Tod A. Clark

Cardiovascular complications of non-insulin-dependent diabetes The JCR:LA-cp rat

Diabetes is a serious medical and financial burden on western societies. It is the seventh leading cause of death in the United States and Canada. The disease is due to a primary defect in glucose tolerance and carbohydrate metabolism resulting from either a deficiency of insulin (Insulin-dependent (type I) diabetes mellitus - IDDM) or a state of insulin resistance (Non-insulin-dependent (type II) diabetes mellitus - NIDDM). NIDDM comprises greater than 80% of total diabetic cases. Associated with the primary metabolic defects are equally deleterious secondary complications affecting the renal, ocular, nervous and cardiovascular systems. The cardiovascular complications account for a major proportion of diabetic mortality. As such, it is of paramount importance to develop or find an animal model expressing complications homologous to the human condition. Many models of NIDDM are available to the diabetic researcher but choosing an accurate one can be difficult. The following compares the advantages and limitations of one such model, the JCR:LA-cp rat to other NIDDM models commonly used today.

Alternative therapies for diabetes and its cardiac complications: role of vanadium

It is now well known that a cardiomyopathic state accompanies diabetes mellitus. Although insulin injections and conventional hypoglycemic drug therapy have been of invaluable help in reducing cardiac damage and dysfunction in diabetes, cardiac failure continues to be a common cause of death in the diabetic population. The use of alternative medicine to maintain health and treat a variety of diseases has achieved increasing popularity in recent years. The goal of alternative therapies in diabetic patients has been to lower circulating blood glucose levels and thereby treat diabetic complications. This paper will focus its discussion on the role of vanadium on diabetes and the associated cardiac dysfunction. Careful administration of a variety of forms of vanadium has produced impressive long-lasting control of blood glucose levels in both Type 1 and Type 2 diabetes in animals. This has been accompanied by, in many cases, a complete correction of the diabetic cardiomyopathy. The oral delivery of vanadium as a vanadate salt in the presence of tea has produced particularly impressive hypoglycemic effects and a restoration of cardiac function. This intriguing approach to the treatment of diabetes and its complications, however, deserves further intense investigation prior to its use as a conventional therapy for diabetic complications due to the unknown long-term effects of vanadium accumulation in the heart and other organs of the body.

A tea/vanadate decoction delivered orally over 14 months to diabetic rats induces long-term glycemic stability without organ toxicity

Vanadium can induce potent hypoglycemic effects in type 1 and type 2 diabetes mellitus animals, but toxic adverse effects have inhibited the translation of these findings. Administration of vanadate in a black tea decoction has shown impressive hypoglycemic effects without evidence of toxicity in short-term studies. The purpose of this study was to investigate the hypoglycemic action and the toxic adverse effects of a tea/vanadate (T/V) decoction in diabetic rats over a 14-month treatment period. Streptozotocin-induced type 1 diabetes mellitus rats were orally gavaged with 40 mg sodium vanadate in a black tea decoction only when blood glucose levels were greater than 10 mmol/L. Glycemic status and liver and kidney function were monitored over 14 months. All of the diabetic rats in this treatment group (n = 25) required treatment with the T/V decoction at the start of the study to reduce blood glucose levels to less than 10 mmol/L. Diarrhea was uncommon among the T/V-treated animals during the first week of T/V treatment and was absent thereafter. There was no evidence of liver or kidney dysfunction or injury. From 2 to 6 months, fewer animals required the T/V treatment to maintain their blood glucose levels. After 9 months of treatment, none of the diabetic animals required any T/V to maintain their blood glucose levels at less than 10 mmol/L. Oral administration of a T/V decoction provides safe, long-acting hypoglycemic effects in type 1 diabetes mellitus rats. The typical glycemic signs of diabetes were absent for the last 5 months of the study.

Restoration of Cardiomyocyte Function in Streptozotocin-Induced Diabetic Rats after Treatment with Vanadate in a Tea Decoction

Diabetes mellitus is associated with abnormal cardiomyocyte Ca(2+) transients and contractile performance. We investigated the possibility that an alteration in inositol trisphosphate/phospholipase C (IP₃/PLC) signalling may be involved in this dysfunction. Phosphatidic acid stimulates cardiomyocyte contraction through an IP₃/PLC signaling cascade. We also tested a novel therapeutic intervention to assess its efficacy in reversing any potential defects. Diabetes was induced in Sprague-Dawley rats by streptozotocin treatment and maintained for an 8 week experimental period. Active cell shortening was significantly depressed in cardiomyocytes obtained from diabetic and insulin-treated diabetic rats in comparison to normal control animals. Perfusion of the cells with phosphatidic acid induced an increase in contraction of control rat cardiomyocytes whereas its effect was inhibitory in cells from streptozotocin-induced diabetic rats. Diabetic rats were also treated orally with vanadate administered in a black tea extract (T/V) for the 8 week period. T/V treatment resulted in a contractile response that was not different from cells of control animals. Furthermore, cardiomyocytes from T/V-treated animals exhibited significantly improved Ca(2+) transients in comparison to diabetic animals and exhibited a normalized response to phosphatidic acid perfusion. It is concluded that a T/V glycemic therapy is capable of preventing the defect in IP₃/PLC signaling that occurs in diabetes and can restore normal cardiac contractile function.

Mg2+-dependent ATPase activity in cardiac myofibrils from the insulin-resistant JCR:LA-cp rat.

There is a great deal of information presently available documenting a cardiomyopathic condition in insulin-deficient models of diabetes. Less information is available documenting a similar status in non insulin-dependent models of diabetes. We have studied the functional integrity of the myofibrils isolated from hearts of JCR:LA rats. The JCR:LA rat is hyperinsulinemic, hyperlipidemic, glucose intolerant and obese. As such, it carries many of the characteristics found in humans with non insulin-dependent diabetes mellitus. These animals also have many indications of heart disease. However, it is not clear if the hearts suffer from vascular complications or are cardiomyopathic in nature. We examined Mg2+-dependent myofibrillar ATPase in hearts of JCR:LA-cp/cp rats and their corresponding control animals (+/?) and found no significant differences (P> 0.05). This is in striking contrast to the depression in this activity exhibited by cardiac myofibrils isolated from insulin-deficient models of diabetes. Our data demonstrate that myofibrillar functional integrity is normal in JCR:LA-cp rats and suggest that these hearts are not in a cardiomyopathic state. Insulin status may be critical in generating a cardiomyopathic condition in diabetes.

Immediate Nerve Transfer for the Treatment of Peroneal Nerve Palsy Secondary to an Intraneural Ganglion: Case Report and Review:

Intraneural ganglion cysts that occur within the common peroneal nerve are a rare cause of foot drop. The current standard of treatment for intraneural ganglion cysts involving the common peroneal nerve involves (1) cyst decompression and (2) ligation of the articular nerve branch to prevent recurrence. Nerve transfers are a time-dependent strategy for recovering ankle dorsiflexion in cases of high peroneal nerve palsy; however, this modality has not been performed for intraneural ganglion cysts involving the common peroneal nerve. We present a case of common peroneal nerve palsy secondary to an intraneural ganglion cyst occurring in a 74-year-old female. The patient presents with a 5-month history of pain in the right common peroneal nerve distribution and foot drop. The patient underwent simultaneous cyst decompression, articular nerve branch ligation, and nerve transfer of the motor branch to the flexor hallucis longus to a motor branch of the anterior tibialis muscle. At final follow-up, the patient demonstrated complete (M4+) return of ankle dorsiflexion, no pain, and no evidence of recurrence and was able to weight bare without the need of orthotic support. Given the minimal donor site morbidity and recovery of ankle dorsiflexion, this report underscores the importance of considering early nerve transfers in cases of high peroneal neuropathy due to an intraneural ganglion cyst.

Open Versus Arthroscopic Tennis Elbow Release: Randomized Controlled Trial

Objectives: The primary objective of this study was to determine if quality of life and function are different following arthroscopic versus open tennis elbow release surgery. Based on retrospective studies, both approaches have been found to be beneficial, but no prospective randomized comparison has been conducted to date. Methods: Following a minimum six-months of conservative treatment, seventy-one patients (>16 yrs old) were randomized intraoperatively to undergo either arthroscopic or open lateral release. Outcome measures were the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH), a 5-question VAS Pain Scale, and grip strength. Study assessments took place pre-, and 6-week, 3-, 6-, and 12-months post-surgery. Comparisons between groups and within groups over time were conducted using repeated measures ANOVA. A minimal clinically significant difference for the DASH had been previously identified as 15 points, and was used to compare groups as well at 12-months post-operative (Beaton et al. 2001). Results: Fifteen women and 19 men underwent the open procedure with a mean age of 47.1 years (6.7) and 13 women and 21 men were in the arthroscopic group with a mean age of 45.0 (6.9). No pre-surgery differences were found between groups based on age, sex, DASH or VAS scores. Both groups demonstrated a significant improvement in subjective measures and grip strength by 12-months post-surgery, and no significant differences were found between groups at any time point. The DASH, our primary outcome, decreased from a mean (SD) of 47.5 (14.5) pre-surgery to 21.9 (21.8) at 12-months post-surgery in the Open group and from 52.7 (16.0) to 22.6 (21.1) in the Arthroscopic group. VAS-pain scores (%) decreased in the Open group from 62.5 (17.2) pre-operatively to 30.0 (26.5) at 12-months. In the arthroscopic group, scores decreased from 63.7 (15.9) to 26.2 (24.6). Grip strength (kg) increased on the affected side from 23.6 (14.9) to 29.3 (16.3) and 21.4 (15.4) to 29.8 (15.4) for Open and Arthroscopic groups, respectively. The number of participants to reach the minimum clinically significant change did not differ between groups, 17 in the open group and 19 in the arthroscopic group. Ten in each group did not reach this threshold. Based on post hoc regression analysis, no factors (age, gender, WCB status, or smoking status) were found to be significant predictors of DASH or VAS outcome at 12-months post-surgery. However, this study was not adequately powered to draw any specific conclusions in this regard. The only significant difference between study groups was that the arthroscopic technique resulted in longer surgery time, 34.0 versus 22.5 minutes (p=0.005). Conclusion: Based on this study, there is no difference between arthroscopic and open tennis elbow release surgery in subjective outcome, specifically DASH and VAS pain scale, or in function, specifically, grip strength, at 12-months post-operative. Therefore, there may not be any benefit to the increased experience and operating room time required to perform a lateral release arthroscopically versus an open approach.

Management of complications of ligament injuries of the wrist.

Despite advances in understanding the anatomy and biomechanics of wrist motion, intrinsic carpal ligament injuries are difficult to diagnose and treat. Even when an accurate diagnosis is made, there is no consensus on the most appropriate and reliable treatment. Injury predisposes to a progressive decline in wrist function and a predictable pattern of degenerative arthritis. To prevent inadequate outcomes, many treatment options exist, all having inherent benefits and complications. This article reviews the complications of intrinsic carpal ligament injuries and complications of their treatment. Methods to prevent and principles to manage the complications are discussed.

Vanadium Effects in Diabetes

Over the past twenty years vanadium compounds have garnered much attention with respect to the treatment of diabetes. Vanadium’s attraction as a hypoglycaemic agent lies in its oral route of administration. Several different vanadium salts have been used to treat both Type 1 and Type 2 diabetes in vivo, including sodium orthovanadate, sodium meta-vanadate and vanadyl sulphate. In addition to the hypoglycaemic action of these agents, several biochemical and cellular changes common in diabetes have been positively affected. However, stepping from the animal model to the human diabetic patient has been hindered by the toxicity of these compounds. Gastrointestinal toxicity has been common while other com-plications including hepatotoxicity and body weight changes remain controversial. Many approaches are being investigated in attempts to reduce the toxicity of vanadium compounds, These include dosing alterations, combining vanadium with chelating agents, organic modi-fication of the species itself and most recently combining nutraceuticals with the treatment. The anti-diabetic actions of vanadium salts and the toxicity of these substances are reviewed here with mention of the more recent approaches to limiting the toxicity.