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51.
The Effects of Permeation Enhancers on the Surface Morphology of the Rat Nasal Mucosa: A Scanning Electron Microscopy Study 总被引:2,自引:0,他引:2
A rat model has been developed to compare relative morphological changes in the nasal mucosa after exposure to potential membrane permeation enhancers. Scanning electron microscopy was used to characterize gross structural and specific cellular changes following exposure. Micrographs of the rat nasal mucosa were scored in four categories: (1) mucosal surface integrity, (2) ciliary morphology, (3) mucus/extracellular debris, and (4) presence of red blood cells. The order of increasing morphological damage resulting from a 5-min exposure to each surfactant was 0.5% Solulan C-24 0.5% Solulan C-24/0.5% sodium tauro-24,25-dihydrofusidate (STDHF) < 0.5% STDHF < 1.0% STDHF 1.0% Laureth-9 < 1.0% sodium taurodeoxycholate 1.0% sodium deoxycholate. The changes observed in the mucosal morphology after exposure to the various surfactants are in general agreement with data in the literature. This model is able to compare rapidly the relative morphological effects on the mucosal membrane of different nasal formulations. 相似文献
52.
Katharine Edgerley Lisa Bryson Lucy Hanington Rachel Irving Shelagh Joss Anne Lampe Isabelle Maystadt Deborah Osio Ruth Richardson Miranda Split Francis H. Sansbury Ingrid Scurr Helen Stewart Alisdair McNeil Karen Low 《American journal of medical genetics. Part A》2023,191(5):1447-1458
To delineate further the clinical phenotype of Lamb–Shaffer Syndrome (LSS) 16 unpublished patients with heterozygous variation in SOX5 were identified either through the UK Decipher database or the study team was contacted by clinicians directly. Clinical phenotyping tables were completed for each patient by their responsible clinical geneticist. Photos and clinical features were compared to assess key phenotypes and genotype–phenotype correlation. We report 16 SOX5 variants all of which meet American College of Medical Genetics/Association for Clinical Genomic Science ACMG/ACGS criteria class IV or V. 7/16 have intragenic deletions of SOX5 and 9/16 have single nucleotide variants (including both truncating and missense variants). The cohort includes two sets of monozygotic twins and parental gonadal mosaicism is noted in one family. This cohort of 16 patients is compared with the 71 previously reported cases and corroborates previous phenotypic findings. As expected, the most common findings include global developmental delay with prominent speech delay, mild to moderate intellectual disability, behavioral abnormalities and sometimes subtle characteristic facial features. We expand in more detail on the behavioral phenotype and observe that there is a greater tendency toward lower growth parameters and microcephaly in patients with single nucleotide variants. This cohort provides further evidence of gonadal mosaicism in SOX5 variants; this should be considered when providing genetic counseling for couples with one affected child and an apparently de novo variant. 相似文献
53.
Harry T. Whelan Lucy H. Kras Kutlan Ozker Dawn Bajic Meic H. Schmidt Yu Liu Lisa Ann Trembath Fusun Uzum Glenn A. Meyer Annette D. Segura B. David Collier 《Journal of neuro-oncology》1994,22(1):7-13
The use of PHOTOFRIN for photodynamic therapy of human gliomas has been studied by i.v. administration and laser photosensitization. Defining the uptake of PHOTOFRIN in the patient's tumor in comparison with the surrounding normal brain tissue is highly desirable for patient selection and study ofin vivo kinetics. We utilized a non-invasive approach to the detection of PHOTOFRIN uptake in brain tumors with111In-oxine radiolabeled PHOTOFRIN and external imaging and quantitation using a gamma camera. Biodistribution of111In-labeled PHOTOFRIN in 13 organs was determined in four dogs and 15 mice with gliomas.99mTc-DTPA was used as a control for nonspecific uptake. The greatest concentration of111In-PHOTOFRIN in the brain tumor occurred at 24 hours post i.v. administration. The brain tumor PHOTOFRIN uptake was seven times greater than that of normal brain. The decreased blood background at 72 hours made this the optimum time for imaging. Specific tumor tissue uptake of111In-PHOTOFRIN occurred, well beyond that resulting from blood-brain-barrier (BBB) breakdown. 相似文献
54.
Disposition in mice of 7-hydroxystaurosporine,a protein kinase inhibitor with antitumor activity 总被引:1,自引:0,他引:1
Donald L. Hill Kathleen F. Tillery Lucy M. Rose Claude F. Posey 《Cancer chemotherapy and pharmacology》1994,35(1):89-92
UCN-01, a hydroxylated derivative of staurosporine, was selected for study because of its promising antitumor activity. For mice dosed intravenously, subcutaneously, or by oral gavage with this compound, the maximum tolerated doses (MTD) were 20, 10, and >100 mg/kg, respectively. UCN-01 was stable in mouse and dog plasma, but in human plasma it was converted to a metabolite in a process not inhibited by standard protease and esterase inhibitors. Following n intravenous dose of 10 mg/kg UCN-01, the half-lives for the initial (t
1/2) and terminal (t
1/2) exponential phases of elimination were 10 and 85 min, respectively; the area under the plasma concentration-time curve (AUC value) was 117 g min ml–1. In mice dosed by oral gavage with 10 mg/kg, the calculated value for the half-life of the elimination phase was 150 min. The AUC value was 15 g min ml–1, giving a value for bioavailability of 13%. After subcutaneous dosing with 10 mg/kg, the calculated values for half-lives for the distribution and elimination phases were 23 and 130 min, respectively; the AUC value was 113 g min ml–1. Since this value is equivalent to that obtained for intravenous dosing, administration of UCN-01 by the subcutaneous route may be an alternative to intravenous dosing in preclinical and clinical trials.This work was supported by contract NO1-CM-27710 (National Cancer Institute, National Institutes of Health, Department of Health and Human Services) 相似文献
55.
Blumenstiel K Schöneck R Yardley V Croft SL Krauth-Siegel RL 《Biochemical pharmacology》1999,58(11):1791-1799
Lipoamide dehydrogenase (LipDH), trypanothione reductase (TR), and glutathione reductase (GR) catalyze the NAD(P)H-dependent reduction of disulfide substrates. TR occurs exclusively in trypanosomatids which lack a GR. Besides their physiological reactions, the flavoenzymes catalyze the single-electron reduction of nitrofurans with the concomitant generation of superoxide anions. Here, we report on the interaction of clinically used antimicrobial nitrofurans with LipDH and TR from Trypanosoma cruzi, the causative agent of Chagas' disease (South American trypanosomiasis), in comparison to mammalian LipDH and GR. The compounds were studied as inhibitors and as subversive substrates of the enzymes. None of the nitrofurans inhibited LipDH, although they did interfere with the disulfide reduction of TR and GR. When the compounds were studied as substrates, T. cruzi LipDH showed a high rate of nitrofuran reduction and was even more efficient than its mammalian counterpart. Several derivatives were also effective subversive substrates of TR, but the respective reaction with human GR was negligible. Nifuroxazide, nifuroxime, and nifurprazine proved to be the most promising derivatives since they were redox-cycled by both T. cruzi LipDH and TR and had pronounced antiparasitic effects in cultures of T. cruzi and Trypanosoma brucei. The results suggest that those nitrofuran derivatives which interact with both parasite flavoenzymes should be revisited as trypanocidal drugs. 相似文献
56.
Lowe G Droz AS Vilaivan T Weaver GW Tweedale L Pratt JM Rock P Yardley V Croft SL 《Journal of medicinal chemistry》1999,42(6):999-1006
A range of (2,2':6',2'-terpyridine)platinum(II) complexes are shown to possess antiprotozoal activity in vitro against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei,the causative organisms of tropical diseases leishmaniasis and trypanosomiasis. The best compounds caused 100% and 78% inhibition of growth of the intracellular amastigote forms of L. donovani and T. cruzi, respectively, at a concentration of 1 microM and 100% inhibition of growth of the bloodstream trypomastigote forms of T. brucei at a concentration of 0.03 microM. The results obtained with complexes in which the fourth ligand to platinum(II) is capable of being substituted with a substitution inert hydroxyethanethiolate complex are compared. The ammine complexes show high antiprotozoal activity suggesting that the trans influence of the 2,2':6',2'-terpyridine ligand has a profound effect on the ease of displacement of the fourth ligand in (2,2':6',2' -terpyridine)platinum(II) complexes, although nonbonded interaction between the ammine ligand and the 6 and 6' ' hydrogens probably also weakens the ligation to Pt(II). 相似文献
57.
Abraham SC Ravich WJ Anhalt GJ Yardley JH Wu TT 《The American journal of surgical pathology》2000,24(12):1678-1682
Involvement of the esophagus by lichen planus is a rarely reported condition. The histologic features of esophageal lichen planus, which may differ from those of cutaneous disease, have only rarely been illustrated. We describe a 58-year-old woman with skin and oral lichen planus who presented with dysphagia and an esophageal stricture that were ultimately diagnosed as esophageal lichen planus. Multiple esophageal biopsies demonstrated a lichenoid, T cell-rich lymphocytic infiltrate, along with degeneration of the basal epithelium and Civatte bodies. Correct diagnosis of esophageal lichen planus is critical because of its prognostic and therapeutic distinction from other more common causes of esophagitis and stricture formation. 相似文献
58.
Until now there has no been no simple, reliable clinical test that assesses the function of the otolith organs. However, recent work has suggested the occurrence of an easily identifiable electromyographic (EMG) waveform in isometrically contracting sternomastoid muscles in response to loud clicks. This is thought to represent an otolith evoked disynaptic reflex. Equipment routinely used for evoked response audiometry (ERA) has been adapted to investigate this response. A short latency (8 ms) positive-negative EMG waveform has been recorded in 31 of 32 normal subjects. The latency of the positive peak (P1) is 11.7 ms ( sd = 0.89), and the negative peak (N1) is 20.5 ms ( sd = 1.89). It is predominantly ipsilateral, although a contralateral response was present in 35.5%. The response has also been recorded in three patients with a severe unilateral sensorineural hearing loss and normal caloric responses, and in a patient undergoing cochlear implantation for profound bilateral sensorineural hearing loss. Further work is required to delineate the value of this technique in investigating vestibular lesions. 相似文献
59.
Lubna Pal Jan L. Shifren Keith B. Isaacson YuChiao Chang Lucy Leykin Thomas L. Toth 《Journal of assisted reproduction and genetics》1998,15(1):27-31
Purpose:
The impact of severity of endometriosis on the outcome of in vitro fertilization (IVF) was analyzed in an uncontrolled, retrospective study in an academic IVF program.
Methods:
Sixty-one patients with a primary diagnosis of endometriosis undergoing 85 cycles of IVF were included in the study. Patients were divided according to the severity of disease based on the revised American Fertility Society (AFS) classification into groups A (stages I/II, or minimal/mild) and B (stages III/IV, or moderate/severe). Group A included 32 patients undergoing 45 IVF-embryo transfer (ET) cycles; group B included 29 patients undergoing 40 IVF cycles. Exclusion criteria were age older than 40 years, basal day 3 follicle stimulating hormone (FSH) greater than 20 IU/L, male-factor infertility, assisted hatching, and gamete intrafallopian transfer cases. Stimulation for IVF cycles was standard using pituitary down-regulation with gonadotropin-releasing hormone agonist in a midluteal protocol. Controlled ovarian hyperstimulation (COH) was achieved using a combination of FSH and human menopausal gonadotropin. Outcomes assessed included response to COH and number, maturity, and quality of oocytes retrieved. Fertilization, implantation, and pregnancy rates after IVF-ET were also analyzed.
Results:
The response to COH and the number, maturity, and quality of the oocytes was comparable between patients with varying severity of endometriosis. Fertilization rates for oocytes of patients in group B (stages III/IV) were significantly impaired compared to those in group A (stages I/II) (P = 0,004). The rates for implantation, clinical pregnancy, and miscarriage were comparable between the two groups.
Conclusions:
The reduced fertilization potential of the oocytes obtained from patients with severe endometriosis in the absence of male-factor infertility suggests an adverse biological impact of the advanced disease on the oocytes. The outcome of IVF-ET, however, is unaffected by increasing severity of endometriosis. This suggests that IVF may compensate for or overcome this reduction in the biological potential of the oocytes associated with severe disease, thus accounting for a comparable outcome irrespective of the severity of endometriosis. 相似文献
60.
目的 建立兔色素性脉络膜黑素瘤动物模型 ,以供人类研究眼黑素瘤新的治疗方法。方法 4种黑素瘤细胞株 (B16F10 ,RPMI 184 6 ,OCM1andIIB)种植于 2 0 6只大白兔眼中以建立脉络膜黑素瘤 ,其中 172只动物注射环孢菌素A (Cyclosporine)进行免疫抑制 ,34只作为对照。肿瘤碎片 (或细胞悬液 )经巩膜种植于兔眼脉络膜下腔 ,用间接眼底镜、超声和眼底照像进行观察。结果 4种黑素瘤细胞生长各异 ,其中B16F10 和RPMI 184 6生长较快 ,典型肿瘤生长 3~ 4mm需 2~ 3周 ,OCM1和IIB生长缓慢。肿瘤生长的位置和形状与种植的肿瘤碎片或细胞悬液有密切关系。结论 兔色素性脉络膜黑素瘤的建立 ,将为人们研究眼黑素瘤新的治疗办法提供更适合的动物模型。 相似文献