Inactive Research Articles

Pharmacokinetics and delta1-cortienic acid excretion after intravenous administration of prednisolone and loteprednol etabonate in rats.

Detailed pharmacokinetic (PK) studies in rats were performed (i)to compare the PK of prednisolone (PRN) and loteprednol etabonate (LE, a soft corticosteroid) as well as their common inactive metabolite delta1-cortienic acid (delta1-CA), (ii) to investigate the excretion of delta1-CA after PRN and LE administration, and (iii) to investigate the effect of delta1-unsaturation on the excretion of delta1-CA versus CA. Following a 10 mg x kg(-1) intravenous bolus dose, the total clearance (CL(tot)) of PRN (27.0 +/- 1.4 mL x min(-1) kg(-1)) was significantly lower than that of LE (67.4 +/- 11.6 mL x min(-1) kg(-1)) or delta1-CA (53.8 +/- 1.4 mL x min(-1) kg(-1)) indicating that the metabolism/elimination of PRN in the liver (primarily, conjugation) may be less efficient than that of LE (primarily, hydrolysis) or delta1-CA (unchanged). The volume of distribution (Vd(ss)) of PRN (823 +/- 78 mL x kg(-1)) was significantly lower than that of LE (3078 +/- 79 mL x kg(-1)) indicating that LE is more distributed to lipophilic tissues. Excretion studies have confirmed that delta1-CA is indeed a metabolite of PRN. After intravenous injection of 10 mg x kg(-1), less than 1% of the administered PRN was excreted as delta1-CA by 4 h (0.38 +/- 0.10% in bile and 0.18 +/- 0.04% in urine), significantly less than for LE (17.01 +/- 2.09% in bile and 2.53 +/- 1.17% in urine) indicating that extent of this metabolic transformation can indeed be affected by molecular design. At doses of 100 mg/kg, the proportion of delta1-CA excreted after PRN administration (0.12 +/- 0.03% in bile and 0.19 +/- 0.03% in urine) was similar to that of CA excreted after hydrocortisone administration (0.11 +/- 0.03% in bile and 0.22 +/- 0.04% in urine) indicating that the presence of the delta1 double bond (delta1-unsaturation) does not affect significantly this metabolic conversion.

AB171. RNA alternative splicing modulator can effectively increase lymphoblast enzyme activity in patients with cardiac fabry disease caused by IVS4+919G >A mutation

Background In Taiwan, DNA-based newborn screening showed a surprisingly high incidence (1/875 in males and 1/399 in females) of a cardiac fabry mutation (IVS4 + 919G >A). The common cardiac variant fabry mutation, IVS4+919G >A, affects the splicing of GLA RNA by introducing a 57-nucleotide insertion between exons 4 and 5 that contains a stop codon and leads to a truncated protein and inactive enzyme. And this mutation affected males have up to 10% residual enzyme activity and present clinically with late-onset hypertrophic cardiomyopathy. Due to the high cost of enzyme replacement therapy and the large number of patients with this mutation, the development of alternative therapies is essential. Several low-molecular-mass compounds, such as histone deacetylase inhibitors or kinase/phosphatase inhibitors, have been identified as modulators of alternative splicing. It may offer a potential alternative to enzyme replacement therapy. We expect to find out a more economic and effective drug by the detailed study of the mechanism of the small molecule modulators on the IVS4+919G >A mutation for the greater benefits of patients with this mutation.

VERITAS: removing inactive NRTIs is safe and reduces costs

VERITAS: removing inactive NRTIs is safe and reduces costs

Changes of B lymphocyte subsets in peripheral blood of patients with rheumatoid arthritis and their significance

Objective To investigate the changes of B lymphocyte subsets (naive B cells, memory B cells and plasmablasts) in peripheral blood of patients with rheumatoid arthritis (RA) and their correlations with the clinical manifestation and laboratory indexes. Methods Sixty-six patients with RA were divided into two groups including the group with active RA and the group with inactive RA according to the disease activity score in 28 Joints (DAS28). A control group with healthy subjects was set up accordingly. The distributions of B lymphocyte subsets in peripheral blood samples were detected with flow cytometry analysis and their correlations with clinical manifestations and laboratory indicators were analyzed. Results (1) Compared with healthy subjevts, the mean fluorescence intensities (MFIs) of CD19 and the percentages of memory B cells in peripheral blood of the patients with RA were significantly decreased, while the percentages of naive B cells were increased (P<0.05). The percentages of plasmablasts in the patients with active RA were significantly increased as compared with those of healthy subjects and the patients with inactive RA (P<0.05). (2) The percentages of plasmablasts in peripheral blood of the patients with RA were positively correlated with the joint tenderness count, joint swelling count and joint swelling index (P<0.05). (3) A positive correlation was found between the MFIs of CD19 and the erythrocyte sedimentation rates (ESRs) among the patients with RA. The percentages of plasmablasts were positively correlated with C reaction protein (CRP) and anti-cyclic citrullinated peptide (anti-CCP) antibody (P<0.05). (4) The percentages of plasmablasts were also positively correlated with the DAS28 among the patients with RA (R2=0.343, P<0.01). Conclusion The distributions of B lymphocyte subsets varied among the patients in different stages of RA, which were related to the patient′s clinical symptoms and laboratory indexes. The study suggested that different subsets of the B lymphocytes might play an important role in the pathological process of RA. Key words: Rheumatoid arthritis; B lymphocyte subsets; CD19; CD27; CD38

Serum angiotensin-converting enzyme for diagnosis and therapeutic evaluation of sarcoidosis.

We have expanded our studies evaluating the usefulness of serum angiotensin-converting enzyme assays for supporting a diagnosis of active sarcoidosis. Increased concentrations (>35 units/ml, >2 SD above the mean for normal control subjects) were found in 57.8 per cent of 391 patients with sarcoidosis; 23.3 per cent of these patients were either receiving corticosteroid medication or had a diagnosis of inactive or resolved disease and had normal serum angiotensin-converting enzyme activity. Thus, 75.3 per cent of the patients with active, untreated disease had increased serum concentrations of angiotensin-converting enzyme. Serum concentrations of angiotensin-converting enzyme tended to be higher in blacks with sarcoidosis than in whites with sarcoidosis. Pediatric control subjects had higher concentrations of angiotensin-converting enzyme than adults; values greater than 50 units/ml were required for the concentration to be considered to be significantly increased. Patients placed on steroid therapy had s...

The diagnostic value of orbital magnetic resonance imaging T2-Mapping in patients with active Graves' ophthalmopathy

Objective To study the clinical value of orbital magnetic resonance imaging(MRI) in diagnosis and making a judgment about the curative effect of glucocorticoid in patients with Graves' ophthalmopathy(GO). Methods A total of 106 patients with GO were divided into active GO group or inactive GO group according to whether clinical activity score(CAS)≥3 or not, respectively. T2 relaxation times(T2RTs)(ms) and areas(mm2) of four extra-ocular muscles (EOMs) (superior, inferior, medial, and lateral rectus) were directly measured by MRI T2-Mapping. Correlation analysis of T2RTs and areas with eyeball motility, diplopia, exophthalmus, visual acuity and intraocular pressure(IOP) were also performed. The T2RTs and areas of EOMs before and after intravenous methylprednisolone(iv MP) pulse therapy were recorded, respectively. Results The mean T2RTs(88.9±13.8) and mean areas(58.1±23.8) of EOMs in active GO were significantly greater than those in inactive GO(80.6±10.0 and 46.2±18.6, respectively), bing both significantly greater than those in volunteers with normal eyes(76.2±4.7 and 30.3±6.1, respectively)(P<0.01). Maximal T2RTs and maximal areas of EOMs showed significant positive correlation(P<0.01), and both were positively correlated weakly with CAS, reduced movement of eyeball, diplopia, exophthalmus and loss of visual acuity(P<0.01). On the contrary, maximal T2RTs and maximal areas of EOMs showed negative correlation or no correlation with spontaneous retrobulbar pain, painful eye movement, redness of eyelids and abnormal IOP. Even if 1≤CAS<3, ophthalmic symptoms and signs also showed a positive responses to iv MP in patients with moderate to severe GO as long as prolonged T2RTs occurred at least in one of EOMs. The maximal T2RTs, maximal areas, mean T2RTs and mean areas of EOMs were significantly decreased at the end of iv MP treatment, meanwhile ophthalmic symptoms and signs were obviously improved. Conclusions Prolonged T2RTs, especially accompanied by enlarged area on the identical EOMs is an remarkable symbols of acute inflamed muscles. The findings suggested that the use of prolonged T2RTs can improve diagnostic sensitivity and predict the curative effect of iv MP in patients with moderate to severe GO and CAS≥1. (Chin J Endocrinol Metab, 2015, 31: 327-332) Key words: Graves' ophthalmopathy; Magnetic resonance imaging; Methylprednisolone

Levetiracetam – epilepsy treatment, pharmacokinetics, mechanism of action, interaction and toxicity

Kozlowski Piotr, Czepinska-Cwik Wioleta, Kozlowska Magdalena, Kozlowska Karolina. Levetiracetam – epilepsy treatment, pharmacokinetics, mechanism of action, interaction and toxicity. Journal of Education, Health and Sport. 2015;5(4):143-150. ISSN 2391-8306. DOI: 10.5281/zenodo.16694 http://ojs.ukw.edu.pl/index.php/johs/article/view/2015%3B5%284%29%3A143-150 https://pbn.nauka.gov.pl/works/553762 http://dx.doi.org/10.5281/zenodo.16694 Formerly Journal of Health Sciences. ISSN 1429-9623 / 2300-665X. Archives 2011 – 2014 http://journal.rsw.edu.pl/index.php/JHS/issue/archive Deklaracja. Specyfika i zawartośc merytoryczna czasopisma nie ulega zmianie. Zgodnie z informacją MNiSW z dnia 2 czerwca 2014 r., ze w roku 2014 nie bedzie przeprowadzana ocena czasopism naukowych; czasopismo o zmienionym tytule otrzymuje tyle samo punktow co na wykazie czasopism naukowych z dnia 31 grudnia 2014 r. The journal has had 5 points in Ministry of Science and Higher Education of Poland parametric evaluation. Part B item 1089. (31.12.2014). © The Author (s) 2015; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland and Radom University in Radom, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 20.01.2015. Revised 27.03.2015. Accepted: 27.03.2015. LEVETIRACETAM – EPILEPSY TREATMENT, PHARMACOKINETICS, MECHANISM OF ACTION, INTERACTION AND TOXICITY Piotr Kozlowski 1 , Wioleta Czepinska-Cwik 2 , Magdalena Kozlowska 3 , Karolina Kozlowska 4 1 Katedra i Zaklad Anatomii Prawidlowej Czlowieka, UM w Lublinie 2 Klinika Chorob Wewnetrznych, 1 Wojskowy Szpital Kliniczny z Polikliniką w Lublinie 3 Katedra i Zaklad Farmakologii doświadczalnej i Klinicznej, UM w Lublinie 4 Instytut Filologii Angielskiej, KUL Uniwersytet Medyczny w Lublinie ul. W. Chodźki 1, 20-093 Lublin e-mail: piotr7176@gmail.com Abstract Epilepsy is a common chronic neurological disorder that requires a long-term antiepileptic drug therapy. Epilepsy affects approximately 1% of the world’s population, so about 50 million people worldwide have epilepsy. It more likely occurs among children and people over the age of 65. This chronic condition is characterized by recurrent, unprovoked epileptic seizures. Although there are many innovative methods of seizure control, such as neurosurgery, vagal nerve stimulations (VNS) and ketogenic diet, pharmacology is most forceful method of epilepsy treatment. Unfortunately, anticonvulsant drugs are not always effective; the number of non-responding patients is higher than 30% [2,25,29,31]. Levetiracetam (LEV) is one of the newest AEDs, marketed worldwide only since 2000 [29]. This novel antiepileptic drug has a unique and non-standard mechanism of action. The structure of LEV is similar to the prototypical nootropic drug piracetam. Its novel mechanism of action is connected with the synaptic vesicle protein SV2A in the brain. The elimination plasma half-live of LEV is approximately from 6 to 8 hours among adults. About 66% of the drug is excreted unchanged and 27% as inactive hydrolysis product [12]. LEV is mainly removed by the kidneys so that elimination parallels kidney function (renal clearance: 0,6 ml/min/kg) [3,12,32]. LEV was found to be well tolerated and effective in all types of seizures in adults and children [18]. It can be also used in combinations with other AEDs. The drug may also be useful in treatment of Lennox-Gastaut syndrome [9]. This article reviews available published data on LEV in the treatment of adults and children, including information about LEV`s pharmacokinetics, chemistry, mechanism of action, interactions and toxicity. Key words: levetiracetam, antiepileptic drugs, seizures, epilepsy.

Hormone Levels and Ultrasound Evaluation ofCaiman latirostris(Crocodylia, Alligatoridae) Ovulation

Fil: Costa Goncalves Portelinha, Thiago. Provincia de Entre Rios. Centro de Investigaciones Cientificas y Transferencia de Tecnologia a la Produccion. Universidad Autonoma de Entre Rios. Centro de Investigaciones Cientificas y Transferencia de Tecnologia a la Produccion. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Santa Fe. Centro de Investigaciones Cientificas y Transferencia de Tecnologia a la Produccion; Argentina. Universidade Federal do Tocantins; Brasil. Universidad Nacional del Litoral; Argentina

Considering the context: factors influencing engagement in life activities following primary knee replacement

Considering the context: factors influencing engagement in life activities following primary knee replacement

Effects of activity of 11β-hydroxysteroid dehydrogenase type 2 on serum potassium levels in Cushing's syndrome patients

To explore the effects of different forms of glucocorticoid excess on cortisol/cortisone ratio and to reveal the mechanisms of hypokalemia in Cushing's syndrome patients. The levels of urinary free cortisol (UFF) and urinary free cortisone (UFE) were determined in 6 adult patients with ectopia adrenocorticotropic hormone (ACTH) syndrome, 6 normal serum level of potassium adults with hypercortisolism due to adrenal tumor, 5 hypokalemic adults with hypercortisolism due to adrenal tumor and 6 healthy volunteers using high-performance liquid chromatography plus tandem mass spectrometry (LC-MS/MS). For 4 groups, the results of UFF+UFE were (2 787 ± 820), (689 ± 163), (697 ± 120) and (70 ± 27)µg/L and UFF/UFE ratio 2.98 ± 0.35, 1.03 ± 0.42, 2.24 ± 0.37 and 0.42 ± 0.20 respectively. The values of UFF+UFE had no statistical difference between normal and low levels of serum potassium adults with hypercortisolism. And the ratio of UFF/UFE of hypokalemic adults with hypercortisolism was significantly higher than that of normal serum level of potassium adults with hypercortisolism. It suggested that the deficiency of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD 2) was present in hypokalemic adults with hypercortisolism. Due to a deficiency of 11β-HSD2, active cortisol can not be transformed into inactive cortisone in some patients with ACTH-independent Cushing's syndrome.

MP1-15 QUANTITATIVE HISTOMORPHOMETRIC ANALYSIS OF PROSTATE BIOPSY IMAGES PREDICT FAVORABLE OUTCOME IN ACTIVE SURVEILLANCE PATIENTS

You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 2015MP1-15 QUANTITATIVE HISTOMORPHOMETRIC ANALYSIS OF PROSTATE BIOPSY IMAGES PREDICT FAVORABLE OUTCOME IN ACTIVE SURVEILLANCE PATIENTS George Lee, Robert Veltri, Guangjing Zhu, H. Ballentine Carter, Patricia Landis, Jonathan Epstein, and Anant Madabhushi George LeeGeorge Lee More articles by this author , Robert VeltriRobert Veltri More articles by this author , Guangjing ZhuGuangjing Zhu More articles by this author , H. Ballentine CarterH. Ballentine Carter More articles by this author , Patricia LandisPatricia Landis More articles by this author , Jonathan EpsteinJonathan Epstein More articles by this author , and Anant MadabhushiAnant Madabhushi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.178AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer (CaP) is well documented as being one of the most overdiagnosed and overtreated diseases. For men with very low risk (VLR) CaP, active surveillance (AS), an accepted monitoring program, may be offered in lieu of immediate intervention to reduce unnecessary treatment and improve quality of life. Our objective is to identify image patterns in prostate cancer, via computational image analysis of digitized biopsy core images, which can stratify favorable and unfavorable outcomes in VLR patients on AS. We specifically chose to look at nuclear shape and orientation as they were previously shown to be related to disease progression. METHODS Based on the NCCN CaP guidelines, CaP patients from the Johns Hopkins Hospital (JHH) were given the option for AS if they were classified as VLR (stage T1c, Prostate Specific Antigen (PSA) < 10ng/mL, Gleason sum (GS) >= 6, >= 2 positive cores, >= 50% core involvement, PSA density (PSAD) < 0.15 ng/mL and life expectancy < 20 years). Outcome was deemed favorable if patients under AS did not require re-classification with follow up and deemed unfavorable if disease demonstrated an upgraded GS, increased tumor volume, and/or PSA/PSAD during monitoring. Image analysis was performed on 65 regions of interest from H&E stained biopsy core images (30 Favorable, 35 Unfavorable) obtained from 51 AS CaP patients managed at the JHH AS program. For each image, nuclear shape and cell orientation entropy (COrE) features, which capture directional disorder of nuclei, were extracted from the segmented nuclei. Cancerous regions of interest were demarcated by the pathologist. RESULTS Nuclear shape-based features (Std. Dev. Perimeter Ratio) and COrE features (standard deviation tensor contrast energy, standard deviation tensor contrast variance) were capable of differentiating favorable from unfavorable outcome in 51 AS patients as shown in Figure 1. This ability to identify patients that will fail AS is supported by a Random Forest classifier using these nuclear shape and COrE features (AUC = 0.70) compared to GS (AUC = 0.60). CONCLUSIONS We demonstrated the ability of computerized image features to predict favorable from unfavorable outcomes in AS patients using biopsy images statistically significantly (p < 0.05) better than GS. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e6-e7 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information George Lee More articles by this author Robert Veltri More articles by this author Guangjing Zhu More articles by this author H. Ballentine Carter More articles by this author Patricia Landis More articles by this author Jonathan Epstein More articles by this author Anant Madabhushi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Kinase-independent role of cyclin D1 in chromosomal instability and mammary tumorigenesis.

Cyclin D1 is an important molecular driver of human breast cancer but better understanding of its oncogenic mechanisms is needed, especially to enhance efforts in targeted therapeutics. Currently, pharmaceutical initiatives to inhibit cyclin D1 are focused on the catalytic component since the transforming capacity is thought to reside in the cyclin D1/CDK activity. We initiated the following study to directly test the oncogenic potential of catalytically inactive cyclin D1 in an in vivo mouse model that is relevant to breast cancer. Herein, transduction of cyclin D1(-/-) mouse embryonic fibroblasts (MEFs) with the kinase dead KE mutant of cyclin D1 led to aneuploidy, abnormalities in mitotic spindle formation, autosome amplification, and chromosomal instability (CIN) by gene expression profiling. Acute transgenic expression of either cyclin D1(WT) or cyclin D1(KE) in the mammary gland was sufficient to induce a high CIN score within 7 days. Sustained expression of cyclin D1(KE) induced mammary adenocarcinoma with similar kinetics to that of the wild-type cyclin D1. ChIP-Seq studies demonstrated recruitment of cyclin D1(WT) and cyclin D1(KE) to the genes governing CIN. We conclude that the CDK-activating function of cyclin D1 is not necessary to induce either chromosomal instability or mammary tumorigenesis.

Effect and mechanism of exogenous carbon monoxide against excessive neutrophil infiltration in liver and lung tissues during sepsis

Objective To determine the inhibitory effect and mechanism of exogenous carbon monoxide against excessive neutrophil infiltration in liver and lung tissues during sepsis. Methods Thirty-two mice were subjected to sham operation (sham group), cecal ligation and perforation (CLP) group, CLP with 8 mg/kg of exogenous carbon monoxide releasing molecule Ⅱ (CORM-2) (CORM-2 group), and CLP with 8 mg/kg of inactive variants of CORM-2 (iCORM-2) (iCORM-2 group) according to the random number table, with 8 mice per group. Liver and lung tissues were collected at 24 hours after surgery to examine the pathologic changes, myeloperoxidase (MPO) activity and malonaldehyde (MDA) content. Another 60 mice were enrolled into the same 4 groups with 15 mice per group and were tested for 72-hour survival rate. Bone marrow neutrophils were isolated and divided into normal control group, 1 μg/ml lipopolysaccharide (LPS) group, 1 μg/ml LPS plus 10 μmol/L CORM-2 group (low dose group), 1 μg/ml LPS plus 50 μmol/L CORM-2 group (high dose group), 1 μg/ml LPS plus 50 μmol/L iCORM-2 group (iCORM-2 group). Under the agarose chemotaxis, qPCR and immunofluorescence detection of formyl peptide receptor 1 (FPR1) were performed. Results CLP group presented enhanced activity of MPO [liver: (9.1±1.1 )U/g, lung: (16.3±2.8)U/g], increased MDA content [liver: (76.5±11.3)nmol/mg, lung: (32.4±10.3)nmol/mg]and 72-hour survival rate of 20% as compared with the sham group (all P<0.05). CORM-2 group showed inhibited activity of MPO [liver: (5.2±0.8)U/g, lung: (7.5±2.4)U/g], increased MDA content [liver: (46.7±6.1)nmol/mg, lung: (23.8±7.3)nmol/mg]and 72-hour survival rate of 67% as compared with the sham group (all P<0.05). LPS enhanced neutrophil migration (61.3±7.1) (P<0.05) and expression of FPR1 which was enriched in the membrane. Meanwhile, neutrophil migration was significantly inhibited in a dose-dependent of CORM-2 (low dose group: 43.3±6.1, high-dose group: 23.3±5.9) (P<0.05). Conclusions Exogenous carbon monoxide is effective to inhibit the excessive neutrophil infiltration, attenuate oxidative stress or pathological injury, and improve the survival from sepsis. The mechanism is associated with the down-regulation of FPR1, inhibition of FPR1 enrichment in the membrane, and decreased neutrophil migration. Key words: Sepsis; Neutrophil infiltration; Carbon monoxide; Migration

Markers of hepatitis B virus infection: current application and prospect

The natural history of chronic HBV infection is diverse and variable, ranging from inactive carriers to progressive chronic hepatitis B (CHB), cirrhosis and hepatocelluar carcinoma. It is estimated that 93 million people are chronically infected with HBV and 20 million cases suffering from chronic hepatitis B in China. Hepatocelluar carcinoma has been the second leading cause of death for male in China. Liver cirrhosis and HCC which have high mortality and morbidity have become the heavy burden for the limited medication resource of China. Here the current clinical applications and consensus progression based on antigen and nuclear acid detection were acknowledged. The reasonable application as well as appropriate clinical interpretation are emphasized indicating that laboratory medicine practitioners should be more actively involved in clinical diagnosis and treatment. More efforts and contributions should be made by the laboratory medicine practitioner for optimizing clinical management of HBV–related diseases in future. (Chin J Lab Med, 2015, 38: 145–147) Key words: Hepatitis B, chronic; Biological markers; Hepatitis B surface antigens; Hepatitis B e antigens; Hepatitis B core ntigens

Current Topics on Vitamin D. Evolution of animals and vitamin D

Vitamin D3 is already found in the early evolution of life, but essentially as inactive products of the photochemical reaction of 7-dehydrocholesterol. The full vitamin D endocrine system characterized by the specific vitamin D transport protein (DBP) , specific vitamin D-metabolizing CYP P450 enzymes, active vitamin D metabolites, 1α,25 (OH) 2D3, specific vitamin D nuclear receptor (VDR), and fibroblast growth factor 23 (FGF23) became essential for maintaining calcium and bone homeostasis in terrestrial animals cope with the challenging of higher gravity and calcium-poor environment. The present review describes the story about the evolution of animals and vitamin D.

The Uranium Mill Tailings Radiation Control Act of 1978

The long-term environmental effects of the Uranium Mill Tailings Radiation Control Act of 1978 address the public health hazards of radioactive wastes and recognize the significance of this issue to public acceptance of nuclear energy. Title I of the Act deals with stabilizing and controlling mill tailings at inactive sites and classifies the sites by priority. It represents a major Federal commitment. Title II changes and strengthens Nuclear Regulatory Commission authority, but it will have little overall impact. It is not possible to assess the Act's effect because there is no way to know if current technology will be adequate for the length of time required. 76 references. (DCK)

Comparative analysis of flexibility in active and inactive elderly women

Com o envelhecimento ocorre um declinio na aptidao fisica, uma variavel muito atingida e a flexibilidade, e a pratica de exercicios fisicos pelos idosos e um importante fator para a manutencao da saude e aptidao fisica no decorrer do processo de envelhecimento. Objetivo: Comparar a flexibilidade de mulheres idosas praticantes hidroginastica, treinamento combinado e nao ativas. Participaram 60 voluntarias, idade entre 60 e 80 anos, agrupadas em: ativas praticantes de hidroginastica (G1) 20 voluntarias; ativas praticantes de treinamento combinado (G2) 20 voluntarias; nao ativas (G3) 20 voluntarias. Metodos: As voluntarias foram submetidas a avaliacao antropometrica com medidas de massa corporal, estatura e circunferencia da cintura e da flexibilidade com medidas da distância alcancada no teste de sentar e alcancar e da amplitude da flexao e extensao do quadril atraves do goniometro. Foram verificados os pressupostos de normalidade por meio do teste de Shapiro-Wilk, para a comparacao entre os grupos (G1, G2, G3) foram realizados o teste Anova one way, seguido do post hoc de Tukey para os dados com distribuicao parametrica, e o teste de Friedman para amostras com distribuicao nao parametrica. Aplicou-se o nivel de significância de p < 0,05. Resultados: Nas variaveis antropometricas nao foram encontradas diferencas significativas entre grupos. Na flexibilidade, foi encontrada diferenca significativa na flexao e na extensao de quadril, os grupos G1 e G2 apresentaram maiores valores que o G3, nao houve diferenca significativa entre G1 e G2, nao existindo outras diferencas significativas entre os grupos. Conclusao: Os resultados sugerem que os treinamentos de hidroginastica e combinado proporcionaram melhora na flexao e extensao do quadril das mulheres idosas, sem influencia nas outras variaveis estudadas.

Progress in Directed Transition Metal-Catalyzed Oxidation of Inactive C(sp3)—H Bonds

近年来,过渡金属催化不活泼C（sp^3）—H键氧化反应取得重要进展.该领域的研究主要集中在过渡金属催化甲烷选择性氧化,以及过渡金属催化导向基团螯合甲基氧化方面,这些研究成果实现了许多传统氧化方法不能完成的高效选择性转化.重点概述导向基团（肟、噁唑啉、吡啶、酰胺、羧酸、羟基）对促进过渡金属催化氧化C（sp^3）—H键的影响,底物的乙酰氧基化、羟基化、羰基化、酯化反应以及催化反应体系和相关机制.

Evaluation of antimicrobial activity and mode of action of Laportea aestuans extracts against urogenital, gut and pulmonary pathogens

Phytochemical screening and antimicrobial activities of Laportea aestuans leaves, stem-bark and whole-plant aqueous, methanol and ethanol extracts were carried-out using standard phytochemical and microbiological methods. The phytochemical procedures indicated the presence of saponins, tannins, phlobatannins, flavonoids, alkaloids and cardiac-glycosides. The yields of the whole-plant extracts were significantly(p ethanol>methanol. The antimicrobial activities of the aqueous, methanol and ethanol extracts of Laportea aestuans leaves, stem-bark and whole-plant against the auchthocthonous urogenital, gut and pulmonary test organisms: Staphylococcus aureus , Staphylococcus saprophyticus , Streptococcus pneumoniae , Escherichia coli , Pseudomonas aeruginosa , Proteus mirabilis , Salmonella typhi , Vibrio cholerae , Shigella dysenteriae , Candida albicans and Aspergillus niger ; assayed by the modified agar-well diffusion technique indicated broad-spectrum antimicrobial activities. Analysis of the antimicrobial activities of the extracts by activity-index, indicated that the leaf extracts, have significantly (p stem-bark extracts >whole- plant extracts. Similarly by activity-index, the ethanol extracts recorded significantly (p methanol extracts>aqueous extracts. The minimum inhibitory concentrations (MIC) of the leaves extracts, assayed by the macrobroth-dilution technique was lowest against Shigella dysentariae ( 1.25 mg/ml),and generally between 2.50 - 5.0 mg/ml against the other bacterial and fungal species tested for both methanol and ethanol extracts; while the aqueous extracts was inactive. Equally, the minimum biocidal concentrations (MBC), and the establishment of mode of activity of the bioactive leaves extracts, assayed by the macrobroth-dilution technique, indicated predominantly static activity for the methanol extract, and a predominantly cidal activity for the ethanol extract. Both methanol and ethanol leaves extracts of Laportea aestuans showed significant (p<0.05) antimicrobial activities compared to the standard antibiotics: chloramphenicol and fluconazole. Keywords: Antimicrobial potency, Activity –spectra, Laportea aestuans Extracts, Auchthocthonous urogenital, gut and pulmonary pathogens

Exercise and older women's wellbeing.

Older women are one of the most inactive groups in the population despite being at an age where they are at greater risk of health problems. Knowing what influences these women to exercise regularly may help the development of strategies to assist sedentary women in this age group to become active. This paper reports the findings of a study that explored why a group of older women attending a fitness centre participate in regular exercise activities. The study used a qualitative approach to data collection and analysis. Data were collected using in-depth interviews from ten women over 50 years of age who exercised on a regular basis. The findings revealed four themes relating to the maintenance of general wellbeing: exercise as a socially supportive activity, exercising to maintain wellbeing, exercising to maintain independence, and exercise as liberating. The implications of the findings for nursing education, clinical practice and research are discussed.