Shear bond strength of zirconia ceramic to the primary tooth dentin.

BACKGROUND: There is no information about the shear bond strengths (SBS) of zirconia ceramic to primary tooth dentin. AIM: To investigate the effect of different surface treatments and cements on the shear bond strength (SBS) of zirconia ceramic to primary tooth dentin. MATERIALS AND METHODS: Prepared zirconia bars were distributed into four groups according to surface treatment procedure: control, sandblasting, CoJet and hot etching. The zirconia specimens in each group were further divided into subgroups according to cement (n = 13): self-adhesive resin (Rely-X Unicem), resin-modified glass ionomer (Ketac-Cem Plus), and universal bioactive (BioCem). Zirconia specimens were bonded to the primary tooth dentin surface by cement. SBS was measured, and the data were subjected to two-way ANOVA and Tukey's tests. RESULTS: Statistical differences were observed in the surface treatment procedures for Rely-X Unicem (P < 0.05), but no statistically significant differences were found in the sandblasting, CoJet and hot-etching groups for Ketac-Cem Plus (P > 0.05). For BioCem, the SBS value for the hot etching group was significantly lower than those for the CoJet and sandblasting groups (P < 0.05). The SBS values for the Rely-X Unicem subgroups (sandblasting, CoJet and hot etching) were significantly higher than those for the other cements (P < 0.05). CONCLUSION: The bond strength of zirconia ceramic to primary tooth dentin is affected by surface treatments and cements.

Activation status of integrated stress response pathways in neurones and astrocytes of HIV-associated neurocognitive disorders (HAND) cortex.

AIMS: Combined anti-retroviral therapy (cART) has led to a reduction in the incidence of HIV-associated dementia (HAD), a severe motor/cognitive disorder afflicting HIV(+) patients. However, the prevalence of subtler forms of neurocognitive dysfunction, which together with HAD are termed HIV-associated neurocognitive disorders (HAND), continues to escalate in the post-cART era. The microgliosis, astrogliosis, dendritic damage, and synaptic and neuronal loss observed in autopsy cases suggest an underlying neuroinflammatory process, due to the neurotoxic factors released by HIV-infected/activated macrophages/microglia in the brain, might underlie the pathogenesis of HAND in the post-cART era. These factors are known to induce the integrated stress response (ISR) in several neurodegenerative diseases; we have previously shown that BiP, an indicator of general ISR activation, is upregulated in cortical autopsy tissue from HIV-infected patients. The ISR is composed of three pathways, each with its own initiator protein: PERK, IRE1α and ATF6. METHODS: To further elucidate the specific ISR pathways activated in the central nervous system of HAND patients, we examined the protein levels of several ISR proteins, including ATF6, peIF2α and ATF4, in cortical tissue from HIV-infected patients. RESULTS: The ISR does not respond in an all-or-none fashion in HAND, but rather demonstrates a nuanced activation pattern. Specifically, our studies implicate the ATF6 pathway of the ISR as a more likely candidate than the PERK pathway for increases in BiP levels in astrocytes. CONCLUSION: These findings begin to characterize the nature of the ISR response in HAND and provide potential targets for therapeutic intervention in this disease.

Site-specific hyperphosphorylation of pRb in HIV-induced neurotoxicity.

HIV-Associated Neurocognitive Disorder (HAND) remains a serious complication of HIV infection, despite combined Anti-Retroviral Therapy (cART). Neuronal dysfunction and death are attributed to soluble factors released from activated and/or HIV-infected macrophages. Most of these factors affect the cell cycle machinery, determining cellular outcomes even in the absence of cell division. One of the earliest events in cell cycle activation is hyperphosphorylation of the retinoblastoma protein, pRb (ppRb). We and others have previously shown increased ppRb expression in the CNS of patients with HIV encephalitis (HIVE) and in neurons in an in vitro model of HIV-induced neurodegeneration. However, trophic factors also lead to an increase in neuronal ppRb with an absence of cell death, suggesting that, depending on the stimulus, hyperphosphorylation of pRb can have different outcomes on neuronal fate. pRb has multiple serines and threonines targeted for phosphorylation by distinct kinases, and we hypothesized that different stimuli may target separate sites for phosphorylation. Thus, to determine whether pRb is differentially phosphorylated in response to different stimuli and whether any of these sites is preferentially phosphorylated in association with HIV-induced neurotoxicity, we treated primary rat mixed cortical cultures with trophic factors, BDNF or RANTES, or with the neurotoxic factor, N-methyl-d-aspartate (NMDA), or with supernatants containing factors secreted by HIV-infected monocyte-derived macrophages (HIV-MDM), our in vitro model of HIV-induced neurodegeneration. We found that, while BDNF and RANTES phosphorylated serine807/811 and serine608 in vitro, treatment with HIV-MDM did not, even though these trophic factors are components of HIV-MDM. Rather, HIV-MDM targets a specific phosphorylation site, serine795, of pRb for phosphorylation in vitro and this ppRb isoform is also increased in HIV-infected brains in vivo. Further, overexpression of a nonphosphorylatable pRb (ppRb S795A) attenuated HIV-MDM-induced neurotoxicity. These findings indicate that HIV-infection in the brain is associated with site-specific hyperphosphorylation of pRb at serine795, which is not induced by other tested stimuli, and that this phosphorylation contributes to neuronal death in this disease, demonstrating that specific pRb sites are differentially targeted and may have diverse impacts on the viability of post-mitotic neurons.

Effects of rapamycin treatment on pancreatic fibrosis, cellular apoptosis and oxidative stress in experimental chronic pancreatitis model.

PURPOSE: Rapamycin reduces hepatic fibrosis by inhibiting hepatic stellate cell activation. The present study investigated whether rapamycin treatment could modify the degree of fibrosis, cellular apoptosis and oxidative stress (OS) in an experimental model of CP. METHODS: Fifty-five male, Sprague-Dawley rats weighing 200-400g were randomized into four groups. CP was induced by intraductal trinitrobenzene sulfonic acid (TNBS) infusion in group A (n = 15) and group B (n = 15). Group C (n = 15) received intraductal TNBS and was killed for histologic confirmation at four weeks. Group D (n = 10) received intraductal saline instead of TNBS. Group A and group D received oral rapamycin (2 mg/kg/d) for two weeks after CP was induced while group B received oral tap water instead of rapamycin. Blood and pancreatic tissue specimens were collected and oxidative stress parameters, fibrosis and cellular apoptosis were determined. RESULTS: Tissue and blood malondialdehyde (MDA) levels were significantly lower in rapamycin treated group compared to controls (p < 0.001). Superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) activities were also significantly higher in the active treatment group (p < 0.001 for both). Tissue and blood MDA, SOD, GSH-Px measurements was similar in rapamycin group and pancreatic cannulation group (p > 0.05). Histopathologic fibrosis scores were similar in rapamycin and control groups. Apoptotic cell counts tended to be lower in rapamycin treated animals. CONCLUSIONS: Administration of rapamycin alleviated OS and, in part, prevented apoptotic cell death in experimental CP, but did not reduce fibrosis.

Investigation of antioxidant enzymes in children with autistic disorder.

Impaired antioxidant mechanisms are unable to inactivate free radicals that may induce a number of pathophysiological processes and result in cell injury. Thus, any abnormality in antioxidant defence systems could affect neurodevelopmental processes and could have an important role in the etiology of autistic disorder. The plasma levels of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and erythrocyte levels of GSH-Px were investigated in 45 autistic children and compared with 41 normal controls. Levels of erythrocyte SOD, erythrocyte and plasma GSH-Px were assayed spectrophotometrically. Activities of erythrocyte SOD, erythrocyte and plasma GSH-Px in autistic children were significantly lower than normals. These results indicate that autistic children have low levels of activity of blood antioxidant enzyme systems; if similar abnormalities are present in brain, free radical accumulation could damage brain tissue.

The effects of Azone and capsaicin on the permeation of naproxen through human skin.

The permeation of naproxen through excised human skin and isolated perfused rabbit ear skin has been determined. It was found that both Azone and capsaicin enhanced the permeation with an enhancement ratio of up to 4-fold. The magnitudes of the effect were similar in human and rabbit skin. The permeation of naproxen from a saturated solution of the drug through skin pre-treated with Azone was similar to that from a commercial preparation (Naprosyn). In the perfused rabbit ear experiments the presence of capsaicin had no effect on the vasodilatation of the blood vessels, inferring that the penetration enhancement was a direct result of capsaicin influencing the barrier function of the skin. Structural similarities between Azone and capsaicin were seen using molecular graphics.

Simultaneous determination of codeine and ethyl morphine HCL in tablet formulations using LC.

A reverse phase high performance liquid chromatography (HPLC) method was developed for the simultaneous determination of codeine (methyl morphine) and dionin (ethyl morphine hydrochloride) in antitussive analgesic tablet formulations. A C(18) column and methanol-water (1:2) mixture mobile phase (pH 3.0) were used. Spectrophotometric detection was carried out at 210 nm. The total elution time was shorter than 7 min. This method was found to be quite precise and reproducible. This proposed method was successfully applied to the determination of codeine and ethyl morphine hydrochloride in tablets produced by the Turkish Army Drug Factory.

Effect of hyperbaric oxygen on experimental acute distal colitis.

It has been demonstrated that hyperbaric oxygen (HBO) is useful as an adjunctive therapy for Crohn's disease. However, its effects on ulcerative colitis have not been investigated. In the present study, HBO was tested for acetic acid-induced colitis, and antioxidant systems were evaluated to clarify its possible mode of action. Thirty-six Sprague-Dawley rats were randomly divided into three groups: sham control (Group I), colitis induced by acetic acid without any therapy (Group II), colitis induced by acetic acid and treated with HBO (Group III). HBO was given for 5 days, 2 sessions per day at 2.5-fold absolute atmosphere pressure (ATA) for a period of 90 min in rats in which colitis had been induced (Group III). Rats were sacrificed on the 5th day after the procedure. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH Px) activity were measured in the intestinal tissue and erythrocyte lysate. MDA and GSH Px were also determined in the plasma. Whereas MDA levels in erythrocyte, plasma and intestinal tissue were decreased, the levels of GSH Px and SOD were significantly increased in Group III as compared to those of Group II. The results of our study suggest that hyperbaric oxygen therapy has beneficial effects on the course of experimental distal colitis and that antioxidant systems may be involved in its mode of action.

The effect of hyperbaric oxygen treatment on oxidative stress in experimental acute necrotizing pancreatitis.

Various protocols may be used for acute pancreatitis treatment. Recently, the benefit of hyperbaric oxygen (HBO) has been demonstrated. To clarify the mechanism of HBO on the process of the acute pancreatitis, we determined the levels of antioxidant enzymes in an acute pancreatitis model. Forty-five Sprague-Dawley rats were randomly divided into three groups: Group I: sham group (n=15), Group II: pancreatitis group (n=15), Group III: pancreatitis group undergoing HBO therapy (n=15). HBO was applied postoperatively for 5 days, two sessions per day at 2.5 fold absolute atmospheric pressure (ATA) for 90 min. Superoxide dismutase (Cu/Zn-SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH Px) activity were measured in pancreatic tissue and erythrocyte lysate. MDA and GSH Px were also determined in plasma. In addition, amylase levels were measured in the serum. While serum amylase levels and MDA values in erythrocyte, plasma and pancreatic tissue were decreased, the levels of GSH Px and SOD were found to be significantly increased in the Group III as compared to those of the Group II. The findings of our study suggest that HBO has beneficial effects on the course of acute pancreatitis and this effect may occur through the antioxidant systems.

Simultaneous determination of acetaminophen, acetylsalicylic acid and ascorbic acid in tablet form using HPLC.

The purpose of the present study was to develop a simple and accurate HPLC method to measure the amount of each agent in a multidrug pharmaceutical formulation. Three drugs, acetaminophen, acetylsalicylic acid and ascorbic acid, were analyzed simultaneously. A commercial pharmaceutical effervescent tablet was examined and the amount of each of these agents successfully determined. The present method appears to be more convenient than the current procedures described in American and British Pharmacopoeias in which each drug is assayed separately.

Antioxidant system activation in prostate cancer.

The activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and the levels of copper, zinc, and malondialdehyde were determined in 21 age-, sex-, and body-mass-index-matched prostate cancer patients; 50 patients diagnosed with benign prostatic obstruction (BPO) were compared to 50 healthy male subjects acting as controls. The patients were divided into two groups depending on the stage of the disease (group 1 [organ-confined] and group II [advanced disease]) and into three subgroups according to differentiation criteria: subgroup A (n = 5, Gleason sum 2-4, well differentiated); subgroup B (n = 9, Gleason sum 5-7, moderately differentiated), and subgroup C (n = 7, Gleason sum 8-10, poorly differentiated). The MDA levels were higher and the antioxidant activity and Zn levels lower in the prostate cancer groups than in the healthy control and BPO groups. These results confirm the value of therapies aimed at increasing the antioxidant capacity and encourage the use of plasma and erythrocyte Zn levels in the differential diagnosis of BPO and prostate cancer. The MDA levels can be used in the diagnosis and follow-up of prostate cancer.

Oxidative stress in patients undergoing high-dose chemotherapy plus peripheral blood stem cell transplantation.

Chemotherapy and radiation therapy are associated with increased formation of reactive oxygen species and depletion of critical plasma and tissue antioxidants. In patients undergoing high-dose chemotherapy, the plasma antioxidant concentration has been shown to decrease. However, these studies in which the oxidative stress status were investigated have a small number of patients and they are heterogeneous. In this study, the changes in certain trace elements together with oxidative stress parameters were investigated in 36 patients who had undergone autologous stem cell transplantation because of solid and hematological malignancies. Blood samples of the patients were examined before the high-dose chemotherapy (baseline), before stem cell transplantation (day -1), and after stem cell transplantation on day 1, 3, and 6. Erythrocyte zinc, silver, and iron levels were measured by atomic absorption spectrophotometry; malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were measured by UV-vis spectrophotometry. After high-dose chemotherapy, significant increases in the levels of MDA, GSH-Px, and SOD were observed. On the other hand, Cu levels remained the same while the levels of erythrocyte Zn and Fe were increased. Significant correlation was observed among MDA, GSH-Px, and SOD (p<0.05). High-dose chemotherapy gives rise to an increase in the oxidative stress and the reactive oxygen species. Standard parenteral nutrition protocols were found to be insufficient to lower this stress.

pH-Metric log K calculations of famotidine, naproxen, nizatidine, ranitidine and salicylic acid.

The octanol/water partition coefficient (log K) is one of the most commonly used parameters in structure-activity relationships in many areas such as drug design (including pesticides), pharmacokinetics, anesthesiology, environmental sciences, toxicology, bioaccumulation and predicting skin permeability as a predictive parameter. log K is generally determined using shake flask method, but the possibility of calculating log K using pH-metric titrations and half neutralization points is demonstrated in this study. The potentiometric pH titration technique has been developed as an automatic technique for log K determination but it can be achieved by manual titrations. This technique uses the pKa of the substance. The pKa of the substance shifts pK'a when the titration is repeated in the presence of octanol. log K value of the substance can be determined using pKa, pK'a values and relevant equation. The aim of the study was to determine the log K values of a series of compounds using pH-metric titrations and to compare pH-metric log K determination results with the other methods. The log K values of famotidine, naproxen, nizatidine, ranitidine and salicylic acid were determined using both shake flask method and potentiometric titrations. Their log K values were also calculated theoretically using computer program and all results were compared. The pH-metric log K values were found to be close to the shake flask method results. This method was found to be useful for the determination of log K values as it provides a high degree of accuracy even in the presence of titratable impurities in the solution.

The protective effects of taurine on experimental acute pancreatitis in a rat model.

The aim of this study was to investigate the protective effects of taurine (Tau) on experimental acute pancreatitis (AP) in a rat model by measuring cytokines and oxidant stress markers. Forty rats were randomly divided into four groups: sham, AP, Tau and AP + Tau. AP was induced with sodium taurocholate. No treatment was given to the AP. All rats were killed 5 days later. Pancreatic tissues of rats and blood samples were obtained. Tau treatment significantly decreased serum amylase activity (p < 0.001), total injury score (p < 0.001), malondialdehyde levels (p < 0.001) and myeloperoxidase (MPO) activity (p < 0.001). There was no significant difference between the Tau and AP + Tau groups in serum and pancreatic tumor necrosis factor-α, interleukin (IL)-1ß and IL-6 levels (p = 1.000). Histopathologic scores in the AP + Tau and Tau groups were significantly lower compared with the AP group (both p < 0.001). These results showed that Tau reduces lipid peroxidation, amylase and MPO activities and the concentrations of proinflammatory cytokines secondary to AP and also increases superoxide dismutase and glutathione peroxidase activities in rats with sodium taurocholate-induced AP. It also has a marked ameliorative effect at histopathologic lesions. With these effects, Tau protects the cells from oxidative damage, reduces inflammation and promotes regression of pancreatic damage.

Association of GPX1 polymorphism, GPX activity and prostate cancer risk.

Prostate cancer is the second most common cancer in men worldwide. Although the aetiology of this disease remains largely unclear, several lines of evidence suggest that oxidative stress plays a role in prostate carcinogenesis. The antioxidant enzyme glutathione peroxidase 1 (GPX1) is part of the enzymatic antioxidant defence, preventing oxidative damage to DNA, proteins and lipids by detoxifying hydrogen and lipid peroxides that may contribute to prostate cancer development. Some studies indicate an association between GPX1 Pro198Leu polymorphism and an increased risk of cancer. The purpose of the present study was to determine the possible association of GPX1 Pro198Leu polymorphism and erythrocyte GPX activity with the risk of developing prostate cancer and to clarify whether erythrocyte GPX activity levels were correlated with the GPX1 Pro198Leu genotype in the Turkish population. The GPX1 Pro198Leu genotype was determined in 33 prostate cancer patients and 91 control individuals. As evident from our results, there was no difference between genotype and/or allele frequencies in prostate cancer patients and controls. No significant difference was found in GPX1 genotype or allele frequency between aggressive and non-aggressive prostate cancer patients. It can be suggested with these findings that individual susceptibility of prostate cancer may be modulated by GPX1 polymorphism, but it needs further studies.

Expression of the endoplasmic reticulum stress response marker, BiP, in the central nervous system of HIV-positive individuals.

The prevalence of HIV-associated neurocognitive impairment (NCI), which includes HIV-associated dementia (HAD) and minor cognitive and motor disorder (MCMD), has been increasing. HIV-infected and/or activated macrophages/microglia in the brain initiate the neurodegeneration seen in HIV-associated NCI via soluble neurotoxic mediators, including reactive oxygen species, viral proteins and excitotoxins. Neurotoxic factors released by macrophages/microglia injure neurones directly and alter astrocytic homeostatic functions, which can lead to excitotoxicity and oxidative stress-mediated neuronal injury. Often, cells respond to oxidative stress by initiating the endoplasmic reticulum (ER) stress response. Thus, we hypothesize that ER stress response is activated in HIV-infected cortex. We used immunofluorescence and immunoblotting to assess expression patterns of the ER stress proteins, BiP and ATF6, in HIV-positive cortical autopsy tissue. Additionally, we performed immunofluorescence using cell type-specific markers to examine BiP staining in different cell types, including neurones, astrocytes and macrophages/microglia. We observed a significant increase in BiP expression by both immunoblotting and immunofluorescence in HIV-positive cortex compared with control tissue. Additionally, phenotypic analysis of immunofluorescence showed cell type-specific increases in BiP levels in neurones and astrocytes. Further, ATF-6beta, an ER stress response initiator, is up-regulated in the same patient group, as assessed by immunoblotting. These results suggest that ER stress response is activated in HIV-infected cortex. Moreover, data presented here indicate for the first time that numbers of macrophages/microglia increase in brains of MCMD patients, as has been observed in HAD.

Trace elements and antioxidant enzymes in Behçet's disease.

Free oxygen radicals and insufficiency of antioxidant enzymes have been implicated in the pathogenesis of Behçet's disease (BD). Trace elements function as cofactors to antioxidant enzymes. The antioxidant system and trace elements were investigated in many different studies, including BD, but these subjects have not been investigated as a whole in these patients. The aim of the present study was to investigate the antioxidative system and trace elements in BD to contribute to the knowledge of pathogenesis and treatment of this disease. We examined glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities together with selenium (Se), copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe) levels in plasma and erythrocytes of 50 patients with BD and 30 healthy controls. It was found that in patients with BD, erythrocyte GSH-Px and SOD activities and erythrocyte Se, plasma Fe, Mn, and Zn levels were significantly lower than those of controls and that plasma Cu, erythrocyte Zn, and Mn levels were significantly higher in patients with BD. Insufficient antioxidant enzyme activities were observed in patients with BD. The mechanism(s) of this phenomenon is not clear. Therefore, supplementation with trace elements involved in the antioxidative processes may increase scavenger enzyme activities, and consequently, an improvement in clinical symptoms may be expected.