to this model, use of SHL rFVIII versus EHL rFVIII products could lead to savings for the Spanish National Health System.

Data Configuration and Publication Trends for the Korean National Health Insurance and Health Insurance Review & Assessment Database.

Background: Big data reports related to diseases and health care for the Korean population have been published since the National Health Insurance Service (NHIS) and the Health Insurance Review & Assessment (HIRA) Service provided limited open access to their databases. Here, we reviewed the structure, content, and means of using data from the National Health Insurance (NHI) system for the benefit of Korean researchers and presented the latest publication trends in Korean healthcare data procured from the NHI and HIRA databases. METHODS: Since 2013, researchers have been able to obtain nationwide population-based studies using the NHI and HIRA databases of the insured. We searched publications using the NHI and the HIRA databases between 2013 and 2019 retrieved from PubMed. RESULTS: The NHI and HIRA databases provide nationwide population-based data. The total number of publications from 2014 to 2019 using NHI and HIRA databases is 2,541 and 655, respectively. A total of 5,465 endocrinology-related studies were performed during 2014 to 2019. CONCLUSION: The NHIS and HIRA databases have provided tools for guidelines to approach world-leading population-based epidemiology and disease research.

Association between Serum Gamma-Glutamyltransferase and Prevalence of Metabolic Syndrome Using Data from the Korean Genome and Epidemiology Study.

BACKGROUND: The aim of this study was to determine whether there is a positive correlation between gamma-glutamyltransferase (GGT) levels and the prevalence of metabolic syndrome and whether GGT can be used as an easily checkable metabolic index using data from the large-scale Korean Genome and Epidemiology Study (KoGES). METHODS: We obtained data of 211,725 participants of the KoGES. The collected data included age, sex, height, weight, waist circumference, and various biochemical characteristics, including serum GGT levels. The data of study participants who ingested more than 40 g/day of alcohol and who were diagnosed with metabolic syndrome at baseline was excluded. We analyzed the prevalence of metabolic syndrome according to GGT quartiles in both genders. RESULTS: The GGT level was significantly higher in subjects with metabolic syndrome compared to normal subjects (37.92±48.20 mg/dL vs. 25.62±33.56 mg/dL). The prevalence of metabolic syndrome showed a stepwise increase with GGT quartiles in both male and female subjects. Compared to the lowest GGT quartile, the odds ratio was 1.534 (95% confidence interval [CI], 1.432 to 1.643), 1.939 (95% CI, 1.811 to 2.076), and 2.754 (95% CI, 2.572 to 2.948) in men and 1.155 (95% CI, 1.094 to 1.218), 1.528 (95% CI, 1.451 to 1.609), and 2.022 (95% CI, 1.921 to 2.218) in women with increasing GGT quartile. The cutoff value of GGT predicting risk of metabolic syndrome was 27 IU/L in men and 17 IU/L in women. CONCLUSION: We suggested that GGT could be an easily checkable marker for the prediction of metabolic syndrome.

Manufacture and characterization of optimized red ginseng drinks containing herbal medicine extracts.

The optimum mixing ratio of red ginseng, herbal medicine extracts, and oligosaccharides for diabetic improvement was investigated and verified through animal experiments. Using the optimum mixing technique, 2% red ginseng extract, 15% oligosaccharides, and 83% herbal medicine extracts were determined to be optimal for red ginseng beverages. The taste was improved as the amount of red ginseng decreased and oligosaccharides increased, whereas antioxidative activity was increased with increased red ginseng. In the animal model in which streptozotocin was administered to BALB-c mice, the red ginseng administration group exhibited lower blood glucose than the diabetic control group, and the blood glucose level was lower in the herbal medicine and red ginseng extract administration group. Insulin concentration was slightly increased by the red ginseng beverage, and hepatotoxicity due to excessive intake of red ginseng beverages was not detected.

[Characteristics Influencing the Occurrence of Respiratory Medical Device-related Pressure Ulcers in the Pediatric Intensive Care Unit]. / 소아중환자실 환아의 호흡기계 의료장치 ê´€ë ¨ 욕창 발생 ê´€ë ¨ 특성.

PURPOSE: This prospective study was conducted to determine the incidence and related characteristics of respiratory medical device-related pressure ulcers (MDRPU) in children admitted to a pediatric intensive care unit (PICU). METHODS: The participants were 184 children who were admitted to the PICU of P University Hospital from April 2016 to January 2017. Data were collected on the occurrence of respiratory MDRPU and characteristics regarding the application of respiratory medical devices. RESULTS: Respiratory MDRPU occurred in 11.9% of participants (58.3%: stage I ulcers, 37.5%: mucosal ulcers). The devices associated with respiratory MDRPU were endotracheal tubes (54.2%), high-flow nasal cannulas (37.5%), and oximetry probes (8.3%). Respiratory MDRPU associated with an endotracheal tube were significant differences according to the site and strength of fixation, the use of a bite block and adhesive tape, skin dryness, and edema. In high-flow nasal cannulas, significant differences were found according to the site of fixation, immobility after fixation, and skin dryness. CONCLUSION: The occurrence of respiratory MDRPU is significantly affected by the method and strength of fixation, as well as skin dryness and edema. Therefore, appropriate consideration of these factors in nursing care can help prevent respiratory MDRPU.

Joint status in Spanish haemophilia B patients assessed using the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score.

AIM: The use of musculoskeletal ultrasound (MSK-US) following protocols for haemophilic arthropathy and the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score can help standardize monitoring in haemophilia. This study evaluated the joint status (elbows, knees and ankles) of patients with haemophilia B (HB) in Spain using MSK-US and the HEAD-US score. METHODS: Haemophilia B patients ≥14 years old were included in this observational, multicentre, cross-sectional study, regardless of their clinical condition, HB severity and treatment received. Two blinded observers were involved in image acquisition and scoring in each centre. RESULTS: Eighty-two patients from 12 centres were enrolled: 27% mild HB, 23% moderate, 50% severe HB. Mean age was 38.9 ± 16.4 years, 60% were treated on demand (OD) and 40% were on prophylaxis. HEAD-US was zero in all joints in 28.6% OD patients and 36.4% on prophylaxis. Mean scores significantly worsened with HB severity, except for the left knee. Patients on primary and secondary prophylaxis had significantly better joint health vs OD patients in all joints, except the right ankle. Among OD patients, those with severe disease presented significantly worse scores in all HEAD-US items related to permanent damage. CONCLUSION: Joint status of HB patients in Spain is influenced by severity and treatment modality, related to the development of arthropathy, which appears prevalent in OD patients with severe HB. Routine assessment with an imaging tool such as ultrasound and HEAD-US system may help to improve joint health by personalizing and adjusting treatment in this population.

Long-Term Experience of Sperm Cryopreservation in Cancer Patients in a Single Fertility Center.

PURPOSE: Sperm cryopreservation before cancer treatment is the most effective method to preserve the fertility of male patients. We present our 21 years experience with sperm cryopreservation for cancer patients, including an examination of semen quality, the current status of cryopreserved sperm, and the rate of sperm use for assisted reproductive technology (ART). MATERIALS AND METHODS: A total of 721 cancer patients at Fertility Center of CHA Gangnam Medical Center successfully performed sperm cryopreservation for fertility preservation from January 1996 to December 2016. Medical chart review was used to analyze patient age, marital status, cancer type, semen volume, sperm counts and motility, length of storage, and current banking status. RESULTS: The major cancers of the 721 patients were leukemia (28.4%), lymphoma (18.3%), testis cancer (10.0%). The mean age at cryopreservation was 27.0 years, and 111 patients (15.4%) performed sperm cryopreservation during or after cancer treatment. The mean sperm concentration was 66.7±66.3 ×106/mL and the mean sperm motility was 33.8%±16.3%. During median follow-up duration of 75 months (range, 1-226 months), 44 patients (6.1%) used their banked sperm at our fertility center for ART and 9 patients (1.2%) transferred their banked sperm to another center. The median duration from cryopreservation to use was 51 months (range, 1-158 months). CONCLUSIONS: Sperm cryopreservation before gonadotoxic treatment is the most reliable method to preserve the fertility of male cancer patients. Sperm cryopreservation should be offered as a standard of care for all men planning cancer therapy.

Factor VIII delivery devices in haemophilia A. Barriers and drivers for treatment adherence.

INTRODUCTION AND OBJECTIVE: To capture the experience of haemophilia A patients with their devices for coagulation factor reconstitution, the barriers for treatment adherence; and to determine their preferences, presenting a new double-chamber syringe (DCS). METHOD: A cross-sectional research through a supervised survey and a DCS testing session. RESULTS: Seventy-four (74) patients participated, 50% of them on prophylaxis treatment, and 7 years (median) with their usual treatment (IQR 17.25). In the survey, the DCS received the highest score (75/100, p < 0.001) and it was the most likely to be used in prophylactic treatment (p < 0.001). In the practical testing session (n = 29), 62.1% preferred the DCS, and required 43 seconds as median time (24.5-82) for preparation, vs. 4 minutes (1-15) with their usual treatment (p < 0.001). The favourable opinion of their doctor regarding prophylaxis was very influential on the attitude of participants towards treatment adherence (OR = 1.324, CI 95% = 1.040-1.685, p = 0.023). CONCLUSIONS: The DCS was the preferred device, and was likely to encourage prophylaxis.

Introducción y objetivo: Recabar la experiencia de pacientes con hemofilia A con sus dispositivos de reconstitucion de factor de coagulacion, barreras para la adherencia y determinar sus preferencias, presentando una nueva jeringa de doble camara (JDC). Método: Investigacion transversal mediante encuesta dirigida y sesion de prueba de la JDC. Resultados: Participaron 74 pacientes, el 50% en tratamiento con profilaxis, y 7 anos (mediana) con su tratamiento habitual (RIC 17,25). En la encuesta, la JDC recibio la mayor puntuacion (75/100, p < 0,001) y la mayor probabilidad de uso en profilaxis (p < 0,001). En la sesion practica (n = 29), el 62,1% prefirio la JDC y necesitaron de mediana 43 segundos (24,5-82) para la preparacion, vs. 4 minutos (1-15) con el tratamiento habitual (p < 0,001). La opinion favorable del medico respecto a la profilaxis resulto muy influyente en la actitud de los participantes hacia la adherencia (OR = 1,324, IC 95% = 1,040-1,685, p = 0,023). Conclusiones: La JDC fue el dispositivo preferido y se mostro con probabilidad de favorecer la profilaxis.

Cytoplasmic phospholipase A2 metabolites play a critical role in pulmonary tumor metastasis in mice.

BACKGROUND: Cytoplasmic PLA(2) (cPLA2) has been shown to be the major enzyme responsible for arachidonic acid (AA) release. Because of this key role of cPLA(2) in AA production, cPLA(2) involvement in tumorigenesis has been suggested. However, contradictory data are found in the literature. Additionally, little is known regarding the role of cPLA(2) in pulmonary tumor metastasis. MATERIALS AND METHODS: Tumor metastases were detected by lung colonization and angiogenesis was assayed as growth of blood vessels from subcutaneous tissue into an implanted matrigel of basement membrane. The matrix metalloproteinases (MMP)-2, and MMP-9 were detected by PCR with sequence-specific primers. RESULTS: In this study, the effects of inhibitors of cPLA2, 5-lipoxygenase (5-LO), and cyclooxygenase (COX)-2 on pulmonary metastasis formation by B16F10 melanoma cells were investigated. All of these inhibitors reduced B16F10 pulmonary metastasis formation in a dose-dependent manner. Importantly, cPLA2, and 5-LO, and COX-2 inhibitors reduced platelet-activating factor-induced angiogenesis in an in vivo mouse model employing Matrigel injected subcutaneously, and also reduced expression of MMP-2 and MMP-9 in the lungs. CONCLUSION: This study demonstrates that cPLA(2) metabolites play critical roles in tumor metastasis via the promotion, at least in part, of angiogenesis and MMP expression.

Measuring adriamycin-induced cardiac hemodynamic dysfunction with a proteomics approach.

Adriamycin is a potent antitumor drug that causes severe cardiotoxicity. However, the toxic mechanisms are not clear. We used a proteomics approach to analyze changes in protein profiles after adriamycin-induced changes in hemodynamic factors. Although adriamycin itself did not affect left ventricular developed pressure (LVDP) or left ventricular end diastolic pressure (LVEDP), the drug did enhance susceptibility to ischemia-reperfusion-induced changes in LVDP, LVEDP and heart rate. Adriamycin altered the expression of 52 proteins, primarily energy metabolism and cytoskeleton proteins. Adriamycin decreased the expression of the metabolism-related proteins, ATP synthase, Sdha protein, Triose phosphate isomerase 1 (TPI-1), pyruvate dehydrogenase E1 alpha1, 6-phosphofructokinase, and fructose-1,6-bisphosphatase, as did cytoskeletal proteins, such as actin. Alterations in energy metabolism and subsequent free radical production may affect cytoskeletal protein expression, producing adriamycin-induced changes in cardiac hemodynamics.