Rat Jejunal Permeability and Metabolism of μ-Selective Tetrapeptides in Gastrointestinal Fluids from Humans and Rats

Purpose. To study intestinal transport and metabolism of three new -selective tetrapeptide enkephalin analogues, LEF537, LEF553 and TAPP These peptides are stabilized against enzymatic hydrolysis by having a D-aminoacid in position 2 and a blocked COOH-terminal. Methods. We used a single-pass perfusion technique to study the transport of the peptides in rat jejunum. To reduce luminal and/or brush-border metabolism during the perfusion we used protease inhibitors (Pefabloc^® SC, bestatin and thiorphan). The rate of metabolism was studied by incubations in rat jejunal homogenate, rat jejunal fluid and human gastric and jejunal fluid with and without these inhibitors. Results. The jejunal permeabilities (P_eff) of the peptides were 0.43–0.78 10^–4 cm/s without inhibitors and 0.09–0.45 10^–4 cm/s in presence of the inhibitors. All three peptides were rather rapidly degraded by enzymes in rat jejunal homogenate with half-lives of between 11.9 ± 0.5 and 31.7 ± 1.5 min. The addition of inhibitors to the homogenate prolonged the half-lives substantially for LEF553 (167 ± 35 min) and TAPP (147 ± 2 min), but only slightly for LEF537 (16.4 ± 0.5 min). LEF553 and TAPP were both hydrolyzed in rat and human jejunal fluid, while LEF537 was metabolized less in these fluids. When LEF553 and TAPP were incubated with intestinal fluid in the presence of inhibitors, metabolism was almost completely inhibited. There was no metabolism for any of the peptides in human gastric juice. Conclusions. The replacement of the terminal free carboxylic group with an amide group did not increase the stability of the peptides in jejunal tissue enough to allow successful oral drug delivery.     

Poly (triethylenglycol monomethacrylate) and poly(glycerol monomethacrylate) cross-linked gel as potential viscoelastics for intraoperative use

Background: The highly swelling poly(glycerol monomethacrylate) gel (polyGLYMA) and hydrophilic polymer poly(triethylenglycol monomethacrylate (polyTEGMA) were tested as potential viscoelastics for intraopertive use in anterior segment surgery. Methods: PolyGLYMA was implanted into the anterior chamber in 5 rabbits, and 40% polyTEGMA in 16 rabbits. The eyes were enucleated 1 week to 3 months after the operation. The corneal endothelium was examined with specular microscopy, and then the whole eye histopathologically. Results: In all eyes of the polyGLYMA group, the clinical findings were characterized by a marked ciliary injection and severe secondary glaucoma, and the histologic ones by a marked inflammatory infiltration and thickening of Descemet's membrane in the anterior chamber angle. Specular microscopy revealed a decrease in the endothelial cell density and polymorphism of the endothelial cells. In the polyTEGMA group, the anterior segment and the fundus were physiologic all the time, and specular microscopy and histologic findings showed no degenerative and/or inflammatory changes. Conclusions: PolyGLYMA proved unsuitable for intracameral application in rabbits. The new polymer polyTEGMA is characterized by high biologic tolerance after its implantation into the anterior chamber of rabbits. PolyTEGMA 40% might be considered as a potential viscoelastic material in humans.     

Quitting smoking in Northern Italy: A cross-sectional analysis of 2621 subjects

To describe the relationship between sociodemographic factors, life-style habits, selected dietary indicators, smoking-related variables, and quitting smoking we analyzed data derived from the comparison group of a case-control study of colorectal and breast cancers based on a network of teaching and general hospitals in Northern Italy. A total of 2621 subjects (1215 women and 1406 men) who were ever cigarette smokers were included for analysis. Age-adjusted rates of stopping smoking (quit rates) and multivariate odds ratios (OR) of quitting smoking were computed. The overall age-adjusted quit rate was 38.6% for males and 24.9% for females, corresponding to an OR of quitting of 0.6 (95% CI: 0.5–0.7) for females vs males. The quitting rate increased with increasing age. After allowing for age, smoking cessation was more frequently reported by more educated or higher social class individuals. No relationship was present between quitting smoking and alcohol consumption, but quitting smoking was inversely related to coffee consumption. The probability of quitting smoking increased directly with number of cigarettes among males but not among females, who showed a J-shaped pattern. Older, heavy smokers were more likely to give up smoking. A general pattern of increasing rates of quitting smoking with higher consumption of vegetables and fruit, and hence -carotene, was present. This study confirms a positive association between quitting smoking and increasing age, higher education, low coffee consumption, heaviness of smoking and high consumption of vegetables and fruit.     

Molecular Human Reproduction: Evidence for {gamma}-aminobutyric acid specific binding sites on human spermatozoa

The possible presence of -aminobutyric acid (GABA) specificbinding sites on human spermatozoa was investigated. Swim-uppreparations of human spermatozoa were incubated with radiolabelledGABA in the presence of unlabelled GABA, alternatively displacersof GABA_A/B receptors and GABA transport proteins. The resultsindicate that GABA specific binding sites are present on thesurface of human spermatozoa, and that these binding sites possiblyindicate the presence of GABA transport proteins. Furthermore,GABA at different concentrations was added to swim-up preparationsof human spermatozoa. Possible effects of GABA on sperm motility,hyperactivation and acrosome reaction were explored. No significantdifferences were observed between treated groups and controlsconcerning motility parameters and hyperactivation. Incubationwith GABA did not cause any increase in spontaneous acrosomereaction. However, spermatozoa treated with the calcium ionophoreA-23187 showed a small but significantly increased ability toundergo the acrosome reaction following preincubation in 10–⁴M GABA (P < 0.05).     

Existential questions in early childhood programs in Sweden: Teachers' conceptions and children's experience

Swedish guidelines for early childhood education emphasize the importance of children's existential questions. The program encourages preschool to offer children different opportunities to work on questions like what it is to be, to live and die, grow old, about religion, beliefs, traditions, etc. at their level of maturity (Social-styrelsen, 1987). Our experience in teacher education and early childhood programs is, however, that this is an area in which many teachers have difficulties. In the present empirical study 13 teachers were interviewed to find outwhat they consider existential questions for their children to be, and whatstrategies or methods they have for dealing with these questions. Teachers' conceptions about the what and how aspects of existential questions are described in terms of their qualitative differences. Each teacher was then asked to keep a diary of the existential questions children raised during the following month. Differences between the teachers' conceptions, which showed hesitation, and the spontaneous approaches and active involvement that emerged in reality, as recorded in their own diaries, are discussed.     

Effects of prolonged uniocular dark adaptation on the direct-current electroretinogram of pigmented and albino rabbits

The direct-current electroretinogram of seven pigmented and seven albino rabbits was recorded from both eyes for almost 4 h in response to repeated identical light stimuli. Stimulus duration was 10 s, light intensity was 6.8 × 10² lux, and the interval between the beginning of succeeding light stimuli was 3 min. The dark-adaptation period preceding light stimulation was 30 min for one of the eyes (unoccluded eye) and 150 min for the contralateral eye (occluded eye), which was patched during the first part (117 min) of the experiment. In pigmented animals, the b- and c-wave amplitudes of the unoccluded eye slowly increased during the first part of the experiment but not significantly during the second. The a-wave amplitude was not significantly changed. After removal of the cover, the a- and b-wave amplitudes of the occluded eye immediately attained but did not exceed the level of those in the unoccluded eye, irrespective of the light adaptation induced by the stimulus flashes previously presented to the unoccluded eye. (Control experiments on six pigmented rabbits confirmed that stimuli identical to those used in the main part of the study caused a light adaptation, since a decrease in a- and b-wave amplitudes occurred after the first light stimulus following an initial dark-adaptation period of 2 h for both eyes.) In albino rabbits, electroretinogram responses were clearly discernible in the occluded eye also during the first part of the experiment, probably because of transillumination of the head. In other respects, the results were essentially similar to those of pigmented animals. The observation that occluded eyes did not dark adapt better, as judged by the electroretinogram responses, than contralateral eyes given repeated light adaptive stimuli may indicate the presence of a mechanism for transfer of adaptation information between the eyes.     

Olive oil,other dietary fats,and the risk of breast cancer (Italy)

Data from a multicenter case-control study on breast cancer conducted in Italy have been used to analyze the relationship of olive oil and other dietary fats to breast cancer risk. Cases were 2,564 women hospitalized with histologically confirmed, incident breast cancer. Controls were 2,588 women admitted to the same network of hospitals for acute, non-neoplastic, non-hormone related, on-digestive tract disorders. Cases and controls were interviewed between 1991 and 1994 using a validated food-frequency questionnaire. The data were modelled through multiple logistic regression controlling for demographic and reproductive breast-cancer risk factors, energy intake and, mutually, for types of dietary fat. For olive oil, compared with the lowest quintile, the odds ratios (OR) were 1.05, 0.99, 0.93, and 0.87 for increasing quintiles of intake; in a model postulating linear logit increase, the OR per unit (30g) was 0.89 (95 percent confidence interval [CI]=0.81–0.99, P=0.03). Among other oils or fats considered, the OR for the highest level of intake was 0.72 (CI=0.6–0.9) for a group of specific seed oils (including safflower, maize, peanut, and soya) compared with nonusers. The ORs for the highest cf lowest level of intake were 0.80 for mixed or unspecified seed oils, 0.95 for butter, and 0.96 for margarine. The study, based on a large dataset from various Italian regions, shows an inverse relationship of breast cancer risk with intake of olive oil and other vegetable oils, but not with butter or margarine.     

University Students'' Knowledge and Awareness of HPV

BACKGROUND: The purpose of this study was to evaluate the knowledge, attitudes, and behaviors of university students regarding the human papillomavirus (HPV). METHODS: A random sample of 500 university students was mailed a self-administered questionnaire that elicited their knowledge and awareness about HPV and compared their knowledge and attitudes with those of other sexually transmitted diseases (STDs). Among the 480 deliverable addresses, 289 students responded (response rate 60%). RESULTS: Only 37% of respondents had ever heard of HPV, and the median score on a 13-item knowledge scale was only 3. Of seven STDs assessed, respondents indicated they knew the least about HPV and perceived that this STD has received the least educational effort. In multivariate analyses, predictors of lower knowledge and awareness about HPV were male gender and sexual behavior (having multiple partners, not using condoms). CONCLUSIONS: Despite the high prevalence of HPV among young adults, most students knew very little about this infection. Implementing HPV educational programs and measuring their effectiveness should be a priority.     

Influence of serum albumin on renal function in nephrotic syndrome

 Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), determined by the clearances of inulin and para-aminohippuric acid, were evaluated in 119 children with different types of nephrotic syndrome and in different stages: the nephrotic stage (serum albumin <25 g/l), recovery stage (25–35 g/l), and remission (>35 g/l). GFR in the nephrotic stage was significantly lower than in remission and in controls, and was lowest at onset of the disease (84±6, 111±4, and 119±2 ml/min per 1.73 m²). ERPF was higher in the nephrotic stage than in recovery, especially in children with histological lesions. Thus the filtration fraction (FF) was greatly decreased in the nephrotic stage. In patients investigated both in the nephrotic and the remission phase, GFR and FF increased significantly. There was a direct correlation between the serum albumin concentration and FF and an inverse correlation between mean arterial pressure (MAP) and GFR and FF in all patients, a direct correlation between the serum albumin concentration and GFR in minimal change nephrotic syndrome patients, and an inverse correlation between ERPF and serum albumin in children with histological lesions. In conclusion, GFR and FF were decreased and ERPF increased in the nephrotic stage, normalizing in remission. The low GFR in the nephrotic stage was thus not dependent on hypoperfusion. We suggest that the low GFR is dependent on a very low ultrafiltration coefficient. The direct correlation between GFR and serum albumin and the indirect correlation between GFR and MAP suggest compensatory mechanisms that increase the ultrafiltration pressure to counteract the severely reduced ultrafiltration coefficient. Received: 19 November 1997 / Revised: 11 April 1998 / Accepted: 14 April 1998