Incidence of cataract operations in Finnish male smokers unaffected by alpha tocopherol or beta carotene supplements

OBJECTIVE: To examine the effect of alpha tocopherol and beta carotene supplementation on the incidence of age related cataract extraction. SETTING: The Alpha-tocopherol Beta-carotene (ATBC) Study was a randomised, double blind, placebo controlled, 2 x 2 factorial trial conducted in south western Finland. The cataract surgery study population of 28,934 male smokers 50-69 years of age at the start. INTERVENTION: Random assignment to one of four regimens: alpha tocopherol 50 mg per day, beta carotene 20 mg per day, both alpha tocopherol and beta carotene, or placebo. Follow up continued for five to eight years (median 5.7 years) with a total of 159,199 person years. OUTCOME MEASURE: Cataract extraction, ascertained from the National Hospital Discharge Registry. RESULTS: 425 men had cataract surgery because of senile or presenile cataract during the follow up. Of these, 112 men were in the alpha tocopherol alone group, 112 men in the beta carotene alone group, 96 men in the alpha tocopherol and beta carotene group, and 105 men in the placebo group. When supplementation with alpha tocopherol and with beta carotene were introduced to a Cox proportional hazards model with baseline characteristics (age, education, history of diabetes, body mass index, alcohol consumption, number of cigarettes smoked daily, smoking duration, visual acuity, and total cholesterol), neither alpha tocopherol (relative risk, RR, 0.91, 95% confidence intervals, CI, 0.74, 1.11) nor beta carotene (RR 0.97, 95% CI 0.79, 1.19) supplementation affected the incidence of cataract surgery. CONCLUSION: Supplementation with alpha tocopherol or beta carotene does not affect the incidence of cataract extractions among male smokers.

 

     

Effects of experimental exposure to triethylamine on vision and the eye

OBJECTIVES: To determine the effect of triethylamine (TEA) on the cornea and to evaluate the cause of blurred vision. To find the lowest observed effect concentration of exposure to TEA. METHODS: Four people were exposed to TEA for 4 hours at concentrations of 40.6, 6.5, and 3.0 mg/m3. Before and after every exposure, symptoms and ocular microscopy findings were recorded. Binocular visual acuity and contrast sensitivity at 2.5% contrast were also measured. Also, before and after the 40.6 mg/m3 exposure, corneal thickness was measured and ocular dimensions were recorded by ultrasonography, endothelial cells of the cornea were analysed, and serum and lacrimal specimens were collected for the analysis of TEA. RESULTS: After exposure to 40.6 mg/m3 TEA there was a marked oedema in the corneal epithelium and subepithelial microcysts. However, corneal thickness increased only minimally because of the epithelial oedema. The lacrimal concentrations of TEA were, on average (range) 41 (18-83) times higher than the serum TEA concentrations. The vision was blurred in all subjects and visual acuity and contrast sensitivity had decreased in three of the four subjects. After exposure to TEA at 6.5 mg/m3 two subjects experienced symptoms, and contrast sensitivity had decreased in three of the four subjects. There were no symptoms or decreases in contrast sensitivity after exposure to a TEA concentration of 3.0 mg/m3. CONCLUSIONS: TEA caused a marked oedema and microcysts in corneal epithelium but only minor increases in corneal thickness. The effects may be mediated by the lacrimal fluid owing to its high TEA concentration. Four hour exposure to a TEA concentration of 3.0 mg/m3 seemed to cause no effects, whereas exposure to 6.5 mg/m3 for the same period caused blurred vision and a decrease in contrast sensitivity.

 

     

In vitro evaluation of acyloxyalkyl esters as dermal prodrugs of ketoprofen and naproxen

A series of acyloxyalkyl esters of ketoprofen and naproxen were synthesized and investigated as topical prodrugs with the aim of improving the dermal delivery of the drugs. In addition, some hydroxyalkyl esters of ketoprofen and naproxen were synthesized as possible intermediates of acyloxyalkyl prodrugs. All of the prodrugs were more lipophilic than their parent molecules, as evaluated by drug partitioning between 1-octanol and phosphate buffer at pH 7.4 (log Papp). However, their solubilities in aqueous solutions decreased markedly compared with the parent molecules. The prodrugs were stable toward chemical hydrolysis in aqueous solutions (pH 7.4), but were hydrolyzed to the parent drug both in 80% human serum and in human skin homogenate, with half-lives ranging from 4 to 137 min and from 13 to 403 min, respectively. The abilities of the selected naproxen acyloxyalkyl prodrugs to deliver naproxen through excised human skin were evaluated. Generally, the prodrugs showed similar dermal delivery as the parent drug through cadaver skin. In the present series of lipophilic prodrugs of naproxen, the prodrug with the highest aqueous solubility was the most effective prodrug to deliver naproxen through the skin.     

An outbreak of Q fever associated with parturient cat exposure at an animal refuge and veterinary clinic in southeast Queensland

Objective: To determine the source of a Q fever outbreak in humans at an animal refuge and veterinary clinic in southeast Queensland from October to December 2016. Methods: Case interviews and a retrospective cohort study of animal refuge and veterinary clinic staff using a self‐administered questionnaire related to clinical history of Q fever, Q fever vaccination status and workplace activities during the exposure period. Results: Seven cases (six confirmed, one probable) were identified. Forty‐three questionnaires were completed (92% response rate). Workplace activities associated with the greatest risk of illness were the disposal of deceased cats or dogs (RR, 14.0; 95%CI, 1.9–104.1) and participating in euthanasia of cats or dogs (RR, 4.6; 95%CI, 1.3–16.9). Five feline birthing events occurred at the animal refuge from 25 September to 19 October 2016, each with subsequent euthanasia of the queen cat and litter. All cases had likely exposure to a specific queen cat and her litter that were euthanised the same day as the birthing event. Conclusions: A parturient cat was the most likely source of the outbreak. Implications for public health: Occupational groups and others with regular exposure to feline or canine parturient products should receive Q fever vaccine.     

Carotid plaque mast cells associate with atherogenic serum lipids, high grade carotid stenosis and symptomatic carotid artery disease. Results from the helsinki carotid endarterectomy study

OBJECTIVE: Increased numbers of mast cells (MCs) are present in ruptured coronary plaques, suggesting to play a role in acute coronary syndromes. We evaluated the distribution densities of MCs, macrophages and T cells in carotid plaques and correlated these findings to stroke risk factors as well as history of stroke or TIA. METHODS AND RESULTS: Seventy-eight carotid samples from 75 patients (16 plaques from asymptomatic patients and 62 from patients with recent ischemic symptoms) undergoing carotid endarterectomy with an internal carotid stenosis >70% that were immunostained and quantified for MCs, macrophages and T cells. The MC distribution density showed positive correlation with the degree of carotid stenosis (p = 0.012), serum levels of total cholesterol (p = 0.021), LDL cholesterol (p = 0.013) and triglycerides (p = 0.005), and an inverse correlation with serum HDL cholesterol levels (p = 0.001). The average MC density (p = 0.023), but not the macrophage (p = 0.58) or T cell (p = 0.74) density, was higher in the symptomatic than in the asymptomatic patients. In a comparison of plaques ipsilateral and contralateral to the thromboembolic event, the densities of the three types of inflammatory cells were similar. CONCLUSIONS: Increased MC distribution density is associated with an atherogenic serum lipid profile, high-grade carotid artery stenosis and symptomatic carotid artery disease. These findings suggest a potential involvement of MCs in the pathophysiology of carotid artery stenosis.     

Immunization of rabbits against a bacterial pathogen with an alginate microparticle vaccine.

Pasteurella multocida is an important bacterial pathogen of domestic rabbits. To evaluate the ability of a thiocyanate extract (PTE) of P. multocida to stimulate an immune response and protect against infection with P. multocida, rabbits were immunized subcutaneously or intranasally on Days 7, 21 and 35. Cholera toxin, a potent mucosal adjuvant, was included in one treatment group. Rabbits immunized subcutaneously (SC) or intranasally (IN) had significant increases in serum anti-PTE IgG but not IgA. In contrast, only rabbits immunized IN with PTE developed significant titers of nasal lavage anti-PTE IgA and cholera toxin significantly enhanced this response. In a second study rabbits were immunized via the drinking water with PTE incorporated into alginate microparticles on Days 7, 14 and 21. Mild increases in serum IgG were noted in rabbits immunized with PTE in microparticles, with or without cholera toxin, and this increase was significant (P相似文献   

Use of microcosm and fish toxicity data to select mesocosm treatment concentrations

Data from Mixed Flask Culture (MFC) microcosms and fish single species toxicity tests were used to select treatment concentrations for littoral enclosure studies. Selected concentrations were evaluated by comparing the predicted responses to those observed in littoral enclosure studies with a pyrethroid pesticide, esfenvalerate (Lozano et al. 1989) and an organophosphate pesticide, azinphos-methyl (Knuth et al. 1992). Comparisons of the effects predicted by these laboratory studies and effects that occurred in the two littoral enclosure trials provided useful information on the accuracy associated with each prediction. Although the approach did not always predict the exact magnitude or breadth of response found in the littoral enclosures, response levels for each of the selected treatment concentrations were adequate to describe the dose-response relationship of the littoral ecosystem for the two pesticides. The evaluation suggests that selection of treatment concentrations for the two littoral enclosure studies could have been improved by using this approach.     

Asthma Programme in Finland: the quality of primary care spirometry is good

AIMS: To assess the quality of primary care spirometry by visual inspection of the flow-volume expiratory curve and to study the quantity of clinical information provided on the spirometry report sheets. METHODS: Retrospective audit of 868 expiratory flow-volume curves referred to three pulmonary clinics assessed against five predefined quality criteria. Clinical information included on the spirometry report sheets was also collected. RESULTS: Quality was good in 78% of pre-bronchodilation curves and in 80% of post-bronchodilation curves. Obtaining a sharp PEF value and full vital capacity exhalation seemed to be the critical points of measurement. Inter-rater reliability of the curve assessment was mainly good. Data on where the spirometry took place, and comments on the use of respiratory medication and patient co-operation were often lacking. CONCLUSIONS: The quality of primary care spirometry was good. Adequate clinical information on the report sheets would further improve the quality of this diagnostic process.     

Impaired absorption of cholesterol and bile acids in patients with an ileoanal anastomosis

Background—No data exist on cholesterolabsorption in patients with an ileoanal anastomosis (IAA).
Aims—To study cholesterol absorption and itseffects on cholesterol and bile acid metabolism in patients with an IAA.
Patients and methods—Cholesterol absorption, andserum, biliary, and faecal lipids were studied in 24 patients with anIAA and 20controls.
Results—Fractional cholesterol absorption wassignificantly lower in the patients (36% versus 47% in controls).Surprisingly, the calculated intestinal influx of endogenouscholesterol was reduced so that the absolute absorption of cholesterolwas decreased; elimination of cholesterol as faecal neutral steroidsremained normal. Thus, the slightly increased cholesterol synthesis was mainly due to increased faecal bile acid excretion, which, in turn, wasassociated with reduced absorption and biliary secretion of bile acids.Serum total and low density lipoprotein (LDL) cholesterol and LDLtriglycerides were lower in the patients. Molar percentage andsaturation index of biliary cholesterol were slightly higher inpatients with an IAA. Proportions of secondary bile acids in bile andfaeces were diminished, and faecal unidentified bile acids were higherin patients.
Conclusions—Cholesterol absorption issignificantly impaired in patients with an IAA, and is closely relatedto changes in serum and biliary lipids observed in these patients.

Keywords:cholesterol absorption; cholesterol synthesis; faecal bile acids; inflammatory bowel disease