The effect of vitamin D treatment on quality of life in patients with fibromyalgia.

BACKGROUND: Fibromyalgia is a syndrome characterized by chronic widespread pain accompanied by fatigue, disrupted sleep quality, cognitive impairments, subjective soft tissue swelling, and somatic symptoms. There are conflicting results in the literature regarding the prevalence of vitamin D deficiency in fibromyalgia patients and the reduction of symptoms after supplementation. AIMS: Our study aims to evaluate the effectiveness and reliability of vitamin D supplementation in patients diagnosed with fibromyalgia. METHODS: In our cross-sectional clinical study, 180 female patients aged 18 to 65 diagnosed with fibromyalgia according to the 2010 American College of Rheumatology Diagnostic Criteria were included. Oral vitamin D3 replacement of 50,000 IU was administered for 12 weeks. Patients' Fibromyalgia Impact Questionnaire (FIQ)and Visual Analogue Scale (VAS) scores were evaluated before and after the study. RESULTS: Significant differences were observed in the FIQ scores of the 180 fibromyalgia patients before and after vitamin D supplementation (p < 0.05). There was also a significant improvement in VAS scores (p < 0.01). A negative correlation between vitamin D and VAS as well as FIQ scores was found in the study. CONCLUSION: We determined that vitamin D deficiency is significantly more prevalent in patients diagnosed with fibromyalgia. Vitamin D supplementation was observed to have a positive effect on quality of life and reduction of pain.

Evaluating the Cytotoxic Effect of Melatonin and Oxyresveratrol on Dental Pulp Stem Cells.

OBJECTIVE: Hypoxia in the pulpitis process, the use of bleaching agents, and resin-containing materials produce reactive oxygen species. Their damage to the pulp tissue can be eliminated by melatonin and oxyresveratrol. However, the cytotoxic effects of these antioxidants on dental pulp stem cells are not well known. The aim of this study was to observe the cytotoxic effects of melatonin and oxyresveratrol for 72 hours on dental pulp stem cells. MATERIALS AND METHODS: Human dental pulp stem cells obtained from the American Type Culture Collection were seeded on E-Plates®, and after 24 hours, 3 different doses of melatonin (100 pM, 100 nM, and 100 µM) and oxyresveratrol (10 µM, 25 µM, and 50 µM) were added. Real-time cell index data was acquired by using xCELLigence® device for 72 hours and inhibitor concentration (IC50) values of experimental groups were obtained. Analysis of covariance was used to compare the cell index values. RESULTS: In comparison with the control group; oxyresveratrol 10 µM and melatonin 100 pM groups increased proliferation whereas oxyresveratrol 25 µM, oxyresveratrol 50 µM, and melatonin 100 µM groups induced cytotoxicity (P < .05). IC50 values at 24th, 48th, and 72th hours were 946 nM, 1220 nM, and 1243 nM for melatonin and 23 µM, 22.2 µM, and 22.5 µM for oxyresveratrol, respectively. CONCLUSION: Cytotoxicity of melatonin was higher than oxyresveratrol and they both increased dental pulp stem cells' proliferation at lower doses and induced cytotoxicity at higher doses.

Roflumilast as a Potential Therapeutic Agent for Cecal Ligation and Puncture-Induced Septic Lung Injury.

PURPOSE/AIMS: This study focused on delineating the possible effects of roflumilast (ROF), a selective phosphodiesterase 4 (PDE4) inhibitor, in rats with cecal ligation and puncture (CLP)-induced polymicrobial sepsis, and investigated whether ROF can act as a protective agent in sepsis-induced lung damage. MATERIAL AND METHODS: Four experimental groups were organized, each comprising eight rats: Control, Sepsis, Sepsis + ROF 0.5 mgkg-1, and Sepsis + ROF 1 mgkg-1 groups. A polymicrobial sepsis model was induced in the rats by cecal ligation and puncture under anesthesia. Twelve hours after sepsis induction, the lungs were obtained for biochemical, molecular, and histopathological analyses. RESULTS: In the sepsis group's lungs, the TNF-α, IL-1ß, and IL-6 mRNA expression levels peaked in the sepsis group's lung tissues, and ROF significantly decreased these levels compared with the sepsis group dose-dependently. ROF also significantly decreased MDA levels in septic lungs and increased antioxidant parameters (SOD and GSH) compared with the sepsis group. Histopathological analysis results supported biochemical and molecular results. CONCLUSIONS: ROF, a PDE4 inhibitor, suppressed the expression levels of pro-inflammatory cytokines, alleviated lung damage (probably by blocking neutrophil infiltration), and increased the capacity of the antioxidant system.

Does the cardiovascular drug levosimendan prevent iodinated contrast medium nephrotoxicity with glycerol aggravation in rats?

BACKGROUND: We investigated whether levosimendan prevents contrast medium nephrotoxicity with glycerol aggravation in rats. METHODS: Forty-eight Wistar albino rats were assigned to eight groups (n = 6 × 8). No medication was administered to group I (controls); glycerol (intramuscular injection of 25% glycerol, 10 mL/kg) group II; intravenous iohexol 10 mL/kg to group III; glycerol and iohexol to group IV; iohexol and intraperitoneal levosimendan 0.25 mg/kg to group V; glycerol, iohexol, and levosimendan 0.25 mg/kg to group VI; iohexol and levosimendan 0.5 mg/kg to group VII; and glycerol, iohexol, and levosimendan 0.5 mg/kg to group VIII. One-day water withdrawal and glycerol injection prompted renal damage; iohexol encouraged nephrotoxicity; levosimendan was administered 30 min after glycerol injection and continued on days 2, 3, and 4. The experiment was completed on day 5. Serum blood urea nitrogen (BUN) and creatinine levels, superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA) levels, tumour necrosis factor-α (TNF-α), nuclear factor kappa ß (NFK-ß), interleukin 6 (IL-6), and histopathological marks were assessed. One-way analysis of variance and Duncan's multiple comparison tests were used. RESULTS: Levosimendan changed serum BUN (p = 0.012) and creatinine (p = 0.018), SOD (p = 0.026), GSH (p = 0.012), and MDA (p = 0.011). Levosimendan significantly downregulated TNF-α (p = 0.022), NFK-ß (p = 0.008), and IL-6 (p = 0.033). Histopathological marks of hyaline and haemorrhagic cast were improved in levosimendan-injected groups. CONCLUSION: Levosimendan showed nephroprotective properties due to its vasodilator, oxidative distress decreasing and inflammatory cytokine preventing belongings.

5-HT7 receptors as a new target for prostate cancer physiopathology and treatment: an experimental study on PC-3 cells and FFPE tissues.

Prostate cancer (PCa) is one of the most common types of cancer seen among men worldwide. Previous studies have demonstrated that serotonin regulates cell proliferation, migration, and invasion in vitro; the presence of 5-HT receptors in cancer cells; and the role of serotonin in tumor development. The most recently discovered of these receptors is 5-HT7 but also least characterized receptors of serotonin. The aim of this study is to investigate the existence and possible role of 5-HT7 receptors in healthy and cancerous prostate tissues and also investigate effects of receptor agonists and antagonists on PC-3 cells to evaluate potential therapeutic effects. PC-3 cells were cultured and effects of 5-HT7 receptor agonist (LP-44) and antagonist (SB-269970) were evaluated on these cells. After proliferation analyses, relative expression of apoptotic markers and 5-HT7 receptor mRNA expression levels were determined through real-time PCR. Annexin V-FITC/PI double staining and Hoechst 33258 staining assay methods were applied to determine apoptosis. Additional PCR studies were performed on healthy and cancerous prostate tissue to see existence of receptors in human samples. The viability of PC-3 cells was decreased by SB-269970 after 48 and 72 h of incubation. However, LP-44 increased PC-3 cell proliferation at all time points. In 10-6 M SB-269970 treated PC-3 cells, there was significant increase in the expression of CAS-3 (4-fold), CAS-9 (2.5-fold), BAX (1.9-fold), and Tp-53 (4.8-fold) gene mRNA levels when compared to non-treated control group. Conversely, there was a significant decrease in NF-κB (2.9-fold) and 5-HT7 receptor (3.6-fold) mRNA expression in cells treated with SB-269970 when compared to control. SB-269970 that antagonized 5-HT7 receptors also induced apoptosis in Annexin V-FITC/PI double staining assay and Hoechst 33258 staining assays when compared with other groups. In human samples, 5-HT7 receptor mRNA expression was approximately 200-fold higher than that of heathy ones. In this study, for the first time, the 5-HT7 receptor antagonist SB-269970 has been shown to inhibit proliferation in PC-3 cells and to be associated with an apoptosis-inducing effect. These results suggest blocking 5-HT7 receptors can be a novel therapeutic target for the treatment of prostate cancer.

LP44 (4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide) exerts anti-ulcer effects via 5-hydroxytryptamine receptor 7 activation on indomethacin-induced gastric ulcers in rats.

AIM: This study aimed to demonstrate the role of serotonin 7 receptor (5-HT7) and the effects of 5-HT7 agonists and antagonists in an indomethacin-induced gastric ulcer. MATERIAL AND METHOD: Male albino Wistar rats (n = 60) were used in the experiments. LP44 (5-HT7 agonist) and SB269970 (5-HT7 antagonist) were administered at 10 mg/kg as a pre-treatment. One hour after the drug treatments, 25 mg/kg of indomethacin (INDO) was administered to all groups except the healthy control group. Six hours after indomethacin administration, all the rats were euthanized. RESULTS: We analyzed the iNOS, eNOS, and 5-HT7 receptor mRNA levels in the stomach tissue of rats by real-time PCR. 5-HT7 mRNA expression was increased in the INDO group compared to the healthy group. LP44 administration exerted a significant upregulatory effect on eNOS mRNA expression and downregulatory effects on iNOS and 5-HT7 mRNA expression compared to the INDO group. However, antagonist (SB269970) administration did not result in such difference in gene expression, but even partially decreased the agonist's effect in combination. Famotidine and agonist exerted similar effects. Histopathological findings supported the beneficial effects of 5-HT7 agonist on gastric tissue. CONCLUSION: The study suggested that activation of 5-HT7 receptor showed a significant anti-ulcerogenic effect in the indomethacin-induced gastric ulcer model.

The investigation of possible roles of central 5-HT7 receptors in antipyretic effect mechanism of paracetamol in LPS-induced hyperthermia model of mice.

AIM: This study aimed to investigate the role of the 5-HT7 receptor in fever mechanisms and its possible effect on the antipyretic mechanism of paracetamol. MATERIALS AND METHODS: The study consisted of eight experimental groups and one control group. Group I: healthy, II: LPS, III: LPS + PARA, IV: LPS + AGO, V: LPS + ANTA, VI: LPS + AGO + ANTA, VII: LPS + AGO + PARA, VIII: LPS + ANTA + PARA, and IX: LPS + AGO + ANTA + PARA. Rectal temperatures were measured with a rectal thermometer. At the end of the experiment, tissues were examined molecularly. Real-time PCR mRNA expression analyses were performed for the 5-HT7 receptor, IL-6, and TNF-α in hypothalamus tissue. RESULTS: The mean differences in rectal temperature increased in the LPS, LPS + ANTA, and LPS + AGO + ANTA groups when compared to the healthy group and decreased in the LPS + PARA, LPS + AGO, LPS + AGO + PARA, and LPS + AGO + ANTA + PARA groups when compared to the healthy group. The IL-6 and TNF-α mRNA expression increased in the LPS, LPS + ANTA, and LPS + AGO + ANTA groups when compared to the healthy group in the 2nd and 4th hours. The IL-6 and TNF-α expression decreased in the LPS + PARA, LPS + AGO, LPS + AGO + PARA, and LPS + AGO + ANTA + PARA groups when compared to the LPS group in the 2nd and 4th hours. The 5-HT7 receptor mRNA expression increased in the LPS group when compared to the healthy group in the 2nd hour. The 5-HT7 receptor mRNA expression decreased in the LPS + AGO and LPS + AGO + PARA groups when compared to the LPS group in the 2nd hour. The 5-HT7 receptor mRNA expression increased the in LPS + ANTA and LPS + ANTA + PARA groups when compared to the LPS group in the 2nd hour. CONCLUSION: The 5-HT7 receptor is a potential defense mechanism in stopping fever and the antipyretic property of paracetamol is not due to the 5-HT7 receptor.

Ameliorative effect of gossypin against acute lung injury in experimental sepsis model of rats.

AIMS: Sepsis is a complex pathophysiological event involving systemic inflammatory response syndrome, multiple organ dysfunction syndrome and tissue damage such as acute lung injury (ALI). Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Antioxidant, antibacterial and antiinflammatory effects of gossypin (GOS)-like flavonoids have been shown and we have hypothesized that GOS have roles in sepsis induced inflammation of lungs. MAIN METHODS: Cecal ligation and puncture (CLP) induced sepsis model was induced in rats. Effects of GOS on oxidative stress, histopathology, nuclear factor kappa B (NF-κB), IL-6 positivity and NLRP3, HMGß1, TNF-α, NF-κB, IL-1ß mRNA expression levels were evaluated in lung tissues of the septic rats. KEY FINDINGS: GOS 20 (20 mg/kg) administration to septic rats decreased oxidative stress and supported antioxidant system in lungs. GOS administration also decreased the tissue NF-κB and IL-6 immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. HMGß1, NLRP3, NF-κB, IL-1ß, and TNF-α mRNA expression significantly increased in the CLP group. Both doses of GOS significantly reduced these mRNA expression as compared with the levels in the CLP group demonstrating its anti-inflammatory potential. SIGNIFICANCE: GOS administration, may represent a novel treatment for the prevention of lung damage occurred after sepsis induction. This effect of GOS might be related to its anti-inflammatory potential that result in decreased cytokine response and improved oxidative status.