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2.
J Pharm Sci ; 111(7): 1952-1961, 2022 07.
Article in English | MEDLINE | ID: mdl-34986358

ABSTRACT

The approximation of euglycemia is the most effective means of preventing diabetic complications, which is achieved through effective insulin delivery. Recent reports indicate that insulin phenolic preservatives, which are found in all commercial insulin formulations, are cytotoxic, pro-inflammatory and induce secondary fibrosis. Therefore, we hypothesize that these preservatives induce an inflammatory response at the site of insulin infusion leading to diminished glycemic control and adverse pharmacokinetic outcomes. Insulin degradation by inflammatory cell proteases was quantitated following protease treatment in vitro. A modified murine air pouch model was utilized to evaluate the relative inflammatory responses following infusions of saline, insulin preservatives, and insulin, utilizing the adjuvant irritant thioglycolate. Blood glucose levels were monitored in diabetic mice with and without air pouch irritation. A pharmacokinetic analysis evaluated insulin effectiveness for diabetic mice between these two conditions. Inflammatory cells are significantly present in insulin preservative-induced inflammation, which effects diminished blood glucose control by both insulin uptake and degradation. Insulin containing these preservatives resulted in similar degrees of inflammation as observed with the irritant thioglycolate. These studies imply that the preservative agents found in commercial insulin formulations induce an intense localized inflammatory reaction. This inflammatory reaction may be responsible for the premature failure of insulin infusion devices. Future studies directed at reducing this inflammatory reaction may prove to be an important step in extending the lifespan of insulin infusion devices.


Subject(s)
Diabetes Mellitus, Experimental , Insulin Infusion Systems , Animals , Blood Glucose/analysis , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/drug therapy , Glycemic Control , Hypoglycemic Agents , Inflammation/drug therapy , Insulin , Insulin Infusion Systems/adverse effects , Irritants , Mice , Thioglycolates
3.
J Foot Ankle Surg ; 48(3): 330-9, 2009.
Article in English | MEDLINE | ID: mdl-19423033

ABSTRACT

UNLABELLED: A retrospective study was performed to evaluate subjective and radiographic outcomes in 41 patients who underwent operative treatment of their ankle fracture. A number of risk factor variables were analyzed, a modified form of the American College of Foot and Ankle Surgeons Ankle Scoring Scale was used to assess subjective patient satisfaction, and independent and multiple variable statistical analyses were undertaken to explain the outcomes that were observed. On the subjective scale, a maximum of 53 points was possible, and a score of > or =50 points was considered a satisfactory result. Fifty-six charts were reviewed and 45 patients met the criteria for inclusion in the study; 41 patients (91.11%) returned postoperative questionnaires. Male gender was the only independent variable that statistically significantly increased the likelihood of scoring > or =50 points on the subjective scoring scale. Being obese, being a current smoker, sustaining a high fibular fracture, undergoing repair of the tibiofibular syndesmosis, and experiencing a painful internal fixation device all statistically significantly decreased the likelihood of scoring > or =50 points. LEVEL OF CLINICAL EVIDENCE: 2.


Subject(s)
Ankle Injuries/surgery , Fractures, Bone/surgery , Outcome Assessment, Health Care , Adolescent , Adult , Aged , Ankle Injuries/classification , Ankle Joint/surgery , Cohort Studies , Female , Fracture Fixation, Internal , Fractures, Bone/classification , Humans , Male , Middle Aged , Obesity/complications , Pain, Postoperative/complications , Patient Satisfaction , Retrospective Studies , Sex Factors , Smoking/adverse effects , Surveys and Questionnaires
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