Occlusion effects of bioactive glass and hydroxyapatite on dentinal tubules: a systematic review.

OBJECTIVE: Bioactive glass and hydroxyapatite are biocompatible materials used as an adjunct to various dental materials. The present study aimed to evaluate the occlusion effects of bioactive glasses and hydroxyapatite on dental tubules. MATERIALS AND METHODS: We searched the PubMed/Medline, Embase, and Web of Science databases for the relevant records. The methodological quality of the studies was assessed by an accepted quality assessment tool. RESULTS: From the electronic databases, 372 articles were retrieved. After evaluating the records, 35 in vitro studies were included. The studies revealed a low risk of bias. The primary outcomes from bioactive glass studies demonstrated the potential efficacy of both bioactive glass and hydroxyapatite in dentin tubule occlusion compared to the control. CONCLUSION: The current systematic review showed that bioactive glass and hydroxyapatite could effectively occlude the dentinal tubules. Thus, desensitizing agents containing bioactive glass and hydroxyapatite can be used to manage dentin hypersensitivity (DH). However, long-term follow-up clinical trials are required in the future before definitive recommendations can be made. CLINICAL RELEVANCE: This work achieved a satisfactorily systematic review for assessing desensitizing agents containing bioactive glass and hydroxyapatite in dentine hypersensitivity treatments recommended for clinical practice and research.

Prebiotics as excipients for enhancement of stability and functionality of Bifidobacterium longum ssp. infantis with potential application as symbiotics in food and pharmaceuticals.

Objective: Formulations containing probiotics are promoted due to health benefits. During lyophilization and subsequent storage in the gastrointestinal tract, bacteria are exposed to stress conditions that can lead to impairment and loss of viability. Methods: The suitability of various excipients for enhancing the stability and functionality of Bifidobacterium longum subsp. infantis during storage as freeze-dried powder and through exposure to acid and bile was investigated. Cells were lyophilized in the presence of sucrose, trehalose, lactose, cellobiose and fructooligosaccharide (FOS) and stored at 4 °C or 25 °C. The effect of diverse protectants on the persistence after exposure to acid and bile environment was examined through determination of the colony forming units, the ß-glucosidase and ß-galactosidase activity and the membrane integrity changes. Results: Cells freeze-dried in the presence of cryoprotectants had comparable survivability during storage at 4 °C whereas the survival rate at 25 °C of cells protected by cellobiose and FOS was higher than for those protected with sucrose and trehalose. Furthermore, the respective excipients used as cryoprotectants enhanced the stability of cells exposed to simulated gastric and small intestinal medium. Stabilization may be achieved through different mechanism of action such as protecting the membrane integrity and as metabolizable substrates. Overall, prebiotic and thus metabolizable protectants including cellobiose and FOS were superior to other protectants used. Conclusion: In symbiotic formulas with B. infantis, these sugars might serve as prebiotics and stabilizers of this probiotic strain during lyophilization, storage and in gastrointestinal conditions simultaneously, potentially increasing its health-promoting effects.

In vitro and in silico characterisation of Tacrolimus released under biorelevant conditions.

This work aims to better understand the in vivo behaviour of modified release (MR) formulations (Envarsus® tablets and Advagraf® capsules) using in vitro properties of tacrolimus and in silico simulations. The in silico concentration profiles of tacrolimus released from the MR formulations were predicted after building a three compartments PK model with GastroPlus™, and using the experimentally determined in vitro physico-chemical properties as input parameters. In vitro-in vivo correlations (IVIVC) were obtained after deconvolution of in vivo data from a clinical trial. The IVIVC showed that the in vitro dissolution was faster than the in vivo deconvoluted dissolution for Advagraf®, while the in vitro dissolution was slightly slower than the in vivo deconvoluted dissolution for Envarsus®. Population PK simulation showed that variability in the simulation was lower for Envarsus® compared to Advagraf®. The in silico predicted preferential absorption sites were the proximal and distal tract for Advagraf® and Envarsus®, respectively. The integration of experimental in vitro solubility, permeability and biorelevant dissolution data allowed to generate in silico tacrolimus concentrations for two different MR formulations. This permitted to compare the two formulations in a single PK profile, in a simulated population PK study and with respect to their absorption sites.

Simulation of optical signaling among nano-bio-sensors: enhancing of bioimaging contrast.

In this article, the nanoparticle-dye systems is designed and simulated to illustrate the possibility of enhancement in optical imaging contrast. For this, the firefly optimization technique is used as an optical signaling mechanism among agents (nanoparticle-dye) because fireflies attract together due to their flashing light and optical signaling that is produced by a process of bioluminescence (also it has been investigated that other parameters such as neural response and brain function have essential role in attracting fireflies to each other). The first parameter is coincided with our work, because the nanoparticle-dye systems have ability to augment of received light and its amplification cause that the designed complex system act as a brightness particle. This induced behavior of nanoparticles can be considered as an optical communication and signaling. Indeed by functionalization of nanoparticles and then due to higher brightness of the tumor site because of active targeting, the other particles can be guided to reach toward the target point and the signaling among agents is done by optical relation similar to firefly nature. Moreover, the fundamental of this work is the use of surface plasmon resonance and plasmons hybridization, in which photonic signals can be manipulated on the nanoscale and can be used in biomedical applications such as electromagnetic field enhancement. Finally, it can be mentioned that by simultaneously using plasmon hybridization, near-field augmentation, and firefly algorithm, the optical imaging contrast can be impressively improved.

Comparison of health status and quality of life of related versus paid unrelated living kidney donors.

The aim of this cross-sectional study was to assess the health status and quality of life (QOL) of paid unrelated versus related living kidney donors postdonation at Shiraz Transplant Center in Iran. We invited all donors (n = 580, 347 paid unrelated, 233 related) who underwent donor nephrectomy at our center from 2004 to 2010 to participate in a health survey and physical examination. Of 580 donors, 144 consented to participate; participation of paid unrelated donors was significantly lower than related (52/347 vs. 92/233; p < 0.001). Participants underwent a complete physical examination, QOL assessment (using a 36-item short form health survey [SF-36] questionnaire) and laboratory work-up. The paid unrelated donors compared with related donors were younger (34.2 ± 7.2 vs. 40.7 ± 9.7 years, p < 0.001), had shorter time since donation (2.9 ± 1.6 vs. 3.8 ± 2 years, p = 0.004), had higher estimated GFR (72.6 ± 22 vs. 63.8 ± 15.3 mL/min/1.73 m(2), p = 0.006) and had a higher percentage of patients with microalbuminuria (35% vs. 0%, p < 0.001). Additionally, general health and social functioning scores among paid unrelated donors were significantly lower (p < 0.001 and p = 0.02, respectively) than related donors. Other SF-36 scores, although lower in paid unrelated donors, did not reach statistical significance. Iranian paid unrelated donors have lower QOL and higher incidence of microalbuminuria compared with related donors.

Reduction of metabolic signs of acute stress in male mice by Papaver rhoaes hydro-alcoholic extract.

In the present study, effects of hydro-alcoholic extract of Papaver rhoeas L. (Papaveraceae) on the metabolic changes induced by electro foot shock stress in male NMRI mice (25-30 g) has been investigated. The mice were received electric foot shock (40 mV) for 100 sec. Plasma corticosterone levels, food and water intake and delay to eating (Anorexia) were assessed 20 min later. Different doses of the plant extract (15, 30 and 60 mg kg(-1)), or saline (10 mL kg(-1)) was injected to the animals intraperitoneally 30 min before the stress. The control groups received saline (10 mL kg(-1)) or the extract (15, 30 and 60 mg kg(-1)) and 30 min later were exposed to the apparatus but did not received stress. Our results indicated that stress can increase plasma corticosterone level significantly and the extract can exacerbate the stress effect. However, stress could reduce food and water intake and increase delay to eating times which were inhibited by the extract pretreatment. The results indicate that administration of the extract of Papaver rhoeas can reduce the side effects of stress but increases plasma corticosterone level which may be due to its effects on the adrenal gland.

"Label and go"--a fast and easy radiolabelling method for pellets.

For the development and process optimization of pharmaceutical equipment, it is important to investigate the underlying processes. Taking the fluidized bed technology as an example, the study of particle flow pattern and convection of the particles within the functional unity is essential for construction and process improvement. With positron emission particle tracking (PEPT) it is possible to study the real-time particle motion with radiolabelled particles. We established a fast and simple labelling technique with [(18)F]fluoride for pellets composed of Avicel and anion exchange resin. The uptake of activity ranged from 1.3% to 1.7% per mg and 8.6% to 16.3% per pellet. A specific binding of [(18)F]fluoride with increasing degree of anion exchange resin in the pellets could be observed.

The effect of simvastatin on lowering panel reactive antibody titer in sensitized dialysis patients: a randomized placebo controlled clinical trial.

BACKGROUND: Patients with panel reactive antibodies (PRA) have many difficulties to find a crossmatch-negative kidney for transplantation and are at a higher risk of post-transplantation rejection. OBJECTIVE: To evaluate the effect of simvastatin on PRA and post-transplant outcome of these sensitized patients. METHODS: 82 patients with end-stage renal disease (ESRD) with a PRA ≥25% were evaluated. In a one-year follow-up, the patients were treated with simvastatin. These patients were compared with 82 matched controls receiving placebo tablets. At the end of the second and 12(th) month, PRA was rechecked in all patients. Those patients who underwent transplantation continued to take simvastatin six months after transplantation. Serum creatinine levels were checked at monthly intervals post-operation. RESULTS: The mean±SD PRA level at the end of the second month was 36.63%±31.14% and 45.34%±24.36% in cases and controls, respectively (P=0.012). Seven patients in the case group and 10 in the control group were lost to follow-up. The remaining patients continued to take simvastatin for 12 month. The mean±SD PRA level at the end of the 12(th) month was 24.02%±31.04% in cases and 43.15%±26.56% in controls (P=0.001). 25 patients underwent renal transplantation and continued to receive simvastatin 6 months after transplantation. These patients were matched with 25 controls treating with placebo. The mean±SD creatinine level 6 months after kidney transplantation was 2.05±1.14 mg/dL and 3.15±1.09 mg/dL in cases and controls consecutively (P=0.02). CONCLUSION: Simvastatin can be safely used to lower PRA and improve post-transplantation outcomes.

Angiotensinogen, angiotensine converting enzyme and plasminogen activator inhibitor-1 gene polymorphism in chronic allograft dysfunction.

Despite dramatic improvements in first-year patient and graft survival rates, chronic allograft dysfunction (CAD) remains the leading cause of late renal allograft loss, while current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays an important role in progression of chronic renal disease. It was shown that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS. This study investigates the possible links between angiotensinogen (AGT M235T), angiotensin-converting enzyme (ACE) and PAI-1 genotypes with CAD. Assessments of polymorphism were performed in 127 renal allograft recipients (77 with CAD and 50 with normal renal function). Fifty healthy subjects were also considered for comparison. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly higher frequencies of the TT than the recipients without CAD (P < 0.05). The transplant recipients with CAD also had significantly higher frequencies of the DD genotype than those without CAD (P < 0.05). No significant differences were observed between the allelic and genotypic distributions of PAI-1 polymorphisms. Therefore, determination of AGT M235T and ACE genotypes prior to transplantation may be useful to identify patients who are at risk for chronic renal transplant dysfunction.

Are large nonfunctional kidneys risk factors for posttransplantation urinary tract infection in patients with end-stage renal disease due to autosomal dominant polycystic kidney disease?

OBJECTIVES: The objective of this study was to evaluate the effect of bilateral nephrectomy on posttransplantation urinary tract infection (UTI) among patients with end-stage renal disease (ESRD) due to autosomal dominant polycystic kidney disease (ADPKD). METHODS: In a retrospective case-control design, 62 patients with ESRD with ADPKD were divided into 2 groups: (A) 24 patients who underwent bilateral nephrectomies, and (B) 38 patients in whom bilateral nephrectomies had not been done. Pretransplantation and posttransplantation urine cultures were evaluated for UTI. RESULTS: Sixty-two patients with ESRD with ADPKD were enrolled in this study. The average age was 42 years (range, 6-60 years). Forty patients (64.5%) were male and 22 (35.5%) were female. The mean duration of hemodialysis was 24 months (range, 2-120 months), which was the same for both groups. Bilateral nephrectomies were done for 24 participants (38.7%). There were 38 patients (61.3%) in group B who did not have the operation. UTI occurred in 23 patients (37.1%): 6 patients (25%) in group A and 17 patients (44.7%) in group B. The incidence of UTI was not statistically different between the 2 groups (P>.05). Furthermore, no relationship was found between age, gender, blood group, and UTI in patients with ADPKD (P>.05). CONCLUSION: According to our study, the presence of large nonfunctional kidneys is not a risk factor for posttransplantation UTI in patients with ADPKD and ESRD.

Association between cyclosporine concentration and genetic polymorphisms of CYP3A5 and MDR1 during the early stage after renal transplantation.

OBJECTIVES: Cyclosporine (CsA) has a narrow therapeutic range, and its pharmacokinetic characteristics vary among individuals. It also is a substrate for cytochrome P450 (CYP) 3A and P-glycoprotein, the product of the multidrug resistance 1 (MDR1) and CYP3A5 genes. Some of the single nucleotide polymorphisms (SNPs) in these genes are associated with deficient protein expression and reduced in vivo activity. We postulated that in renal transplant recipients, these SNPs should be associated with interindividual variations in CsA pharmacokinetics. MATERIALS AND METHODS: In 88 Iranian renal transplant patients receiving CsA, CYP3A5 and MDR1 genotypes were determined by polymerase chain reaction, followed by restriction fragment length polymorphism analysis. Whole blood trough CsA concentrations were measured by radioactive immunosorbent assay. The dose-adjusted concentration (ng/mL per mg/kg/d) was calculated at 1 day (+/-2 days), 7 days, and 1 month after transplantation. RESULTS: The MDR-1 wild-type genotype (3435CC) was observed in 17 patients (19%), whereas 45 patients (51%) were heterozygous (3435CT), and 26 patients (30%) were homozygous (3435 TT) for the mutation. In the days immediately after transplantation, we found a correlation between the concentration/dose ratio and the exon 26 MDR single nucleotide polymorphisms (33.3+/-15.24 microg mg/L/kg in the CT group vs 44.1+/-28.4 microg mg/L/kg in the TT group, P=.019). This ratio was significantly higher in subjects homozygous for the mutation (3435TT). This significant difference was not seen 1 week or 1 month after transplantation. All patients had the CYP3A5*3/*3 genotype, so no differences among the CYP3A5*1/*3 genotypes were found. CONCLUSIONS: MDR-1 (3435CC) polymorphisms are associated with CsA pharmacokinetics and dose requirements in the first few days after renal transplantation. Pharmacogenetic methods could be used to help select the initial dosage and individualize immunosuppressive therapy. According to our results, the major genotype of our recipients is CYP3A5*3/*3. According to the literature, the recommended starting dosage of CsA is 9-14 mg/kg/day; however, the Iranian population has a good response with lower dosages (3-5 mg/kg/day), which may be explained by genetic differences.

Long-term results of renal transplantation: A single-center analysis of 1200 transplants.

The present study is a report of long-term results of the first 1200 operations from December 1988 to December 2003. Graft and patient survival rates in eligible cases were computed with Kaplan-Meier analysis. Recipients were 808 men, 392 women of mean age 33.6 +/- 12.5 years. Eighty six percent of cases used organs from living donors (40% related, 41% unrelated, and 5% spouses) and 14% from cadaveric source. The most common causes of end-stage renal disease were chronic glomerulonephritis (18.2%); reflux nephropathy (13.4%); and diabetic nephropathy (10.1%). Among 215 (17.9%) patients, 156 patients (13%) died in the posttransplant period. Most common causes of death were cardiovascular (28.3%), graft loss (20.7%), and infections (19.6%). The 1- and 3-year patient survival rates were 94% and 91.5%, and graft survival rates were 88% and 84%. Although the success rate of operations was not satisfactory at the beginning, the current data reflect a >90% survival rate comparable to the major centers in the world.

Cytokine gene polymorphisms in renal transplant recipients.

OBJECTIVE: Acute rejection remains an important cause of graft loss after renal transplantation, and cytokines are key mediators in the induction and effector phases of all immune and inflammatory responses. However, the influence of gene polymorphisms on the functional immune response of transplant recipient outcomes remains controversial. MATERIALS AND METHODS: The amplification refractory mutation system polymerase chain reaction was used to detect the interleukin-10 (IL-10) (-1082 G/A), tumor necrosis factor-alpha (TNF-alpha) (-308 G/A), and interferon-gamma (IFN-gamma) (+874 T/A) single nucleotide polymorphisms in 100 of the first adult kidney recipients at our institution who were receiving cyclosporine-based immunosuppressive therapy. The diagnosis of acute rejection was based on clinical and histologic findings according to the Banff criteria. RESULTS: The results of multivariate analyses showed no significant association between episodes of acute rejection and single nucleotide polymorphisms in IL- 10, TNF-alpha genes, or dinucleotide repeat polymorphisms in the IFN-gamma gene. CONCLUSIONS: Our results demonstrate that cytokine gene polymorphisms did not influence the early outcome of kidney transplantation.

Effect of body mass index at time of transplantation and weight gain after transplantation on allograft function in kidney transplant recipients in Shiraz.

Chronic renal allograft dysfunction is the most common cause of graft loss, for which there are multiple risk factors, including obesity before transplantation, which is believed to lower long-term renal allograft survival. One hundred eighty-two kidney transplant recipients were studied. Body mass index (BMI) at the date of transplantation was calculated. BMI values were classified into 4 categories: (1) patients with BMI <20, (2) BMI between 20 and <25, (3) BMI between 25 and <30, and (4) BMI > or =30. The minimum follow-up period in this study was 3 years after transplantation. The link between categorized BMI and the presence of renal allograft dysfunction and mortality within 3 years posttransplantation was investigated using independent sample t test. BMI at the date of transplantation showed statistically significant association with presence of renal allograft dysfunction and mortality within 3 years posttransplantation (P = .008, P = .01, respectively). BMI at the date of transplantation has a strong association with outcomes after renal transplantation. The extremes of very high and very low BMI are important risk factors for chronic renal allograft dysfunction; therefore, weight adjustment before kidney transplantation can be useful in improving the function of a transplanted kidney and increasing patient's survival.

Outcome of hepatitis B and C virus infection on graft function after renal transplantation.

INTRODUCTION: Chronic liver disease resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is still a major concern in kidney recipients. It is unclear whether HCV antibody status and markers of HBV infection are associated with renal dysfunction. Thus, we designed a study to investigate the incidence of HBV and HCV infection after renal transplantation and whether these infections alter graft function. METHODS: Fifty-eight patients who underwent renal transplantation participated in the study. Serum creatinine and aminotransferase levels were measured with standard automated analyzers. Anti-HCV antibodies were detected with an enzyme immunoassay, and a reverse transcriptase-polymerase chain reaction (RT-PCR) technique was used to test for HCV-RNA. Serological markers for HBV (HBsAg and anti-HBc antibody) were detected by enzyme immunoassay. All samples from patients who were seropositive for HBsAg or anti-HBc antibody were PCR-tested for HBV-DNA. A serum sample collected from living donors was tested for anti-HCV antibodies and serological markers for HBV. Serum creatinine and aminotransferase levels were also measured in living donors. RESULTS: Anti-HCV was not detected in serum samples of any cases before transplantation. However, 10 (17.2%) tested positive after transplantation. HCV-RNA was detected in 2 of the 10 patients (3.4% of all patients). None of the pretransplantation serum samples tested positive for HBsAg. However, anti-HBc antibody was identified in 8 (13.8%) of the 58 patients.. No HBV DNA was detected in serum samples of the patients with anti-HBc or HBsAg-positive. HBsAg was only detected in 1 (1.7%) recipient after transplantation. None of the 58 patients showed clinical signs or symptoms of renal dysfunction during the study period. CONCLUSION: Our data suggest that, neither HBV nor HCV infection appears to cause or contribute to renal dysfunction in the early period (1 year) after renal transplantation. Nevertheless, a long-term consequence of chronic HBV or HCV liver disease or graft loss is not impossible in renal transplant recipients.

A randomized, double-blind, placebo-controlled trial of supplementary vitamins E, C and their combination for treatment of haemodialysis cramps.

BACKGROUND: Muscle cramps that improve after carnitine or vitamin E therapies are common in haemodialysis (HD) patients. Because vitamin C participates in carnitine biosynthesis, and its levels are reduced in uraemia, subclinical vitamin C depletion may contribute to HD cramps. Our aim was to determine the effects of vitamins C, E and their combination on the frequency and intensity of HD cramps. METHODS: In this placebo-controlled, double-blind study, 60 HD-patients were randomized into four therapeutic groups. Each group (n=15) received six identical capsules daily for 8 weeks, containing one of the following: vitamin E (400 mg), vitamin C (250 mg), their combination, or placebo. RESULTS: The frequency and intensity of HD cramps decreased significantly in all three vitamin groups compared with the placebo group at the end of the trial, and compared with the pre-treatment values. At the end of the trial, vitamins E, C, their combination, and placebo produced cramp reductions of 54, 61, 97 and 7%, respectively. The percentage cramp reduction had no significant correlation with age, sex, aetiology of end-stage renal disease, serum electrolytes or HD duration, but showed a positive correlation (r=0.33, P=0.01) with the type of therapy. No vitamin-related adverse effects were encountered during the trial. CONCLUSION: Short-term treatment with the combination of vitamins E and C is safe and effective in reducing HD cramps; however, its safety for prolonged therapy has yet to be evaluated in HD patients.