Prognostic and predictive significance of GITR in metastatic renal cell carcinoma.

OBJECTIVE: Renal cell carcinoma (RCC) has gradually increased in recent years. There have been significant developments in metastatic RCC in recent years with the introduction of immune control point inhibitors. Glucocorticoid-induced tumor necrosis factor (TNF) receptor-related protein (GITR) is a co-stimulatory molecule and is seen in the highest amounts in activated CD4+ T lymphocytes and CD8+ T lymphocytes, forkhead box protein 3 (FOXP3) positive regulatory T cells (Treg). GITR leads to an increase in interleukin (IL)-2 and CD25 and Interferon Gamma. It shows an anti-tumoural effect by inhibiting the suppressive functions of FOXP3+ regulatory cells (Treg). Therefore, we aimed to evaluate the prognostic and predictive effect of GITR, tumor-infiltrating lymphocytes (CD4+CD8) (TIL), and FOXP3 in patients with metastatic RCC. PATIENTS AND METHODS: Patients diagnosed with pathologically confirmed metastatic renal cancer between 2016 and 2021 were included in our study. Clinicopathological features and some laboratory tests were recorded. GITR, CD4, CD8, and FOXP3 were evaluated by immunohistochemistry (IHC) from biopsies or nephrectomy material and recorded. RESULTS: The study included 41 patients. The median progression-free survival (PFS) was 10.5 months, and the median overall survival (OS) was 13.9 months. Median PFS was 7.9 months for the GITR-low group and 18.9 months for the GITR-high group. Median PFS was statistically significant and longer for the GITR-high group than the GITR-low group (p=0.003). When patients who received nivolumab in the 2nd line were evaluated, median PFS was found to be 5.7 months in the GITR-low group and 15.7 months in the GITR-high group. Median PFS was statistically significantly higher in the GITR-high group than in the GITR-low group (p=0.026). CONCLUSIONS: In patients with metastatic RCC, higher GITR was associated with better PFS. At the same time, in patients using nivolumab, better PFS was seen in the GITR high group. If supported by prospective studies, GITR can be used as both a prognostic and predictive marker.

Comparison of the Surface Properties of 3D-printed Permanent Restorative Resins and Resin-based CAD/CAM Blocks.

OBJECTIVE: This study aimed to investigate the surface roughness, microhardness, and color changes of resin-based computer-aided design/computer-aided manufacturing (CAD/CAM) blocks and 3D-printed permanent resins in different beverages. METHODS AND MATERIALS: Resin-based CAD/CAM blocks (Cerasmart 270 and Grandio Blocs) and 3D-printed permanent restorative resins (Crowntec and Permanent Crown) were used in this study. A total of 96 specimens were prepared from CAD/CAM blocks and 3D-printed permanent resins. The initial surface roughness, microhardness, and shade value of the specimens were measured. Then, the specimens prepared from each material were divided into three subgroups (n=8) and immersed in tea, coffee, and distilled water for 30 days. After the specimens were immersed in the beverages, the surface roughness, microhardness, and tone values were measured again. The data were statistically analyzed using a two-way analysis of variance test (p<0.05). RESULTS: No statistically significant difference was found in the surface roughness values of the resin-based CAD/CAM blocks and 3D-printed resins (p<0.05). Resin-based CAD/CAM blocks showed statistically significantly higher microhardness than 3D-printed permanent resins (p<0.05). Although the color changes in 3D-printed resins in tea and coffee were similar to those in resin-based CAD/CAM blocks on the first and seventh days, more color changes appeared in the 3D-printed resins after 30 days. The surface roughness and microhardness values of the specimens submerged in tea, coffee, and distilled water showed no statistically significant changes (p<0.05). CONCLUSIONS: Although the surface roughness of 3D-printed permanent resins was similar to that of resin-based CAD/CAM blocks, they had a lower microhardness value. Moreover, 3D-printed permanent resins showed more color changes in tea and coffee.

Resistance of Single-shade Composites to Discoloration.

The aim of this study was to examine the color change of single-shade resin composites, which can be used for all tooth shades. In this study, samples were prepared using resin composites with single-shade (Omnichroma, Vitra Unique) and multishade composite systems (G-aenial A'Chord, Clearfil Majesty ES-2 Premium). The initial color values were measured with a spectrophotometer. Then, samples were kept in wine, coffee, black tea, and distilled water and color measurements were made after days 1, 7, and 30. Color change (ΔE00) and whiteness index (WID) values were statistically analyzed using a one-way analysis of variance (ANOVA) test (α=0.05). Single-shade resin composites showed more color change from wine, coffee, and black tea than multishade resin composites (p<0.001). Single-shade composites have a greater discoloration potential. Single-shade resin composites may show more color change from beverages than multishade resin composites, which may negatively affect clinical success.

Performance of butyl rubber-based macroporous sorbents as passive samplers.

In this study, two macroporous butyl rubber (BR)-based sorbents prepared in benzene (H-BR) and in cyclohexane (L-BR) with different porosities were synthesized by cryogelation technique. Their performances as a passive sampler were studied and then compared with commercially available silicon rubber (polydimethylsiloxane, PDMS) passive sampler. For that aim, polycyclic aromatic hydrocarbon (PAH) absorption rates of the sorbents in the short-term and their accumulation capacities in the long-term periods were investigated. Four PAHs (naphthalene, phenanthrene, fluoranthene, and pyrene) with a different number of aromatic rings were utilized. The concentrations of the PAHs in solutions were quantified by fluorescence spectrophotometer. The results showed that the BR sampler prepared in benzene (H-BR) generally has the highest absorption rates for all PAHs. The rate constants k (h-1) of the H-BR, L-BR, and PDMS samplers were found as 1.07, 0.55, and 0.55 for naphthalene; 0.73, 0.16, and 0.09 for phenanthrene; 0.24, 0.26, and 0.08 for fluoranthene; and 0.97, 0.38, and 0.17 for pyrene, respectively. The highest PAH absorption capacity was found for the BR sorbents prepared in benzene for all PAHs. Thus, benzene was selected as the organic solvent rather than cyclohexane for further studies in the preparation of butyl rubber-based samplers. The H-BR possessing the highest absorption rate and capacity underlines their usage as a capable passive sampler for both short- and long-term monitoring activities in the aquatic environments.

Evaluation of the cytotoxicity of contemporary glass-ionomer cements on mouse fibroblasts and human dental pulp cells.

PURPOSE: This study aimed to evaluate the cytotoxic effects of different types of contemporary GICs on human dental pulp cell (hDPCs) and mouse fibroblast (L929) cultures. METHODS: Three high-viscosity GICs (HVGIC; GC Equia Forte, Riva Self Cure, IonoStar Plus), three resin-modified GICs (RMGIC; Photac Fil, Riva Light Cure, Ionolux), and a metal-reinforced GIC (MRGIC; Riva Silver) were investigated. Twelve disc-shaped specimens of each material were prepared and stored in Dulbecco's modified Eagle medium (DMEM). L929 fibroblasts and DPCs were then cultured in 96-well plates. Uncultured DMEM was used as a negative control. Mitochondrial dehydrogenase activity (MTT) assays were performed to detect cell viability after 24, 48, and 72 h. Data were analysed using Mann-Whitney U and Friedman tests followed by a Bonferroni-corrected Wilcoxon signed rank test, with the statistical significance set at P < 0.05. RESULTS: Toxicity levels varied between the cell-culture systems. MTT assays of L929 cells showed significant differences in percentages of viable cells, as follows: Riva Self Cure = Riva Silver > GC Equia Forte > IonoStar Plus = Riva Light Cure = Photac Fil > Ionolux. MTT assays of DPCs showed the percentages of viable cells to be significantly lower for the Ionolux group when compared to the other GICs, which did not differ significantly from one another. With the exception of Ionolux, none of the other GICs tested showed any toxicity, and in fact, they all induced cell proliferation (> 100% cell viability). CONCLUSIONS: Although the degree of toxicity varied between the two cell-culture systems investigated, all the GICs tested, with the exception of Ionolux, performed favorably with regard to cytotoxicity (> 100% cell viability in both cell systems).

Single-, Double-, and Triple-Network Macroporous Rubbers as a Passive Sampler.

Over the past decades, large quantities of organic compounds including polycyclic aromatic hydrocarbons (PAHs) entering aquatic systems create acutely toxic effects and chronic abnormalities in aquatic organisms. Passive sampling is an effective technique to detect organic compounds at very low concentrations in water by accumulating them in their structure to a measurable concentration level. Polymeric passive samplers reported so far have a nonporous structure, and hence, the absorption of organic compounds into the passive sampler is governed by their slow diffusion process. We present here novel macroporous rubber sorbents as monophasic passive samplers with tunable pore morphologies, extraordinary mechanical properties, and high sorption rates and capacities for PAHs. Sorbent materials based on single-network (SN), double-network (DN), and triple-network (TN) butyl rubber were prepared via the cryogelation technique from butyl rubber solutions in benzene as the solvent at -18 °C using a sulfur monochloride cross-linker. To obtain macroporous rubbers with DN and TN structures, the reactions were conducted in the macropores of SN and DN rubber networks, respectively. The porous morphology and the mechanical behavior of the rubbers can be tuned by adjusting the weight ratio wR of the network components. The rubbers exhibit two generations of pores, namely, large and small pores with diameters 40-240 and 14-54 µm, respectively. The sizes of both large and small pores decrease and approach each other as wR is increased. Four PAH compounds, namely, naphthalene, phenanthrene, fluoranthene, and pyrene with two to four aromatic rings, dissolved in filtered seawater with a salinity of 22 ppt were used to highlight the correlations between the properties of macroporous rubbers and their absorption rates and capacities. Nonporous silicone rubber reported before as a passive sampler has the lowest absorption rate and capacity as compared to the macroporous rubbers. The SN rubber absorbs most rapidly PAHs because of its largest porosity, whereas the TN rubber with the smallest pores exhibits the highest sorption capacity.

Association of Toll-like receptors 2, 3, and 4 genes polymorphisms with periapical pathosis risk.

BACKGROUND: The aim of this study was to investigate the role of gene variations of Toll-like receptors (TLR) 2, 3, and 4 on genetic susceptibility to periapical pathosis. MATERIAL AND METHODS: One hundred patients were included in the study and divided into two groups as follows; Control Group (n=50) that have root canal treatment and no periapical lesion, Patient Group (n=50) that have root canal treatment and periapical lesion. TLR2 Arg753Gln, TLR3 (c.1377C/T) and TLR4 Asp299Gly and Thr399Ile polymorphisms were genotyped by using PCR-RFLP. Genotypical analysis of control and patient groups were investigated to disclose whether there is any association between periapical lesions and gene variations. RESULTS: There are no significant statistical differences between control and patient groups according to TLR 2 and 4 gene sequence. On the contrary, CC allele detected 74% for TLR 3 in patient group, and this difference was found to be statistically significant (p < 0.005). CONCLUSIONS: According to these results, it can be suggested that patients with Toll-like receptor 3 gene polymorphisms could be susceptible to periapical pathosis.

Dynamic assessment of Capparis spinosa buds on survival of periodontal ligament cells using a real-time cell analysis method.

BACKGROUND: Tooth avulsion is the most severe type of traumatic dental injuries and it results in the complete displacement of the tooth out of its socket in alveolar bone. Reimplantation of the tooth is considered to be a best treatment modality due to its biological and psychological advantages. Its prognosis depends on the extra alveolar time, the storage medium, and the patient's general health. OBJECTIVE: The aim of this study was to evaluate the effect of Capparis spinosa (C. spinosa) in maintaining the viability of human periodontal ligament (PDL) cells using a real-time cell analysis method. MATERIALS AND METHODS: Periodontal ligament cells were obtained from healthy human third molars extracted for orthodontic purposes. The storage media tested were: Dulbecco's Modified Eagle Medium (DMEM), C. spinosa, Hank's Balanced Salt Solution (HBSS), and light milk. A real-time cell analyzer system was used to evaluate cell viability. After seeding cell suspensions into the wells of the E-plate 96, PDL cells were treated with each of tested media and monitored for every 5 min for 26 h. Statistical analysis of the data was accomplished using one-way analysis of variance complemented by the Tukey test. The level of significance was set at P < 0.05. RESULTS: Dulbecco's Modified Eagle Medium (control) and C. spinosa groups had significantly higher cell index values compared with the HBSS and light milk (P < 0.05). Although, C. spinosa showed better results than DMEM (control), but this difference was not found statistically significant. CONCLUSION: Capparis spinosa can be a suitable, alternative storage medium for avulsed teeth.

Evaluation of residual antimicrobial effects and surface changes of gutta-percha disinfected with different solutions.

AIM: To determine the possible residual antibacterial effects and possible surface changes caused by 5.25% NaOCl, 2.5% NaOCl, 2% CHX and 0.05% Octenisept on in vitro gutta-percha points after different disinfection protocols. MATERIALS AND METHODS: A total of 121 standard # 40, 0.2% gutta-percha cones were cut 10 mm from the tip, sterilized with ethylene oxide. The samples were divided into five groups, and each group was divided into three subgroups according to immersion periods of gutta-percha cones into solutions. One gutta-percha cone from each group was selected for SEM evaluation. RESULTS: All of the tested solutions were effective on the selected microorganisms when compared with the control solution. No surface alterations were detected on the gutta-percha cones. CONCLUSION: In the limits of this study, immersion of gutta-percha into 2% CHX for one minute was found the most effective method to eliminate the selected microorganisms. CLINICAL SIGNIFICANCE: Although gutta-percha points are aseptic in their package, once opened and used, gutta-percha cones may be contaminated. In order to eliminate bacteria and not to cause surface changes on gutta-percha cones, disinfection solution must be selected carefully.

[Gastritis localization and GERD incidence in patients with Cag A(+) and Cag A(-) Helicobacter pylori infection]. / Gastritislokalisation und gastroösophageale Refluxinzidenz bei der Helicobacter-pylori-Infektion mit Cag-A-positiven und Cag-A-negativen Stämmen.

The relationship between Helicobacter pylori (HP) and gastroesophageal reflux disease (GERD) is very complex and still not well understood. However, many issues, even those as basic as whether HP induces or protects against GERD, are still controversial. The gastritis location could play also a role in the induction of GERD. Some investigators suggested that infection by the Cag A strain of HP seems to have a positive association with reflux esophagitis. Therefore, the aim of this study was to investigate the relationship between GERD, gastritis location, HP infection and Cag A positivity.

[Meta-analysis of determining the pathogen eradicating efficacy of various therapeutic regimens in Helicobacter pylori infection]. / Metaanalyse zur Feststellung der keimeradizierenden Potenz verschiedener Therapieschemata bei Helicobacter-pylori-Infektion.

Helicobacter pylori is the most common bacterial pathogen world-wide and has been identified in all countries. As long-term infection with H. pylori could potentially lead to duodenal or gastric ulcer disease, asymptomatic chronic gastritis, chronic dyspepsia, or gastric malignancy, including both adenocarcinoma and B-cell lymphoma, a large number of different treatment regimens aimed at eradicating H. pylori has been evaluated and reported. Despite numerous H. pylori treatment studies the optimum regimen for its eradication remains unclear. A treatment regimen, which is effective, safe and inexpensive could be used widespread and reduce the risks of the long-term complications of infection. In this study we compared the efficacy, side effects and cost-effectiveness of 12 different therapy regimens for H. pylori eradication by using meta-analysis methodology. 486 patients (256 male, 230 female; mean age 40.8 years) with H. pylori associated duodenal ulcer (n = 140), gastritis (n = 254), gastroduodenitis (n = 92) were treated with 12 different therapy-regimens. Endoscopy was performed at baseline and 6 weeks after discontinuation of eradication therapy. H. pylori status was assessed by urease test and histology. The therapy with a H2-receptor antagonist is less effective than the triple therapies with omeprazole or lansoprazole. Bismuth-based triple therapies have a mean overall eradication rate of 68%, but are limited by frequent side effects causing poor drug compliance.

Hydrazine sulfate influence on nutritional status and survival in non-small-cell lung cancer.

This randomized, prospective, placebo-controlled clinical trial compares the influence on nutritional status and survival of hydrazine sulfate with placebo addition to cisplatin-containing combination chemotherapy in patients with unresectable non-small-cell lung cancer (NSCLC). The trial consisted of 65 patients with advanced, unresectable NSCLC who had had no prior chemotherapy, were at least partially ambulatory (Eastern Cooperative Oncology Group [ECOG] performance status [PS] level 0-2), and who had adequate hematologic, renal, and hepatic function. All patients received the same defined combination chemotherapy (cisplatin, vinblastine, and bleomycin) and the same defined dietary counseling with the addition of either three times daily oral hydrazine sulfate (60 mg) or placebo capsules. Hydrazine sulfate compared with placebo addition to chemotherapy resulted in significantly greater caloric intake and albumin maintenance (P less than .05). Considering all patients, survival was greater for the hydrazine sulfate compared with placebo group (median survival, 292 v 187 days), but the difference did not achieve statistical significance. In favorable PS patients (PS 0-1), survival was significantly prolonged (median survival, 328 days v 209 days; P less than .05) for hydrazine sulfate compared with placebo addition. In a multifactor analysis, PS, weight loss, and liver involvement were the final variables. Objective response frequency and toxicity were comparable on both arms. Hydrazine sulfate may favorably influence nutritional status and clinical outcome of patients with NSCLC. Further definitive studies of hydrazine sulfate addition to therapeutic regimens in NSCLC are warranted.

Hydrazine sulfate in cancer patients with weight loss. A placebo-controlled clinical experience.

Hydrazine sulfate was evaluated using 24-hour dietary recalls and body weight determinations before and after 30 days of either placebo or hydrazine (60 mg, 3 times/d) oral administration in 101 heavily pretreated cancer patients with weight loss. After 1 month, 83% of hydrazine and only 53% of placebo patients completing repeat evaluation maintained or increased their weight (P less than 0.05). In addition, appetite improvement was more frequent in the hydrazine group (63% versus 25%, P less than 0.05). Although caloric intake was only slightly greater in hydrazine-treated patients, an increased caloric intake was more commonly associated with weight gain in patients receiving hydrazine compared with those receiving placebo (81% versus 53%, respectively). Hydrazine toxicity was mild, with 71% of patients reporting no toxic effects. Hydrazine sulfate circulatory levels were obtained from a subset of 14 patients who completed 30 days of treatment, with a single sample obtained in the morning at least 9 hours after the last dose. Mean maintenance hydrazine sulfate levels, determined using a spectrofluorometric assay, ranged from 0 to 89 ng/ml (mean 45 +/- 16 ng/ml). These data, which demonstrate an association between 1 month of hydrazine sulfate administration and body weight maintenance in patients with cancer, suggest future clinical trials of hydrazine sulfate are indicated to definitively assess its long-term impact on important clinical outcome parameters in defined cancer populations.

Influence of nandrolone decanoate on weight loss in advanced non-small cell lung cancer.

The short term addition of nandrolone decanoate to combination chemotherapy given to patients with unresectable non-small cell lung cancer was evaluated in a randomized, prospective trial. Patients were treated with doxorubicin 50 mg/M2 intravenously, cyclophosphamide 300 mg/M2 intravenously, CCNU 50 mg/M2 orally, vincristine 1.4 mg/M2 intravenously, with and without cisplatin 50 mg/M2 intravenously, all given every 28 days. In addition, patients were randomized to receive either nandrolone decanoate 200 mg intramuscularly weekly for 4 weeks or no additional therapy. Patient age, disease extent, performance score, and pretreatment weight loss were similar in the two treatment arms. Objective antitumor response frequency was comparable on both treatment arms with median survival somewhat longer for patients receiving the androgen (median survival 5.5 months without and 8.2 months with nandrolone decanoate). There was a trend for less severe weight loss on the nandrolone decanoate arm (average weight loss 0.8 +/- 0.15 kg versus 0.21 +/- 0.18 kg, respectively), with half as many patients experiencing weight loss on nandrolone decanoate (25% versus 12%). A separate concurrent study has demonstrated decreased free testosterone levels in 66% of patients with advanced cancer studied prior to chemotherapy treatment, therefore, further prospective studies in which pretreatment testosterone levels are used to guide androgen administration are needed to define more precisely a role for androgen replacement therapy in non-small cell lung cancer.

Doxorubicin, cyclophosphamide, CCNU, and vincristine with or without cisplatinum in non-small cell lung cancer.

To evaluate the role of cisplatinum in the treatment of advanced non-small cell lung cancer, 48 patients received either a doxorubicin (adriamycin) 50 mg/m2 I.V., cyclophosphamide 300 mg/m2 I.V., lomustine (CCNU) 50 mg/m2 p.o., vincristine (oncovin) 1.2 mg/m2 I.V. (ACCO) combination or the same drugs plus cisplatinum 50 mg/m2 I.V. (PACCO) in a prospective sequential trial. No patient had received prior chemotherapy. Patients receiving the two regimens were comparable with regard to median age, performance status, histologic subtype, disease extent, and weight loss. Objective response frequency was only 5% in the initial 20 patients receiving ACCO treatment compared to a response frequency of 28% (7% complete) in the 28 patients receiving cisplatinum in the PACCO treatment arm (p less than 0.06). Patients achieving objective response lived significantly longer than nonresponders (9.1 months vs. 3.8 months, p less than 0.05). Although median survival was similar on the two regimens (6.1 months for ACCO vs. 7.6 months for PACCO), more than four times as many patients were alive after 1 year in the PACCO treatment group (24% vs. 5%). Predominant toxicity consisted of moderately severe nausea and vomiting (63% on PACCO vs. 34% on ACCO, p less than 0.05) and myelosuppression with WBC less than 3,000/mm3 occurring in the majority of patients on both regimens. These results suggest cisplatinum addition to a doxorubicin, cyclophosphamide, lomustine, and vincristine combination may be associated with increased 1-year survival in the non-small cell lung cancer patient population.