Niels Follak

Influence of diabetic metabolic state on fracture healing in spontaneously diabetic rats

Type 1 diabetes mellitus (DM) has been shown to alter the properties of bone and impair fracture healing in both humans and animals. The objective of this study was to examine changes in the histomorphometrical, histological and mechanical parameters of bone and remodeling during fracture healing, depending on the diabetic metabolic state in spontaneously diabetic BB/O(ttawa)K(arlsburg) rats, a rat strain that represents a close homology to DM in man.

Diabetes per se and metabolic state influence gene expression in tissue-dependent manner of BB/OK rats

Several epidemiologic studies have clearly established that long‐term near normoglycaemia strongly protects against onset and progression of late complication of diabetes. Therefore, insulin treatment plays a crucial role in determining the quality of life of affected individuals. Here we studied the effects of exogenous insulin on gene expression levels in well‐ and poorly compensated diabetic subjects in comparison to non‐diabetic BB/OK rats to find out whether diabetes per se and the quality of insulin treatment have an effect on gene expression and whether it is tissue specific.

Postoperative analgesic value of the intra-articular instillation of bupivacaine and morphine after arthroscopic knee surgery

Abstract This prospective, randomized, double-blind study was carried out with 320 patients, subdivided into 4 groups of 80 patients each, who underwent arthroscopic knee surgery during the time period from March 1995 to February 1997. Each of the 4 groups received a different solution: 15 ml of bupivacaine 0.5%, 5 mg of morphine in 15 ml of isotonic saline solution, 15 ml of bupivacaine 0.5% with epinephrine 0.0005%, or 15 ml of isotonic saline solution (control group). Within each study group, the following operations were performed: 15 cruciate ligament plasties with autologous patellar tendon grafts, 30 meniscus resections, 15 notch-plasties as preparation for anterior cruciate ligament surgery, and 20 other types of operation (plica resection, diagnostic biopsy, etc.). Pain intensity was assessed with the visual analogue scale obtained from questioning patients at 2, 4, 8, 12, and 24 h postoperatively. In terms of reducing postoperative pain and decreasing the consumption of analgesics after arthroscopic knee surgery, bupivacaine 0.5% with epinephrine 0.0005% was found to be the most effective.

Histomorphometric and radiographical changes after lumbar implantation of the PEEK nonfusion interspinous device in the BB.4S rat model

Study Design. An experimental animal study. Objective. To investigate histomorphometric and radiographical changes in the BB.4S rat model after PEEK (polyetheretherketone) nonfusion interspinous device implantation. Summary of Background Data. Clinical effectiveness of the PEEK nonfusion spine implant Wallis (Abbott, Bordeaux, France; now Zimmer, Warsaw, IN) is well documented. However, there is a lack of evidence on the long-term effects of this implant on bone, in particular its influence on structural changes of bone elements of the lumbar spine. Methods. Twenty-four male BB.4S rats aged 11 weeks underwent surgery for implantation of a PEEK nonfusion interspinous device or for a sham procedure in 3 groups of 8 animals each: 1) implantation at level L4–L5; 2) implantation at level L5–L6; and 3) sham surgery. Eleven weeks postoperatively osteolyses at the implant-bone interface were measured via radiograph, bone mineral density of vertebral bodies was analyzed using osteodensitometry, and bone mineral content as well as resorption of the spinous processes were examined by histomorphometry. Results. Resorption of the spinous processes at the site of the interspinous implant was found in all treated segments. There was no significant difference in either bone density of vertebral bodies or histomorphometric structure of the spinous processes between adjacent vertebral bodies, between treated and untreated segments and between groups. Conclusion. These findings indicate that resorption of spinous processes because of a result of implant loosening, inhibit the targeted load redistribution through the PEEK nonfusion interspinous device in the lumbar spinal segment of the rat. This leads to reduced long-term stability of the implant in the animal model. These results suggest that PEEK nonfusion interspinous devices like the Wallis implants may have time-limited effects and should only be used for specified indications.

Transplantation of adipose tissue protects BB/OK rats from type 1 diabetes development

B(io) B(reedding)/O(ttawa) K(alsburg) rats spontaneously develop insulin-dependent type 1 diabetes. Days before BB/OK rats become diabetic, their body seems to be flabby which may be attributed to loss of subcutaneous fat. However, the rats are normoglycemic and manifest 3-4 days later. This observation prompted us to search for possibilities to avoid the loss of adipose tissue. BB/OK rats were subcutaneously grafted with visceral adipose tissue. In total, 34 (71%) out of 48 male and 23 (49%) out of 47 female BB/OK rats grafted with adipose tissue developed type 1 diabetes so that significantly more females than males were protected from diabetes development (p=0.03). In the control group, 17 (85%) out of 20 male and 20 (95%) out of 21 female BB/OK rats were diabetic. Adipose tissue transplantation can protect BB/OK rats from type 1 diabetes development in a sex specific manner. One could conclude that the manipulations have influenced fat accumulation and/or fat metabolism which prevent type 1 diabetes development in about 50% of BB/OK rats. This idea is supported by the finding that a mutation in the leptin receptor of NOD mice suppresses type 1 diabetes progression.

High-fat diet protects BB/OK rats from developing type 1 diabetes.

It is well known that lipid metabolism plays an important role in the early stages of type 1 diabetes (T1D). For that reason, we examined factors that influence lipid metabolism of BioBreeding/Ottawa Kalsburg (BB/OK) rats that spontaneously develop an insulin‐dependent T1D.

Phenotypic and gene expression differences between DA, BN and WOKW rats.

Background Because inbred rat strains are widely used as laboratory models, knowledge of phenotypic and genetic variations between strains will be useful to obtain insight into the relationship between different strains. Methods and Results We studied phenotypic traits: of each strain – BN/K, DA/K and WOKW –10 male rats were studied for body weight and serum constituents at an age of 10 and 30 weeks. In addition, a total of 95 rats were studied for life expectancy. At an age of 30 weeks, these male rats were killed by an overdose of anesthetic (Sevofluran, Abbott), and the subcutaneous and visceral adipose tissue as well as bone tissue were removed to study the expression of 20 genes. There were significant differences in body weight, serum lipids and leptin at an age of 30 weeks between strains. Regarding life expectancy, BN rats lived longest (1072±228d). The highest gene expression was found in bone of BN rats. In adipose tissues, Nfkb1 is only expressed in subcutaneous adipocytes, and 5 genes, Col2a1, Mmp9, Tnfa, Ins1 and Cyp24a1, are not expressed in adipocytes. The ranking BN = DA>WOKW was observed in only one gene in subcutaneous (Fto) and visceral adipocytes (Col6a1). There were no significant differences in gene expression of one gene in subcutaneous adipocytes and of 3 genes in visceral adipocytes. Comparing the gene expression in visceral and subcutaneous adipocytes, only one gene showed a comparable behavior (Bmp1). Conclusion From these results, it can be concluded that obvious phenotypic differences are caused by genetic differences between three rat strains, BN, DA and WOKW, as supported by gene expression studies in bone and adipose tissues. Especially BN rats can be used to study the genetic basis of long life.