[Show abstract][Hide abstract]ABSTRACT: Background:
Primary Sjögren's syndrome (pSS) is associated with immunological dysfunctions-a well-known risk factor of shingles. This study aimed to examine the incidence and risk of shingles in adults with pSS and pharmacological treatments.
This retrospective population-based cohort study was conducted using National Health Insurance claims data. Using propensity scores, 4,287 pSS adult patients and 25,722-matched cohorts by age, gender, selected comorbidities and Charlson comorbidity index scores were identified. Kaplan-Meier analysis and Cox regression were conducted to compare the differences in developing shingles. In pSS, oral and eye dryness are treated with substitute agents. Extraglandular features are often treated with pharmacological drugs including steroids and immunosuppressants. pSS patients were grouped as follows: no pharmacological drugs, steroids alone; immunosuppressants alone; combined therapies.
During the follow-up, 463 adults with pSS (10.80%) and 1,345 control cohorts (5.23%) developed shingles. The cumulative incidence of shingles in pSS patients (18.74/1,000 patient-years) was significantly higher than controls (8.55/1,000 patient-years). The adjusted hazard ratio (HR) of shingles was 1.69 (95% confidence interval (CI) 1.50-1.90). In age-subgroup analyses, incidences of shingles in pSS increased with age and peaked in pSS patients aged ≧60; however, adjusted HRs decreased with age. Compared to control cohorts with no drugs, adjusted HRs for shingles in pSS patients were ranked from high to low as: combined therapies (4.14; 95% CI 3.14-5.45) > immunosuppressants alone (3.24; 95% CI 2.36-4.45) > steroids alone (2.54; 95% CI 2.16-2.97) > no pharmacological drugs (2.06; 95% CI 1.76-2.41). Rates of shingles-associated hospitalization and postherpetic neuralgia were 5.62% and 24.41%, both of which were significantly higher than those (2.60%; 13.01%) in the control cohorts.
Adults with pSS were at greater risk for shingles than control cohorts. Drug exposures significantly increased the risk of shingles in pSS.
[Show abstract][Hide abstract]ABSTRACT: Tianeptine, an atypical tricyclic antidepressant with unique characteristics, can improve memory and prevent stress-induced hippocampal damage. It has neuroplastic and neurotrophic effects on hippocampal neurons and can prevent dendritic atrophy of the hippocampus in certain pathological conditions. To obtain a better understanding of the underlying mechanisms, we performed a proteomic analysis on tianeptine-treated hippocampal neurons. Primary hippocampal neurons were prepared from fetal Sprague-Dawley rats, eliminating glia cells by addition of cytosine beta-D-arabinofuranoside at day 2 in vitro (DIV2). The neurons were treated with tianeptine (10 microg/mL) or vehicle at DIV3, then harvested at DIV4 or DIV9 for immunocytochemical analysis of, respectively, neurite outgrowth or synapse formation. A proteomics analysis was performed on DIV4 neurons and the data were confirmed by Western blot analysis. Using specific markers, we demonstrated that tianeptine can augment neurite growth and promote synaptic contacts in cultured hippocampal neurons. The proteomics analysis identified 11 differentially expressed proteins, with roles in neurite growth, metabolism of neurotrophic substances, synaptogenesis, and synaptic activity homeostasis. The data shed light on the mechanisms underlying the neurotrophic effect of tianeptine observed in both animal studies and the clinic.
[Show abstract][Hide abstract]ABSTRACT: Ketorolac is a potent nonsteroidal anti-inflammatory drug. Recently, a ketorolac prodrug, ketorolac propyl ester, was synthesized in our laboratory. The aim of the study was to evaluate the antinociceptive and anti-inflammatory effects of ketorolac propyl ester in five depot formulations. The vehicles used in these formulations were injectable vegetable oils, i.e., sesame oil, peanut oil, soybean oil, castor oil, and cottonseed oil. The traditional therapentic form of ketorolac tromethamine in saline was used as control.
Six studies were carried out to test the antinociceptive and anti-inflammatory effects of intramuscular ketorolac tromethamine (in saline) and its propyl ester (in five depot formulations) 240 micromol/kg on Sprague-Dawley rats treated with intraplantar carrageenin.
Ketorolac tromethamine (in saline) produced an 8 h duration of action on both antinociception and anti-inflammation, whereas ketorolac propyl ester in five oily vehicles produced 54- to 78-h durations of actions in both antinociception and anti-inflammation. Ketorolac propyl ester in cottonseed oil produced a duration of action of 78h in both antinociception and anti-inflammation.
All five depot formulations of ketorolac propyl ester produced longer durations of antinociceptive and anti-inflammatory effects.