Clinical Comparison of Three Indirect Pulp Capping Restorative Protocols: A Randomized Controlled Prospective Study.

OBJECTIVES: The objective of this prospective double-blind clinical trial was to compare clinical outcomes of indirect pulp capping restorative protocols on permanent teeth over a 12-month period. METHODS AND MATERIALS: Deep carious lesions in permanent teeth (90) were randomly assigned to three indirect pulp capping protocols (n=30: TheraCal LC, Dycal, and no liner). All teeth were restored with resin composite. The outcome measures were pain (VAS scale) and success rate (pulp vitality based on percussion, palpation, cold test, and radiographic findings), collected at screening, intervention, and 24-hour, 7-day, 3-month, 6-month, and 12-month follow-up visits. RESULTS: There was no statistically significant difference in tooth sensitivity among the three indirect pulp capping protocols nor in success rates among the restorative protocols after 1 year of follow-up (p>0.1).The respective success rates, as defined by the tooth remaining vital, after 1 year were: 96.2% for TheraCal LC, 100% for Dycal, and 100% for no liner. CONCLUSIONS: After 12-month evaluation, the success rate of indirect pulp capping therapy on permanent teeth was not affected by the pulp capping restorative protocol.

Slow rusting resistance in 19 promising wheat lines to yellow rust in Ardabil, Iran.

Yellow rust caused by Puccinia striiformis f. sp. tritici is undoubtedly, the most important fungal disease of wheat especially in central and Western Asia that causes significant annual yield losses. Production and use of cultivars with durable resistance is the best controlling method. For this purpose, study on reaction of 19 promising lines to yellow rust was carried out in Ardabil in 2008-2009 cropping year. Assessment of adult plant reaction was conducted under field condition with artificial inoculation. Seedling test was also conducted in greenhouse. Slow rusting resistance at adult plant stage was assessed through the Infection Type (IT), Disease Severity (DS), Relative Area Under Disease Progress Curve (rAUDPC) and Coefficient of Infection (CI). Results of mean comparison of CI and rAUDPC indicated that the lines; C-87-1, C-87-2, C-87-3 and C-87-18 had the highest CI and rAUDPC. The lines C-87-6, C-87-8 and C-87-11 had the susceptible reaction at seedling test and were moderately resistant to moderately susceptible at adult plant stage. Consequently, these lines with low rAUDPC (15.2 to 27.8%) most probably could have slow rusting resistance. The lines C-87-4, C-87-5, C-87-13, C-87-14 and C-87-17 had not any infection or were at low level of infection, thus, they were selected as immune or resistant lines. The rest lines were moderately resistant to moderately susceptible. In this study, correlation analysis of different parameters also showed highly strong relationship of CI with rAUDPC and disease severity (R2 = 0.91 and 0.98, respectively).

Gene effects and combining ability in some bread wheat genotypes to yellow rust disease.

Ten wheat lines were studied to determine gene effects and combining ability in some bread wheat genotypes to yellow rust disease. Ten parental lines and F1 were evaluated in a randomized complete block design with three replications in Agricultural and Natural Resources Research Center, Mashhad, Iran. Two races (134E134A+ and 4E0A+) were used for this study. Latent Period (LP) and Infection Type (IT) were measured in the field and greenhouse. Results showed significant differences between races in their pathogenicity and between genotypes in their resistance to the pathogen. Diallel cross carried out between the parents and progenies and thereafter were analyzed by the method of Griffing and Haymans. The General Combining Ability (GCA) and Special Combining Ability (SCA) for all traits were significant and showed additive variance was more important. Test for validity of diallel hypothesis proved epistasis effect for all traits. P1, P2 and F1 showed significant difference between all traits in generations mean analysis. Average degree of dominance ranged from partial to over dominance for resistance or susceptibility. Dominance, additive and epistatic types of gene action were responsible for the genetic control of the traits. However, except for additive-additive component, non-additive effect of genes could not be fixed by self-fertilization.

Moderate exercise attenuates caspase-3 activity, oxidative stress, and inhibits progression of diabetic renal disease in db/db mice.

Diabetic nephropathy, the leading cause of end-stage renal disease, is characterized by a proapoptotic and prooxidative environment. The mechanisms by which lifestyle interventions, such as exercise, benefit diabetic nephropathy are unknown. We hypothesized that exercise inhibits early diabetic nephropathy via attenuation of the mitochondrial apoptotic pathway and oxidative damage. Type 2 diabetic db/db and normoglycemic wild-type mice were exercised for an hour everyday at a moderate intensity for 7 wk, following which renal function, morphology, apoptotic signaling, and oxidative stress were evaluated. Exercise reduced body weight, albuminuria, and pathological glomerular expansion in db/db mice independent of hyperglycemic status. Changes in renal morphology were also related to reduced caspase-3 (main effector caspase in renal apoptosis), caspase-8 (main initiator caspase of the "extrinsic" pathway) activities, and TNF-alpha expression. A role for the mitochondrial apoptotic pathway was unlikely as both caspase-9 activity (initiator caspase of this pathway) and expression of regulatory proteins such as Bax and Bcl-2 were unchanged. Kidneys from db/db mice also produced higher levels of superoxides and had greater oxidative damage concurrent with downregulation of superoxide dismutase (SOD) 1 and 3. Interestingly, although exercise also increased superoxides, there was also upregulation of multiple SODs that likely inhibited lipid (hydroperoxides) and protein (carbonyls and nitrotyrosine) oxidation in db/db kidneys. In conclusion, exercise can inhibit progression of early diabetic nephropathy independent of hyperglycemia. Reductions in caspase-3 and caspase-8 activities, with parallel improvements in SOD expression and reduced oxidative damage, could underlie the beneficial effects of exercise in diabetic kidney disease.

The effects of diethyldithiocarbamate, a SOD inhibitor, on endothelial function in sedentary and exercised db/db mice.

The study was designed to evaluate the effects of diethyldithiocarbamate (DDC), an superoxide dismutase (SOD) blocker on endothelial function in db/db mice. The db/db and wild-type (WT) mice were randomly divided into low intensity exercise, moderate intensity exercise and control (sedentary) groups. Mice were exercised daily, 5 days per week. After 6 weeks, ring segments of aortae were mounted in wire myograph and acetylcholine (ACh) concentration response curves were recorded in absence or presence of DDC and DDC plus SOD. Results showed that ACh concentration response curve was similar in WT and WT exercised groups. Incubation of aorta rings of WT mice with DDC suppressed the maximum ACh response (p<0.05). Subsequent incubation with SOD restored vasodilatory response in WT mice. The vasodilatation to ACh was significantly reduced in sedentary db/db mice compare to WT (p<0.05) and incubation with DDC did not further decrease this response, however, addition of SOD restored the vasodilatation to ACh to that observed in WT mice. Mild and moderate exercised db/db mice had ACh response similar to that in WT mice. Incubation with DDC incubation reduced ACh induced vasodilatation and addition of SOD restored this response. Our results support the conclusion that SOD mimetics can be used to improve superoxide-mediated endothelial dysfunction in diabetic db/db mice.

Improving RPE adhesion to Bruch's membrane.

Age-related macular degeneration is the leading cause of blindness in the developing world. Retinal pigmented epithelium (RPE) transplantation in subretinal space, has been assessed in various animal models of age-related macular degeneration and in humans as a potential technique to preserve the visual function. However, the RPE cell survival posttransplantation is limited because of lack of attachment of the transplanted cells to the pathological Bruch's membrane and also partly because of iatrogenic removal of adhesive elements in the membrane during the removal of choroidal new vessels before transplantation procedure. Although pathological Bruch's membrane is well studied, there is still much debate as to why and how changes in the structure and components of this membrane leads to loss of RPE cells and disruption of their function and subsequent death of photoreceptors leading to visual loss. Integrins on RPE cells have been characterized and shown to be important for attachment of cells to Bruch's membrane. Considering the essential role of integrins in functions such as cell migration and adhesion, it is plausible that lack of attachment of RPE cells posttransplantation can be overcome by improving integrin function. Here, we have focused on some of the recent findings on the use of integrins and modulation of their function to improve the adhesion of RPE cells to normal and pathological Bruch's membrane. This work also aims at elucidating a potential mechanism by which accumulating inhibitory molecules in the Bruch's membrane in the pathological state, interferes with integrin function.

Vascular endothelial function in health and diseases.

The vascular endothelium constitutes approximately 1% of body mass (1kg) and has a surface area of approximately 5000m(2). The endothelium is a multifunctional endocrine organ strategically placed between the vessel wall and the circulating blood, and has a key role in vascular homeostasis. The endothelium is both a target for and mediator of cardiovascular disease. The endothelium releases several relaxing and constricting factors, which can affect vascular homeostasis. Endothelial dysfunction, whether caused by physical injury or cellular damage, leads to compensatory responses that alter the normal homeostatic properties of the endothelium. In this review, we summarized some physiological aspects of endothelial function and then we discussed endothelial dysfunction during some pathological conditions.

Exercise restores endothelial function independently of weight loss or hyperglycaemic status in db/db mice.

AIMS/HYPOTHESIS: Exercise ameliorates oxidative stress-mediated diabetic vascular endothelial dysfunction through poorly defined mechanisms. We hypothesised that, in addition to improving metabolic parameters, upregulation of antioxidants such as superoxide dismutase (SOD) mediates exercise-induced reductions of oxidative stress and increased nitric oxide (NO) bioavailability, and also restores vasodilatation. METHODS: Type 2 diabetic db/db and normoglycaemic wild-type mice were exercised at moderate intensity for 1 h a day for 7 weeks, leading to a 10% body weight loss. Sedentary animals or those undergoing a low-intensity exercise regimen causing non-significant weight loss were also used. We examined aortic endothelial cell function, NO bioavailability and various biomarkers of oxidative stress. RESULTS: Moderate-intensity exercise lowered body weight, increased mitochondrial manganese SOD (MnSOD) and both total and phosphorylated (Ser1177) endothelial nitric oxide synthase (eNOS) protein production; it also reduced whole-body (plasma 8-isoprostane) and tissue oxidative stress (nitrotyrosine immunostaining or protein carbonyl levels in the aorta). Low-intensity exercise did not alter body weight; however, it upregulated cytosolic Cu/Zn-SOD instead of MnSOD, and still demonstrated all the above benefits in the db/db aorta. Importantly, both exercise protocols improved endothelial-dependent vasodilatation and NO bioavailability without altering hyperglycaemic status in db/db mice. CONCLUSIONS/INTERPRETATION: Exercise reverses diabetic vascular endothelial dysfunction independently of improvements in body weight or hyperglycaemia. Our data suggest that upregulation of eNOS and specific SOD isoforms could play important roles in improving NO bioavailability, as well as in reversing endothelial dysfunction in type 2 diabetes patients through lifestyle modifications in the management of diabetes.

Effect of exercise on augmented aortic vasoconstriction in the db/db mouse model of type-II diabetes.

We evaluated the effects of exercise on the vascular constrictor responses to alpha-adrenergic stimulation in the db/db mice. Twenty male db/db and their age-matched wild-type (WT) mice were exercised (1 hour/day, five days a week). Mice were anesthetized 7 weeks later, thoracic aortae were mounted in wire myograph and constrictor responses to phenylephrine (PE, 1 nM-10 microM) were obtained. Citrate synthase activity measured in the thigh adductor muscle was significantly increased in db/db mice that were exercise trained. Maximal force generated by PE was markedly greater in db/db aortae and exercise did not attenuate this augmented contractile response. Vessels were incubated with inhibitors of nitric oxide synthase (L-NAME, 200 microM), endothelin receptors (bosentan, 10 microM), protein kinase C (PKC) (calphostin C, 5 microM), cyclooxygenase (indomethacin, 10 microM) or Rho-kinase (Y-27632, 0.1 microM). Only calphostin-C normalized the augmented PE-induced constriction in db/db and db/db- exercised mice to that observed in WT (p<0.05). Cumulative additions of indolactam, a PKC activator, induced significantly greater constrictor responses in aortic rings of db/db mice compared to WT and exercise did not affect this response. Our data suggest that the augmented vasoconstriction observed in the aorta of db/db mice is likely due to increased PKC activity and that exercise do not ameliorate this increased PKC-mediated vasoconstriction.

Yr32 for resistance to stripe (yellow) rust present in the wheat cultivar Carstens V.

Stripe or yellow rust of wheat, caused by Puccinia striiformis f. sp. tritici, is an important disease in many wheat-growing regions of the world. A number of major genes providing resistance to stripe rust have been used in breeding, including one gene that is present in the differential tester Carstens V. The objective of this study was to locate and map a stripe rust resistance gene transferred from Carstens V to Avocet S and to use molecular tools to locate a number of genes segregating in the cross Savannah/Senat. One of the genes present in Senat was predicted to be a gene that is present in Carstens V. For this latter purpose, stripe rust response data from both seedling and field tests on a doubled haploid population consisting of 77 lines were compared to an available molecular map for the same lines using a non-parametric quantitative trait loci (QTL) analysis. Results obtained in Denmark suggested that a strong component of resistance with the specificity of Carstens V was located in chromosome arm 2AL, and this was consistent with chromosome location work undertaken in Australia. Since this gene segregated independently of Yr1, the only other stripe rust resistance gene known to be located in this chromosome arm, it was designated Yr32. Further QTLs originating from Senat were located in chromosomes 1BL, 4D, and 7DS and from Savannah on 5B, but it was not possible to characterize them as unique resistance genes in any definitive way. Yr32 was detected in several wheats, including the North American differential tester Tres.

Effect of cyclic AMP on the expression of myelin basic protein species and myelin proteolipid protein in committed oligodendrocytes: differential involvement of the transcription factor CREB.

Our previous results support the idea that CREB (cyclic AMP-response element binding protein) may be a mediator of neuroligand and growth factor signals that, coupled to different signal transduction pathways, play different roles at specific stages of oligodendrocyte development. In the early stages, when cells are immature precursors, CREB may play a role as a mediator of protein kinase C (PKC)/mitogen-activated protein kinase (MAPK) pathways regulating cell proliferation. In contrast, at a later stage, when cells are already committed oligodendrocytes, CREB seems to play an important role as a mediator in the stimulation of myelin basic protein (MBP) expression by cyclic AMP (cAMP). In this study, we have investigated whether cAMP and CREB play a role in regulating the expression of all or on the other hand particular MBP isoforms. The results indicated that treatment of committed oligodendrocytes with the cAMP analogue db-cAMP results in a pattern of expression of MBP-related polypeptides that most closely resembles the pattern of MBPs observed in cerebra from adult animals. Experiments in which CREB expression was inhibited using a CREB antisense oligonucleotide, suggested that CREB is involved in the cAMP-dependent stimulation of all the MBP isoforms. In contrast, we have found that db-cAMP stimulates the expression of myelin proteolipid protein (PLP) in a process that occurs despite inhibition of CREB expression. These results support the idea that cAMP stimulates the maturation of oligodendrocytes and stress the fact multiple mechanisms may convey the action of this second messenger modulating oligodendrocyte differentiation and myelination.

Normal CNS myelination in transgenic mice overexpressing MHC class I H-2L(d) in oligodendrocytes.

In demyelinating diseases, such as multiple sclerosis, an upregulation of MHC class I expression is thought to contribute to oligodendrocyte/myelin damage. In order to investigate potential physiological consequences of upregulated MHC class I expression in oligodendrocytes, we generated transgenic mice that overexpress H-2L(d) under the control of the proteolipid protein (PLP) promoter (PLP-L(d) mice). We focused our studies on the MHC class I molecule H-2L(d), because of its unique intracellular transport characteristics. In the CNS of PLP-L(d) mice, H-2L(d) was expressed by oligodendrocytes. Furthermore, H-2L(d) protein was transported to and expressed on the surface of oligodendrocytes. Most importantly, this upregulation of MHC class I expression in the CNS of PLP-L(d) mice did not by itself result in a de- or dysmyelinating phenotype. These transgenic mice are likely to provide a unique and novel tool for the analysis of potential roles of MHC class I-mediated mechanisms in demyelinating pathologies.