Insulin Solution Stability and Biocompatibility with Materials Used for an Implantable Insulin Delivery Device Using Reverse Phase HPLC Methods

open access articleAbstract: Insulin (Humulin® R IU500) has been delivered from an implantable artificial pancreas in diabetic rats and pigs. The artificial pancreas which was implanted in the peritoneum was fabricated from several biocompatible materials such as polycarbonate, stainless steel, polyurethane, titanium and a polyurethane resin. The device also contains a glucose responsive smart gel which controls the di usion of insulin dependent on the surrounding glucose environment. As the insulin reservoir is refillable and in contact with the device materials, assessing its biocompatibility with these various device component materials was conducted. Insulin can undergo chemical degradation mainly via a deamidation reaction on glutamine and asparagine residues rendering its biological hormone functionality. Two Reverse Phase High Performance Liquid Chromatography (RP-HPLC) methods were developed and validated for detection of insulin and degradant Asn A21 desamido insulin (method A) and insulin and degradant Asn B3 desamido insulin (method B). Material biocompatibility studies show that stainless steel and titanium are suitable for an implantable insulin delivery device design over a 31-day period. The use of polycarbonate and polyurethane could be considered if the insulin reservoir in the device was only to remain in the device for less than 11 days after which time there is a loss in cresol which acts in a protective capacity for insulin stability

Manipulations of egg-gallery length to vary brood density in spruce beetle, Dendroctonus rufipennis (Coleoptera: Scolytidae): Effects on brood survival and quality

Different brood densities were produced under a constant bark surface area of the spruce host, by excising egg-producing female <i>Dendroctonus rufipennis</i> from the host material after they had excavated galleries of specified lengths. This procedure allowed a constant attack density. The numbers of adult progeny produced/cm of egg-gallery were significantly greater from bark slabs with short galleries and low densities: the sizes (pronotal widths) of adult progeny of both sexes were also significantly greater from low than from high densities; and the distribution patterns of chromatin differed significantly among high, medium and low densities

Glucose lowering strategies with insulin

open access journalPeople with type 1 diabetes must use insulin and a large fraction of those with type 2 condition also do so. Many therefore struggle with the unpredictable balancing of insulin dose with calorie intake and utility. A healthy pancreas makes meticulous adjustment on a continuous basis that present therapeutic insulin administration cannot match. However, much progress has been made to make it simpler to inject both background and fast-acting boost insulins with a view to better mimicking normal pancreatic output. The present fast insulins are reviewed with accent on the primary amino acid structures of the biosynthetic types that diffuse more quickly than regular insulin that associates in hexamers. This makes boost doses kinetically and clinically more effective, allowing people to inject better estimated boost and corrective doses. Formulation advances are discussed for their present and potential contributions. The newer slow-acting insulins are also described and compared, their advantage also being kinetic with a lower likelihood of inducing overnight hypoglycaemia when used optimally. Finally, the appreciation of the advantages of alternative routes of administration such as oral and peritoneal are included in this review because of the possibility of altering the hepatic to peripheral ratio, the reasons for which are more effective but less obesogenic insulin activity. The logistics of oral insulin are summarised in terms of the risks to the insulin structure, the facilitation of paracellular uptake at the apical surface and the paradoxically advantageous hepatic first pass. Other non-invasive routes are also included in the review

Manipulations of egg-gallery length to vary brood density in spruce beetle, Dendroctonus rufipennis (Coleoptera: Scolytidae): Effects on brood survival and quality

Different brood densities were produced under a constant bark surface area of the spruce host, by excising egg-producing female Dendroctonus rufipennis from the host material after they had excavated galleries of specified lengths. This procedure allowed a constant attack density. The numbers of adult progeny produced/cm of egg-gallery were significantly greater from bark slabs with short galleries and low densities: the sizes (pronotal widths) of adult progeny of both sexes were also significantly greater from low than from high densities; and the distribution patterns of chromatin differed significantly among high, medium and low densities

Thermoresponsive Gels

An invited review and relates to the responsive gel used in the "artificial pancreas" work og INsmart, DMU. This article is an Open Access journal.Thermoresponsive gelling materials constructed from natural and synthetic polymers can be used to provide triggered action and therefore customised products such as drug delivery and regenerative medicine types as well as for other industries. Some materials give Arrhenius-type viscosity changes based on coil to globule transitions. Others produce more counterintuitive responses to temperature change because of agglomeration induced by enthalpic or entropic drivers. Extensive covalent crosslinking superimposes complexity of response and the upper and lower critical solution temperatures can translate to critical volume temperatures for these swellable but insoluble gels. Their structure and volume response confer advantages for actuation though they lack robustness. Dynamic covalent bonding has created an intermediate category where shape moulding and self-healing variants are useful for several platforms. Developing synthesis methodology—for example, Reversible Addition Fragmentation chain Transfer (RAFT) and Atomic Transfer Radical Polymerisation (ATRP)—provides an almost infinite range of materials that can be used for many of these gelling systems. For those that self-assemble into micelle systems that can gel, the upper and lower critical solution temperatures (UCST and LCST) are analogous to those for simpler dispersible polymers. However, the tuned hydrophobic-hydrophilic balance plus the introduction of additional pH-sensitivity and, for instance, thermochromic response, open the potential for coupled mechanisms to create complex drug targeting effects at the cellular level

Acceptability of bisphosphonates among patients, clinicians and managers: a systematic review and framework synthesis

Objective: To explore the acceptability of different bisphosphonate regimens for the treatment of osteoporosis among patients, clinicians and managers, payers and academics. Design: A systematic review of primary qualitative studies. Seven databases were searched from inception to July 2019. Screening, data extraction and quality assessment of full-articles selected for inclusion were performed independently by two authors. A framework synthesis was applied to extracted data based on the theoretical framework of acceptability (TFA). The TFA includes seven domains relating to sense-making, emotions, opportunity costs, burden, perceived effectiveness, ethicality and self-efficacy. Confidence in synthesis findings was assessed. Setting: Any developed country healthcare setting. Participants: Patients, healthcare professionals, managers, payers and academics. Intervention: Experiences and views of oral and intravenous bisphosphonates. Results: Twenty-five studies were included, mostly describing perceptions of oral bisphosphonates. We identified, with high confidence, how patients and healthcare professionals make sense (coherence) of bisphosphonates by balancing perceptions of need against concerns, how uncertainty prevails about bisphosphonate perceived effectiveness and a number of individual and service factors that have potential to increase self-efficacy in recommending and adhering to bisphosphonates. We identified, with moderate confidence, that bisphosphonate taking induces concern, but has the potential to engender reassurance, and that both side effects and special instructions for taking oral bisphosphonates can result in treatment burden. Finally, we identified with low confidence that multimorbidity plays a role in people’s perception of bisphosphonate acceptability. Conclusion: By using the lens of acceptability, our findings demonstrate with high confidence that a theoretically informed, whole-system approach is necessary to both understand and improve adherence. Clinicians and patients need supporting to understand the need for bisphosphonates, and clinicians need to clarify to patients what constitutes bisphosphonate treatment success. Further research is needed to explore perspectives of male patients and those with multimorbidity receiving bisphosphonates, and patients receiving intravenous treatment

Assessing the effectiveness of bisphosphonates for the prevention of fragility fractures: an updated systematic review and network meta-analyses

Bisphosphonates have been found to be effective in preventing fragility fractures. However, their comparative effectiveness in populations at risk has yet to be defined. In light of recent clinical trials, we aimed to compare four bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate) and to identify which are the most effective for the prevention of fragility fractures. This is an update of a systematic review previously published as part of a NICE HTA report. We conducted a systematic review and network meta-analysis, updating the estimates regarding the comparative effectiveness of the aforementioned bisphosphonates. Studies identified from published and unpublished sources between 2014 and 2021 were added to the studies identified in the previous review. Screening, data extraction and risk of bias assessment were independently undertaken by two reviewers. Outcomes were fractures, femoral neck bone mineral density (BMD), mortality, and adverse events. We identified 25 additional trials, resulting in a total population of 47,007 participants. All treatments had beneficial effects on fractures versus placebo with zoledronate being the most effective treatment in preventing vertebral fractures HR = 0.38 (95%CrI: 0.28, 0.49). Zoledronate HR = 0.71 (95%CrI: 0.61, 0.81) and risedronate HR = 0.70 (95%CrI: 0.53, 0.84) were found to be the most effective treatments in preventing non-vertebral fractures. All treatments were associated with increases in femoral neck BMD versus placebo with zoledronate being the most effective treatment MD = 4.02 (95%CrI: 3.2, 4.84). There was a paucity of data regarding hip and wrist fractures. Depending on its cost-effectiveness, zoledronate could be considered a first-line option for people at increased risk of fragility fractures

A Survey Comparing the Management of Diabetes, Hypoglycaemia and Hyperglycaemia by Type 1 and Type 2 Insulin Users

Aim: The opinions and attitudes of type 1 (T1) and type 2 (T2) insulin users toward their diagnosis, management, treatment and complications as a result of their diabetes were sought. Methods: A bottom-up survey design consisting of 66 open and closed questions was used to determine both positive and negative experiences of patients currently using insulin by injection only. Results: 707 insulin users (71% T1 and 29% T2) predominately from the UK completed the questionnaire. A comparison between T1 and T2 insulin users found that exercise, diet, BG testing and excursions from normoglycaemia were the most common source of difficulty amongst these insulin dependent patients. The majority of T1 participants were found to use a basal bolus insulin regimen (Lantus/Levemir and a short-acting insulin such as Novorapid®, Humalog® or Actrapid® but only 34% of T2 insulin users used a similar system with 35% using biphasic insulin aspart 30 (Novomix®) which may have due to lesser hypoglycaemic events. Conclusions: The results from this survey which focus on the common needs of insulin users show that careful follow-up after diagnosis, frequent testing and education about calorie turnover from intake and exercise are required for both T1 patients but more so for T2 patients whose needs become similar to those of T1 patients once they begin to inject insulin

Trialling technologies to reduce hospital in‐patient falls: an agential realist analysis

This paper analyses the 'failure' of a patient safety intervention. Our study was part of an RCT of bed and bedside chair pressure sensors linked to radio pagers to prevent bedside falls in older people admitted to hospital. We use agential realism within science and technology studies to examine the fall and its prevention as a situated phenomenon of knowledge that is made and unmade through intra-actions between environment, culture, humans and technologies. We show that neither the intervention (the pressure sensor system), nor the outcome (fall prevention) could be disentangled from the broader sociomaterial context of the ward, the patients, the nurses and (especially) their work through the RCT. We argue that the RCT design, by virtue of its unacknowledged assumptions, played a part in creating the negative findings. The study also raises wider questions about the kind of subjectivities, agencies and power relations these entanglements might effect and (re)produce in the hospital ward

Decrease of resistance to air flow with nasal strips as measured with the airflow perturbation device

BACKGROUND: Nasal strips are used by athletes, people who snore, and asthmatics to ease the burden of breathing. Although there are some published studies that demonstrate higher flow with nasal strips, none had directly measured the effect of the strips on nasal resistance using the airflow perturbation device (APD). The APD is an inexpensive instrument that can measure respiratory resistance based on changes in mouth pressure and rate of airflow. METHOD: This study tested forty-seven volunteers (14 men and 33 women), ranging in age from 17 to 51. Each volunteer was instructed to breathe normally into the APD using an oronasal mask with and without nasal strips. The APD measured respiratory resistance during inhalation, exhalation, and an average of the two. RESULTS: Results of a paired mean t-test comparing nasal strip against no nasal strip were statistically significant at the p = 0.05 level. The Breathe Right™ nasal dilator strips lowered nasal resistance by an average of 0.5 cm H(2)0/Lps from an average nasal resistance of 5.5 cm H(2)0/Lps. CONCLUSIONS: Nasal strips reduce nasal resistance when measured with the APD. The effect is equal during exhalation and during inhalation