Microfibrillated cellulose films containing chitosan and tannic acid for wound healing applications

The effectiveness of tannic acid as antimicrobial and wound healing for burns have been shown for a century; however, uncontrolled target dosage may result in undesirable side-effects. Remarkably, tannic acid polyphenols compounds crosslinked with polymeric materials produce a strong composite containing the beneficial properties of this tannin. However, investigation of the crosslink structure and its antibacterial and regenerative properties are still unknown when using nanocellulose by mechanical defibrillation; additionally, due to the potential crosslink structure with chitosan, its structure can be complex. Therefore, this work uses bleach kraft nanocellulose in order to investigate the effect on the physical and regenerative properties when incorporated with chitosan and tannic acid. This film results in increased rigidity with a lamellar structure when incorporated with tannic acid due to its strong hydrogen bonding. The release of tannic acid varied depending on the structure it was synthesised with, whereas with chitosan it presented good release model compared to pure cellulose. In addition, exhibiting similar thermal stability as pure cellulose films with antibacterial properties tested against S. aureus and E. coli with good metabolic cellular viability while also inhibiting NF-κB activity, a characteristic of tannic acid.

Lidocaine and bupivacaine as part of multimodal pain management in a C57BL/6J laparotomy mouse model

While the use of local anesthesia as part of multimodal pain management is common practice in human and veterinarian surgery, these drugs are not applied routinely in rodent surgery. Several recommendations on the use of local anesthesia exist, but systematic studies on their efficacy and side effects are lacking. In the present study, male and female C57BL/6J mice were subjected to a sham vasectomy or a sham embryo transfer, respectively. We tested whether a mixture of subcutaneously injected Lidocaine and Bupivacaine in combination with systemic Paracetamol applied via drinking water results in superior pain relief when compared to treatment with local anesthesia or Paracetamol alone. We applied a combination of methods to assess behavioral, emotional, and physiological changes indicative of pain. Voluntary Paracetamol intake via drinking water reached the target dosage of 200 mg/kg in most animals. Local anesthesia did not lead to obvious side effects such as irregular wound healing or systemic disorders. No relevant sex differences were detected in our study. Sevoflurane anesthesia and surgery affected physiological and behavioral measurements. Surprisingly, Paracetamol treatment alone significantly increased the Mouse Grimace Scale. Taken together, mice treated with a combination of local anesthesia and systemic analgesia did not show fewer signs of post-surgical pain or improved recovery compared to animals treated with either local anesthesia or Paracetamol.

A MEMS Based Drug Delivery Device with Integrated Micro-Needle Array - Design and Simulation

One of the most effective treatments for type 1 and 2 diabetes is the administration of Insulin. Single needle mechanical insulin pumps are heavy and painful. Micro-needle based MEMS drug delivery devices can be an excellent solution for insulin dosing. The use of Micro-Needle Array provides a safe, painless and robust injection application. A stackable structure results in minimum dimensions and the final product can be in the form of a patch that can be applied to any flat area of human skin. The design of positive volumetric insulin pump is a multi-physics problem where the volumetric changes of the main pump chamber and the pumped fluid are directly coupled. We used a multiphysics simulation platform to investigate the performance of a MEMS based Insulin Micro-Pump driven by a piezoelectric actuator which acts on a diaphragm. The positive and negative movement of the diaphragm results in generation of a discharge pressure at the microneedle array. The pressure and flow rate is controlled by varying the excitation voltage and frequency applied to the actuator. The model was used to evaluate the performance of the Micro-Pump. It was found to be capable of generating the required interfacial pressures at the human skin to deliver the target dosage by matching the minimum and maximum range of diabetic patients' operating parameters.

Prescription bias in the treatment of chronic systolic heart failure impacts outcome

Background There is evidence that medical therapy with beta-blockers (BB) and renin-angiotensin-system-inhibitors, uptitrated to target dosage (TD) decreases mortality and hospitalizations in HFrEF. However, physicians seemingly do not sufficiently follow the guidelines and a great number of patients do not receive recommended dosages. As humans are visually deceivable, it might be that absolute numerical values of equipotent recommended TD and the “milligram-based” subjective weighting of tolerability by the individual physician influences the maximal prescribed dosage. Purpose We sought to assess whether different numerical TD of equipotent medications affect prescription patterns, potentially biases uptitration and impacts outcome. Methods 3737 HFrEF outpatients were identified from a prospective registry. Maximal achieved dosages of BB, ACEi and ARB after one year of repeated visits for uptitration were assessed. BB, ACEi and ARB with largest numerical differences in TD (10mg/d bisoprolol/nebivolol vs 200mg/d metoprolol; 10mg/d ramipril vs 40mg/d lisinopril/enalapril/fosinopril; and 32mg/d candesartan vs 320mg/d valsartan) were compared using the individually achieved dose as percentage of the defined TD at one year of FUP. The association of maximal achieved TD with HF hospitalization and overall survival were determined. Results Median age was 65 years (IQR: 55–74), 2720 patients (73%) were male. Within the whole study population, 1434 patients (38%) received bisoprolol/nebivolol, 280 (8%) metoprolol. Ramipril was prescribed in 599 (16%) patients, lisinopril/enalapril/fosinopril in 1138 (30%). 409 patients (11%) were on candesartan, 173 (5%) on valsartan. Significant differences at baseline were not clinically meaningful and there were no contraindications for uptitration in all subgroups. After one year aiming for up-titration dosages increased significantly in all medication-groups (p<0.001 for all). However, significantly less patients were treated with the TD when TD was numerically higher (BB: metoprolol (57 (20%)) vs bisoprolol/nebivolol (446 (31%), p<0.001); ACEi: lisinopril/enalapril/fosinopril (231 (20%) vs ramipril (313 (52%), p<0.001); ARB: valsartan (45 (26%) vs candesartan (166 (41%), p<0.001)). At 45 (IQR: 32–68) months of FUP, 859 (23%) of the patients were hospitalized for HF or died. Achievement of TD significantly improved outcome (Fig. 1A-C) and showed association with mortality and HF-hospitalization (BB: adj.HR=0.87, 95% CI: 0.79–0.95, p<0.001; ACEi: adj.HR=0.89, 95% CI: 0.81–0.97, p=0.023; ARB: adj.HR=0.74, 95% CI: 0.69–0.91, p=0.009). Conclusion The present analysis described the influence of the numerical values of recommended TD of equipotent drugs on the prescription behavior of the treating physician and on outcome. This psychological phenomenon was identified a substantial confounder at least partly responsible for the underuse of BB, ACEi and ARB in HF. Moreover, it was never shown that this cognitive illusion based on risk aversion is linked to outcome. Figure 1 Funding Acknowledgement Type of funding source: None