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31.
The aim of this study was to investigate the influence of experimental conditions on levothyroxine sodium release from two
immediate-release tablet formulations which narrowly passed the standard requirements for bioequivalence studies. The in vivo study was conducted as randomised, single-dose, two-way cross-over pharmacokinetic study in 24 healthy subjects. The in vitro study was performed using various dissolution media, and obtained dissolution profiles were compared using the similarity
factor value. Drug solubility in different media was also determined. The in vivo results showed narrowly passing bioequivalence. Considering that levothyroxine sodium is classified as Class III drug according
to the Biopharmaceutics Classification System, drug bioavailability will be less sensitive to the variation in its dissolution
characteristics and it can be assumed that the differences observed in vitro in some of investigated media probably do not have significant influence on the absorption process, as long as rapid and
complete dissolution exists. The study results indicate that the current regulatory criteria for the value of similarity factor
in comparative dissolution testing, as well as request for very rapid dissolution (more than 85% of drug dissolved in 15 min),
are very restricted for immediate-release dosage forms containing highly soluble drug substance and need further investigation.
The obtained results also add to the existing debate on the appropriateness of the current bioequivalence standards for levothyroxine
sodium products. 相似文献
32.
The chemical composition and the antimicrobial activity of the essential oil isolated from the needles of endemic Dalmatian black pine (Pinus nigra ssp. dalmatica) from Croatia were investigated. The chemical composition of the essential oil was determined by GC and GC/MS analyses, and the main compounds identified were α-pinene, β-pinene, germacrene D, and β-caryophyllene. Disc-diffusion and broth-microdilution assays were used for the in vitro antimicrobial screening. The Dalmatian black pine essential oil exhibited a great potential of antibacterial activity against Gram-positive bacteria (MIC=0.03-0.50% (v/v)) and a less pronounced activity against Gram-negative bacteria (MIC=0.12-3.2% (v/v)). The volatile compounds also inhibited the growth of all fungi tested, including yeast. 相似文献
33.
Mirjana Bjelo Ana uri Benedict Rak Mladen Bui Biljana Kuzmanovi Elabjer 《Current issues in molecular biology》2022,44(12):6397
RPE65, an abundant membrane-associated protein present in the retinal pigment epithelium (RPE), is a vital retinoid isomerase necessary for regenerating 11-cis-retinaldehyde from all-trans retinol in the visual cycle. In patients with inherited retinal dystrophy (IRD), precise genetic diagnosis is an indispensable approach as it is required to establish eligibility for the genetic treatment of RPE65-associated IRDs. This case report aims to report the specific phenotype–genotype correlation of the first patient with a homozygous missense variant RPE65 c.499G>T, p. (Asp167Tyr). We report a case of a 66-year-old male who demonstrated a unique phenotype manifesting less severe functional vision deterioration in childhood and adolescence, and extensive nummular pigment clusters. The underlying causes of the differences in the typical bone spicule and atypical nummular pigment clumping are unknown, but suggest that the variant itself influenced the rate of photoreceptor death. Functional studies are needed to define whether the substitution of aspartate impairs the folding of the tertiary RPE65 structure only and does not lead to the complete abolishment of chromophore production, thus explaining the less severe phenotype in adolescence. 相似文献
34.
Protein Kinase B Localization and Activation Differentially Affect S6 Kinase 1 Activity and Eukaryotic Translation Initiation Factor 4E-Binding Protein 1 Phosphorylation 总被引:10,自引:0,他引:10 下载免费PDF全文
Almut Dufner Mirjana Andjelkovic Boudewijn M. T. Burgering Brian A. Hemmings George Thomas 《Molecular and cellular biology》1999,19(6):4525-4534
Recent studies indicate that phosphatidylinositide-3OH kinase (PI3K)-induced S6 kinase (S6K1) activation is mediated by protein kinase B (PKB). Support for this hypothesis has largely relied on results obtained with highly active, constitutively membrane-localized alleles of wild-type PKB, whose activity is independent of PI3K. Here we set out to examine the importance of PKB signaling in S6K1 activation. In parallel, glycogen synthase kinase 3beta (GSK-3beta) inactivation and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation were monitored as markers of the rapamycin-insensitive and -sensitive branches of the PI3K signaling pathway, respectively. The results demonstrate that two activated PKBalpha mutants, whose basal activity is equivalent to that of insulin-induced wild-type PKB, inhibit GSK-3beta to the same extent as a highly active, constitutively membrane-targeted wild-type PKB allele. However, of these two mutants, only the constitutively membrane-targeted allele of PKB induces S6K1 activation. Furthermore, an interfering mutant of PKB, which blocks insulin-induced PKB activation and GSK-3beta inactivation, has no effect on S6K1 activation. Surprisingly, all the activated PKB mutants, regardless of constitutive membrane localization, induce 4E-BP1 phosphorylation and the interfering PKB mutant blocks insulin-induced 4E-BP1 phosphorylation. The results demonstrate that PKB mediates S6K1 activation only as a function of constitutive membrane localization, whereas the activation of PKB appears both necessary and sufficient to induce 4E-BP1 phosphorylation independently of its intracellular location. 相似文献
35.
Quality assessment of clinical health care with the programme of quality standard is a method of health management, through which better efficiency and safety of health outcomes can be achieved. In the period from 2002 to 2004, a pilot program of quality has been carried out on the Department of Ophthalmology, University Hospital Center in Zagreb. Seven internal audit teams of hospital commission and teams of hospital departments were evaluating introducing practice for quality standards every three months. In the period of two years improvement in all standards of quality has been noticed (expressed in percent of progress towards the ideal result of 100%): personnel 20%, patient rights 15%, medical equipment 40%, quality of emergency service 60%, implementation of clinical guidelines and criteria for elective admission 55%, quality of risk prevention 70%, quality of medical records 60%. The two-years-improvement dynamics of about 46%, first year 24%. 相似文献
36.
The aim of this study is to estimate the influence of war in Croatia on the frequency of gynecological cancer (cancer of corpus and cervix uteri and ovary) in the Clinical Hospital Osijek, particularly the relation between the pre-war and post-war period. We analyzed 1455 patients with corpus uteri and cervix uteri cancer and ovarian cancer treated in the Clinical Hospital Osijek in the period 1985-2002 (group I). Patients from Osjecko-Baranjska County were analyzed separately--1273 women, (group II) and in the group III there were 182 patients from other counties. The analyzed period was divided into: pre-war 1985-1990, war 1991-1993 and post-war period 1997-2002. In all three groups the number of patients treated for gynecological cancer was significantly larger in the post-war period (group I, N = 611, group II, N = 498, group III, N = 113) than in the pre-war period (group I, N = 457, group II, N = 433, group III, N = 24). The analysis of cancer frequency in relation to the site shows that a total number of patients treated for cervical cancer was larger in the post-war (N = 229) than in the pre-war period (N = 214), but the difference wasn't significant. However, the number of patients from Osjecko-baranjska County treated for cervical cancer was larger in the pre-war (N = 207) than in the post-war period (N = 178) but still, the difference wasn't significant. The number of patients treated for corpus uteri cancer and ovarian cancer was significantly larger for the I group in the post-war (N = 225 and N = 157 respectively) than in the pre-war period (N = 136, and N = 107 respectively). In the group II the number of patients treated for corpus uteri cancer and ovarian cancer was larger in the post-war (N = 196 and N = 124 respectively) than in the pre-war period (N = 130 and N = 96 respectively) but the difference was significant only for corpus uteri cancer. Significantly more women were treated for gynecological cancer in the post-war than in the pre-war period. However, the war had probably an indirect influence on the increased number of patients treated for gynecological cancer mainly because many more women arrived from other counties. 相似文献
37.
Gasi KM Stojanović SZ Sakac MN Popsavin M Santa SJ Stanković SM Klisurić OR Andrić N Kovacević R 《Steroids》2005,70(1):47-53
Starting from D-seco derivatives of 5-androstene 1-3, the D-homo lactones, 4 and 5, were synthesized. By the Oppenauer oxidation and/or by dehydration of 4 and 5 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil), the corresponding D-lactones 6-12 were obtained. The structures of 6 and 10 were unambiguously proved by the appropriate X-ray structural analysis. Anti-aromatase assay showed that tested compounds possess inhibition potency, however, two to four times smaller (IC50 from 0.2 to 0.7 microM, respectively) in comparison to aminoglutethimide (AG). 相似文献
38.
Dimitrijević M Stanojević S Vujić V Beck-Sickinger A von Hörsten S 《Regulatory peptides》2005,124(1-3):163-172
It is well documented that neuropeptide Y (NPY) exerts a wide range of biological functions through at least five NPY Y receptor subtypes (Y1-Y5), but its immunological effects only recently came into focus. Using NPY family peptides and NPY-related receptor-specific peptides as well as Y1 and Y2 receptor antagonists, we have tested which NPY Y receptors are involved in NPY-induced modulation of rat peritoneal macrophage function in vitro. NPY and PYY increased oxidative burst in phorbol myristate acetate (PMA)-stimulated macrophages involving activation of protein kinase C (PKC), and decreased it in zymosan-stimulated cells resembling inhibition of signaling pathways subsequent to binding of zymosan particles for the iC3b fragment receptor on macrophages. The combined treatment with NPY and NPY Y receptor antagonists revealed that NPY-induced potentiation of oxidative burst in PMA-stimulated cells is mediated through Y1 and Y2 receptors, while NPY-induced suppression in zymosan-stimulated cells is mediated through Y2 receptors only. NPY-related peptides differently modulated macrophage function, confirming involvement of NPY Y2 receptor in both potentiation and suppression of oxidative burst in these cells. Additionally, it was shown that NPY Y5 receptor mediated suppression of oxidative burst in PMA- and zymosan-stimulated macrophages. Taken together, the present data reveal an NPY Y1 and Y2/Y5 receptor interaction in NPY-induced modulation of macrophage functions related to inflammation. 相似文献
39.
Bonaci-Nikolic B Nikolic MM Andrejevic S Zoric S Bukilica M 《Arthritis research & therapy》2005,7(5):R1072-R1081
Clinical and serological profiles of idiopathic and drug-induced autoimmune diseases can be very similar. We compared data
from idiopathic and antithyroid drug (ATD)-induced antineutrophil cytoplasmic antibody (ANCA)-positive patients. From 1993
to 2003, 2474 patients were tested for ANCA in the Laboratory for Allergy and Clinical Immunology in Belgrade. Out of 2474
patients, 72 (2.9%) were anti-proteinase 3 (PR3)- or anti-myeloperoxidase (MPO)-positive and their clinical and serological
data were analyzed. The first group consisted of ANCA-associated idiopathic systemic vasculitis (ISV) diagnosed in 56/72 patients:
29 Wegener's granulomatosis (WG), 23 microscopic polyangiitis (MPA) and four Churg-Strauss syndrome. The second group consisted
of 16/72 patients who became ANCA-positive during ATD therapy (12 receiving propylthiouracil and four receiving methimazole).
We determined ANCA and antinuclear (ANA) antibodies by indirect immunofluorescence; PR3-ANCA, MPO-ANCA, anticardiolipin (aCL)
and antihistone antibodies (AHA) by ELISA; and cryoglobulins by precipitation. Complement components C3 and C4, alpha-1 antitrypsin
(α1 AT) and C reactive protein (CR-P) were measured by nephelometry. Renal lesions were present in 3/16 (18.8%) ATD-treated
patients and in 42/56 (75%) ISV patients (p <0.001). Skin lesions occurred in 10/16 (62.5%) ATD-treated patients and 14/56 (25%) ISV patients (p <0.01). ATD-treated patients more frequently had MPO-ANCA, ANA, AHA, aCL, cryoglobulins and low C4 (p <0.01). ISV patients more frequently had low α1 AT (p = 0.059) and high CR-P (p <0.001). Of 16 ATD-treated patients, four had drug-induced ANCA vasculitis (three MPA and one WG), while 12 had lupus-like
disease (LLD). Of 56 ISV patients, 13 died and eight developed terminal renal failure (TRF). There was no lethality in the
ATD-treated group, but 1/16 with methimazole-induced MPA developed pulmonary-renal syndrome with progression to TRF. ANCA-positive
ISV had a more severe course in comparison with ATD-induced ANCA-positive diseases. Clinically and serologically ANCA-positive
ATD-treated patients can be divided into two groups: the first consisting of patients with drug-induced WG or MPA which resemble
ISV and the second consisting of patients with LLD. Different serological profiles could help in the differential diagnosis
and adequate therapeutic approach to ANCA-positive ATD-treated patients with symptoms of systemic disease. 相似文献
40.
Popsavin V Benedeković G Popsavin M Srećo B Djoković D 《Carbohydrate research》2005,340(11):1866-1871
Methyl 2,3-anhydro-4-O-methanesulfonyl-alpha-d-ribopyranoside (12) was prepared through a new six-step sequence starting from d-arabinose. Chemical behaviour of 12 was further studied under solvolytic conditions and in the presence of azide anion as a nucleophile. Factors governing the regiochemistry of epoxide ring opening are briefly discussed. 相似文献