The Incidence of and Factors Associated with Vitamin D Deficiency in Newly Diagnosed Children with Cancer

This retrospective chart review study aimed to assess vitamin D status and identify risk factors associated with vitamin D deficiency and bone parameters in children with cancer at admission. The data of 86 (50 males and 36 females) patients between April 2013 and June 2015 were analyzed. Calcium, phosphorus, alkaline phosphatase (ALP), 25(OH)D, age, gender, diagnostic category, body mass index, duration of complaints, and season of blood sampling were recorded. Median age was 7.17 years (range 0.31—17.40) in 29 hematological malignancy and 57 solid tumor patients. According to cut-off level of 20 ng/ml, 63% of children with cancer had vitamin D deficiency at diagnosis with a median 25(OH)D of 16.75 ng/ml. The mean vitamin D value of children >10 years was significantly low in comparison to that observed in younger children [11.83, 95% confidence interval (CI) = = 8.85—14.81 ng/ml vs. 19.81, 95% CI = = 17.02—22.60 ng/ml]. Vitamin D measurement between November and May was a risk factor for vitamin D deficiency (P < 0.05). The frequency of hypocalcemia and hypophosphatemia was not different between two groups of vitamin D. Further longitudinal studies are needed to investigate whether monitoring vitamin D status and supplementation in children with cancer might prevent future complications related to vitamin D deficiency.     

The effect of triamcinolone acetonide aqueous nasal spray on the nasal carriage of Staphylococcus aureus

BACKGROUND: In this study we aimed to investigate the effect of triamcinolone acetonide aqueous (TAA) intranasal spray that was used for 2 months to treat allergic rhinitis (AR) on the nasal carriage of Staphylococcus aureus (NCSA). METHODS: A total of 125 adult AR patients (study group) and 133 healthy individuals (control group) were enrolled for the study. The subjects were diagnosed with AR after a detailed history, physical examination, and prick testing. The AR subjects were administered TAA in a daily dosage of a 220-microg intranasal route. Nasal cultures were obtained on the 1st (baseline), 55th, and 60th days, and the subjects in the last two cultures of whom S. aureus was detected were accepted as NCSA. RESULTS: After all exclusion criteria were used, 110 AR and 114 control group subjects were enrolled in the study. Based on the culture results that were obtained on the 55th and 60th days, 10 (%9.1) patients from the study group and 18 (%15.7) individuals from the control group were defined to be NCSA (p > 0.05). CONCLUSION: We conclude that the use of TAA treatment for AR does not increase the prevalence of NCSA. However, additional studies with a larger series are required to explain the effects of steroids on nasal colonization of S. aureus.     

Cochlear involvement in Familial Mediterranean Fever: a new feature of an old disease

Objectives

In this study we first aimed to assess the cochlear functions in children with Familial Mediterranean Fever. The second aim was to investigate the correlation between the hearing levels and some clinical features of Familial Mediterranean Fever including the duration of the disease, age at onset, genetic analysis and colchicine use.

Methods

Thirty-four children with Familial Mediterranean Fever and 27 age matched children were included in the study. Following otologic examination, all children underwent audiometric evaluation, including Pure Tone Average measurements and Distortion Product Otoaoustic Emission testing. Audiological results of the two groups were compared and correlation between the audiologic status and clinical parameters of the disease like the duration of disease, age at onset, mutations and colchicine treatment were studied.

Results

Pure tone audiometry hearing levels were within normal levels in both groups. Hearing thresholds of Familial Mediterranean Fever patients were found to be increased at frequencies 8000, 10,000, 12,500 and 16,000 (p < 0.05). In otoacoustic emission evaluation, distortion products and signal-noise ratio of FMF children were lower in the tested frequencies, from 1400 Hz to 4000 Hz (p < 0.05). Interaction of the disease duration and age of disease onset was found to predict hearing levels, distortion products and signal-noise ratios of children with Familial Mediterranean Fever (F value = 2.034; p = 0.033).

Conclusions

To our knowledge this is the first study demonstrating cochlear involvement in children with Familial Mediterranean Fever which showed increased hearing thresholds at higher frequencies in audiometry together with decreased distortion products and signal-noise ratios demonstrated by distortion product otoacoustic emission testing. Similar studies must be carried out on adult patients to see if a clinical hearing impairment develops. The possible mechanisms that cause cochlear involvement and the effect of colchicine treatment on cochlear functions must be enlightened.     

Inhibition of growth and telomerase activity by novel cationic ceramide analogs with high solubility in human head and neck squamous cell carcinoma cells.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) is notoriously resistant to chemotherapy. The sphingolipid ceramide and its analogs have been demonstrated to exert antitumor activity in many cell types; however, the effectiveness of these analogs has been limited by potency and solubility. This study focuses on the effects of novel highly soluble cationic pyridinium-ceramides, alone and in combination with various chemotherapeutic agents, on cell survival, telomerase activity, and cell cycle arrest in HNSCC cell lines in vitro. METHODS: The concentration of pyridinium-ceramides and chemotherapeutic agents that inhibited cell growth by 50% (IC50) was determined by MTT cell survival assays. The cell cycle profiles were determined by flow cytometry. Telomerase activity was determined by telomerase repeat amplification protocol (TRAP) assay. RESULTS: Treatment of the human UM-SCC-22A (SCC of the hypopharynx) cells, as well as various other HNSCC cell lines, with C6-Pyr-Cer resulted in the inhibition of cell survival with an IC50 concentration of approximately 250 to 300 nM at 96 hours, whereas its IC50 was greater than 1000 nM in noncancerous Wi-38 human lung fibroblasts, and adult human epidermal keratinocytes. Moreover, treatment with C6-Pyr-Cer also resulted in cell cycle arrest in G0/G1, which correlated with a significant inhibition of telomerase activity in UM-SCC-22A cells. Additional results demonstrated that the combination of C6-Pyr-Cer with gemcitabine (GMZ) or doxorubicin (DOX), which have the lowest IC50 concentrations among various chemotherapeutic drugs in these cells, enhances the effects of these drugs in the inhibition of telomerase and cell growth. CONCLUSIONS: These data suggest that the novel C6-Pyr-Cer with high solubility and bioavailability may lead to the development of new therapeutic strategies that target telomerase for the treatment of HNSCC.     

Enhancement of vinorelbine-induced cytotoxicity and apoptosis by clomipramine and lithium chloride in human neuroblastoma cancer cell line SH-SY5Y

The aim of this work is to investigate whether clomipramine (CIM) and lithium chloride (LiCl) potentiate the cytotoxicity of vinorelbine (VNR) on SH-SY5Y human neuroblastoma cells in vitro and whether midkine (MK) can be a resistance factor for these treatments. Four groups of experiments were performed for 96 h using both monolayer and spheroid cultures of SH-SY5Y cells: (1) control group, (2) singly applied VNR, CIM, and LiCl, (3) VNR with CIM, and (4) VNR with LiCl. Their effects on monolayer and spheroid cultures were determined by evaluating cell proliferation, bromodeoxyuridine labeling index (BrdU-LI), apoptosis, cyclic adenosine monophosphate (cAMP) and midkine levels, colony-forming efficiency, spheroid size, and ultrastructure. In comparison with the control group, single and combination drug treatments significantly reduced the proliferation index (PI) for 96 h. The most potent reduction of PI was observed with VNR in combination with CIM and LiCl for all time intervals. VNR with CIM and LiCl seemed to be ineffective in reducing BrdU-LI of both monolayer cell and spheroid cultures, spheroid size, and cAMP level. VNR with LiCl increased apoptosis at 24 h, however VNR with CIM increased apoptosis at 96 h. VNR was the most potent drug in inhibiting colony-forming efficiency. The combination of VNR with CIM was the most potent in reducing midkine levels among all groups. Interestingly, the combination of VNR with LiCl led to both nuclear membrane breakdown and disappearance of the cellular membranes inside the spheroids. Both CIM and LiCl seemed to potentiate VNR-induced cytotoxicity, and MK was not a resistance factor for VNR, LiCl, and CIM.     

Resveratrol attenuates doxorubicin-induced cellular damage by modulating nitric oxide and apoptosis

Although doxorubicin (DOX) is a commonly used chemotherapeutic agent its clinical use is restricted due to its organ toxicities. The present investigation relates to reducing DOX induced side effects to the liver, kidney and ileum by usage of the antioxidant, anti-inflammatory agent, resveratrol (RES) and to investigate the role of nitric oxide synthase (NOS) in the process. Wistar rats were divided into four groups: control (saline i.p); DOX (20 mg/kg i.p), RES (20 mg/kg i.p) and DOX (20 mg/kg i.p) + RES (20 mg/kg i.p). Immunohistochemical activity of both iNOS and eNOS were evaluated after DOX treatment and ultrastructural changes such as cellular damage and mitochondrial degeneration were evaluated. Degenerative ultrastructural changes were demonstrated especially in the DOX treated group. Variations in biochemical marker levels of oxidative stress on ischemia in tissues were not observed. Our data indicate that RES may prevent cellular damage in the early phase of DOX induced toxicity. RES could be used with its beneficial effects during early cellular damage in organ toxicity after DOX treatment in cancer patients.     

Differential effects of doxorubicin and docetaxel on nitric oxide production and inducible nitric oxide synthase expression in MCF-7 human breast cancer cells

Anthracyclines and docetaxel are frequently used agents in the chemotherapy of breast cancer. In this study we examined the role of inducible nitric oxide synthase (iNOS) expression during the cytotoxicity of these drugs in the MCF-7 breast cancer cell line. Cell viability and cytotoxicity were evaluated by the trypan blue dye exclusion method. Apoptosis and necrosis were determined by the acridine orange/ethidium bromide dye method. The percentage of apoptotic cells was significantly higher with doxorubicin. However, total cytotoxic cell numbers were higher in the docetaxel group compared with doxorubicin, with respect to the control. Most of the cells were seen to be necrotic with the dye method. Cell extracts during the apoptotic process were applied to immunoblot by anti-iNOS monoclonal antibodies. While there was an increase in iNOS expression during docetaxel induced-cytotoxicity, a significant decrease in iNOS expression was detected during doxorubicin-induced cytotoxicity. The Griess method was used for detection of nitrate levels. It was compatible with immunoblot results. These data open a window for further studies to understand the mechanism underlining the cytotoxicity of docetaxel and doxorubicin.