Antihyperglycemic Effect of Methanol Extract of Syzygium polyanthum (Wight.) Leaf in Streptozotocin-Induced Diabetic Rats

Syzygium polyanthum (S. polyanthum), a plant belonging to Myrtaceae, is widely used in Indonesian and Malaysian cuisines. Diabetic patients in Indonesia also commonly use it as a traditional medicine. Hence, this study was conducted to investigate the antihyperglycemic effect of the methanol extract (ME) of S. polyanthum leaf and its possible mechanisms of action. To test for hypoglycemic activity, ME was administered orally to normal male Sprague Dawley rats after a 12-h fast. To further test for antihyperglycemic activity, the same treatment was administered to glucose-loaded (intraperitoneal glucose tolerance test, IPGTT) and streptozotocin (STZ)-induced diabetic rats, respectively. Hypoglycemic test in normal rats did not show significant reduction in blood glucose levels (BGLs) by the extract. Furthermore, IPGTT conducted on glucose-loaded normal rats also did not show significant reduction of BGLs. However, repeated administration of metformin and three doses of ME (250, 500 and 1000 mg/kg) for six days caused significant reduction of fasting BGLs in STZ-induced diabetic rats. The possible mechanisms of action of S. polyanthum antihyperglycemic activity were assessed by measurement of intestinal glucose absorption and glucose uptake by isolated rat abdominal muscle. It was found that the extract not only inhibited glucose absorption from the intestine but also significantly increased glucose uptake in muscle tissue. A preliminary phytochemical qualitative analysis of ME indicated the presence of tannins, glycosides, flavonoids, alkaloids and saponins. Additionally, Gas Chromatography-Mass Spectrometry (GC-MS) analysis detected squalene. In conclusion, S. polyanthum methanol leaf extract exerts its antihyperglycemic effect possibly by inhibiting glucose absorption from the intestine and promoting glucose uptake by the muscles.     

Oral aphthous-like ulceration due to tiotropium bromide

Unwanted side-effects of a drug therapy are well known to oral medicine specialists and other colleagues. Usually they manifest itself as dry mouth, taste disturbances, various allergic or toxic reactions on the lips and/or in the oral cavity. However, the list of the drugs which might induce unwanted reactions is everyday becoming longer as more and more drugs are introduced on the market. Certain problems when diagnosing and reporting unwanted side effects of the drugs exist as only accurate method of diagnosis is repeated drug use in controlled clinical setting where fatal consequences due to the anaphilactic shock could be avoided. We report a side effect reaction to tiotropium bromide (Spiriva) cap used with HandiHaler manifesting itself as an oral ulceration in a 65 yrs old male. On the third day of drug intake the patient developed oral ulceration two times in a period of few months. Other medications he has been using for several years. To our knowledge this is a first report as an oral side-effect of this drug used for treatment of chronic obstructive pulmonary disease (COPD).     

Shear bond strength of one-step self-etch adhesives with different co-solvent ingredients to dry or moist dentin

Objective

To evaluate the shear bond strength of one-step self-etch adhesives with different co-solvent ingredients to dry or moist dentin.

Materials and methods

A total of 60 extracted teeth were used in this study, and were divided according to the adhesive systems and dentin conditions into 6 groups of 10 teeth each [Xeno III – dry dentin, Xeno III – moist dentin, Adper Prompot L-Pop – dry dentin, Adper Prompot L-Pop – moist dentin, iBond – dry dentin, and iBond – moist dentin]. Resin composite cylinder was built up on each specimen, and then thermocycled. A shear load was applied to the specimens using universal testing (Instron machine) at a cross-head speed of 0.5 mm/min until failure occurred. Data were statistically analyzed by one-way ANOVA and Bonferroni multiple comparison test at 95% confidence level.

Results and conclusion

Based on the findings of this study: The highest mean shear bond strength to dry dentin was seen when Xeno III containing ethanol co-solvent ingredient was used. The highest mean shear bond strength to moist dentin was seen when iBond which contains acetone co-solvent ingredient was used. In the absence of a co-solvent ingredient in self-etch adhesive (Adper Prompot L-Pop), the mean shear bond strengths to dry and moist dentin were low with no significant difference between them.     

Genomic detection of a familial 382 Kb 6q27 deletion in a fetus with isolated severe ventriculomegaly and her affected mother

Terminal deletions of the chromosome 6q27 region are rare genomic abnormalities, linked to specific brain malformations and other neurological phenotypes. Reported cases have variable sized genomic deletions that harbor several genes including the DLL1 and TBP. We report on an inherited 0.38 Mb terminal deletion of chromosome 6q27 in a 22‐week fetus with isolated bilateral ventriculomegaly and her affected mother using microarray‐based comparative genomic hybridization and fluorescent in situ hybridization (FISH). The deleted region harbors at least seven genes including DLL1 and TBP. The affected mother had a history of hydrocephalus, developmental delay, and seizures commonly associated with DLL1 and TBP 6q27 deletions. This deletion is one of the smallest reported isolated 6q27 terminal deletions. Our data provides additional evidence that haploinsufficiency of the DLL1 and TBP genes may be sufficient to cause the ventriculomegaly, seizures, and developmental delays associated with terminal 6q27 deletions, indicating a plausible role in the abnormal development of the central nervous system.     

The versatility of the CD1 lipid antigen presentation pathway

The family of non‐classical major histocompatibility complex (MHC) class‐I like CD1 molecules has an emerging role in human disease. Group 1 CD1 includes CD1a, CD1b and CD1c, which function to display lipids on the cell surface of antigen‐presenting cells for direct recognition by T‐cells. The recent advent of CD1 tetramers and the identification of novel lipid ligands has contributed towards the increasing number of CD1‐restricted T‐cell clones captured. These advances have helped to identify novel donor unrestricted and semi‐invariant T‐cell populations in humans and new mechanisms of T‐cell recognition. However, although there is an opportunity to design broadly acting lipids and harness the therapeutic potential of conserved T‐cells, knowledge of their role in health and disease is lacking. We briefly summarize the current evidence implicating group 1 CD1 molecules in infection, cancer and autoimmunity and show that although CD1 are not as diverse as MHC, recent discoveries highlight their versatility as they exhibit intricate mechanisms of antigen presentation.     

Amelioration of radiation-induced oxidative stress and biochemical alteration by SOD model compounds in pre-treated gamma-irradiated rats

INTRODUCTION: The role of metalloelements in tissue maintenance, function and response to injury offer a new approach to decreasing and/or treating radiation injury. We investigated the roles of CuL(2)SO(4), [MnL(2)O](2)Cl(4)(H(2)O)(2) and [(VL(2)O)(VL(2)H(2)O)]Cl(6) complexes (L=2-methylaminopyridine) of SOD-mimetic activities, in ameliorating the radiation-induced oxidative stress and alterations in some biochemical parameters in liver, kidney, spleen and brain in pretreated female rats exposed to gamma-irradiation. METHODS: Both untreated-rats and rats treated with the above complexes were subjected to whole-body gamma-irradiation (6 Gy). 5'-Nucleotidase (5'-NT), acetylcholinesterase (AChE), adenosne triphosphatase (ATPase), superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSSG-R) were assessed as well as liver DNA and RNA contents and total protein concentration were estimated in tissue homogenates of the above organs. The same parameters were assessed in non-irradiated treated rats and normal control rats. Results were compared to irradiated non-treated and normal control rats. RESULTS: Pretreatment of gamma-irradiated rats with Mn(IV) or V(IV) complex produced a significant decrease in liver 5'-NT activity compared to the corresponding value of the untreated irradiated rats. In contrast, liver DNA and RNA contents and brain AChE and ATPase activities were significantly increased in irradiated rat group pre-treated with these metal complexes. Cu II, Mn IV or V IV complex inoculation prior to irradiation of normal rats exhibited a significant increase in SOD, CAT, GSSG-R activities and protein content of liver, kidney, spleen and brain homogenates compared with that of the untreated irradiated rats. The treatment of non-irradiated rats with these complexes produced a highly significant increase in mean activities of SOD and CAT, with no changes in other parameters vs. controls. CONCLUSIONS: Cu(II), Mn(IV) and V(IV) 2-methylaminopyridine complexes offer a physiological approach to ameliorate the radiation-induced biochemical alterations. In addition, they provide sufficient protection against radiation injury of radiosensitive tissues.     

Accuracy of delayed (24 hours) processing of bronchoalveolar lavage for diagnosing bacterial pneumonia

OBJECTIVE: Pneumonia in the intensive care unit is associated with a high mortality rate. Diagnostic accuracy is mandatory to improve prognosis. However, in many hospitals, samples from the respiratory tract cannot be immediately processed bacteriologically around the clock. This may complicate therapeutic choice based on invasive diagnostic procedures. We evaluated the effect of storing bronchoalveolar lavage fluid at 4 degrees C for 24 hrs on direct examination and culturing for diagnosing pneumonia. DESIGN: Prospective, paired comparison study. SETTING: Intensive care unit in a university hospital. PATIENTS: A total of 93 bronchoalveolar lavages were performed on 66 intensive care unit patients who were suspected to have bacterial pneumonia. INTERVENTION: Each sample was divided into two; one half was processed immediately (H0), and the other was processed after refrigeration at 4 degrees C for 24 hrs (H24). MEASUREMENTS AND MAIN RESULTS: All negative H0 culture samples (n = 31) were also negative for pathogens in H24 samples. Sixty two bronchoalveolar lavage cultures yielded one or more microorganisms, giving a total of 113 microorganisms in one or both samples. The results of positive cultures at H0 and H24 for the culturing diagnostic threshold of 10 colony forming units/mL agreed well (Kappa coefficient, 0.84); agreement was even better (Kappa coefficient, 0.85) when possible contaminants were excluded. The bias calculated as the mean difference between paired culture results was 0.195 +/- 1.31 (Delta log). When considering the accepted threshold of 10 colony forming units/mL, specificity at H24 compared to H0 was excellent (100%), but sensitivity was slightly lower (80%). CONCLUSION: Delayed processing of bronchoalveolar lavage sampling is an acceptable alternative when immediate culturing cannot be performed because it enables antibiotic administration.     

Early Renal Injury Induced by Caffeine Consumption in Obese,Diabetic ZSF1 Rats

Our previous studies indicate that prolonged caffeine consumption exacerbates renal failure in nephropathy associated with the metabolic syndrome. Reduced activity of the antioxidant defense system and beneficial effects of antioxidant therapy have been reported in diabetic rats and humans. The purpose of this study was to examine the early renal effects of caffeine consumption and the effects of concomitant antioxidant therapy in young obese, diabetic ZSF1 rats. Eleven-week-old male ZSF1 rats were randomized to drink tap water, caffeine (0.1%), tempol (1 mmol/L), or a solution containing caffeine and tempol for nine weeks. Caffeine significantly reduced body weight and glycosuria (weeks 2–9), improved glucose tolerance (week 9), had no effect on elevated plasma triglycerides, plasma cholesterol (week 9) and blood pressure (week 9), and significantly increased plasma cholesterol level (weeks 5 and 9). Yet, as early as after two weeks, caffeine greatly augmented proteinuria and increased renal vascular resistance (RVR) and heart rate (HR: week 9). Tempol had no effects on metabolic status and development of proteinuria, did not alter caffeine-induced metabolic changes and early proteinuria, and attenuated caffeine-induced increase in HR and RVR. Immunohistochemical analysis revealed significant glomerular and interstitial inflammation, proliferation, and fibrosis in control animals. Caffeine augmented the influx of glomerular and interstitial macrophages (ED1+ cells) influx, glomerular and tubular proliferative response, and glomerular collagen IV content. Tempol abolished the exacerbation of renal inflammation, proliferation, and fibrosis induced by caffeine. In conclusion, in nephropathy associated with the metabolic syndrome, caffeine—most likely through the interaction with adenosine receptors and interference with anti-inflammatory and/or glomerular hemodynamic effects of adenosine—augments proteinuria and stimulates some of the key proliferative mechanisms involved in glomerular remodeling and sclerosis. Tempol does not prevent early renal injury (i.e., proteinuria) induced by caffeine, yet abolishes late renal inflammatory, proliferative, and fibrotic change induced by chronic caffeine consumption in obese ZSF1 rats.     

Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell-dependent antitumor effects

Mutant isoforms of the KIT or PDGF receptors expressed by gastrointestinal stromal tumors (GISTs) are considered the therapeutic targets for STI571 (imatinib mesylate; Gleevec), a specific inhibitor of these tyrosine kinase receptors. Case reports of clinical efficacy of Gleevec in GISTs lacking the typical receptor mutations prompted a search for an alternate mode of action. Here we show that Gleevec can act on host DCs to promote NK cell activation. DC-mediated NK cell activation was triggered in vitro and in vivo by treatment of DCs with Gleevec as well as by a loss-of-function mutation of KIT. Therefore, tumors that are refractory to the antiproliferative effects of Gleevec in vitro responded to Gleevec in vivo in an NK cell-dependent manner. Longitudinal studies of Gleevec-treated GIST patients revealed a therapy-induced increase in IFN-gamma production by NK cells, correlating with an enhanced antitumor response. These data point to a novel mode of antitumor action for Gleevec.