Geraniol,a natural monoterpene,ameliorates hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats

Context: Geraniol, an acyclic monoterpene alcohol is found in medicinal plants, is used traditionally for several medical purposes including diabetes.

Objectives: The present study evaluates the antihyperglycemic potential of geraniol on key enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats.

Materials and methods: Diabetes was induced in experimental rats, by a single intraperitoneal (i.p) injection of STZ [40?mg/kg body weight (b.w.)]. Different doses of geraniol (100, 200 and 400?mg/kg b.w.) and glyclazide (5?mg/kg b.w.) were administrated orally to diabetic rats for 45?days. Body weight, food intake, plasma glucose, insulin, blood haemoglobin (Hb), glycosylated haemoglobin (HbA_1c), hepatic glucose metabolic enzymes and glycogen were examined.

Results: The LD₅₀ value of geraniol is 3600?mg/kg b.w. at oral administration in rats. Administration of geraniol in a dose-dependent manner (100, 200, 400?mg/kg b.w.) and glyclazide (5?mg/kg b.w.) for 45?days significantly improved the levels of insulin, Hb and decreased plasma glucose, HbA_1C in diabetic-treated rats. Geraniol at its effective dose (200?mg/kg b.w.) ameliorated the altered activities of carbohydrate metabolic enzymes near normal effects compared with two other doses (100 and 400?mg/kg b.w.). Geraniol treatment to diabetic rats improved hepatic glycogen content suggesting its anti-hyperglycemic potential. Geraniol supplement was found to preserve the normal histological appearance of hepatic cells and pancreatic β-cells in diabetic rats.

Discussion and conclusions: The present findings suggest that geraniol can potentially ameliorate key enzymes of glucose metabolism in experimental diabetes even though clinical studies used to evaluate this possibility are warranted.     

Troxerutin attenuates diet‐induced oxidative stress,impairment of mitochondrial biogenesis and respiratory chain complexes in mice heart

Mitochondrial abnormality is thought to play a key role in cardiac disease originating from the metabolic syndrome (MS). We evaluated the effect of troxerutin (TX), a semi‐synthetic derivative of the natural bioflavanoid rutin, on the respiratory chain complex activity, oxidative stress, mitochondrial biogenesis and dynamics in heart of high fat, high fructose diet (HFFD) ‐induced mouse model of MS. Adult male Mus musculus mice of body weight 25‐30 g were fed either control diet or HFFD for 60 days. Mice from each dietary regimen were divided into two groups on the 16th day and were treated or untreated with TX (150 mg/kg body weight [bw], per oral) for the next 45 days. At the end of experimental period, respiratory chain complex activity, uncoupling proteins (UCP)‐2 and ‐3, mtDNA content, mitochondrial biogenesis and dynamics, oxidative stress markers and reactive oxygen species (ROS) generation were analyzed. Reduced mtDNA abundance with alterations in the expression of genes related to mitochondrial biogenesis and fission and fusion processes were observed in HFFD‐fed mice. Disorganized and smaller mitochondria, reduction in complexes I, III and IV activities (by about 55%) and protein levels of UCP‐2 (52%) and UCP‐3 (46%) were noted in these mice. TX administration suppressed oxidative stress, improved the oxidative capacity and biogenesis and restored fission/fusion imbalance in the cardiac mitochondria of HFFD‐fed mice. TX protects the myocardium by modulating the putative molecules of mitochondrial biogenesis and dynamics and by its anti‐oxidant function in a mouse model of MS.     

Evolution of ADAMTS13 antibodies in a fatal case of thrombotic thrombocytopenic purpura

In a patient with fatal thrombotic thrombocytopenic purpura, the inhibitory activity of antibodies against ADAMTS13 rapidly escalated to extremely high levels despite daily plasma exchange and corticosteroid therapy. This increase was found to be because of a combination of higher antibody concentration and potency. Furthermore, during her course of the disease, the percentage of IgG(1) antibody progressively decreased whereas that of IgG(2) antibody increased, suggesting Th1-type cytokine response. These changes suggest that the course of TTP may be exacerbated by complex immune reactions. Further characterization of the factors contributing to this exacerbation may have important pathogenetic and therapeutic implications.     

Esophageal leiomyoma detected by transesophageal contrast echocardiography

Transesophageal echocardiography (TEE) provides valuable information in the evaluation of intra- and extracardiac masses. There is no report demonstrating its usefulness in identifying esophageal mass lesions. This is because generally it is contraindicated in patients with esophageal diseases. However, endoscopic ultrasound is used in the evaluation of gastrointestinal pathology. We report a case of an esophageal tumor detected by TEE and the value of contrast echocardiography in further definition of the tumor.     

A new DTPw-HBV/Hib vaccine: immune memory after primary vaccination and booster dosing in the second year of life

The response to booster vaccination at 15-18 months of age and the presence of immune memory in 10-month old children, primed with a new combined diphtheria-tetanus-hepatitis B-whole cell pertussis vaccine extemporaneously mixed with Haemophilus influenzae type b-tetanus toxoid conjugate (DTPw-HBV/Hib) from new antigen sources and containing 2.5 microg polyribosyl-ribitol-phosphate (PRP) was assessed. Primary vaccination with the new DTPw-HBV/Hib vaccine was immunogenic and of comparable tolerability to commercially available Tritanrix HepB/Hiberix. Children were boosted with DTPw-HBV, DTPw-HBV/Hib or separate DTPw-HBV+Hiberix. Immune memory was assessed through administration of 10 microg PRP polysaccharide. Anti-PRP antibody GMCs increased substantially after the challenge in DTPw-HBV/Hib-primed subjects indicating the presence of immune memory. One month after the booster dose, 100% of subjects had seroprotective antibody concentrations against PRP, diphtheria and tetanus, >95% were seroprotected against hepatitis B, > or =94.0% had a pertussis booster response. Substantial increases in antibody GMCs against all antigens were observed. Swelling >20 mm was the most common Grade 3 solicited symptom reported (up to 26.0% of subjects). Fever >39.5 degrees C was uncommon (>2.5%). Eleven large swelling reactions were reported; none involved an adjacent joint. One serious adverse event occurred that was considered unrelated to vaccination. This new DTPw-HBV/Hib vaccine with new vaccine components and 2.5 microg PRP induced effective priming against Hib evidenced by a vigorous anamnestic response on exposure to PRP polysaccharide. The booster dose was immunogenic and the safety profile was acceptable. Combined DTPw-HBV and DTPw-HBV/Hib vaccines using new vaccine antigen sources will promote continued supply of combined DTPw-based vaccines to global mass vaccination campaigns.     

Evaluation of Mosquito Repellent Activity of Isolated Oleic Acid,Eicosyl Ester from Thalictrum javanicum

To evaluate the traditional use, the mosquito repellent property of Thalictrum javanicum and to confirm the predicted larvicidal activity of the isolated compound, oleic acid, eicosyl ester from its aerial parts by PASS software, the present study was carried out using 4th instar stage larvae of the mosquitoes, Aedes aegypti (dengue vector) and Culex quinquefasciatus (filarial vector). Insecticidal susceptibility tests were conducted and the mortality rate was observed after 24 h exposure. The chitinase activity of isolated compound was assessed by using purified β-N-acetyl glucosaminidase (chitinase). Ecdysone 20-monooxygenase assay (radioimmuno assay) was made using the same larval stage of A. aegyptiand C. quinquefasciatus. The results were compared with the crude methanol extract of the whole plant. The isolated compound, oleic acid, eicosyl ester was found to be the most effective larvicide against A. aegypti (LC₅₀/24 h -8.51 ppm) and C. quinquefasciatus (LC₅₀/24 h - 12.5 ppm) than the crude methanol extract (LC₅₀/24 h - 257.03 ppm and LC₅₀/24 h - 281.83 ppm, respectively). The impact of oleic acid, eicosyl ester on reducing the activity of chitinase and ecdysone 20-monooxygenase was most prominent in both the target species, A. aegyptiand C. quinquefasciatus than the control. The results therefore suggest that the compound, oleic acid, eicosyl ester from Thalictrum javanicum may be considered as a potent source of mosquito larvicidal property.     

Fibrinogen Philadelphia, a hypodysfibrinogenemia characterized by abnormal polymerization and fibrinogen hypercatabolism due to gamma S378P mutation

Fibrinogen Philadelphia, a hypodysfibrinogenemia described in a family with a history of bleeding, is characterized by prolonged thrombin time, abnormal fibrin polymerization, and increased catabolism of the abnormal fibrinogen. Turbidity studies of polymerization of purified fibrinogen under different ionic conditions reveal a reduced lag period and lower final turbidity, indicating more rapid initial polymerization and impaired lateral aggregation. Consistent with this, scanning and transmission electron microscopy show fibers with substantially lower average fiber diameters. DNA sequence analysis of the fibrinogen genes A, B, and G revealed a T>C transition in exon 9 resulting in a serine-to-proline substitution near the gamma chain C-terminus (S378P). The S378P mutation is associated with fibrinogen Philadelphia in this kindred and was not found in 10 controls. This region of the gamma chain is involved in fibrin polymerization, supporting this as the polymerization defect causing the mutation. Thus, this abnormal fibrinogen is characterized by 2 unique features: (1) abnormal polymerization probably due to a major defect in lateral aggregation and (2) hypercatabolism of the mutant protein. The location, nature, and unusual characteristics of this mutation may add to our understanding of fibrinogen protein interactions necessary for normal catabolism and fibrin formation.