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  • 1
    Online Resource
    Online Resource
    Good Manufacturing Practice-Compliant Expansion of Marrow-Derived Stem and Progenitor Cells for Cell Therapy
    SAGE Publications ; 2007
    In:  Cell Transplantation Vol. 16, No. 7 ( 2007-08), p. 685-696
    Details
    In: Cell Transplantation, SAGE Publications, Vol. 16, No. 7 ( 2007-08), p. 685-696
    Abstract: Ex vivo expansion is being used to increase the number of stem and progenitor cells for autologous cell therapy. Initiation of pivotal clinical trials testing the efficacy of these cells for tissue repair has been hampered by the challenge of assuring safe and high-quality cell production. A strategy is described here for clinical-scale expansion of bone marrow (BM)-derived stem cells within a mixed cell population in a completely closed process from cell collection through postculture processing using sterile connectable devices. Human BM mononuclear cells (BMMNC) were isolated, cultured for 12 days, and washed postharvest using either standard open procedures in laminar flow hoods or using automated closed systems. Conditions for these studies were similar to long-term BM cultures in which hematopoietic and stromal components are cultured together. Expansion of marrow-derived stem and progenitor cells was then assessed. Cell yield, number of colony forming units (CFU), phenotype, stability, and multilineage differentiation capacity were compared from the single pass perfusion bioreactor and standard flask cultures. Purification of BMMNC using a closed Ficoll gradient process led to depletion of 98% erythrocytes and 87% granulocytes, compared to 100% and 70%, respectively, for manual processing. After closed system culture, mesenchymal progenitors, measured as CD105+CD166+CD14–CD45– and fibroblastic CFU, expanded 317- and 364-fold, respectively, while CD34+ hematopoietic progenitors were depleted 10-fold compared to starting BMMNC. Cultured cells exhibited multilineage differentiation by displaying adipogenic, osteogenic, and endothelial characteristics in vitro. No significant difference was observed between manual and bioreactor cultures. Automated culture and washing of the cell product resulted in 181 × 106 total cells that were viable and contained fibroblastic CFU for at least 24 h of storage. A combination of closed, automated technologies enabled production of good manufacturing practice (GMP)-compliant cell therapeutics, ready for use within a clinical setting, with minimal risk of microbial contamination.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    URL: Article
    DOI: 10.3727/000000007783465172
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2007
    detail.hit.zdb_id: 2020466-8
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  • 2
    Online Resource
    Online Resource
    Additive Effect of Coexistent Type 2 Diabetes and Arterial Hypertension on Endothelial Dysfunction in Resistance Arteries of Human Forearm Vasculature
    SAGE Publications ; 2000
    In:  Angiology Vol. 51, No. 7 ( 2000-07), p. 545-554
    Details
    In: Angiology, SAGE Publications, Vol. 51, No. 7 ( 2000-07), p. 545-554
    Abstract: Population studies suggest that vascular complications accumulate when arterial hyper tension supervenes on diabetes mellitus. Although it has been demonstrated that endothelial function is impaired in patients with either diabetes mellitus or arterial hypertension it is unknown whether or not both diseases exert additive effects on endothelial dysfunction. The authors therefore investigated endothelium-dependent and endothelium-independent vasodilation in the forearm vasculature of 44 individuals: in 10 type 2 diabetic patients (DM), in 12 patients with arterial hypertension (HT), in 10 patients with both DM and HT (DM+HT), and in 12 healthy control subjects (C). Forearm blood flow (FBF) was measured by venous occlusion plethysmography at rest and following intraarterial infusion of acetylcholine (ACh) and the NO-donor sodium nitroprusside (SNP) at increasing doses. FBF at rest was significantly lower in diabetic patients: 2.2 ±0.1 (DM) and 2.6 ±0.2 (DM+HT) versus 3.1 ±0.1 (HT) and 3.4 ±0.2 (C) mL/min per 100 mL of tissue. ACh and SNP both increased FBF dose-dependently in each group. The maximum response to ACh was progressively decreased in DM and HT: 13.7 (C) 〉 8.1 (DM) 〉 7.6 (HT) 〉 and 5.7 (DM+HT) mL/min per 100 mL of ( continued on next page) tissue. Reduction of the endothelium-dependent flow reserve assessed as percent increase in maximum FBF was also impaired following the same rank order: 349 (C) 〉 268 (DM) 〉 160 (HT) 〉 126 (DM+HT) %. The flow response to the NO-donor SNP amounted to: 327 (C), 306 (DM), 200 (HT), and 194% (DM+HT). In DM+HT the reduction of endothelium-dependent flow response was more pronounced compared with the endothelium-independent flow response. The present data provide evidence that type 2 diabetes and arterial hypertension impair endothelium-dependent dilation of resistance arteries in an additive manner suggesting that this progressive endothelial dysfunction might contribute to the increased incidence of cardiovascular complications when both diseases are coexistent.
    Type of Medium: Online Resource
    ISSN: 0003-3197 , 1940-1574
    URL: Article
    DOI: 10.1177/000331970005100703
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2000
    detail.hit.zdb_id: 2065911-8
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  • 3
    Online Resource
    Online Resource
    Non-invasive imaging for coronary artery disease in diabetes
    SAGE Publications ; 2004
    In:  The British Journal of Diabetes & Vascular Disease Vol. 4, No. 4 ( 2004-07), p. 245-250
    Details
    In: The British Journal of Diabetes & Vascular Disease, SAGE Publications, Vol. 4, No. 4 ( 2004-07), p. 245-250
    Abstract: Diabetic patients are at greater risk of cardiovascular disease than non-diabetic individuals, coronary artery disease (CAD) has a less favourable prognosis and is more likely to be silent in diabetic than in non-diabetic patients. Thus, screening is an integral component of risk-reduction strategies for such patients. The available non-invasive testing options include exercise tolerance testing (ETT), stress echocardiography, and stress myocardial perfusion imaging (MPI) with or without gated single-photon emission computed tomography (SPECT). Calcium scoring with electron beam computed tomography (EBCT) and magnetic resonance imaging (MRI) are promising techniques, requiring further validation. Stress MPI with gated SPECT enables assessment of myocardial ischaemia, viability, and function, and allows for risk stratification to improve clinical management in diabetic patients.
    Type of Medium: Online Resource
    ISSN: 1474-6514 , 1753-4305
    URL: Article
    DOI: 10.1177/14746514040040040601
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2004
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    detail.hit.zdb_id: 3018522-1
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  • 4
    Online Resource
    Online Resource
    Real-World Data Collection Regarding Titration Algorithms for Insulin Glargine in Patients With Type 2 Diabetes Mellitus
    SAGE Publications ; 2016
    In:  Journal of Diabetes Science and Technology Vol. 10, No. 5 ( 2016-09), p. 1122-1129
    Details
    In: Journal of Diabetes Science and Technology, SAGE Publications, Vol. 10, No. 5 ( 2016-09), p. 1122-1129
    Abstract: The primary objective of this study was to collect data regarding the effectiveness of different dose titration algorithms (TAs) for optimization or initiation of basal insulin supported oral therapy (BOT) in patients with type 2 diabetes. A total of 50 patients were enrolled in this trial (17 women, 33 men, age 63 ± 8 years, HbA1c 7.9 ± 0.8%). The investigator decided on an individual basis to apply any of 4 standard TAs: standard (S: fasting glucose target 90-130 mg/dL, n = 39), standard-fast titration (S-FT: 90-130 mg/dL, larger dose increments at FBG 〈 180 mg/dl, n = 1), less tight (LT: 110-150 mg/dL, n = 5), and tight (T: 70-100 mg/dL, n = 5). During the next 30 days daily contacts were used to adapt the insulin dose. The majority of all patients (70%) achieved a stable insulin glargine dose within 5 ± 6 days after initiation of the dose titration. HbA1c improved from 7.9 ± 0.8% to 7.5 ± 0.7% ( P 〈 .001). In total, 1300 dose decisions were made (1192 according to the TA and 108 by the physicians independently from the TA in 29 patients [58% of study population]). Reasons for TA-overruling dosing decisions were hypoglycemic events (14 mild/4 moderate) in 9 patients. In the majority of these cases (89.8%), the physician recommended continuation of the previous dose or a higher dose. The majority of FBG values were within the respective target range after 4 weeks. In conclusion, the insulin glargine TAs delivered safe dose recommendations with a low risk of hypoglycemia, which successfully led to a stable dose in the vast majority of patients.
    Type of Medium: Online Resource
    ISSN: 1932-2968 , 1932-2968
    URL: Article
    DOI: 10.1177/1932296816654714
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
    detail.hit.zdb_id: 2467312-2
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  • 5
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    Online Resource
    Pathobiology and cell interactions of platelets in diabetes
    SAGE Publications ; 2005
    In:  Diabetes and Vascular Disease Research Vol. 2, No. 1 ( 2005-02), p. 16-23
    Details
    In: Diabetes and Vascular Disease Research, SAGE Publications, Vol. 2, No. 1 ( 2005-02), p. 16-23
    Abstract: Diabetes is a well-recognised risk factor for atherosclerotic cardiovascular disease and in fact most diabetic patients die from vascular complications. The Diabetes Control and Complications Trial (DCCT) and the UK Prospective Diabetes Study (UKPDS) indicate a consistent relationship between hyperglycaemia and the incidence of chronic vascular complications in patients with diabetes. Platelets are essential for haemostasis, and abnormalities of platelet function may cause vascular disease in diabetes. Diabetic patients have hyperreactive platelets with exaggerated adhesion, aggregation and thrombin generation. In summary, the entire coagulation cascade is dysfunctional in diabetes. This review provides a comprehensive overview of the physiological role of platelets in maintaining haemostasis and of the pathophysiological processes that contribute to platelet dysfunction in diabetes and associated cardiovascular diseases, with special emphasis on proteomic approaches and leukocyte-platelet cross-talk.
    Type of Medium: Online Resource
    ISSN: 1479-1641 , 1752-8984
    URL: Article
    DOI: 10.3132/dvdr.2005.001
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2005
    detail.hit.zdb_id: 2250797-8
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  • 6
    Online Resource
    Online Resource
    Peripheral oscillometric arterial performance does not depict coronary status in patients with type 2 diabetes mellitus
    SAGE Publications ; 2021
    In:  Diabetes and Vascular Disease Research Vol. 18, No. 6 ( 2021-11), p. 147916412110465-
    Details
    In: Diabetes and Vascular Disease Research, SAGE Publications, Vol. 18, No. 6 ( 2021-11), p. 147916412110465-
    Abstract: Arterial stiffness is associated with cardiovascular events. Matrix metalloproteases (MMPs), their tissue inhibitors (TIMPs) and galectin-3 are involved in the pathogenesis of end organ damage. This study aimed to evaluate the contribution of arterial stiffness, MMPs, TIMPs and galectin-3 with the current vascular status in type 2 diabetes mellitus (T2DM). Methods 74 patients with T2DM, 36 with coronary heart disease (CHD) (T2DM + CHD) and 38 without CHD (T2DM − CHD) were included. Aortic pulse wave velocity (PWVao), aortic and brachial augmentation indices (AIx aortic and AIx brachial) and central-aortic blood pressure values were determined by non-invasive arteriography. MMPs, TIMPs and galectin-3 plasma concentrations were analysed by ELISA. Results Patients with T2DM and CHD presented with significantly increased arterial stiffness determined as AIx and significantly elevated values for TIMP-4 and galectin-3. Heterogeneous peripheral vascular status regardless of the CHD status was observed, and increasing severity of CHD was associated with an increased arterial stiffness. TIMP-4 correlated significantly with an elevated PWVao in the whole cohort independently from CHD status. Conclusion Determination of arterial stiffness is an effective and, compared to laboratory markers, more reliable method for determining the peripheral vascular situation in patients with T2DM, but it does not clearly depict coronary situation.
    Type of Medium: Online Resource
    ISSN: 1479-1641 , 1752-8984
    URL: Article
    DOI: 10.1177/14791641211046522
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 7
    Online Resource
    Online Resource
    Incidence, characteristics and impact of hypoglycaemia in patients receiving intensified treatment for inadequately controlled type 2 diabetes mellitus
    SAGE Publications ; 2016
    In:  Diabetes and Vascular Disease Research Vol. 13, No. 1 ( 2016-01), p. 2-12
    Details
    In: Diabetes and Vascular Disease Research, SAGE Publications, Vol. 13, No. 1 ( 2016-01), p. 2-12
    Abstract: With the intensification of antidiabetic treatment, there is an increasing risk of hypoglycaemia. We aimed to determine incidence, characteristics and outcomes. Methods: Prospective, observational, multicenter cohort study. The included 3810 patients with type 2 diabetes had their treatment intensified at baseline. Results: The incidence of hypoglycaemia was 11.4% per year with 4.2 ± 4.4 episodes per patient. Hypoglycaemia was more frequent in patients with high blood glucose variability. Predictors were heart failure (odds ratio: 1.66; 95% confidence interval: 1.20–2.29) and insulin use (odds ratio: 4.03; 95% confidence interval: 3.05–5.33), with dipeptidyl peptidase–4 inhibitors being associated with reduced risk (odds ratio: 0.69; 95% confidence interval: 0.53–0.89). Macrovascular events were more frequent among patients reporting severe episodes of hypoglycaemia (odds ratio: 3.39; 95% confidence interval: 1.32–8.73). Microvascular events were more frequent in patients with non-severe episodes (odds ratio: 1.92; 95% confidence interval: 1.49–2.49). Conclusion: Case-by-case evaluation of patients as well as appropriate selection of antidiabetic pharmacotherapy and blood glucose treatment goals could maximize the benefits while reducing the risks of antidiabetic treatment.
    Type of Medium: Online Resource
    ISSN: 1479-1641 , 1752-8984
    URL: Article
    DOI: 10.1177/1479164115610470
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
    detail.hit.zdb_id: 2250797-8
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