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301.
Armin Mooranian Rebecca Negrulj Sangeetha Mathavan Jorge Martinez Jessica Sciarretta Nigel Chen-Tan TK Mukkur Momir Mikov Mladena Lalic-Popovic Maja Stojančević Svetlana Golocorbin-Kon Hani Al-Salami 《Journal of pharmaceutical innovation》2014,9(2):150-157
Introduction
In previous studies carried out in our laboratory, a bile acid (BA) formulation exerted a hypoglycaemic effect in a rat model of type-1 diabetes (T1D). When the antidiabetic drug gliclazide (G) was added to the bile acid, it augmented the hypoglycaemic effect. In a recent study, we designed a new formulation of gliclazide-cholic acid (G-CA), with good structural properties, excipient compatibility and exhibits pseudoplastic-thixotropic characteristics. The aim of this study is to test the slow release and pH-controlled properties of this new formulation. The aim is also to examine the effect of CA on G release kinetics at various pH values and different temperatures.Method
Microencapsulation was carried out using our Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) and G-CA-SA (test) at a constant ratio (1:3:30), respectively. Microcapsules were examined for efficiency, size, release kinetics, stability and swelling studies at pH 1.5, pH 3, pH 7.4 and pH 7.8 and temperatures of 20 and 30 °C.Results
The new formulation is further optimised by the addition of CA. CA reduced microcapsule swelling of the microcapsules at pH 7.8 and pH 3 at 30 °C and pH 3 at 20 °C, and, even though microcapsule size remains similar after CA addition, percent G release was enhanced at high pH values (pH 7.4 and pH 7.8, p?<?0.01).Conclusion
The new formulation exhibits colon-targeted delivery and the addition of CA prolonged G release suggesting its suitability for the sustained and targeted delivery of G and CA to the lower intestine. 相似文献302.
Background
A case control study was carried out to study the emerging risk factors for coronary artery disease in Indians. Methods: The diagnosis of coronary artery disease was based on correlation of clinical, biochemical, electrocardiography, echocardiography, treadmill testing and coronary arteriography findings. The study comprised 100 cases of coronary artery disease (acute coronary syndrome and chronic coronary artery disease) and 100 controls in two tertiary care service hospitals. The subjects were evaluated for total plasma homocysteine, insulin, C-reactive protein (CRP), lipoprotein fibrinogen and anti-chlamydial anti-bodies.Result
Male to female ratio was 10:1 in study group with similar predominance of males in controls. Mean age of the cases was 47 years (range 25-59 years) and that of controls was 43 years (range 23-56 years). 64% cases had acute coronary syndrome and 34% had chronic coronary artery disease. In the coronary artery disease population, 76% cases had hyperhomocyteinemia, 9% hyperinsulinaemia, 11% abnormal CRP values, 23% abnormal lipoprotein (a) levels, 40% IgG anti-chlamydial anti-bodies and only 11% had Ig M anti-chlamydial antibodies. In the control population, 72% had hyperhomocystinaemia and 6% hyperinsulinaemia while 23% and 9% controls had IgG and IgM anti chlamydial antibodies respectively. In control group 19% cases had abnormal lipoprotein(a) levels and only 2% had abnormal C reactive protein values. Significant correlation of CAD was seen with CRP values and Ig G anti-chlamydial antibodies. Both the study group and controls had higher homocysteine levels than that observed in some Indian and Western studies.Conclusion
High C reactive protein levels and Ig G anti-chlamydial antibodies are associated with coronary artery disease in Indians. Insulin, lipoprotein A, fibrinogen, lgM anti-chlamydial antibodies and higher levels of total plasma homocysteine have no significant association with coronary artery disease.Key Words: Emerging risk factors, Coronary artery disease 相似文献303.
Fanconi anemia genes act to suppress a cross-linker-inducible p53- independent apoptosis pathway in lymphoblastoid cell lines 总被引:5,自引:1,他引:5
Hypersensitivity to cross-linking agents such as mitomycin C (MMC) is characteristic of cells from patients suffering from the inherited bone marrow failure syndrome. Fanconi anemia (FA). Here, we link MMC hypersensitivity of Epstein-Barr virus (EBV)-immortalized FA lymphoblasts to a high susceptibility for apoptosis and p53 activation. In MMC-treated FA cells belonging to complementation group C (FA-C), apoptosis followed cell cycle arrest in the G2 phase. In stably transfected FA-C cells, plasmid-driven expression of the wild-type cytoplasmic FAC protein relieved MMC-dependent G2 arrest and suppressed p53 activation. However, in both FA and non-FA lymphoblasts, p53 seemed not to be instrumental in the induction of MMC-dependent apoptosis, since overexpression of a dominant-negative p53 mutant failed to affect cell survival. In addition, no differences in the level of Bcl-2 expression, an inhibitor of apoptosis, were detected between FA and non- FA cells either in the absence or presence of MMC. Our findings suggest that FAC and the other putative FA gene products may function in a yet to be identified p53-independent apoptosis pathway. 相似文献
304.
Zeidler HK; Kvien TK; Hannonen P; Wollheim FA; Forre O; Geidel H; Hafstrom I; Kaltwasser JP; Leirisalo-Repo M; Manger B; Laasonen L; Markert ER; Prestele H; Kurki P 《Rheumatology (Oxford, England)》1998,37(8):874-882
OBJECTIVE: This study compared the progression of joint damage in patients
with early active severe rheumatoid arthritis (RA) treated with cyclosporin
or parenteral gold. METHODS: In this open, randomized, multicentre study
with a blinded radiological endpoint, 375 patients who had suffered from
active severe RA for <3 yr were randomized to be treated for 18 months
with low-dose cyclosporin or parenteral gold. The groups were stratified
with regard to corticosteroid use. Primary efficacy variables were numbers
of erosions, erosion score and the Larsen-Dale joint damage score. RESULTS:
Joint damage progressed at similar rates in both treatment arms. In both
groups, patients receiving corticosteroids had less X-ray progression.
Rheumatoid factor positivity, high swollen joint count, high erythrocyte
sedimentation rate and pre-existing X-ray abnormalities predicted
progression of joint damage. Although numbers of serious adverse events
were similar, more gold patients (n = 65) than cyclosporin patients (n =
45) withdrew from study medication because of adverse events. CONCLUSION:
Cyclosporin was comparable to parenteral gold in retarding progression of
joint damage and was better tolerated in terms of adherence to therapy. The
open label design should be kept in mind when assessing this difference.
相似文献
305.
306.
Tiina M. Reijonen Matti Korppi Liisa Kuikka Kari Savolainen Marjaana Kleemola Ilkka Mononen Kyllikki Remes 《Pediatric pulmonology》1997,23(6):397-402
We have evaluated the role of eosinophil cationic protein (ECP) concentrations in serum in predicting wheezing after bronchiolitis, during infancy and early childhood. A prospective study at a university hospital serving all pediatric patients in a defined area was designed. Serum ECP concentrations were measured in 92 infants under the age of 2 years on admission for acute bronchiolitis, and 6 and 16 weeks after hospitalization. Nebulized anti-inflammatory therapy was initiated during hospitalization: 32 patients received cromolyn sodium and 32 patients received budesonide for 16 weeks; 30 control patients received no maintenance therapy. The numbers of subsequent physician-diagnosed wheezing episodes and hospital admissions for obstructive airway disease were recorded during 16 weeks of follow-up. At entry, 14 of 92 (15%) children had high (≥16 μg/L) levels of ECP in their serum. During the 16-week follow-up period, this group of patients had significantly more physician-diagnosed episodes of wheezing (86% vs. 43%, P < 0.01) and hospital admissions for wheezing (64% vs. 19%, P = 0.001) than those with serum levels of ECP < 16 μg/L. The number of patients with serum ECP ≥ 8 μg/L was 25 (27%); 76% of this group developed physician-diagnosed wheezing (P < 0.01), and 48% had hospital admissions for wheezing (P < 0.01). Serum ECP levels decreased significantly with respect to time after bronchiolitis and did not differ among the three intervention groups. We conclude that a high serum ECP concentration during the acute phase of bronchiolitis is a specific but insensitive predictor of wheezing after bronchiolitis. Pediatr. Pulmonol. 1997; 23:397–403. © 1997 Wiley-Liss, Inc. 相似文献
307.
A novel missense mutation in exon 4 of the factor VIII:C gene resulting in moderately severe hemophilia A 总被引:2,自引:0,他引:2
A new point mutation due to C----T transition at codon 189 (TCA) of the factor VIII:C gene was found in a Chinese patient with moderately severe hemophilia A. This mutation abolishes the EcoRI site (GAATTC) in exon 4 and can be directly detected by polyacrylamide gel electrophoresis of amplified genomic DNA. 相似文献
308.
Robert D. Mayer Kan-ei Lee Abraham TK Cockett 《Journal of cancer research and clinical oncology》1989,115(5):418-422
Summary Male Sprague Dawley rats were treated with buthionine sulfoximine (BSO) and cisplatin in different doses and schedules to optimize the chemoprotective effect of BSO against cisplatin nephrotoxicity. BSO at 4 mmol/kg, administered s.c. 2 h prior to cisplatin, resulted in normal blood urea nitrogen (BUN) levels in rats treated with 3 or 4 mg/kg cisplatin, and modestly, but significantly reduced the toxicity of cisplatin at 5 mg/kg. Administration of BSO (4 mmol/kg) at intervals ranging from 0 to 16 h prior to cisplatin (5 mg/kg) resulted in a significant reduction in BUN values. A BSO dose as low as 0.04 mmol/kg was found to be as effective as 4 mmol/kg against nephrotoxicity associated with cisplatin at 4 mg/kg. Repetitive injections of BSO (1 mmol/kg every 12 h, four times, beginning 2 h prior to cisplatin) significantly inhibited elevations of BUN associated with high-dose cisplatin (6 mg/kg), whereas a single BSO injection of 4 mmol/kg was ineffective. The degree and duration of renal glutathione depletion was related to the dose of BSO. Renal glutathione content following 4 mmol/kg BSO was 38% of control at 2 h and 40% at 24 h; following 0.04 mg/kg, glutathione was 47% at 2 h and almost 100% at 24 h. Simultaneous in vitro administration of BSO did not inactivate cisplatin cytotoxicity as measured by the colony-forming ability of MBT-2 cells in soft agar. These data indicate that repeated injections of BSO, beginning prior to cisplatin administration, would improve the nephroprotective effect without compromising the chemotherapeutic efficacy of cisplatin. It is suggested that the ability of BSO to reduce cisplatin nephrotoxicity may not correlate with the degree of renal glutathione depletion and that the mechanism of action is unlikely to involve direct inactivation of cisplatin.Abbreviations BSO
-buthionine sulfoximine
- BUN
blood urea nitrogen 相似文献