How is Biodegradable Scaffold Effective in Gap Non-union? Insights from an Experiment

ObjectiveTo evaluate the role of composite (Chitosan/Chondroitin sulphate/gelatin/nano-bioglass) scaffold in the union of critical size bone defect created in the rabbit’s ulna.MethodsThe composite (Chitosan/Chondroitin sulphate/gelatin/nano-bioglass) scaffold was fabricated using the freeze-drying technique under standard laboratory conditions. The scaffold was cut into the appropriate size and transferred into the defect created (critical bone size defect 1 cm) over the right ulna in the rabbit. The scaffold was not implanted on the left side thus the left side ulna served as control. Results were assessed on serial radiological examination. Rabbits were sacrificed at 20 weeks for histopathological examination (Haematoxylin–Eosin staining and Mason’s trichrome staining) and scanning electron microscope observation. Radiological scoring was done by Lane and Sandhu’s scoring.ResultsAmong 12 rabbits, 10 could complete the follow-up. Among those 10 rabbits, 8 among the test group showed good evidence of bone formation at the gap non-union scaffold implanted site. Histological evidence of new bone formation, collagen synthesis, scaffold resorption, minimal chondrogenesis was evident by 20 weeks in the test group. Two rabbits had poor bone formation.ConclusionThe chitosan-chondroitin sulphate-gelatin-nano-bioglass composite scaffold is efficient in osteoconduction and osteoinduction in the gap non-union model as it is biocompatible, bioactive, and non-immunogenic as well.     

Dietary vitamin e supplementation attenuates hypertension in Dahl salt-sensitive rats

There is strong evidence that excess dietary salt (NaCl) is a major factor contributing to the development of hypertension. Salt-sensitive humans and rats develop hypertension even on a normal-salt diet. Salt sensitivity is associated with glucose intolerance and insulin resistance in both humans and animal models, including Dahl salt-sensitive (DSS) rats. In insulin resistance, impaired glucose metabolism leads to elevated endogenous aldehydes that bind sulfhydryl groups of membrane proteins, altering calcium channels, and increasing cytosolic free calcium ([Ca2+]i) and blood pressure. Vitamin E lowers tissue aldehyde conjugates, cytosolic [Ca2+]i, and blood pressure in spontaneously hypertensive rats and fructose-induced hypertensive Wistar Kyoto rats, models of insulin resistance. This study investigated the effect of a normal-salt diet on tissue aldehyde conjugates, cytosolic [Ca2+]i, and blood pressure in DSS rats and the effect of vitamin E supplementation on blood pressure and associated biochemical changes in these animals. Seven-week-old DSS rats were divided into 3 groups of 6 animals each and treated for 6 weeks with diets as follows: low-salt (0.4% NaCl); normal-salt (0.7% NaCl) and normal salt (0.7% NaCl) plus vitamin E (34 mg/kg feed). At completion, animals in the normal-salt group had significantly elevated systolic blood pressure, cytosolic [Ca2+]i, and tissue aldehyde conjugates compared with the low-salt group. They also showed smooth muscle cell hyperplasia in small arteries and arterioles of the kidney. Dietary vitamin E supplementation significantly attenuated the increase in systolic blood pressure and associated biochemical and histopathologic changes.     

Progeria (Hutchison-Gilford syndrome) in siblings: in an autosomal recessive pattern of inheritance

Progeria is an autosomal dominant, premature aging syndrome. Six and three year old female siblings had sclerodermatous changes over the extremities, alopecia, beaked nose, prominent veins and bird-like facies. Radiological features were consistent with features of progeria. The present case highlights rarity of progeria in siblings with a possible autosomal recessive pattern.     

Altered calcium homeostasis is correlated with abnormalities of fasting serum glucose, insulin resistance, and beta-cell function in the Newfoundland population

Alteration of extracellular calcium concentration may be involved in glucose metabolism in a number of pathways. The present study was designed to investigate the relationship between total serum calcium and 1) fasting serum glucose, 2) insulin, 3) insulin resistance, and 4) beta-cell function in 1,182 healthy subjects from the province of Newfoundland and Labrador, Canada. All variables were log10 transformed, and confounding factors including age, trunk fat percentage, serum phosphorus, magnesium, 25-OH vitamin D, and parathyroid hormone were adjusted before analyses. Significant positive correlations between glucose and insulin resistance with calcium were found in both sexes, whereas an inverse correlation between beta-cell function and calcium was found only in women. Similar results were found in medication-free women and men, as well as in pre- and postmenopausal women. Subjects with low calcium levels had the lowest concentration of glucose and the least insulin resistance, whereas subjects with high calcium levels had the highest concentration of glucose and insulin resistance in women but not in men. This relationship remained after calcium was adjusted for 25-OH vitamin D and parathyroid hormone. Our results suggest that alteration of serum calcium homeostasis is significantly correlated with the abnormality of glucose level, insulin resistance, and beta-cell function.     

Anticlastogenic activity of morin against whole body gamma irradiation in Swiss albino mice

Anticlastogenic activity of morin was explored against whole body gamma radiation, at a dose rate of 1.66 Gy/min in Swiss albino mice pretreated intraperitoneal or orally. Pretreatment with morin 10, 25, 50, 75, 100, 125, and 150 mg/kg, i.p. delayed and reduced percentage mortality and increased mean survival times in mice irradiated with 10 Gy gamma radiation. Intraperitoneal route was found superior to oral route. An i.p. dose of 100 mg/kg was found to be the most effective dose in preventing radiation-induced weight loss, increasing the mean survival times and reducing percentage mortality. Morin (100 mg/kg) pretreatment effectively maintained spleen index (spleen weight/body weight x 100) and stimulated endogenous spleen colony forming units. Pretreatment with morin (100 mg/kg) significantly reduced dead, inflammatory, and mitotic cells in irradiated mice jejunum along with a significant increase in goblet cells and rapidly multiplying crypt cells. Morin (100 mg/kg) also maintained the villus height close to normal, prevented mucosal erosion and basement membrane damage in irradiated jejunum. Nuclear enlargement in epithelial cells of jejunum was lower in morin treated mice compared to radiation control. Morin (100 mg/kg) also significantly elevated the endogenous antioxidant enzymes viz. glutathione S transferase (GST), superoxide dismutase (SOD) and reduced glutathione (GSH), in normal mice at 2, 4 and 8 h post treatment. Drastic decrease in endogenous enzymes (GSH, GST, catalase and SOD) and total thiols was observed in irradiated mice at 2, 4 and 8 h post irradiation, while pretreatment with morin (100 mg/kg) prevented this decrease. Morin (100 mg/kg) also elevated radiation LD(50) from 9.2 to 10.1 Gy, indicating a dose modifying factor (DMF) of 1.11.     

Synthesis and in vitro antiproliferative activity of 2,5-disubstituted-1,3,4-oxadiazoles containing trifluoromethyl benzenesulfonamide moiety

A series of new 2,5-disubstituted-1,3,4-oxadiazoles 6(a–j) have been conveniently synthesized by intermolecular oxidative cyclization of (E)-2-(arylbenzylidene)-2-[(4-methoxyphenyl)amino]acetohydrazides promoted by iodobenzene diacetate as an oxidant. The synthesized compounds were characterized by elemental analyses, FT-IR, LCMS, ¹H NMR, and ¹³C NMR spectral studies. All the compounds were evaluated for their in vitro antiproliferative effect using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay method against four human cancer cell lines (K562, Colo-205, MDA-MB 231, IMR-32) for the time period of 24 h. Among the analogs, compounds 6h and 6i showed good activity on all cell lines, whereas the other compounds in the series exhibited moderate activity.     

Relationship between serum magnesium values, lipids and anthropometric risk factors

Serum magnesium (SMg) has been reported to negatively correlate with an atherogenic lipid profile in individuals with diabetes mellitus (DM) and metabolic syndrome. This study examines whether the relationships between SMg levels and biochemical and anthropometric risk factors for these conditions are also present in the general adult population.Design and methodsBiochemical parameters and anthropometric variables were assessed in 1318 healthy adult subjects recruited from the Newfoundland population.ResultsSMg positively correlated with age, and serum phosphate, calcium, albumin, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride levels. SMg negatively correlated with HOMA-β and percent body fat measured by DEXA. On sub-grouping subjects according to sex, menopausal status or after excluding subjects with DM, only a significant correlation of SMg with albumin, calcium, phosphate, and total cholesterol was common to all. Stepwise linear regression analysis revealed albumin, phosphate, age, total cholesterol, glucose, and body mass index as independent predictors of SMg levels.ConclusionsThese results indicate that SMg levels positively correlate with total cholesterol and possibly all lipoproteins in a large adult study population which suggests that variation of SMg with serum lipid levels may be different in healthy individuals compared with those with DM. We speculate on a possible binding interaction.