Hyaluronic Acid/Parecoxib-Loaded PLGA Microspheres for Therapy of Temporomandibular Disorders.

OBJECTIVE: This study aimed to fabricate Hyaluronic Acid (HA)/parecoxib-loaded PLGA microspheres for the treatment of Temporomandibular Disorders (TMD) and investigate the in vitro and in vivo effect of the microsphere system to solve the issues of poor drug delivery and short duration on drug concentration in conventional TMD therapy. METHODS: The microspheres were prepared by the double emulsion (w/o/w) method. Various formulations were compared in terms of particle size, drug loading rate and encapsulation rate. Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC) and FT-IR spectroscopy were performed to evaluate physicochemical properties. The drug release behavior of microspheres and toxicity assay on synovial cells were investigated. The in vitro anti-inflammatory effect on inflammatory markers, such as IL-1ß, TNF-α and COX-2, was assessed by real-time PCR. Then, the in vivo therapeutic effect of microspheres was investigated using mechanically-induced rat synovitis model. Protein levels of inflammatory cytokines (IL-1ß, TNF-α and COX-2) from TMJ periarticular tissues were quantified by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: The results showed that microspheres were morphologically regular, smooth and non-cohesive. The average particle size of the microspheres was (25.32 ± 1.01) µm. The drug loading rate of parecoxib was 17.12%-20.95% with encapsulation efficiency reaching 51.9%-54.7%. In vitro drug release tests showed a successful sustained release over 28 days with a burst of 19.98% of the total drug substance. Treatment with HA/parecoxib-loaded PLGA microspheres declined the mRNA expression of IL-1ß, TNF-α and COX-2 induced by LPS in articular synovial cells. Moreover, in vivo results demonstrated that the intra-articular microspheres significantly reduced protein levels of inflammatory cytokines (IL-1ß, TNF-α and COX-2) for more than two weeks and stopped the mechanically-induced synovitis in its tracks in rat models. CONCLUSION: The study presented new and potential insights into treatments of TMD using PLGA microspheres loaded with HA and parecoxib as a successful drug delivery system.

Independent effect of depression and anxiety on chronic obstructive pulmonary disease exacerbations and hospitalizations.

RATIONALE: Depression and anxiety are significant comorbid and potentially modifiable conditions in chronic obstructive pulmonary disease (COPD), but their effects on exacerbations are not clear. OBJECTIVES: To investigate the independent effect of depression and anxiety on the risk of COPD exacerbations and hospitalizations. METHODS: A multicenter prospective cohort study in 491 patients with stable COPD in China. Multivariate Poisson and linear regression analyses were used, respectively, to estimate adjusted incidence rate ratios (IRRs) and adjusted effects on duration of events. MEASUREMENTS AND MAIN RESULTS: Depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS) at baseline. Other measurements included sociodemographic, clinical, psychosocial, and treatment characteristics. Patients were then monitored monthly for 12 months to document the occurrence and characteristics of COPD exacerbations and hospitalizations. Exacerbation was determined using both symptom-based (worsening of > or =1 key symptom) and event-based definitions (> or =1 symptom worsening plus > or =1 change in regular medications). A total of 876 symptom-based and 450 event-based exacerbations were recorded, among which 183 led to hospitalization. Probable depression (HADS depression score > or = 11) was associated with an increased risk of symptom-based exacerbations (adjusted IRR, 1.51; 95% confidence interval [CI], 1.01-2.24), event-based exacerbations (adjusted IRR, 1.56; 95% CI, 1.02-2.40), and hospitalization (adjusted IRR, 1.72; 95% CI, 1.04-2.85) compared with nondepression (score < or = 7). The duration of event-based exacerbations was 1.92 (1.04-3.54) times longer for patients with probable anxiety (HADS anxiety score > or = 11) than those with no anxiety (score < or = 7). CONCLUSIONS: This study suggests a possible causal effect of depression on COPD exacerbations and hospitalizations. Further studies are warranted to confirm this finding and to test the effectiveness of antidepressants and psychotherapies on reducing exacerbations and improving health resource utilizations.

A Long-term Safety Study of Latanoprost in Pediatric Patients With Glaucoma and Ocular Hypertension: A Prospective Cohort Study.

PURPOSE: The objective was to assess the long-term effect of treatment with latanoprost on ocular development and safety in pediatric patients with glaucoma and ocular hypertension. DESIGN: Prospective cohort study. METHODS: This was a prospective 3-year cohort study conducted in 14 countries in Europe and South America. Patients aged < 18 years with glaucoma or ocular hypertension were enrolled into either the latanoprost or non-prostaglandin (non-PG) group in this observational study. The primary endpoint was change in best-corrected visual acuity (BCVA) from baseline to 3 years. Several secondary endpoints were evaluated, including corneal thickness and ocular hyperpigmentation. For treatment comparison, analysis of covariance (ANCOVA) was used for continuous endpoints and Fisher exact test was applied for proportion of participants with clinically significant deterioration events. RESULTS: A total of 175 patients were enrolled: 102 in the latanoprost group (median follow-up: 36.7 months) and 73 in the non-PG group (median follow-up: 36.1 months). There was no statistically significant difference between the latanoprost and the non-PG groups (aged 5 to <18 years) in BCVA change from baseline (least square mean logMAR difference -0.03 [95% confidence interval: -0.12, 0.06]), corneal thickness, or ocular hyperpigmentation. CONCLUSIONS: Latanoprost had an acceptable safety profile with no evidence of inducing clinically meaningful or statistically significant changes in ocular development or ocular hyperpigmentation in pediatric patients with glaucoma and ocular hypertension.

The cross-sectional and longitudinal association of the BODE index with quality of life in patients with chronic obstructive pulmonary disease.

BACKGROUND: The body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index was shown at predicting the risk of death, exacerbation and disease severity among patients with COPD, but few studies verified relationship between BODE index and health related quality of life (HRQoL) among Chinese COPD patients. The objective of this study was to evaluate the relationship between BODE index and HRQoL in cross-sectional and longitudinal association analyses. METHODS: A multi-center prospective cohort study was initially conducted in 491 stable COPD patients in Beijing, China. Health status (HRQoL) was assessed by St. George's Respiratory Questionnaire (SGRQ); the BODE index was calculated for each patient; dyspnea was assessed using the 5-grade Medical Research Council dyspnea scale. Other measurements included socio-demographic, body mass index (BMI), lung function test and 6-minute-walk test (6MWT). Patients were then followed monthly for 12 months. RESULTS: Only 450 patients completed the 1-year follow up and were enrolled in our present analyses. Mean age was (65.2 +/- 10.6) years, men 309 (68.7%). The BODE index was categorized into 4 subgroups: 0 - 2, 3 - 4, 5 - 6 and 7 - 10. At baseline BODE index was gradually increased with baseline total SGRQ and SGRQ subscales (P trend < 0.001). For individual components of BODE index, with the decrease of airflow limitation, and 6MWD, and with the increase of Medical Research Council (MRC) dyspnea grade, total SGRQ and SGRQ subscales were increased correspondingly, P trend < 0.05, respectively. Similar association patterns were found between baseline BODE index and its individual components and mean SGRQ scores at the end of 1-year follow up. By multiple linear regression analyses, baseline BODE index was not only significantly associated with SGRQ score at baseline but also with SGRQ score at the end of 1-year follow up after adjustment for age, male, current smoking, betas being 0.434 and 0.378, respectively. CONCLUSIONS: BODE index is associated with SGRQ score cross-sectionally and longitudinally among stable COPD patients. BODE index might have potential to be used as a sensitive tool to assess the status of quality of life and to monitor disease progression among stable COPD patients.

Use of antidepressants and risk of colorectal cancer: a nested case-control study.

BACKGROUND: Animal studies suggest that selective serotonin reuptake inhibitors (SSRI) retard the growth of colorectal tumours, whereas tricyclic antidepressants increase the risk of colorectal cancer. We aimed to assess whether SSRI use was associated with a decreased risk of colorectal cancer, and tricyclic-antidepressant use with an increased risk of colorectal cancer. METHODS: We did a population-based nested case-control study from Jan 1, 1981, to Dec 31, 2000, of people aged 5-85 years who were registered with Saskatchewan Health and eligible for prescription-drug benefit. Between Jan 1, 1981, and Dec 31, 2000, 6544 cases with colorectal cancer were identified from the Saskatchewan Cancer Agency registry and analysed for use of tricyclic antidepressants; between Jan 1, 1991, and Dec 31, 2000, 3367 cases with colorectal cancer were identified from the Saskatchewan Cancer Agency registry and analysed for SSRI use. For every case, four eligible controls matched for age, sex, and calendar time (ie, free of any cancer in calendar month of case diagnosis) were selected randomly by a statistician who used incidence density sampling. By use of conditional logistic regression, we assessed incidence-rate ratios of having colorectal cancer in association with use of antidepressants, analysing dose and time of use. FINDINGS: A decreased risk of colorectal cancer was associated with high (ie, >6.0x10(-6) mol per day) daily SSRI dose during 0-5 years before diagnosis (incidence-rate ratio 0.70 [95% CI 0.50-0.96], p for trend=0.0172), adjusted for age, sex, use of non-steroidal anti-inflammatory drugs in the same period, and SSRI use during 6-10 years before index date (ie, date of diagnosis for a case and the same date for matched controls). No consistent relation was recorded for risk of colorectal cancer and use of tricyclic antidepressants. INTERPRETATION: SSRI use might inhibit the growth of colorectal tumours through an antipromoter effect or direct cytotoxic effect. Further investigation is needed, with more complete assessment of confounders such as lifestyle factors (eg, diet), use of drugs, and comorbidity (eg, diabetes or inflammatory bowel disease) that might affect the occurrence of colorectal cancer.

[Blood leptin level of 154 Chinese children 0 - 14 years of age].

OBJECTIVE: To study blood Leptin level of 154 (78 male, 76 female) Chinese obese/non-obese children aged 0 - 14 years during 1999 - 2001. METHODS: The gender- and age-specific distribution pattern of Leptin and its relationship with anthropometric parameters (waist circumference, waist/hip ratio, lean body mass, fat mass, body fat percentage, BMI/Kaup index etc.) and blood insulin level were recorded. RESULTS: (1) The blood Leptin level in healthy non-obese kids ranged from 1.01 - 29.92 (ng/ml), the mean values and SD were 2.99 +/- 2.13 (ng/ml) [90% confidence interval was 1.36 - 14.21 (ng/ml) in boys and 1.74 - 21.17 (ng/ml) in girls]. There was no significant difference in the blood Leptin level between serum and plasma. (2) The blood Leptin level was higher in overweight/obese kids than that in non-obese kids (P < 0.001). (3) There was significant difference in the blood Leptin levels between boys and girls groups (P = 0.023), especially in non-obese group (P = 0.004). The multiple regression analysis showed that there was no correlation between gender and blood Leptin level when body fat factor was added (P = 0.138, 0.241, 0.990), but there was still a strong correlation between blood leptin level and BMI, FM and BF% (P < 0.001). (4) There was a correlation between blood Leptin level and age (P = 0.005), especially in overweight/obese group and in girls (P = 0.001). The blood Leptin level rose from early puberty, especially in girl group (P = 0.045). There was significant difference in blood Leptin level in different age groups (P < 0.001) (5) There were strong positive correlation between blood Leptin level and BMI, BM and FM%, a weak correlation with LBM, and no correlation with W/H ratio in boys and a positive relationship in girls. The Quatatic equation was better than the linear equation in description of the correlation mentioned above. (6) There was a correlation between blood Leptin from 0 to 7 yr and birth weight (P = 0.001), after 7 yr of age this correlation disappeared (P = 0.456). (7) A positive correlation was seen between blood Leptin level and blood insulin level (P < 0.001). CONCLUSION: The blood Leptin level of 0 - 14 years old children is consistent with the level of growth of adiposity tissue and the degree of adiposity rebound.