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81.
Denisa Diblíková Monika Kopečná Barbora Školová Marcela Krečmerová Jaroslav Roh Alexandr Hrabálek Kateřina Vávrová 《Pharmaceutical research》2014,31(4):1071-1081
Purpose
In this work, we investigate prodrug and enhancer approaches for transdermal and topical delivery of antiviral drugs belonging to the 2,6-diaminopurine acyclic nucleoside phosphonate (ANP) group. Our question was whether we can differentiate between transdermal and topical delivery, i.e., to control the delivery of a given drug towards either systemic absorption or retention in the skin.Methods
The in vitro transdermal delivery and skin concentrations of seven antivirals, including (R)- and (S)-9-[2-(phosphonomethoxy)propyl]-2,6-diaminopurine (PMPDAP), (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine ((S)-HPMPDAP), its 8-aza analog, and their cyclic and hexadecyloxypropyl (HDP) prodrugs, was investigated with and without the penetration enhancer dodecyl-6-(dimethylamino)hexanoate (DDAK) using human skin.Results
The ability of ANPs to cross the human skin barrier was very low (0.5–1.4 nmol/cm2/h), and the majority of the compounds were found in the stratum corneum, the uppermost skin layer. The combination of antivirals and the penetration enhancer DDAK proved to be a viable approach for transdermal delivery, especially in case of (R)-PMPDAP, an anti-HIV effective drug (30.2?±?2.3 nmol/cm2/h). On the other hand, lysophospholipid-like HDP prodrugs, e.g., HDP-(S)-HPMPDAP, reached high concentrations in viable epidermis without significant systemic absorption.Conclusions
By using penetration enhancers or lysolipid prodrugs, it is possible to effectively target systemic diseases by the transdermal route or to target cutaneous pathologies by topical delivery. 相似文献82.
Petar Filipović Grčić Meri Matijaca Ivica Bilić Gordan Džamonja Ivo Lušić Krešimir Čaljkušić Vesna Čapkun 《Acta neurologica Belgica》2013,113(4):397-402
Walking limitation assessment in multiple sclerosis patients (MSPs) is a demanding task, especially in the clinical setting. The aim of this study is to correlate the visual analogue scale (VAS), a simple method for measuring subjective experience, with measures of walking ability used in clinical research of MS. The study included 82 ambulatory MSPs who have resided in the local community. The applied measures of walking ability were the following: the single-item and patient-rated Walking Ability Visual Analogue Scale (WA-VAS), the Expanded Disability Status Scale (EDSS), the 25-foot walk test (25FWT), the Six Spot Step Test (SSST), the 2 min timed walk (2 min TW), the Multiple Sclerosis Walking Scale-12 (MSWS-12), and step activity monitor accelerometer (SAM) during 7 day period. The SAM analysis included the average daily step count, the average steps/min of the highest 1 min of a day, and the average steps/min of the highest continuous 60 min of a day. The WA-VAS scores significantly and strongly correlated with EDSS (ρ = 0.679, P < 0.001), 25FWT (ρ = 0.606, P < 0.001), SSST (ρ = 0.729, P < 0.001), 2 min TW (ρ = ?0.643, P < 0.001), MSWS-12 (ρ = 0.746, P < 0.001), average daily step count (ρ = –0.507, P < 0.001), average steps/min of the highest 1 min of a day (ρ = –0.544, P < 0.001), and average steps/min of the highest continuous 60 min of a day (ρ = ?0.473, P < 0.001). Correlations between WA-VAS and measures of walking ability used in clinical research of MS were satisfactory. The results obtained in this research indicate that the WA-VAS could be an instrument for simple measurement of walking limitations in MSPs in the clinical setting. 相似文献
83.
Kreß H 《Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz》2012,55(9):1085-1092
"Health" and "illness" are multilayered terms. The understanding of human health depends, apart from scientific aspects, on people's individual perceptions as well as on aspects of culture and world view. The ideal of patient-centered medicine requires that a physician does not merely have to establish an objectifiable diagnosis. Rather, a physician should also respect the patients' right to self-determination, their personal values, and their subjective view of health and illness. The philosophy of dialogue, which developed in the twentieth century, offers a conceptual background for this ideal. On an empirical basis, the successful communication between doctor and patient can be interpreted as a useful placebo phenomenon. Alternative medicine puts great emphasis on the doctor's attentive care. This also explains why the alternative branch of medicine has appealed to many patients. Therefore, science-oriented medicine should review methods in which the doctor's empathy and dialogue ability are crucial to treatment success. It is part of the physician's responsibility to appreciate the personal perspectives of patients, to respect them and, if necessary, to engage with them critically. 相似文献
84.
Kre?imir Ba?i? Kristina Pero? Ivana ?utej Kata Ro?in-Grget 《Acta stomatologica Croatica》2015,49(3):221-227
Objective
The aim of this in vitro preliminary study was to assess the effect of smokers’ saliva (assuming their higher calcium concentration) in combination with fluoridated toothpaste on the enamel uptake of alkali-soluble (KOH-soluble) fluoride.Materials and methods
Four enamel slabs were cut from each of 14 impacted third molars and randomly assigned into 4 groups. Unstimulated saliva samples were collected from two age and sex matched volunteers. One of the samples was taken from a heavy smoker and the other sample was taken from a non-smoker. Two groups (A and B) were shaken in saliva (A in smoker''s saliva, B in nonsmoker''s saliva) for 5 min and then shaken for 3 min in a toothpaste/deionized water slurry (1:3 w/w). One of the groups (group C) received no saliva treatment and was only shaken in toothpaste slurry for 3 min. The treatment was repeated after a 6-hour period. One of the groups (D) served as a control group with no treatment.Results
Calcium concentration in the smoker’s saliva was higher than in the nonsmoker’s saliva. The enamel uptake of KOH-soluble fluoride in group A was significantly higher than that in the other two treatment groups, B and C. The enamel uptake of KOH-soluble fluoride in all 3 groups was statistically different from that in the control group.Conclusion
These results demonstrate that saliva collected from a heavy smoker, which had higher salivary calcium concentration, enhances enamel uptake of alkali-soluble fluoride and encourages us to conduct a large-scale study.Key words: Salivary calcium, fluoride, smoking, enamel 相似文献85.
86.
The use of monoclonal antibodies in diagnostic tests for Becker and Duchenne muscular dystrophy 总被引:1,自引:0,他引:1
Monoclonal antibodies recognizing different epitopes of dystrophin have now been widely applied in diagnostic tests for Duchenne and Becker muscular dystrophy (BMD). The preservation of the C-terminus in BMD patients necessitates the routine use of one antibody raised against this region. Additional antibodies against deletion-prone regions of dystrophin further increase the diagnostic power of the tests. We describe two cases which illustrate that the combined use of different antibodies is necessary to avoid misdiagnoses of BMD at the protein level. 相似文献
87.
Darjan Kardum Ivana Serdarušić Borna Biljan Krešimir Šantić Vinko Živković Martina Kos 《Jornal de pediatria》2021,97(4):440-444
ObjectiveTo assess the accuracy of umbilical cord bilirubin values to predict jaundice in the first 48 h of life and neonatal infection.MethodNewborn infants treated at a regional well-baby nursery born at ≥36 weeks of gestation were included in this retrospective cohort study. All infants born in a 3-year period from mothers with O blood type and/or Rh-negative were included and had the umbilical cord bilirubin levels measured. Hyperbilirubinemia in the first 48 h was defined as bilirubin levels above the phototherapy threshold. Neonatal infection was defined as any antibiotic treatment before discharge.ResultsA total of 1360 newborn infants were included. Two hundred and three (14.9%) newborn infants developed hyperbilirubinemia in the first 48 h of life. Hyperbilirubinemic infants had smaller birth weight, higher levels of umbilical cord bilirubin, a higher rate of infection and were more often direct antiglobulin test positive. Umbilical cord bilirubin had a sensitivity of 76.85% and a specificity of 69.58% in detecting hyperbilirubinemia in the first 48 h, with the cut-off value at 34 μmol/L. The area under the receiver operating characteristic curve was 0.80 (95% CI: 0.78–0.82). Umbilical cord bilirubin had a sensitivity of 27.03% and specificity of 91.31% in detecting perinatal infection. The area under the receiver operating characteristic (ROC) curve was 0.59 (95% CI: 0.57–0.63).ConclusionsA positive correlation was found between umbilical cord bilirubin and hyperbilirubinemia in the first 48 h of life. Umbilical cord bilirubin is a poor marker for predicting neonatal infection. 相似文献
88.
Kress H 《Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz》2008,51(9):965-972
In exceptional cases, the German Stem Cell Act allows research on human embryonic stem cells. However, it does not allow the implementation of the research results if this in turn requires the use of further embryonic stem cell lines. It has, in the meantime, transpired that such research results could be of concrete use. Thus, in the distant future, it could be used in the clinical treatment of patients. Already in the nearer future the use of human embryonic stem cell lines can be envisaged for both the development and testing of medicines as well as in the field of toxicology. To this end, research concerning embryo toxicity and neurotoxicity is ground-breaking. The toxicological and pharmacological use of human embryonic stem cell lines should serve the protection of human health as well as the safe and reliable use of medicines. In addition, animal experiments could be reduced, which is desirable from a point of view of animal protection ethics. Since research on human embryonic stem cell lines is actually permitted in Germany, the use of the respective research results should be allowed all the more. This follows from the basic human right to health protection and health care. Legal ambiguities, which still exist in this respect, should be removed. 相似文献
89.
90.