Evaluation of Tableting and Tablet Properties of Kollidon SR: The Influence of Moisture and Mixtures with Theophylline Monohydrate

The aim of the study was firstly to investigate the influence of moisture on the tableting and tablet properties of Kollidon SR and secondly to investigate the influence of theophylline monohydrate on the tableting behavior and tablet properties produced from binary mixtures with Kollidon SR. In comparison to Kollidon SR, microcrystalline cellulose (MCC) was used. The glass transition temperature (T_g) of the powder over the whole range of RH (0–90%), and in addition, the T_g of tablets of Kollidon SR were measured. Densities and flowability of the powders were analyzed. The tablets were produced at five different maximum relative densities (ρ_{rel, max}) on an instrumented eccentric tableting machine. They were produced at three different relative humidities (RH), 30%, 45%, and 60% RH for the pure substances and binary mixtures with different ratios of drug and excipient were tableted at 45% RH. The tableting properties were analyzed by 3D modeling, force-displacement profiles, and compactibility plots. First, the T_g of the powder decreased with increasing RH and the T_g of the tablet was 4–8 K lower than the powder. The predominant deformation of Kollidon SR is plastic deformation and Kollidon SR showed a higher compactibility than MCC. The parameters of the 3D model showed an extreme change between 45 and 60% RH, and at higher RH more and more particles deformed elastically. This was confirmed by analysis of force-displacement profiles. At 60% RH, the radial tensile strength of the Kollidon SR tablets was half of the radial tensile strength at 45% RH. The reason is a higher relative energy of plastic deformation than for MCC. This results in a better utilization of the energy to deform the powder into a tablet and the exceeding of the glass transition temperature at higher RH. In conclusion, at 60% RH at the same ρ_{rel, max}, tableting and tablet properties of Kollidon SR are extremely changed since plasticity is significantly higher. In the second part of the study, the insufficient flowability of theophylline monohydrate can be compensated by using Kollidon SR in a mixture with up to 20% theophylline. Further, pressure plasticity ε of MCC and Kollidon SR was lowered in the mixture with theophylline monohydrate. The same is valid for the compactibility. The influence of theophylline monohydrate on the pressure plasticity e of the mixtures was better compensated in the mixture with MCC than in a mixture with Kollidon SR. This compensation was also visible by analyzing the force-displacement-profiles. However, hardly any influence on the radial tensile strength could be detected. Kollidon SR and Kollidon SR mixtures exhibited a higher compactibility than MCC and MCC mixtures. The differences became smaller with increasing theophylline content.     

Circulating levels of MCP-1 are increased in women with gestational diabetes

OBJECTIVE: We investigated whether gestational diabetes mellitus is associated with monocyte-chemoattractant-protein-1 (MCP-1) and soluble CD40 ligand (sCD40L), the functional relevant proteins in the inflammatory process. METHODS: In all 32 women with gestational diabetes mellitus, 18 women without gestational diabetes mellitus and 40 nonpregnant women were included. MCP-1 and sCD40L were measured at the time of the oral glucose tolerance test (second trimester), in the third trimester and postpartum. RESULTS: MCP-1 was higher in pregnant women (women with gestational diabetes mellitus and without) than in nonpregnant women (p < 0.001) in the third trimester, and also in the second trimester and postpartum. MCP-1 was elevated in patients with gestational diabetes mellitus in the third trimester compared to healthy pregnant women (p = 0.007). In gestational diabetes mellitus, MCP-1 increased from the second to the third trimester (p = 0.003). We found no association of sCD40L and gestational diabetes mellitus. CONCLUSION: The elevation of MCP-1 in the third trimester in gestational diabetes mellitus suggests an association between inflammation and GDM. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Analysis of Mechanical Properties Related to Fiber Length of Closed-Loop-Recycled Offcuts of a Thermoplastic Fiber Composites (Organo Sheets)

Increasing demand for energy-efficient means of transport has steadily intensified the trend towards lightweight components. Thermoplastic glass fiber composites (organo sheets) play a major role in the production of functional automotive components. Organo sheets are cut, shaped and functionalized by injection molding to produce hybrid components, such as those used in car door modules. The cutting process produces a considerable amount of production waste, which has thus far been thermally recycled. This study develops a closed mechanical recycling process and analyzes the different steps of the process. The offcuts were shredded using two shredding methods and implemented directly in the injection-molding process. Using tensile tests and impact bending tests, the material properties of the recycled materials were compared with the virgin material. In addition, fiber length degradation via the injection-molding process and the influence of the waterjet-cutting process on the mechanical properties are investigated. Recycled offcuts are both comparable to new material in terms of mechanical properties and usability, and are also economically and ecologically advantageous. Recycling polypropylene waste with glass fiber reinforcement in a closed loop is an effective way to reduce industrial waste in a sustainable and economical production process.     

Intensity of care in cancer patients in the last year of life: a retrospective data linkage study

Background Delivering high-quality palliative and end-of-life care for cancer patients poses major challenges for health services. We examine the intensity of cancer care in England in the last year of life.Methods We included cancer decedents aged 65+ who died between January 1, 2010 and December 31, 2017. We analysed healthcare utilisation and costs in the last 12 months of life including hospital-based activities and primary care.Results Healthcare utilisation and costs increased sharply in the last month of life. Hospital costs were the largest cost elements and decreased with age (0.78, 95% CI: 0.73–0.72, p < 0.005 for age group 90+ compared to age 65–69 and increased substantially with comorbidity burden (2.2, 95% CI: 2.09–2.26, p < 0.005 for those with 7+ comorbidities compared to those with 1–3 comorbidities). The costs were highest for haematological cancers (1.45, 95% CI: 1.38–1.52, p < 0.005) and those living in the London region (1.10, 95% CI: 1.02–1.19, p < 0.005).Conclusions Healthcare in the last year of life for advanced cancer patients is costly and offers unclear value to patients and the healthcare system. Further research is needed to understand distinct cancer populations’ pathways and experiences before recommendations can be made about the most appropriate models of care.Subject terms: Cancer, Cancer     

Chronic venous leg ulcers benefit from surgery: long-term results from 173 legs

OBJECTIVE: The purpose of this retrospective study was to present 7 years of data from operations of currently active, chronic venous leg ulcers (CEAP: C6), focusing on the short- and long-term effects of healing and recurrence and considering concomitant risk factors. METHODS: Between January 1997 and March 2004, 173 patients (239 legs) with a currently active, chronic venous leg ulcer were surgically treated. The surgical procedures included two main steps: (1) the surgical interruption of reflux in the superficial and perforating veins to reduce venous hypertension in the entire leg and/or the affected area and (2) the surgical procedure involving the ulcer. A total of 123 patients (173 legs) who came to the follow-up were examined. The follow-up period ranged from 3 months to 7 years. The data collection integrated a preoperative examination that included medical history and clinical diagnoses and incorporated measurements such as body mass index, ankle-brachial pressure index, and the neutral position method at the follow-up. The function of the veins was measured with duplex ultrasonography. Finally, the data were analyzed by using various statistical methods, including Kaplan-Meier analysis, Cox regression analysis, and paired t tests. RESULTS: Initially, ulcer healing occurred in 87% of the cases (151 legs). A total of 13% (22 legs) of the venous ulcers never healed, and recurrent venous ulcers occurred in 5% (9 legs). The Kaplan-Meier analyses of ulcer healing showed a healing rate of 85% in 6 months for all legs. The mean time of healing was 1.5 months. Furthermore, the Kaplan-Meier analyses of ulcer recurrence showed a 1.7% rate of recurrence in 6 months for all legs. The 5-year ulcer recurrence rate was 4.6%. The mean time of recurrence was 70.4 months. CONCLUSIONS: On the basis of the results from the 7 years of data from functional surgery of venous leg ulcers and as a result of the outcomes of our study, we recommend surgical treatment of venous leg ulcers at any stage. We therefore conclude that surgery is indicated before an ulcer is intractable to treatment. In general, our findings are based on the understanding and identification of the causes and symptoms of venous ulceration and illustrate that standard surgical methods can be applied for the therapy of venous leg ulcers at any stage.     

The role of nitric oxide radicals in removal of hyper-radiosensitivity by priming irradiation

In this study, a mechanism in which low-dose hyper-radiosensitivity (HRS) is permanently removed, induced by low-dose-rate (LDR) (0.2–0.3 Gy/h for 1 h) but not by high-dose-rate priming (0.3 Gy at 40 Gy/h) was investigated. One HRS-negative cell line (NHIK 3025) and two HRS-positive cell lines (T-47D, T98G) were used. The effects of different pretreatments on HRS were investigated using the colony assay. Cell-based ELISA was used to measure nitric oxide synthase (NOS) levels, and microarray analysis to compare gene expression in primed and unprimed cells. The data show how permanent removal of HRS, previously found to be induced by LDR priming irradiation, can also be induced by addition of nitric oxide (NO)-donor DEANO combined with either high-dose-rate priming or exposure to prolonged cycling hypoxia followed by reoxygenation, a treatment not involving radiation. The removal of HRS appears not to involve DNA damage induced during priming irradiation as it was also induced by LDR irradiation of cell-conditioned medium without cells present. The permanent removal of HRS in LDR-primed cells was reversed by treatment with inducible nitric oxide synthase (iNOS) inhibitor 1400W. Furthermore, 1400W could also induce HRS in an HRS-negative cell line. The data suggest that LDR irradiation for 1 h, but not 15 min, activates iNOS, and also that sustained iNOS activation is necessary for the permanent removal of HRS by LDR priming. The data indicate that nitric oxide production is involved in the regulatory processes determining cellular responses to low-dose-rate irradiation.