Medications and cataract. The Blue Mountains Eye Study

PURPOSE: Corticosteroids are known to cause cataracts, but the effects of other medications on the lens are unclear. The aim of this study was to investigate the relationships between cataracts and a range of medications, including allopurinol, aspirin, chloroquine, diuretics, phenothiazines, and simvastatin. DESIGN: Population-based cross-sectional study. PARTICIPANTS: 3654 individuals 49 to 97 years of age (response rate, 82%) from an urban community near Sydney, Australia, were included. TESTING: Lens photography. PRIMARY OUTCOME MEASURE: Lens photographs were graded for the presence and severity of cortical, nuclear, and posterior subcapsular cataract. RESULTS: After adjusting for numerous potential confounders in ordinal regression models, use of phenothiazines was associated with nuclear cataract (adjusted odds ratio [OR], 2.18; 95% confidence interval [CI], 1.01-4.74); long-term aspirin users (> or = 10 years) had higher prevalence of posterior subcapsular cataract than did nonusers and short-term users (test for trend, P = 0.02); and the antimalarial drug mepacrine was associated with posterior subcapsular cataract (adjusted OR, 3.56; 95% CI, 1.56-8.13). There was a suggestion that use of chloroquine-like drugs for more than 1 year (test for trend, P = 0.12) might also be associated with posterior subcapsular cataract. Antihypertensive medications, cholesterol-lowering drugs, and allopurinol were not associated with any type of cataract. Potassium-sparing diuretics were the only diuretic to show any evidence of an association with cataract (test for trend for posterior subcapsular cataract, P = 0.14). Amiodarone was associated with cortical cataract (age- and gender-adjusted OR, 3.84; 95% CI, 1.01-14.81), but there were too few users to do analyses adjusted for multiple confounders. CONCLUSIONS: Most drugs commonly used in the community do not appear to be associated with cataract. The findings of this study do not support the hypothesis that aspirin protects against cataract.     

Esophagitis in Sprague-Dawley rats is mediated by free radicals

Free radical-mediated esophagitis was studied during duodenogastroesophageal reflux (mixed reflux) or acid reflux in rats. The influence of reflux on esophageal glutathione levels was also examined. Mixed reflux caused more gross mucosal injury than acid reflux. Gross mucosal injury occurred in the mid-esophagus. Total glutathione (GSH) in the esophageal mucosa of control rats was highest in the distal esophagus. The time course of esophageal GSH in rats treated by mixed reflux showed a significant decrease 4 hr after initiation of reflux, followed by a significant increase from the 12th hour on. Mucosal GSH was increased in both reflux groups after 24 hr but significantly more so in the mixed than in the acid reflux group. The free radical scavenger superoxide dismutase (SOD) prevented esophagitis and was associated with decreased GSH levels. GSH depletion by buthionine sulfoximine (BSO) prevented esophagitis and stimulated SOD production in the esophageal mucosa. It is concluded that gastroesophageal reflux is associated with oxidative stress in the esophageal mucosa. The lower GSH levels in the mid-esophagus may predispose to damage in this area. Duodenogastroesophageal reflux causes more damage than pure acid reflux. Oxidative stress leads to GSH depletion of the esophageal mucosa in the first few hours following damage but then stimulates GSH production. GSH depletion by BSO does not worsen esophagitis since it increases the esophageal SOD concentration.     

The STOP-NIDDM Trial: an international study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance: rationale, design, and preliminary screening data. Study to Prevent Non-Insulin-Dependent Diabetes Mellitus

OBJECTIVE: To describe the rationale and design, and to discuss the preliminary screening data, of the Study to Prevent NIDDM (STOP-NIDDM Trial), an international study on the efficacy of the alpha-glucosidase inhibitor acarbose in preventing or delaying the development of type 2 diabetes in a population with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A total of 1,418 subjects diagnosed with IGT according to the World Health Organization's criteria and having a fasting plasma glucose concentration > or =5.6 mmol/L were randomized in a double-blind fashion to receive either acarbose (100 mg t.i.d.) or placebo for a predictive median follow-up period of 3.9 years. The primary outcome is the development of type 2 diabetes diagnosed using a 75-g oral glucose tolerance test according to the new criteria. The secondary outcomes are changes in blood pressure, lipid profile, insulin sensitivity, cardiovascular events, and morphometric profile. RESULTS: Screening was performed in a high-risk population. As of 1 March 1997, 4,424 subjects had been screened, and data were available for 3,919 (88.5%) subjects. Of these subjects, 1,200 (30.6%) had glucose intolerance. Of the subjects with glucose intolerance, 521 (13.3%) had previously undetected type 2 diabetes, and 679 (17.3%) had IGT. Of the IGT population, 412 (60.7%) subjects were eligible for the study This population had the following characteristics: the mean age was 54.8 years, 52% of the subjects were female, 53% had more than one risk factor for type 2 diabetes, >90% had a family history of diabetes, 78.2% had a BMI > or =27 kg/m2, 47.5% had high blood pressure, 51.2% had dyslipidemia, and 22.8% of the women had a history of gestational diabetes. CONCLUSIONS: Screening of a high-risk population yields one eligible subject per every 10 volunteers screened. This study should definitely answer the question of whether acarbose can prevent or delay the progression of IGT to type 2 diabetes mellitus.     

Phlebotomus papatasi sand fly salivary gland lysate down-regulates a Th1, but up-regulates a Th2, response in mice infected with Leishmania major

A vertebrate host becomes infected with Leishmania major when the sand fly vector injects parasites into skin along with saliva. Previous studies showed that salivary gland lysate of the New World sand fly Lutzomyia longipalpis markedly enhanced L. major infection in CBA mice. However, L. major is an Old World parasite transmitted in nature by the Old World sand fly Phlebotomus papatasi. Here we examine the ability of P. papatasi salivary gland lysate to enhance infection (lesion size and parasite burden) by L. major. In addition, we examine the effects of salivary gland lysate on the immune response to L. major by monitoring the levels of cytokine mRNA from the lymph nodes draining cutaneous lesions. We found that P. papatasi salivary gland lysate dramatically exacerbated lesion development in disease-resistant CBA mice. This exacerbation of disease correlated with inhibition of the production of Thl cytokines and associated factors (IFN-gamma, IL-12, and inducible nitric oxide synthase), but with enhancement of the Th2 cytokine IL-4, whereas no changes in the levels of IL-10 and TGF-beta were noted. Importantly, salivary gland lysate directly up-regulated expression of IL-4 mRNA in mice in the absence of infection with L. major.     

Synthesis and biological activities of phenyl piperazine-based peptidomimetic growth hormone secretagogues

A new class of potent, orally active phenyl piperazine-based GH secretagogues have been discovered from attempts to mimic the arrangement of the phenyl substituent in the spiroindanyl piperidine and spiroindoline sulfonamide privileged structures of 4 and 1, respectively. The best of these compounds, 18 (EC50 = 2.8 nM) is nearly as potent as MK-0677 for releasing GH from rat pituitary cells.     

Dentine hypersensitivity: a clinical trial to compare 2 strontium densensitizing toothpastes with a conventional fluoride toothpaste

Sixty-nine patients, aged 63-98 years and admitted at the Geneva Geriatric Hospital, were included in the present retrospective study. They received clomipramine orally, 50 or 75 mg/day. Blood concentrations of clomipramine were measured as part of a routine drug monitoring program. Comparison with a reference population of patients aged < or = 65 years indicated that elderly patients with concomitant somatic diseases reach higher dose-normalized concentrations of clomipramine and increased parent drug to demethylated metabolite ratios, as a consequence of impaired demethylation (approximately 50%) and hydroxylation (approximately 25%). Sixty-five percent of patients showed clinical improvement, with a maximum rate of satisfactory response observed in major depression. Severe side effects, such as symptomatic hypotension or confusion, were seen in 20% of patients. Because of 10- and 15-fold interindividual variations in the concentrations of clomipramine and its metabolite, respectively, therapeutic drug monitoring can provide valuable assistance to clinical judgment in individual dose adjustment for patients whose old age, associated somatic diseases, and comedication necessitate additional precautions.     

A magnetic sense amplifier

A new mode of operation of a balanced magnetic circuit is described. With this new mode of operation, which utilizes pulsed current excitation, the detection sensitivity of the magnetic modulator circuit is combined with the high-speed amplification of parametric buildup. This combination permits detection of low-level current pulses applied during a specified time interval of the excitation sequence and provides subsequent amplification of the detected signal. Matched square-loop toroids are used. Signal currents which are a small fraction of the coercive MMF have been successfully detected. The limit of detection sensitivity depends upon the matching of the two cores. The parametric buildup has been made to occur for pump cycle times of 30 μs to 120 μs, depending upon the magnetic material used. The signal information is retained when the pulse excitation sequence is interrupted during buildup because the signal information is stored as a flux unbalance in the two cores during the time interval between excitation pulses. The use of this circuit mode as a sense amplifier for the detection and amplification of sense winding currents in magnetic memories is suggested.