Polyol pathway in tissues of spontaneously diabetic Chinese hamsters (Cricetulus griseus) and the effect of an aldose reductase inhibitor, ONO-2235

1. Sorbitol and fructose levels were significantly elevated in the lens, the sciatic nerve, the retina and the kidney of diabetic Chinese hamsters and inositol level was significantly decreased in the lens and sciatic nerve of diabetics. 2. The activity of an aldose reductase in the kidney was not different between normal and diabetic Chinese hamsters. 3. An aldose reductase inhibitor (ONO-2235) had no effect in sorbitol, fructose and inositol contents of all these tissues from diabetic Chinese hamsters. 4. These results suggest that diabetic Chinese hamsters produce polyol accumulation in tissues but that there is a clear species-specific difference to inhibition of aldose reductase.     

Comparison of glucose, sorbitol and fructose accumulation in lens and liver of diabetic and insulin-treated rats and mice

1. The accumulation of glucose, fructose and sorbitol was determined in the lens, liver, and blood from normal, streptozotocin-induced diabetic, and insulin-treated diabetic rats and mice. 2. Sorbitol concentration in rat lens was 10-100 times greater than that in mouse lens, with the highest concentrations in the diabetic animals. 3. Sorbitol levels in rat and mouse liver, and mouse lens were similar and increased only slightly under hyperglycemic conditions. 4. Fructose accumulation was similar in rat and mouse liver and was elevated in the diabetic mouse blood and diabetic rat lens. 5. Aldose reductase activity in rat lens was approximately 350 times that of mouse lens. 6. Lenticular sorbitol dehydrogenase activity in rats was approximately ten times that in mouse lens. 7. Administration of insulin tended to lower liver glucose and subsequent sorbitol formation in the diabetic rat and mouse.     

Development of novel pyrazolone derivatives as inhibitors of aldose reductase: An eco-friendly one-pot synthesis,experimental screening and in silico analysis

Aldose reductase is the key enzyme of polypol pathway leading to accumulation of sorbitol. Sorbitol does not diffuse across the cell membranes easily and therefore accumulates within the cell, causing osmotic damage which leads to retinopathy (cataractogenesis), neuropathy and other diabetic complications. Currently, aldose reductase inhibitors like epalrestat, ranirestat and fidarestat are used for the amelioration of diabetic complications. However, such drugs are effective in patients having good glycemic control and less severe diabetic complications. In present study we have designed novel pyrazolone derivative and performed eco-friendly synthesis approach and tested the synthesized compounds as potential inhibitors of aldose reductase activity. Additional in silico analysis in current study indicates presence of highly conserved chemical environment in active site of goat lens aldose reductase. The reported data is expected to be useful for developing novel pyrazolone derivatives as lead compounds in the management of diabetic complications.     

Quantitative histochemistry of the sorbitol pathway in glomeruli and small arteries of human diabetic kidney.

Recent evidence has suggested a role for the polyol pathway in pathogenesis of cell damage in diabetes Glucose may be phosphorylated to glucose-6-phosphate via hexokinase and enter glycolysis or reduced to sorbitol via aldose reductase to enter the polyol pathway. The poorly diffusible sorbitol is converted via sorbitol dehydrogenase to fructose. Hexokinase, aldose reductase and sorbitol dehydrogenase activities were measured in glomeruli (G) and small arteries (SA) taken from normal and diabetic human kidneys, Hexokinase in diabetic G was 1688, which was significantly decreased from normal, 3147 mmoles/kg-1/h-1. Alodse reductase was significantly elevated in diabetic G,56-6, compared to normal G,10-8 mmoles/kg-1/h-1. In contrast, sorbitol dehydrogenase was significantly depressed in diabetic G, 3-7 VERSUs 10-9 mmoles/kg-1/h-1. The enzymatic changes observed in diabetic G would facilitate accumulation of sorbitol and therefore could contribute to the progression of glomerulosclerosis. The activity of hexokinase was also significantly reduced in SA, whereas aldose reductase and sorbitol dehydrogenase were unchanged.     

Efficacy of lower doses of vanadium in restoring altered glucose metabolism and antioxidant status in diabetic rat lenses

Vanadium compounds are potent in controlling elevated blood glucose levels in experimentally induced diabetes. However the toxicity associated with vanadium limits its role as therapeutic agent for diabetic treatment. A vanadium compound sodium orthovanadate (SOV) was given to alloxan-induced diabetic Wistar rats in lower doses in combination withTrigonella foenum graecum, a well-known hypoglycemic agent used in traditional Indian medicines. The effect of this combination was studied on lens morphology and glucose metabolism in diabetic rats. Lens, an insulin-independent tissue, was found severely affected in diabetes showing visual signs of cataract. Alterations in the activities of glucose metabolizing enzymes (hexokinase, aldose reductase, sorbitol dehydrogenase, glucose-6-phosphate dehydrogenase) and antioxidant enzymes (glutathione peroxidase, glutathione reductase) besides the levels of related metabolites, [sorbitol, fructose, glucose, thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH)]were observed in the lenses from diabetic rats and diabetic rats treated with insulin (2 IU/day), SOV (0.6 mg/ml),T. f. graecum seed powder (TSP, 5%) and TSP (5%) in combination with lowered dose of vanadium SOV (0.2 mg/ml), for a period of 3 weeks. The activity of the enzymes, hexokinase, aldose reductase and sorbitol dehydrogenase was significantly increased whereas the activity of glucose-6-phosphate dehydrogenase, glutathione peroxidase and glutathione reductase decreased significantly in lenses from 3 week diabetic rats. Significant increase in accumulation of metabolites, sorbitol, fructose, glucose was found in diabetic lenses. TBARS measure of peroxidation increased whereas the levels of antioxidant GSH decreased significantly in diabetic condition. Insulin restored the levels of altered enzyme activities and metabolites almost to control levels. Sodium orthovanadate (0.6 mg/ml) andTrigonella administered separately to diabetic animals could partially reverse the diabetic changes, metabolic and morphological, while vanadate in lowered dose in combination withTrigonella was found to be the most effective in restoring the altered lens metabolism and morphological appearance in diabetes. It may be concluded that vanadate at lowered doses administered in combination withTrigonella was the most effective in controlling the altered glucose metabolism and antioxidant status in diabetic lenses, these being significant factors involved in the development of diabetic complications, that reflects in the reduced lens opacity     

Obese and diabetic db/db mice develop marked liver fibrosis in a model of nonalcoholic steatohepatitis: role of short-form leptin receptors and osteopontin

Obesity and type 2 diabetes are associated with nonalcoholic steatohepatitis (NASH), but an obese/diabetic animal model that mimics human NASH remains undefined. We examined the induction of steatohepatitis and liver fibrosis in obese and type 2 diabetic db/db mice in a nutritional model of NASH and determined the relationship of the expressions of osteopontin (OPN) and leptin receptors to the pathogenesis of NASH. db/db mice and the corresponding lean and nondiabetic db/m mice were fed a diet deficient in methionine and choline (MCD diet) or control diet for 4 wk. Leptin-deficient obese and diabetic ob/ob mice fed similar diets were used for comparison. MCD diet-fed db/db mice exhibited significantly greater histological inflammation and higher serum alanine aminotransferase levels than db/m and ob/ob mice. Trichrome staining showed marked pericellular fibrosis in MCD diet-fed db/db mice but no significant fibrosis in db/m or ob/ob mice. Collagen I mRNA expression was increased 10-fold in db/db mice, 4-fold in db/m mice, and was unchanged in ob/ob mice. mRNA expressions of OPN, TNF-alpha, TGF-beta, and short-form leptin receptors (Ob-Ra) were significantly increased in db/db mice compared with db/m or ob/ob mice. Parallel increases in OPN and Ob-Ra protein levels were observed in db/db mice. Cultured hepatocytes expressed only Ob-Ra, and leptin stimulated OPN mRNA and protein expression in these cells. In conclusion, our results demonstrate the development of an obese/diabetic experimental model for NASH in db/db mice and suggest an important role for Ob-Ra and OPN in the pathogenesis of NASH.     

Formation of sorbitol 6-phosphate by bovine and human lens aldose reductase, sorbitol dehydrogenase and sorbitol kinase

Formation of sorbitol 6-phosphate by bovine and human lens aldose reductase and sorbitol dehydrogenase by the reduction of glucose 6-phosphate and fructose 6-phosphate, respectively, has been demonstrated. The reaction product has been identified by Dowex-formate column chromatography, gas chromatography and mass spectrometry. Sorbitol 6-phosphate can also be formed by the phosphorylation of sorbitol by lens sorbitol kinase in the presence of ATP.     

Regulation and control of glucose overutilization in erythrocytes by vanadate

The insulin mimetic effect of vanadate inin vitro incubation of erythrocytes with high glucose concentrations showed an increase in sorbitol accumulation and glucose utilization using U-¹⁴C-glucose. Aldose reductase inhibitors and vanadate addition reversed the sorbitol accumulation, whereas insulin could not reverse it. Increased glucose utilization was also normalized with vanadium compounds. Increased activity of aldose reductase and sorbitol levels in diabetic animals were also normalized with vanadate treatment.     

Stress-induced changes in accumulation of sorbitol and in activities of concomitant enzymes in digestive gland of freshwater snail

Sorbitol content was determined in the digestive gland of freshwater snail (Viviparus viviparus L.) in different seasons and in a short-term experiment on the water temperature decrease and on intoxication with cadmium chloride. In the model experiments, changes in activities of enzymes involved in sorbitol metabolism (acid phosphatases, sorbitol dehydrogenase, and aldose reductase) were also studied. Sorbitol was accumulated by the snail in response to the temperature decrease (as a cryoprotectant) and under conditions of acute intoxication (as a probable metabolic regulator or a nonspecific protective factor). However, the mechanisms of this accumulation are different: on cold adaptation sorbitol is produced as a result of reduction of glucose under the influence of aldose reductase, and on intoxication sorbitol is mainly produced from fructose under the influence of sorbitol dehydrogenase. Pathways of the sorbitol accumulation and its re-involvement into metabolism are not always the same, and this might be a mechanism for regulation of carbohydrate metabolism (at the initial stage of glycolysis) on adaptation to unfavorable factors of the environment.     

Diabetic neuropathies. Metabolism of sorbitol in sciatic nerve tissue in streptozotocin diabetes

The increase of sorbitol and fructose levels caused by aldose reductase activation and sorbitol dehydrogenase inhibition were observed in sciatic nerve of streptozotocin-diabetic rats. Elevated polyol pathway activity has been implicated in the development of diabetic complications such as neuropathy. The regulation of polyol pathway enzymes is based on the changes of redox state of free nicotinamide nucleotides. The decrease of the NADP+/NADPH ratio in cytosolic compartment of sciatic nerve cells activated aldose reductase and the decrease of the NAD+/NADH ratio inhibited sorbitol dehydrogenase. Nicotinamide as a precursor of NAD+ biosynthesis increased the free NADP+/NADPH and NAD+/NADH ratios and inhibited the activity of polyol pathway. The sorbitol level decreased in sciatic nerve of nicotinamide-treated streptozotocin-diabetic rats as compared to non-treated ones. Thus, the data provide evidence for important role of nicotinamide, as an antidiabetic drug, in prevention or correction of diabetic neuropathy.     

Substance P, neurokinin A, vasoactive intestinal polypeptide and gastrin releasing peptide in the intestine and pancreas of spontaneously obese-diabetic mice

The concentrations and contents of immunoreactive substance P (SP), neurokinin A (NKA), vasoactive intestinal polypeptide (VIP) and gastrin releasing peptide (GRP) were measured in acid-ethanol extracts of intestine (duodenum-jejunum-ileum) and pancreas of C57BL/KsJ diabetes-obese (db/db) mice, Aston obese-hyperglycaemic (ob/ob) mice, and their respective lean controls. The intestinal concentration of GRP and pancreatic concentrations of VIP and GRP were 36-57% lower in lean Aston mice than lean C57BL/KsJ mice, indicating the influence of genetic background in control mice. Intestinal concentrations of SP and NKA were reduced by 19-33% in the db/db and ob/ob mutants compared with their lean controls, but the intestinal contents of these peptides were normal or greater than normal due to intestinal hypertrophy of the mutant mice. The intestinal VIP concentration was not altered, but the content was increased by 87% and 25% respectively in db/db and ob/ob mice, whereas the intestinal GRP concentration was reduced by 51% in ob/ob mice. Pancreatic concentrations and contents of NKA, VIP and GRP were similar in lean and db/db C57BL/KsJ mice. However, pancreatic concentrations and contents of VIP and GRP were reduced by 51-55% in ob/ob mice compared with their lean controls. The sensitivity of the present assay did not permit accurate determination of the low pancreatic concentrations of SP. The results suggest that the spontaneous ob/ob and db/db syndromes of obesity and diabetes in mice are associated with reduced intestinal concentrations of SP and NKA. The ob/ob mouse also exhibited reductions of intestinal GRP and pancreatic GRP and VIP concentrations. These changes in regulatory peptides may relate to abnormalities of intestinal and possibly pancreatic function in obese and diabetic mutant mice.     

In vitro aldose reductase inhibitory activity of some flavonyl-2,4-thiazolidinediones

Aldose reductase (AR) is implicated to play a critical role in diabetes and cardiovascular complications because of the reaction it catalyzes. AR enzyme appears to be the key factor in the reduction of glucose to sorbitol. Synthesis and accumulation of sorbitol in cells due to AR activity is the main cause of diabetic complications, such as diabetic cataract, retinopathy, neuropathy and nephropathy. Aldose reductase inhibitors have been found to prevent sorbitol accumulation in tissues. Numerous compounds have been prepared in order to improve the pharmacological prophile of inhibition of aldose reductase enzyme. In this study, seventeen flavonyl-2,4-thiazolidinediones (flavonyl-2,4-TZD) (Ia-e, IIa-e and IIIa-g) were tested for their ability to inhibit rat kidney AR. Compound Ib showed the highest inhibitory activity (88.69 +/- 1.46%) whereas Ia, IIa, IIIa, IIIb also showed significant inhibitory activity (49.26 +/- 2.85, 67.29 +/- 1.09, 71.11 +/- 1.95, 64.86 +/- 1.21%, respectively).     

Induction of the enzyme aldose reductase in a lens epithelial cell line from a transgenic mouse

A lens epithelial cell line established from a transgenic mouse synthesizes high levels of the enzyme aldose reductase which converts sugars to polyols. This enzyme has been implicated in the formation of sugar cataracts in animals and with diabetic complications in man. The mouse aldose reductase has been characterized and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis has an apparent molecular mass of 38,000, similar to the enzyme in rat and man. The cellular enzyme is inhibited by two aldose reductase inhibitors: Sorbinil (IC50 = 1.8 X 10(-7) M) and Alcon 1576 (IC50 = 7.8 X 10(-8) M). The amount and the specific activity of the aldose reductase can be further increased in the cells by raising the osmolarity of the medium to 500 mOSM. Although the amount of aldose reductase is increased approximately sevenfold under these conditions, alpha-crystallin, one of the main lens specific proteins, remained at about the same concentration. No detectable increase in sorbitol was found within the cells, in contrast to published reports on renal cells in which this polyol increases under similar hyperosmotic conditions; however, in the lens cells there was a five-fold increase in the inositol content, suggesting that this polyol rather than sorbitol may be used to compensate for some of the changes in the osmolarity. The induction of the enzyme aldose reductase without the apparent accumulation of its product suggests a complex mechanism for osmoregulation in the lens cells.     

Beneficial influence of fungal metabolite nigerloxin on eye lens abnormalities in experimental diabetes

Osmotic and oxidative stress have been implicated in the pathogenesis of diabetic cataract. Nigerloxin, a fungal metabolite, has been shown to possess aldose reductase inhibitory and free radical scavenging potential, in vitro. In the present study, the beneficial influence of nigerloxin was investigated on diabetes-induced alteration in the eye lens of rats treated with streptozotocin. Groups of diabetic rats were administered nigerloxin orally (100?mg·(kg body mass)(-1)·day(-1)) for 30?days. The activity of lens polyol pathway enzymes?(aldose reductase and sorbitol dehydrogenase), lipid peroxides, and advanced glycation end products (AGEs) were increased in the diabetic animals. Levels of glutathione as well as the activity of antioxidant enzymes?(superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase) were decreased in the eye lens of the diabetic animals. The administration of nigerloxin significantly decreased levels of lipid peroxides and AGEs in the lens of the diabetic rats. Increase in the activity of aldose reductase and sorbitol dehydrogenase in the lens was countered by nigerloxin treatment. The activity of glutathione and antioxidant enzyme in the lens was significantly elevated in nigerloxin-treated diabetic rats. Examination of the treated rats' eyes indicated that nigerloxin delayed cataractogenesis in the diabetic rats. The results suggest the beneficial countering of polyol pathway enzymes and potentiation of the antioxidant defense system by nigerloxin in diabetic animals, implicating its potential in ameliorating cataracts in diabetics.     

Potential role for the sorbitol pathway in the meiotic dysfunction exhibited by oocytes from diabetic mice

Complications common to type I diabetes, such as cataracts and cardiovascular disorders, have been associated with activation of the polyol pathway, which converts glucose to fructose via the intermediate, sorbitol. Under normal glycemic conditions, glucose is typically targeted for glycolysis or the pentose phosphate pathway through phosphorylation by hexokinase. When glucose levels are elevated under diabetic conditions, hexokinase becomes saturated, and the excess glucose is then shunted to aldose reductase, which converts glucose to sorbitol. In the present study, we examined the potential effects of this pathway on the maturation process in mouse oocytes. Increasing concentrations of sorbitol suppressed FSH-induced maturation in oocytes from control mice. Culturing oocytes from diabetic mice in the presence of inhibitors of aldose reductase reversed the suppression of FSH-induced meiotic maturation. When oocytes from control mice were cultured with activators of aldose reductase, FSH-induced maturation was compromised. In addition, treatment with sorbitol or activators of the polyol pathway led to reduced cell-cell communication between the oocyte and the cumulus cells, as well as compromised FSH-mediated cAMP production and de novo purine synthesis. These data indicate that the suppression of FSH-induced meiotic maturation observed in oocytes from diabetic mice may result from a shunting of glucose through the polyol pathway.     

Aldose reductase induced by hyperosmotic stress mediates cardiomyocyte apoptosis: differential effects of sorbitol and mannitol

Cells adapt to hyperosmotic conditions by several mechanisms, including accumulation of sorbitol via induction of the polyol pathway. Failure to adapt to osmotic stress can result in apoptotic cell death. In the present study, we assessed the role of aldose reductase, the key enzyme of the polyol pathway, in cardiac myocyte apoptosis. Hyperosmotic stress, elicited by exposure of cultured rat cardiac myocytes to the nonpermeant solutes sorbitol and mannitol, caused identical cell shrinkage and adaptive hexose uptake stimulation. In contrast, only sorbitol induced the polyol pathway and triggered stress pathways as well as apoptosis-related signaling events. Sorbitol resulted in activation of the extracellular signal-regulated kinase (ERK), p54 c-Jun N-terminal kinase (JNK), and protein kinase B. Furthermore, sorbitol treatment resulting in induction and activation of aldose reductase, decreased expression of the antiapoptotic protein Bcl-xL, increased DNA fragmentation, and glutathione depletion. Apoptosis was attenuated by aldose reductase inhibition with zopolrestat and also by glutathione replenishment with N-acetylcysteine. In conclusion, our data show that hypertonic shrinkage of cardiac myocytes alone is not sufficient to induce cardiac myocyte apoptosis. Hyperosmolarity-induced cell death is sensitive to the nature of the osmolyte and requires induction of aldose reductase as well as a decrease in intracellular glutathione levels.     

Epidermal growth factor in serum, urine, submandibular glands and kidneys of diabetic mice

Levels of epidermal growth factor (EGF) in serum were significantly decreased in streptozotocin (STZ)-diabetic mice (446 +/- 168 pg/ml after 1 week and 423 +/- 52 after 4 weeks vs 766 +/- 162 pg/ml in controls, P.002 and less than .001. respectively) and in genetically diabetic ob/ob mice (455 +/- 285 vs 962 +/- 453 pg/ml in nondiabetic ob/+ controls, P.043). The urinary excretion of EGF was significantly increased in STZ mice (104 +/- 53 vs 51 +/- 23 ng/h, P.013) but unchanged in ob/ob mice (33 +/- 9 vs 45 +/- 16 ng/h, P.134). However, when expressed per mg creatinine it was decreased in both cases: in STZ mice to 680 +/- 250 ng/mg at 1 week and 684 +/- 211 at 4 weeks vs 1250 +/- 303 ng/mg in controls (P less than .01); and in the ob/ob mice to 552 +/- 117 vs 1237 +/- 300 ng/mg in ob/+ controls (P less than .01). EGF content of the submandibular glands of STZ mice remained unchanged at 1 week (13.1 +/- 2.9 vs 11.0 +/- 1.8 micrograms/mg protein, P.170) but dropped by 4 weeks (4.7 +/- 1.2 micrograms/mg, P less than .001); in the ob/ob mice it was less than 20% that of controls (2.1 +/- 0.8 vs 12.2 +/- 3.6 micrograms/mg protein). In kidneys, the EGF content was not altered in either ob/ob (524 +/- 50 vs 571 +/- 33 pg/mg protein) or STZ mice (652 +/- 183 vs 665 +/- 80 pg/mg). The preproEGF mRNA level in STZ-treated mice was reduced after 4 weeks in submandibular glands but not in kidneys. The results show that diabetes affects EGF production, utilization and/or excretion in mice and that kidneys are spared from suppression of EGF synthesis that is pronounced in the submandibular glands.     

Insulin receptor tyrosine kinase activity is unaltered in ob/ob and db/db mouse skeletal muscle membranes

Insulin binding and insulin receptor tyrosine kinase activity were examined in two rodent models with genetic insulin resistance using partially-purified skeletal muscle membrane preparations. Insulin binding activity was decreased about 50% in both 12-week (219 +/- 184 vs 1255 +/- 158 fmoles/mg, p less than 0.01) and 24-week old (2120 +/- 60 vs 1081 +/- 60 fmoles/mg, p less than 0.01) ob/ob mice. In contrast, insulin binding to membrane derived from 24-week old db/db mice was not significantly different from lean controls (1371 +/- 212 vs 1253 +/- 247 fmoles/mg). Insulin-associated tyrosine kinase activity of membranes from ob/ob skeletal muscle was decreased, compared to its normal lean littermate, when compared on a per mg of protein basis in both 12-week (37 +/- 3 vs 21 +/- 3 pmoles/min/mg, p less than 0.05) and 24-week old (71 +/- 5 vs 37 +/- 6 pmoles/min/mg, p less than 0.01) mice. However, no significant differences in kinase activities were observed when the data were normalized and compared on a per fmole of insulin-binding activity basis for the 12-week (12 +/- 1 vs 11 +/- 2) and 24-week (27 +/- 2 vs 20 +/- 3) age groups. Insulin receptor tyrosine kinase activity of db/db skeletal muscle membranes was not different than its normal lean littermate whether expressed on a protein (34 +/- 7 vs 30 +/- 3) or fmole of insulin-binding activity (21 +/- 4 vs 18 +/- 4) basis. These data suggest that insulin receptor tyrosine kinase is not associated with the insulin resistance observed in ob/ob and db/db mice and demonstrate differences in receptor regulation between both animal models.     

Application of Electron Paramagnetic Resonance (EPR) Oximetry to Monitor Oxygen in Wounds in Diabetic Models

A lack of oxygen is classically described as a major cause of impaired wound healing in diabetic patients. Even if the role of oxygen in the wound healing process is well recognized, measurement of oxygen levels in a wound remains challenging. The purpose of the present study was to assess the value of electron paramagnetic resonance (EPR) oximetry to monitor pO₂ in wounds during the healing process in diabetic mouse models. Kinetics of wound closure were carried out in streptozotocin (STZ)-treated and db/db mice. The pO₂ was followed repeatedly during the healing process by 1 GHz EPR spectroscopy with lithium phthalocyanine (LiPc) crystals used as oxygen sensor in two different wound models: a full-thickness excisional skin wound and a pedicled skin flap. Wound closure kinetics were dramatically slower in 12-week-old db/db compared to control (db/+) mice, whereas kinetics were not statistically different in STZ-treated compared to control mice. At the center of excisional wounds, measurements were highly influenced by atmospheric oxygen early in the healing process. In pedicled flaps, hypoxia was observed early after wounding. While reoxygenation occurred over time in db/+ mice, hypoxia was prolonged in the diabetic db/db model. This observation was consistent with impaired healing and microangiopathies observed using intravital microscopy. In conclusion, EPR oximetry using LiPc crystals as the oxygen sensor is an appropriate technique to follow wound oxygenation in acute and chronic wounds, in normal and diabetic animals. Nevertheless, the technique is limited for measurements in pedicled skin flaps and cannot be applied to excisional wounds in which diffusion of atmospheric oxygen significantly affects the measurements.     

NADPH-dependent reduction of glyceraldehyde: a unusually high activity in the lens of the camel (Camelus dromedarius)

The enzymes of the polyol pathway, namely aldose reductase and sorbitol dehydrogenase, were measured in camel lens extracts. A NADPH-dependent glyceraldehyde and erythrose reductase activity 25 times higher than that of calf lens was observed in camel lens. A preliminary comparison between this enzyme activity present in the camel and aldose reductase of calf lens is reported.