-
1.
Pullulan based oral thin film formulation of zolmitriptan: Development and optimization using factorial design.
Prajapati, VD, Chaudhari, AM, Gandhi, AK, Maheriya, P
International journal of biological macromolecules. 2018;(Pt B):2075-2085
Abstract
The goal of study was to formulate and characterize pullulan based oral thin film (OTF) of zolmitriptan by solvent casting method. Based on preliminary trials, glass, PEG 400 and sucralose were selected as casting surface, water-miscible plasticizer and sweetener for OTF, respectively. A 32 factorial design was used to study the effect of amount of PEG 400 (X1) and sucralose (X2) as independent variables on tensile strength (Y1), elasticity (Y2), % in-vitro drug release in phosphate buffer of pH 6.8 at 5min (Q5min, Y3) and overall taste of OTF (Y4) as responses. OTF of batch F4 (PEG 400, 200mg; sucralose, 12mg) was identified as an optimized batch showing in-vitro, in-vivo disintegration time 20.70 and 21.58s, respectively; 95.53% Q5min; satisfactory thickness, strength, % elongation, ease of handling, smooth mouthfeel, excellent overall taste; even distribution of all ingredients in pullulan OTF (SEM study); and stable film at specified conditions concluding that pullulan, PEG 400 and sucralose are used in combination to make palatable, stable OTF of zolmitriptan.
-
2.
Icodextrin reduces insulin resistance in non-diabetic patients undergoing automated peritoneal dialysis: results of a randomized controlled trial (STARCH).
de Moraes, TP, Andreoli, MC, Canziani, ME, da Silva, DR, Caramori, JC, Ponce, D, Cassi, HV, de Andrade Bastos, K, Rio, DR, Pinto, SW, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2015;(11):1905-11
Abstract
BACKGROUND Insulin resistance is a common risk factor in chronic kidney disease patients contributing to the high cardiovascular burden, even in the absence of diabetes. Glucose-based peritoneal dialysis (PD) solutions are thought to intensify insulin resistance due to the continuous glucose absorption from the peritoneal cavity. The aim of our study was to analyse the effect of the substitution of glucose for icodextrin on insulin resistance in non-diabetic PD patients in a multicentric randomized clinical trial. METHODS This was a multicenter, open-label study with balanced randomization (1:1) and two parallel-groups. Inclusion criteria were non-diabetic adult patients on automated peritoneal dialysis (APD) for at least 3 months on therapy prior to randomization. Patients assigned to the intervention group were treated with 2L of icodextrin 7.5%, and the control group with glucose 2.5% during the long dwell and, at night in the cycler, with a prescription of standard glucose-based PD solution only in both groups. The primary end-point was the change in insulin resistance measured by homeostatic model assessment (HOMA) index at 90 days. RESULTS Sixty patients were included in the intervention (n = 33) or the control (n = 27) groups. There was no difference between groups at baseline. After adjustment for pre-intervention HOMA index levels, the group treated with icodextrin had the lower post-intervention levels at 90 days in both intention to treat [1.49 (95% CI: 1.23-1.74) versus 1.89 (95% CI: 1.62-2.17)], (F = 4.643, P = 0.03, partial η(2) = 0.078); and the treated analysis [1.47 (95% CI: 1.01-1.84) versus 2.18 (95% CI: 1.81-2.55)], (F = 7.488, P = 0.01, partial η(2) = 0.195). CONCLUSIONS The substitution of glucose for icodextrin for the long dwell improved insulin resistance measured by HOMA index in non-diabetic APD patients.
-
3.
Polydextrose: its impact on short-term food intake and subjective feelings of satiety in males-a randomized controlled cross-over study.
Ranawana, V, Muller, A, Henry, CJ
European journal of nutrition. 2013;(3):885-93
Abstract
PURPOSE Polydextrose is a low-calorie highly branched-chain glucose polymer that is poorly digested in the upper gastrointestinal tract and therefore demonstrates fibre-like properties. Fibre has been shown to increase satiety and possibly reduce food intake. Therefore, the objective of the current study was to examine the effects of polydextrose on short-term satiety and energy intake. METHODS In a repeated-measures randomized blind cross-over design, 26 healthy males consumed a 400-g fruit smoothie containing 12 g (3 %) of polydextrose, and a buffet lunch 60 min after the smoothie. Motivational ratings for satiety and palatability and lunch energy intake were measured. The effects of the polydextrose-containing smoothie were compared against a polydextrose-free control smoothie. RESULTS Polydextrose did not significantly alter the taste and palatability of the fruit smoothie. Consuming the polydextrose-containing smoothie resulted in a significantly lower energy intake at lunch (102 kcal less) compared to the control. CONCLUSION Polydextrose may be a good fortificant for reducing short-term food intake.
-
4.
Relationship between Icodextrin use and decreased level of small low-density lipoprotein cholesterol fractioned by high-performance gel permeation chromatography.
Kanda, E, Ai, M, Iwamoto, A, Okazaki, M, Maeda, Y, Sasaki, S, Yoshida, M
BMC nephrology. 2013;:234
Abstract
BACKGROUND Because of the absorption of glucose in peritoneal dialysis (PD) solution, PD patients show an atherogenic lipid profile, which is predictive of poor survival in PD patients. Lipoprotein subclasses consist of a continuous spectrum of particles of different sizes and densities (fraction). In this study, we investigated the lipoprotein fractions in PD patients with controlled serum low-density lipoprotein (LDL) cholesterol level, and evaluated the effects of icodextrin on lipid metabolism. METHODS Forty-nine PD patients were enrolled in this cross-sectional study in Japan. The proportions of cholesterol levels to total cholesterol level (cholesterol proportion) in 20 lipoprotein fractions were measured using an improved method of high-performance gel permeation chromatography (HPGPC). RESULTS Twenty-six patients used icodextrin. Although no significant differences in cholesterol levels in LDL and high-density lipoprotein (HDL) were observed between the patients using icodextrin (icodextrin group) and control groups, HPGPC showed that the icodextrin group had significantly lower cholesterol proportions in the small LDL (t-test, p=0.053) and very small LDL (p=0.019), and significantly higher cholesterol proportions in the very large HDL and large HDL than the control group (p=0.037; p=0.066, respectively). Multivariate analysis adjusted for patient characteristics and statin use showed that icodextrin use was negatively associated with the cholesterol proportions in the small LDL (p=0.037) and very small LDL (p=0.026), and positively with those in the very large HDL (p=0.040), large HDL (p=0.047), and medium HDL (p=0.009). CONCLUSIONS HPGPC showed the relationship between icodextrin use and the cholesterol proportions in lipoprotein fractions in PD patients. These results suggest that icodextrin may improve atherogenic lipid profiles in a manner different from statin.
-
5.
Dose-dependent effects of NY-ESO-1 protein vaccine complexed with cholesteryl pullulan (CHP-NY-ESO-1) on immune responses and survival benefits of esophageal cancer patients.
Kageyama, S, Wada, H, Muro, K, Niwa, Y, Ueda, S, Miyata, H, Takiguchi, S, Sugino, SH, Miyahara, Y, Ikeda, H, et al
Journal of translational medicine. 2013;:246
Abstract
BACKGROUND Cholesteryl pullulan (CHP) is a novel antigen delivery system for cancer vaccines. This study evaluated the safety, immune responses and clinical outcomes of patients who received the CHP-NY-ESO-1 complex vaccine, Drug code: IMF-001. METHODS Patients with advanced/metastatic esophageal cancer were enrolled and subcutaneously vaccinated with either 100 μg or 200 μg of NY-ESO-1 protein complexed with CHP. The primary endpoints were safety and humoral immune responses, and the secondary endpoint was clinical efficacy. RESULTS A total of 25 patients were enrolled. Thirteen and twelve patients were repeatedly vaccinated with 100 μg or 200 μg of CHP-NY-ESO-1 with a median of 8 or 9.5 doses, respectively. No serious adverse events related to the vaccine were observed. Three out of 13 patients in the 100-μg cohort and 7 out of 12 patients in the 200-μg cohort were positive for anti-NY-ESO-1 antibodies at baseline. In the 100-μg cohort, an antibody response was observed in 5 out of 10 pre-antibody-negatives patients, and the antibody levels were augmented in 2 pre-antibody-positive patients after vaccination. In the 200-μg cohort, all 5 pre-antibody-negative patients became seropositive, and the antibody level was amplified in all 7 pre-antibody-positive patients. No tumor shrinkage was observed. The patients who received 200 μg of CHP-NY-ESO-1 survived longer than patients receiving 100 μg of CHP-NY-ESO-1, even those who exhibited unresponsiveness to previous therapies or had higher tumor burdens. CONCLUSIONS The safety and immunogenicity of CHP-NY-ESO-1 vaccine were confirmed. The 200 μg dose more efficiently induced immune responses and suggested better survival benefits. (Clinical trial registration number NCT01003808).
-
6.
Antibody responses against NY-ESO-1 and HER2 antigens in patients vaccinated with combinations of cholesteryl pullulan (CHP)-NY-ESO-1 and CHP-HER2 with OK-432.
Aoki, M, Ueda, S, Nishikawa, H, Kitano, S, Hirayama, M, Ikeda, H, Toyoda, H, Tanaka, K, Kanai, M, Takabayashi, A, et al
Vaccine. 2009;(49):6854-61
Abstract
Combination vaccines of the NY-ESO-1 protein complexed with cholesteryl pullulan (CHP), CHP-NY-ESO-1, and the truncated 146HER2 protein with CHP, CHP-HER2, were subcutaneously administered with the immuno-adjuvant OK-432 to eight esophageal cancer patients. Vaccination was well-tolerated. NY-ESO-1- and HER2-specific antibody responses were analyzed using the patients' sera and samples from previous single CHP-NY-ESO-1 or CHP-HER2 vaccine trial. The responses to NY-ESO-1 in the combination vaccine study were comparable to the single vaccine. For responses to HER2, there were fewer antibody responses in the combination vaccines. Although there were marked individual variations in the antibody responses to the NY-ESO-1 and HER2 antigens, the reaction patterns to these antigens were comparable within each patient. Antibodies to OK-432 were not augmented. Protein cancer vaccines targeting multiple antigens are feasible.
-
7.
Anal submucosal carbon bead injection for treatment of idiopathic fecal incontinence: a preliminary report.
Aigner, F, Conrad, F, Margreiter, R, Oberwalder, M, ,
Diseases of the colon and rectum. 2009;(2):293-8
Abstract
PURPOSE Submucosal injection of bulking agents is a treatment option for idiopathic fecal incontinence. This study sought to assess whether the injection of carbon beads can significantly improve anal continence. METHODS Consecutive patients presenting with fecal incontinence were evaluated with standardized incontinence grading and quality-of-life grading scores, by anoproctoscopy, endoanal ultrasound, and anomanometry before, 3, 6, 12, and 24 months after injection. Injection therapy was performed in patients with anatomically intact anal sphincters. Patients kept a two-week incontinence diary. Data were obtained from a two-year follow-up period. RESULTS Eleven women with a mean age of 66 (range, 56 to 74) years met the inclusion criteria. Mean incontinence score was 12.27 +/- 0.97 at baseline, 6.82+/-1.64 at three-month, 6.73 +/- 1.47 at six-month, 5.91 +/- 0.95 at one-year, and 4.91 +/- 0.87 at two-year follow-up (P = 0.003). Quality-of-life items like coping and embarrassment improved significantly from baseline 2.3 to 3 at three months and 2.8 at six months (P < 0.05). Anomanometry showed a trend toward increase in measured pressures. No major complications occurred. CONCLUSIONS The injection of carbon beads via an intersphincteric approach is a promising new treatment option for old patients with idiopathic fecal incontinence.
-
8.
Beta glucan induces proliferation and activation of monocytes in peripheral blood of patients with advanced breast cancer.
Demir, G, Klein, HO, Mandel-Molinas, N, Tuzuner, N
International immunopharmacology. 2007;(1):113-6
Abstract
AIM: Glucans are glucose polymers that constitute a structural part of fungal cell wall. They can stimulate the innate immunity by activation of monocytes/macrophages. In human studies it has been shown that beta glucan has an immunomodulatory effect and can increase the efficacy of the biological therapies in cancer patients. In this prospective clinical trial we assessed in vivo effects of short term oral beta glucan administration on peripheral blood monocytes and their expression of activation markers in patients with advanced breast cancer. METHODS 23 female patients with advanced breast cancer were included in the study. Median age of the patients was 52 years. Sixteen healthy females with a median age of 48 years served as the control group for comparing the initial blood samples. Peripheral blood samples were drawn on day zero and patients started receiving oral 1-3, 1-6, D-beta glucan daily. Blood samples were recollected on the 15th day. In the initial samples mean lymphocyte count was significantly lower in the patients with breast cancer (1281+/-306/mm(3) versus 1930+/-573/mm(3), p=0.04). In the patients with breast cancer, mean monocyte count which was 326+124/mm(3) at the beginning, was increased to 496+194/mm(3) at the 15th day (p=0.015). Expression of CD95 (Apo1/Fas) on CD14 positive monocytes was 48.17% at the beginning, which was increased to 69.23 % at the 15th day (p=0.002). Expression of CD45RA on CD14 positive monocytes was 49.9% at the beginning; it was increased significantly to 61.52% on day 15 (p=0.001). CONCLUSION Oral beta glucan administration seems to stimulate proliferation and activation of peripheral blood monocytes in vivo in patients with advanced breast cancer.
-
9.
Comparison of peritoneal equilibrium test with icodextrin and 2.5% glucose dialysis solutions.
Hwang, JC, Wang, HY, Wang, CT, Chen, HC
Journal of nephrology. 2006;(6):758-63
Abstract
BACKGROUND Icodextrin provides a different ultrafiltration mechanism than glucose-based dialysate. METHODS To evaluate the difference in the peritoneal equilibrium test (PET) with regard to using icodextrin (Ico-PET) and glucose dialysate we designed a prospective study using Ico-PET and 2 cross-over conventional 2.5% glucose-based dialysate PETs (Gluco 1-PET and Gluco 2-PET) administered 3 months before and after the Ico-PET in 58 chronic peritoneal dialysis patients. RESULTS More patients demonstrated higher transport types with the Ico-PET than the Gluco 1-PET and Gluco 2-PET (p<0.001). After a dwell time of 4 hours, the Ico-PET did not show an ultrafiltration benefit compared with the Gluco-PET (272.8 +/- 137.1 mL vs. 348.3 +/- 215.2 mL, p<0.001). The Ico-PET not only showed significantly higher values in the 0-hour, 2-hour and 4-hour dialysate to plasma creatinine concentration ratio (D/P Cr) than those of the Gluco 1-PET (p=0.029 and p<0.001, respectively), but also showed higher values in the 0-hour and 4-hour D/P Cr than those of the Gluco 2-PET (both p<0.001). The total ultrafiltration volume was positively correlated with the 4-hour D/P Cr with the Ico-PET (r=0.41, p=0.001), but the correlation was negative with the Gluco 1-PET (r=-0.33, p=0.012) and Gluco 2-PET (r=-0.51, p<0.001). The ratio of the glucose concentration in the outflow dialysate compared with baseline level (D/Do glucose), was also significantly higher with the Ico-PET than with the Gluco 1-PET and Gluco 2-PET after both 2 and 4 hours (both p<0.001). CONCLUSIONS The Ico-PET showed a completely different result from the conventional Gluco-PET. The Ico-PET provi-des a superior solute transport and inferior ultrafiltration rates, and the prevalence of high transporters was also increased with the Ico-PET.
-
10.
Inaccurate self-monitoring of blood glucose readings in patients on chronic ambulatory peritoneal dialysis with icodextrin.
Pavlicek, V, Garzoni, D, Urech, P, Brändle, M
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2006;(3):124-6
Abstract
Patients on chronic ambulant peritoneal dialysis (CAPD) are increasingly likely to be treated with a new solution of corn starch-derived glucose polymers called icodextrin. This solution involves a very low carbohydrate absorption leading to a better glycemic control in diabetic patients. However these glucose polymers pass to the blood and are metabolized to oligosaccharids which interfere with blood glucose in distinct capillary glucose analyzers leading to overestimation of glycemia. We assessed the accuracy of glucose measurements with the three most commonly used glucose analyzers compared to venous plasma glucose measurement at our institution in 8 patients (4 patients with type 2 diabetes) on CAPD using icodextrin. Glycemia was measured simultaneously in plasma of venous blood using a reference laboratory method and in capillary blood using Accu-Chek sensor (Rotkreuz, Switzerland) (glucose dehydrogenase method), Glucotrend 2 (Rotkreuz, Switzerland) (glucose-dye-oxyreductase method) and Ascensia elite (Zurich, Switzerland) (glucose oxidase method) glucose analyzers. Only glucose readings with Ascensia elite correspond correctly with venous plasma glucose results (+0.3 mmol/l; n. s.), whereas glycemia was significantly overestimated by Accu-Chek sensor (+4.3 mmol/l; p<0.0001) and Glucotrend 2 glucose analyzers (+3.7 mmol/l; p<0.0001). Thus we conclude that distinct glucose analyzers overestimate real blood glucose concentration and are not suitable for monitoring glycemia in patients on CAPD with icodextrin. On the basis of our results, these patients should use glucose analyzers using glucose oxidase methods. All glucose analyzers should be cross-checked with a laboratory reference method before the application in patients on CAPD with icodextrin is recommended.