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31.
Sarika Namjoshi Istvan Toth Joanne T. Blanchfield Nicholas Trotter Ricardo L. Mancera Heather A. E. Benson 《Pharmaceutical research》2014,31(12):3304-3312
Purpose
Efficient delivery of therapeutic peptides to the skin will facilitate better outcomes in dermatology. The tetrapeptide AAPV, an elastase inhibitor with potential utility in the management of psoriasis was coupled to short chain lipoamino acids (Laa: C6-C10) to enhance the peptide permeation into and through human epidermis.Methods
AAPV was conjugated to Laas by solid phase synthesis. Peptide stability, skin distribution and permeation, elastase activity and surface activity were determined.Results
Laas increased peptide permeation into the skin. The permeation lag time and amount of peptide remaining in the skin increased with the carbon chain length of the Laa conjugate. We also demonstrated stereoselective permeation enhancement in favour of the D-diastereomer. Importantly, the elastase inhibition activity of the peptide was largely retained after coupling to the Laa conjugates, showing potential therapeutic utility. The Laa-peptide structures were shown to be surface active, suggesting that this surfactant-like activity coupled with enhanced lipophilicity may contribute to their interaction with and permeation through the lipid domains of the stratum corneum.Conclusions
This study suggests that the Laa conjugation approach may be useful for enhancing the permeation of moderately sized peptide drugs with potential application in the treatment of skin disorders. 相似文献32.
Eszter Vojcek V. Anna Gyarmathy Rozsa Graf Anna M. Laszlo Laszlo Ablonczy Zsolt Prodan Istvan Seri 《Congenital heart disease》2022,17(4):447-461
Objective: Neonates with congenital heart disease (CHD) and perinatal stroke have high mortality and survivors are at risk for poor long-term neurodevelopmental outcome. The aim of this study was to assess the risk factors and outcome of neonates with both CHD and MRI-confirmed perinatal stroke (Study Group) and compare those to the risk factors and outcome of infants matched for CHD without stroke (Control-1) and of infants matched for MRI-confirmed stroke without CHD (Control-2). Methods: We conducted a population-based case-control study enrolling 28 term neonates with CHD and MRI-confirmed acute perinatal stroke born between 2007–2017 in the Central-Hungarian Region. Each of the control groups included 56 infants. The Bayley Scales of Infant Development-II, the Brunet-Lézine test and the Binet Intelligence scales-V were used for neurodevelopmental follow-up at a median age of 61 months. Results: Mortality was highest in the Study Group (25% compared to 5% and 2%, respectively, p = 0.001). Adverse neurodevelopmental outcome was prevalent in the Study (53%) and Control-2 Groups (52%, p = 0.03). Significantly different parameters among the three groups included Apgar scores, mode of delivery, gestational age at birth, cardiac interventions and twin pregnancy. In a multivariable regression analysis adjusted for clinically relevant parameters, patients in the Study Group had significantly higher odds for mortality compared to patients in the Control-1 Group (OR: 6.5 95% CI: 1.1–39.4). Conclusions: Neonates with perinatal stroke and CHD are at a higher risk for dying compared to neonates with CHD without stroke. In addition, the stroke-associated direct insult to the brain likely plays an important role in the development of neurodevelopmental morbidity in these patients. 相似文献
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BACKGROUND: In laboratory research, nicotine administration is associated with increases in blood pressure. In epidemiologic research, however, the amount of reported cigarette smoking has no consistent relation with blood pressure. The objective of this study was to examine the relation of a nicotine metabolite (salivary cotinine) to systolic and diastolic blood pressure in current smokers being screened for entry to a clinical trial. METHODS AND RESULTS: Data were obtained from 5164 middle-aged cigarette smokers during screening for the Lung Health Study. Multiple linear regression was used to examine the association of salivary cotinine and number of cigarettes smoked per day to systolic and diastolic blood pressure with age, body mass, years of education, alcohol intake, and recent caffeinated beverage use controlled in all analyses. Although smoking frequency was unrelated to blood pressure, salivary cotinine was related to greater systolic blood pressure in both men and women and greater diastolic blood pressure in men. CONCLUSIONS: The association between salivary cotinine and blood pressure in these analyses suggests that long-term nicotine exposure may be related to modest elevations in blood pressure in cigarette smokers. 相似文献
35.
Equations fitting the normative values for gender-specific brain size changes are available. However, these equations do not fit for all age ranges across the human lifespan and particularly have failed to examine the fit across the continuum of prenatal and postnatal human life. We sought to develop a parametric equation that best describes the changes in gender-specific brain size as a function of age across the continuum of prenatal and postnatal human life. Brain weight and brain volume data retrieved from the literature were combined to perform a meta-analysis. Additions to previously published findings included collecting a dataset that spanned the continuum of human lifespan, logarithmic transformation of the data and utilization of the Birch equation. We used Akaike’s Information Criterion (AIC) for quantitative evaluation of the new equations. A total of 2,011 brain weight data points spanning from 10 weeks of fetal gestation to over 90 years of age were retrieved. Using our approach, we developed equations with improved fits and lower or similar AIC values compared to the published equations. The new equations are modifications of the basic Birch model. These equations are the first to describe the gender-specific brain weight changes through the continuum of both prenatal and postnatal human life while achieving a level of accuracy similar to or better than the previous, more age-restricted models. The new equations are improved compared to previously used equations and may be useful to those who study brain development, particularly researchers interested in prenatal and postnatal brain size. 相似文献
36.
Paul J. Shughrue Malcolm V. Lane Istvan Merchenthaler 《The Journal of comparative neurology》1996,372(3):395-414
The tachykinin family of neuropeptides, which includes substance P, neurokinin A, and neurokinin B, have three distinct receptors; NK-1, NK-2, and NK-3. With the cloning of the rat NK-3 cDNA, it is now possible to evaluate the distribution of NK-3 mRNA in the rat brain. Female rat brains were sectioned and hybridized with a riboprobe complimentary to NK-3 mRNA. The results of these studies revealed an extensive distribution of NK-3 mRNA throughout the rostral-caudal extent of the brain, spinal cord, and retina. In agreement with previous binding studies, we observed NK-3 mRNA in the cortex, the amygdala, the hippocampus, the medial habenula, the zona incerta, the paraventricular and supraoptic nuclei of the hypothalamus, the substantia nigra, the ventral tegmental area, the interpeduncular nucleus, the raphe nuclei, the dorsal tegmental nucleus, and the nucleus of the solitary tract. In contrast with binding data, only a few NK-3 mRNA cells were detected in the striatum. In addition, the present study detected NK-3 mRNA in the olfactory bulb, the dentate gyrus and subiculum, the medial septum, the diagonal band of Broca, the ventral pallidum, the globus pallidus, the bed nucleus of the stria terminalis, the arcuate, the premammillary and mammillary nuclei, the dorsal and lateral regions of the posterior hypothalamus, the central gray, the cerebellum, the parabrachial nuclei, the nucleus of the spinal trigeminal tract, the dorsal horn of the spinal cord, and the retina. The results of these in situ hybridization histochemical studies have provided detailed and novel information about the distribution of NK-3 mRNA and have elucidated the putative sites of neurokinin B action in the rat central nervous system. © 1996 Wiley-Liss, Inc. 相似文献
37.
Edward Baral Eva Nagy Lauri Kangas Istvan Berczi 《International journal of cancer. Journal international du cancer》1996,67(4):580-585
Tamoxifen (TX) and toremifene (TO) enhanced the lysis of P815 mastocytoma cells in vitro by syngeneic DBA2 spleen cells that have been activated by human recombinant interleukin-2 (IL-2) for 6 days (lymphokine-activated killer [LAK] cells). Similarly, enhanced tumor suppression occurred when TX- or TO-treated P815 cells were mixed with LAK cells and injected s.c. into normal DBA2 recipients. Tumor suppression could be increased further by treating such recipients orally with TX or TO and by the repeated injections of LAK cells into the tumor site. The treatment of animals bearing tumors (5 mm in diameter) orally with TX or TO or with LAK cells i.p. resulted in tumor suppression. When the drug treatment was combined with LAK cells, tumor suppression was more pronounced, and complete tumor regression was induced in a significant number of the animals so treated. Our results indicate that the immunotherapeutic effect of LAK cells can be significantly amplified by combined treatment with the anti-estrogens TX or TO. © 1996 Wiley-Liss, Inc. 相似文献
38.
39.
Bekesi G Tulassay Z Lengyel G Schaff Z Szombath D Stark J Marczell I Nagy-Repas P Adler I Dinya E Racz K Magyar K 《Journal of neural transmission (Vienna, Austria : 1996)》2012,119(1):25-30
Selegiline is a selective irreversible inhibitor of the B-type of monoamine oxidase (MAO-B). The spectrum of its pharmacological activity is wide, possesses antioxidant, antiapoptotic and neuroprotective properties and, additionally, we found it is effective on the total scavenger capacity (TSC), and the regulation of fat content in rat liver kept on lipid-rich diet. Our aim was to clarify whether the oral treatment with selegiline is protective on oxidative damage of Sprague?CDawley adult rats in vivo. Four groups of rats (five animals in a group) were examined: (1) lipid-rich diet, (2) normal rat food, (3) lipid-rich diet?+?selegiline and (4) normal rat food?+?selegiline. Selegiline solution (2.5???g/ml) was supplied with the drinking water, which was freely available for the animals. Regarding the drinking habit of the rats (20?C30?ml/day), the daily dose was roughly equal with that used in the human therapy (5?C10?mg/day). TSC was determined both at the beginning (0?day) and at the end of the study (28?days), when the blood samples were taken for chemiluminometric assay. Fat content of the liver was determined in the freshly frozen tissue by Sudan staining. TSC was increased in both the selegiline-treated groups. Selegiline treatment prevented the increase of liver fat in the group fed with lipid-rich diet. Our results led us to the conclusion that prolonged selegiline administration can raise the antioxidant capacity of the animals and prevents the accumulation of fat in their livers. 相似文献
40.
Than NG Abdul Rahman O Magenheim R Nagy B Fule T Hargitai B Sammar M Hupuczi P Tarca AL Szabo G Kovalszky I Meiri H Sziller I Rigo J Romero R Papp Z 《Virchows Archiv : an international journal of pathology》2008,453(4):387-400
Placental protein 13 (PP13) is a galectin expressed by the syncytiotrophoblast. Women who subsequently develop preterm pre-eclampsia
have low first trimester maternal serum PP13 concentrations. This study revealed that third trimester maternal serum PP13
concentration increased with gestational age in normal pregnancies (p < 0.0001), and it was significantly higher in women presenting with preterm pre-eclampsia (p = 0.02) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome (p = 0.01) than in preterm controls. Conversely, placental PP13 mRNA (p = 0.03) and protein, as well as cytoplasmic PP13 staining of the syncytiotrophoblast (p < 0.05) was decreased in these pathological pregnancies compared to controls. No differences in placental expression and
serum concentrations of PP13 were found at term between patients with pre-eclampsia and control women. In contrast, the immunoreactivity
of the syncytiotrophoblast microvillous membrane was stronger in both term and preterm pre-eclampsia and HELLP syndrome than
in controls. Moreover, large syncytial cytoplasm protrusions, membrane blebs and shed microparticles strongly stained for
PP13 in pre-eclampsia and HELLP syndrome. In conclusion, parallel to its decreased placental expression, an augmented membrane
shedding of PP13 contributes to the increased third trimester maternal serum PP13 concentrations in women with preterm pre-eclampsia
and HELLP syndrome. 相似文献