Chlorogenic acid attenuates cisplatin-induced ovarian injury in rats.

The aim of this study was to determine the possible therapeutic effect of chlorogenic acid (CGA) on cisplatin (CDDP)-induced ovarian damage in rats. Rats were first exposed to CDDP (5 mg/kg) and then treated CGA (1.5 and 3 mg/kg) for three days. Oxidative stress (OS), inflammation and apoptosis markers were determined using spectrophotometric methods. Ovarian tissues were also evaluated histologically. The levels of OS, inflammation and apoptosis biomarkers increased by CDDP administration (p < 0.05). Treatments with CGA significantly alleviated these markers dose-dependently (p < 0.05). These data reveal that CGA may exert an ovoprotective effect by reducing pro-inflammatory mediators and enhancing antioxidant status in ovarian tissue.

Ethyl pyruvate attenuates cisplatin-induced ovarian injury in rats via activating Nrf2 pathway.

Although cisplatin (CDDP) is an antineoplastic drug widely used for the treatment of various tumors, its toxicity on the reproductive system is a concern for patients. Ethyl pyruvate (EP) possesses potent antioxidant and anti-inflammatory activities. The objective of this study was to evaluate the therapeutic potential of EP on CDDP-mediated ovotoxicity for the first time. Rats were exposed to CDDP (5 mg/kg) and then treated with two doses of EP (20 and 40 mg/kg) for 3 days. Serum fertility hormone markers were evaluated using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers were also determined. In addition, how CDDP affects the nuclear factor erythroid 2-associated factor 2 (Nrf2) pathway and the effect of EP on this situation were also addressed. EP improved CDDP-induced histopathological findings and restored decreasing levels of fertility hormones. EP treatment also reduced the levels of CDDP-mediated OS, inflammation, ERS and apoptosis. In addition, EP attenuated CDDP-induced suppression in the levels of Nrf2 and its target genes, including heme oxygenase-1, NAD(P)H quinone dehydrogenase-1, superoxide dismutase and glutathione peroxidase. Histological and biochemical results showed that EP can have therapeutic effects against CDDP-induced ovotoxicity with antioxidant, anti-inflammatory and Nrf2 activator activities.

The therapeutic effect of silibinin against 5-fluorouracil-induced ovarian toxicity in rats.

5-Fluorouracil (5-FU) is a fluoropyrimidine group antineoplastic drug with antimetabolite properties and ovotoxicity is one of the most important side effects. Silibinin (SLB) is a natural compound that is used worldwide and stands out with its antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the therapeutic effect of SLB in 5-FU-induced ovototoxicity using biochemical and histological analysis. This study was carried out in five main groups containing six rats in each group: control, SLB (5 mg/kg), 5-FU (100 mg/kg), 5-FU + SLB (2.5 mg/kg), and 5-FU + SLB (5 mg/kg). The levels of ovarian malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), catalase (CAT), 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), and caspase-3 were determined using spectrophotometric methods. Hematoxylin and eosin staining method was employed for histopathological examination. MDA, TOS, 8-OHdG, TNF-α, MPO, and caspase-3 levels in 5-FU group were significantly increased compared with the control group, while the levels of TAS, SOD, and CAT were decreased (p < 0.05). SLB treatments statistically significantly restored this damage in a dose-dependent manner (p < 0.05). Although vascular congestion, edema, hemorrhage, follicular degeneration, and leukocyte infiltration were significantly higher in the 5-FU group compared with the control group, SLB treatments also statistically significantly restored these damages (p < 0.05). In conclusion, SLB has a therapeutic effect on the ovarian damage induced by 5-FU via decreasing the levels of oxidative stress, inflammation, and apoptosis. It may be helpful to consider the usefulness of SLB as an adjuvant therapy to counteract the side effects of chemotherapy.

Ameliorative effect of gallic acid on cisplatin-induced ovarian toxicity in rats.

The aim of the present study was to evaluate the protective effect of gallic acid (GA) against cisplatin (CDDP)-induced ovarian toxicity, for the first time. The ovarian damage was generated with CDDP (5 mg/kg) intraperitoneally (i.p.) administration in rats. GA (2.5 and 5 mg/kg) were administered i.p. for 3 consecutive days. The study was carried out in 5 main groups containing 6 rats in each group: control, GA (5 mg/kg), CDDP, CDDP + GA (2.5 mg/kg) and CDDP + GA (5 mg/kg). The levels of ovarian malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), catalase (CAT), 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3 and tumor necrosis factor-alpha (TNF-α) were determined. Hematoxylin and eosin staining method was employed for the histopathological examination. In the CDDP group, it is determined that statistically significant decreasing in the levels of TAS and CAT, and increasing in the levels of MDA, TOS, OSI, 8-OHdG, caspase-3 and TNF-α (p < 0.05) compared with control group. GA administrations statistically significantly restored this damage (p < 0.05). Although vascular congestion, edema, hemorrhage, follicular degeneration and leukocyte infiltration were significantly higher in the CDDP group than in the control group, GA administrations statistically significantly restored these damages (p < 0.05). In conclusion, this study showed that GA prevented CDDP-induced ovarian damage with its antioxidant, anti-apoptotic and anti-inflammatory activities. More comprehensive studies are needed to see the underlying mechanisms.

The ameliorative effect of Primula vulgaris on cisplatin-induced nephrotoxicity in rats and quantification of its phenolic components using LC-ESI-MS/MS.

Cisplatin (CDDP) is an important chemotherapeutic agent, accumulation of which in kidney tissue causes nephrotoxicity and renal failure. The aim of this study was to evaluate, for the first time in the literature, the protective effect of dimethyl sulfoxide (DMSO) extract of Primula vulgaris leaf (PVE) against CDDP-induced nephrotoxicity in rats. The PVE content was characterized using liquid chromatography-mass spectrometry. Nephrotoxicity was induced with a single dose of CDDP (7.5 mg/kg). Thirty female Wistar-Albino rats were divided into five groups (control, DMSO, CDDP (7.5 mg/kg), CDDP + PVE (25 mg/kg), and CDDP + PVE (50 mg/kg)). Biochemical and histopathological analyses were then performed. Rutin, gallic acid, p-coumaric acid and protocatechuic acid were identified as major components of PVE. Total antioxidant status and glutathione (GSH) values increased significantly in the serum samples from the treatment group compared to the CDDP group, while blood urea nitrogen, creatinine, oxidative stress index, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), total oxidant status, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) values decreased significantly. GSH levels increased significantly in the treatment group compared to the CDDP group, while TNF-α, caspase-3, 8-OHdG, MDA levels and damage scores decreased significantly. In conclusion, PVE exhibited strong protective effects through its anti-apoptotic, antioxidant, and anti-inflammatory activities against nephrotoxicity and oxidative damage caused by CDDP in rats.

An Investigation of the Antiproliferative Effect of Rhododendron luteum Extract on Cervical Cancer (HeLa) Cells via Nrf2 Signaling Pathway.

The aim of the present study was to investigate the role of Rhododendron luteum extract (RLE) in the induction of Nrf2­related oxidative stress and endoplasmic reticulum (ER) stress in human cervical cancer (HeLa) cells. The antiproliferative effect of RLE on HeLa and fibroblast cells was determined using the MTT assay. The effects of RLE on the cell cycle, apoptosis, and production of reactive oxygen species (ROS) in HeLa cells were evaluated using fluorescent probes. The mRNA expression levels of Nrf2 [and its targets glutamate-cysteine ligase catalytic subunit (GCLC), and glucose-6-phosphate dehydrogenase (G6PD)], and C/EBP homologous protein (CHOP, an ER stress marker were determined using reverse transcription­quantitative polymerase chain reaction (RT-PCR). The results demonstrated that RLE exhibited a selective cytotoxic effect (2.9-fold) on HeLa cells compared to fibroblast cells. RLE arrested the cell cycle at the S phase, and induced apoptosis, ER stress, and ROS formation. In addition, RLE significantly suppressed the expression levels of Nrf2, GCLC and G6PD (0.65, 0.69, and 0.54-fold, respectively) and increased the expression of CHOP (4.48-fold) in HeLa cells at 72 h of treatment (p < 0.05). These results show that the antiproliferative effect of RLE occurs through the Nrf2 and ER stress pathways, and the results should now be supported by further in vivo studies.

p-Coumaric acid alleviates cisplatin-induced ovarian toxicity in rats.

OBJECTIVE: The therapeutic value of cisplatin (CDDP) as an anticancer drug is limited by its ovo-otoxicity. The effect of natural phenolic acids in the prevention of many diseases related to oxidative stress has been reported. Here, the ability of p-coumaric (pCA) acid, a member of phenolic acids, to protect rat ovary tissue against CDDP-induced oxidative stress was investigated. METHODS: The study was carried out in five main groups containing six rats in each group: control, pCA (4 mg/kg), CDDP, CDDP plus pCA (2 mg/kg), and CDDP plus pCA (4 mg/kg). The levels of ovarian malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), catalase (CAT), 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, and tumor necrosis factor-alpha (TNF-α) were determined. Hematoxylin and eosin staining method was employed for the histopathological examination. RESULTS: In the CDDP group, it is determined that statistically significant decreasing in the levels of TAS and CAT, and increasing in the levels of MDA, TOS, OSI, 8-OHdG, caspase-3, and TNF-α compared with control group (p < 0.05). pCA administration statistically significantly restored this damage in a dose-dependent manner (p < 0.05). Although vascular congestion, edema, hemorrhage, follicular degeneration, and leukocyte infiltration were significantly higher in the CDDP group than in the control group, pCA administrations statistically significantly restored these damages (p < 0.05). CONCLUSIONS: The data presented here indicate that pCA protects ovarian tissues of rats against CDDP-induced oxidative stress, inflammation, and apoptosis. It may be worthy to consider the usefulness of pCA as adjuvant therapy in cancer management.

Suppression of cisplatin-induced ovarian injury in rats by chrysin: an experimental study.

The aim of this study was to investigate the potential therapeutic efficacy of chrysin (CHS) against ovotoxicity caused by intraperitoneal administration of cisplatin (CDDP) in rats. In this experimental study, 24 female rats were randomly divided into four groups: control, CHS (2 mg/kg), CDDP (5 mg/kg) and CDDP (5 mg/kg) + CHS (2 mg/kg). The levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), interleukin-6 (IL-6) and myeloperoxidase (MPO) were determined in the ovarian tissues using spectrophotometric methods. In addition, the ovarian samples were evaluated histopathologically by hematoxylin&eosin staining. The results revealed that the levels of MDA, TOS, IL-6 and MPO significantly increased by CDDP administration compared with control group (p < 0.05). Also, it was found that CDDP significantly decreased TAS and SOD levels (p < 0.05). CHS ameliorated CDDP-induced the increased levels of MDA, TOS, IL-6, MPO and increased the levels of TAS and SOD significantly (p < 0.05). Histological findings also supported the therapeutic effect of CHS against CDDP-induced ovarian damage parameters. In conclusion, our results showed that CHS exhibits a therapeutic effect against CDDP-induced ovotoxicity and therefore the use of CHS after chemotherapy may improve the side effets of CDDP. IMPACT STATEMENTWhat is already known about this subject? Cisplatin (CDDP) is an effective and widely used chemotherapeutic agent to treat various malignancies, but its therapeutic use is limited due to dose-related tissue toxicity. Chrysin (CHS), a natural flavone, exhibits various beneficial activities, including antioxidant, anti-inflammatory and anticancer. There are increasing evidences in the literature that CHS reduces the toxicity of various chemotherapeutic agents, such as CDDP, doxorubicin and cyclophosphamide, in colon, kidney and liver tissues through its antioxidant and anti-inflammatory potential.What do the results of this study add? This study demonstrated that CHS can abolish CDDP-induced in vivo ovarian injury by decreasing MDA, TOS, IL-6 and MPO levels and increasing SOD and TAS levels through its antioxidant and anti-inflammatory potential.What are the implications of these findings for clinical practice and/or further research? This study revealed the therapeutic potential of CHS against CDDP-induced acute ovotoxicity, for the first time. Further pre-clinical studies are necessary to prove the beneficial effect of CHS on the prevention of CDDP-induced ovarian toxicity.

Effect of Turkish Propolis on miRNA Expression, Cell Cycle, and Apoptosis in Human Breast Cancer (MCF-7) Cells.

Enriched in flavonoid compounds, phenol acids, and terpene derivatives, propolis has been shown to regulate apoptosis signaling pathways and alter the expression of microRNAs (miRNAs). In the present study, it has been aimed to examine the effects of Turkish propolis on miRNA levels of breast cancer (MCF-7) cells, and its relationship with cell proliferation and apoptosis. Cytotoxic activity of ethanolic propolis extract (EEP) was evaluated using MTT assay. Mechanisms involved in the cytotoxic action of Turkish propolis in MCF-7 cells were investigated with regard to apoptosis and cell cycle using flow cytometry and western blot. Mitochondrial membrane potential (MMP) were evaluated by spectrofluorometric method. miRNA levels were detected by qRT-PCR method. EEP exhibited selective toxicity against MCF-7 cells compared to normal fibroblast cells. EEP increased the cell cycle arrest at the G1 phase. EEP elevated the apoptotic cell death through increasing pro-apoptotic protein levels (p21, Bax, p53, p53-Ser46, and p53-Ser15), decreasing MMP and altering the expression levels of specific tumor suppressors (miR-34, miR-15a, and miR-16-5p) and oncogenic (miR-21) miRNAs. These data support that Turkish propolis may be evaluated as a potential natural agent for new anticancer drugs in future.

Rosa canina Extract has Antiproliferative and Proapoptotic Effects on Human Lung and Prostate Cancer Cells.

Although several studies have investigated the cytotoxic effects of different Rosa species, there has been only limited research into the cytotoxic effect of Rosa canina. The purpose of this research was to evaluate the antioxidant properties, phenolic characterization, and cytotoxic effects of R. canina on human lung (A549) and prostate (PC-3) cancer cells and the possible mechanisms involved. The antioxidant properties and phenolic characterization of the extract were determined using spectrophotometric methods and RP-HPLC, respectively. The cytotoxic activity of the extract was determined using the MTT assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis, the cell cycle, mitochondrial membrane potential (MMP), and caspase activity using fluorometric and luminometric methods. The TPC value of the extract was 58.97 ± 2.22 mg gallic acid equivalents per gram sample, and ascorbic acid and p-coumaric acid were detected as major phenolics in the extract. R. canina extract exhibited a selective cytotoxic effect on A549 and PC-3 cells compared to normal fibroblast cells. The extract induced cell cycle arrest at the G1 phase and apoptosis via reduced MMP and increased caspase activity in these cells. Phytomedical applications of R. canina may represent promising approaches in the treatment of cancer.

Dorycnium pentaphyllum Extract Has Antiproliferative Effect on Human Cervix and Colon Cancer Cells.

Although several studies have investigated the cytotoxic effects of different Fabaceae species, limited researches have been conducted on the cytotoxic effect of Dorycnium pentaphyllum. The aim of this study was to evaluate the phenolic characterization and the cytotoxic effect of D. pentaphyllum on human cervix (HeLa) and colon (WiDr) cancer cells and the possible mechanisms involved. Total phenolic content (TPC) and phenolic characterization of the extract were investigated using the Folin-Cioceltau method and RP-HPLC, respectively. The cytotoxic effect of the extract was evaluated using the MTT assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis and the cell cycle using flow cytometry, while mitochondrial membrane potential (MMP) was investigated using the fluorometric method. The TPC value of the extract was 141.2 ± 0.8 mg gallic acid equivalent per g sample, and quercetin was detected as major phenolics. D. pentaphyllum extract exhibited a selective cytotoxic effect on HeLa and WiDr cells compared to normal fibroblast and colon cells, respectively. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in these cells. Further studies may be useful in developing a natural product based new generation pharmacological agent.

Berberine inhibits the ischemia-reperfusion induced testicular injury through decreasing oxidative stress.

PURPOSE: The aim of this study was to investigate the effect of berberine (BBR) on oxidative stress in an experimental testicular I/R injury model. METHODS: Eighteen rats were divided into three groups: control group, torsion-detorsion (T/D) group, and BBR + T/D group. In the pre-treatment of the BBR group, 200 mg/kg BBR was given intraperitoneally 30 min before detorsion. Tissue malondialdehyde (MDA), total oxidant status (TOS), and total antioxidant status (TAS) levels were determined using colorimetric methods. Histological evaluation of the tissue samples was evaluated using hematoxylin-eosin staining. RESULTS: In T/D group, tissue MDA, TOS, and oxidative stress index levels were higher than control group. These increases were significantly reversed with BBR pre-treatment. Although Johnsen scores were lower in T/D group than the control group, BBR pre-treatment recovered the Johnsen scores. CONCLUSION: These results suggest that BBR can inhibit I/R-induced testicular injury by suppressing oxidative stress. Further studies may prove that BBR is a useful agent as an adjunctive treatment in surgical repair in human cases.

Dimethyl Sulfoxide Extract of Dianthus carmelitarum Induces S Phase Arrest and Apoptosis in Human Colon Cancer Cells.

Although several studies have investigated the cytotoxic effects of different Dianthus species, there has been only limited research into the cytotoxic effect of Dianthus carmelitarum. The purpose of this research was to evaluate the phenolic characterization and the cytotoxic effect of D. carmelitarum on human colon cancer (WiDr) cells and the possible mechanisms involved. Total polyphenolic contents (TPC) and phenolic characterization of the extract were evaluated using the Folin-Cioceltau method and reversed-phase high performance liquid chromatography (RP-HPLC), respectively. The cytotoxic activity of the extract was determined using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis and the cell cycle using flow cytometry, while mitochondrial membrane potential (MMP) was investigated using the fluorometric method. The TPC value of the extract was 784.8 ± 40.3 mg gallic acid equivalent per 100 g sample, and sinapic acid and benzoic acid were detected as major phenolics in the extract. D. carmelitarum extract exhibited a selective cytotoxic effect (3.6-fold) on WiDr cells compared to normal colon cells. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in WiDr cells. Phytomedical and nutraceutical applications of D. carmelitarum may represent promising approaches in the treatment of cancer.

Blood levels of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha and cognitive functions in patients with obsessive compulsive disorder.

BACKGROUND: Cognitive dysfunction and immune system disorders are two actual issues for the patients with Obsessive Compulsive Disorder (OCD). The cognitive dysfunctions have been considered to substantial part of clinical phenomenon of OCD but exploration of various etiopathogenesis of cognitive dysfunction is needed. Immune dysfuncion has been implicated to be important part of pathopysiology of OCD and different lines of evidence suggests immune abnormalities in OCD. But whether these immune changes are traits of disease or secondary to clinical burden of the disease such as cognitive dysfunctions has not been determined. Data regarding relation between the cognitive dysfunctions and immune system disorders in OCD is unsatisfied. In this study we aimed to investigate the relation of blood levels of interleukin 1-beta (IL-1ß), interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α) with various neurocognitive functions in patients with OCD in comparison with its autogenous/reactive subtypes and healthy controls. Further exploration of the effects of various clinical variables on cognitive functioning in patients with OCD and additional investigation of whether the cognitive dysfunction associated with this disorder differs from or overlap with that in other anxiety disorders are needed. METHODS: Forty-two patient with OCD and 45 age, sex and educational level matched healthy control were enrolled in the study. The diagnosis of OCD was made with Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Yale- Brown Obsessive-Compulsive Scale, Beck Anxiety and Depression Inventory Scales were administered. Neuropsychological test battery including Wisconsin Card Sorting Test (WCST), Trail Making Test A and B (TMT-A, TMT-B) were used for evaluation of the patients and healthy control. The plasma of interleukin-1beta (IL-1ß), interleukin-6 (IL-6), Tumor Necrosis Factor-Alpha (TNF-α) of both groups were measured with ELISA kits. RESULTS: Blood levels of IL-1ß, IL-6 and TNF-α were significantly higher in patients with OCD than the healthy control. There was significant difference in IL-1ß, IL-6 but not in TNF-α between autogenous/reactive subtypes and healthy controls. TNF-α is positively correlated with TMT-A, TMT-B and Stroop Test Part 5, negatively correlated with immediate memory, verbal learning, interference effect, immediate recall, delayed recall and recognition in RAVLT. IL-1ß was positively correlated with TMT-A score. IL-6 was positively correlated with scores of TMT-A, TMT-B. IL-6 was negatively correlated with immediate memory, verbal learning, interference effect, immediate recall and delayed recall in RAVLT, positively correlated with number of perseverative error and negatively correlated with the number of categories completed in WCST. CONCLUSION: This is the first study that investigates the relation of IL- 1ß, IL-6 and TNF-α levels with cognitive functions in OCD. There may be a contribution to pathogenesis of OCD and subtypes then new choices for treatment might be developed. Moreover, uncovering the effect of cytokine blood levels on cognitive function of OCD, new data concerning etiopathogenesis and further treatment choices can be gained.

The value of endoplasmic reticulum stress markers (GRP78 and CHOP) in the diagnosis of acute mesenteric ischemia.

AIM: To evaluate levels of the endoplasmic reticulum (ER) stress markers GRP78 and CHOP in acute mesenteric ischemia (AMI) and to examine relations with degrees of AMI-related intestinal injury. MATERIALS AND METHODS: Twenty-four rats were divided into four groups. Group I and Group III represented the control groups, from which blood and tissue specimens were collected 2 and 6 h after laparotomy without superior mesenteric artery (SMA) ligation. Group II and Group IV constituted the ischemia groups, from which blood and tissue specimens were collected 2 and 6 h after SMA ligation. The ER stress markers GRP78 and CHOP, total oxidant status (TOS), total antioxidant status (TAS), and the oxidative stress index (OSI) were investigated in each group. Ileum specimens were assessed in terms of ischemic injury, and appropriate comparisons were performed. RESULTS: Significantly higher GRP78, CHOP, TOS, and TAS values were determined in the ischemia groups (groups II and IV) compared to the control groups (groups I and III). This elevation was greater in the 6 h ischemia group, the group exposed to the greatest ischemic injury (Group IV). Significant and powerful correlation was present between histopathological damage and levels of the ER stress markers and oxidative markers. CONCLUSION: According to our results, ER stress markers (GRP78 and CHOP) increase significantly following ischemic injury. This elevation has the potential to be used diagnostically and also in prognostic terms due to the powerful correlation it exhibits with AMI-related ischemic injury.

Biotin deficiency in hyperemesis gravidarum.

The aim of this study was to determine the serum biotin levels in patients with hyperemesis gravidarum (HG). Ninety pregnant women with HG (mild (n = 30), moderate (n = 30) and severe (n = 30)), and 80 pregnant women without HG were included for this study. In both groups, serum biotin levels were measured. There were no statistically significant differences in demographic and clinical characteristics between the HG groups and the control group except for PUQE scores. Serum biotin levels in all hyperemesis gravidarum groups were statistically significantly lower than control group. Negative statistically significant correlation between hyperemesis gravidarum severity and serum biotin levels was noted. This is the first study that shows low serum biotin levels in women with hyperemesis gravidarum. Impact statement What is already known on this subject? Almost 80% of pregnant women have nausea and vomiting. If nausea and vomiting became severe and the symptoms combined with weight loss and ketonuria; the diagnosis should be hyperemesis gravidarum (HG). The etiopathogenetic factors of this unwanted condition have not been exactly known. Biotin is an essential water-soluble vitamin. Biotin catabolism increases in pregnancy. Marginal biotin deficiency occurs in approximately 50% of the gestations despite the "normal" biotin intake on the diet. What do the results of this study add? Current study results elucidated that serum biotin levels were lower in HG cases compared to non HG cases. This study is the first study that reports the association between low serum level of biotin and HG. What are the implications of these findings for clinical practice and/or further research? Further research is needed to show the importance of biotin supplementation in women with hyperemesis gravidarum.

Is ovarian volume a good predictor to determine metabolic syndrome development in polycystic ovary patients.

The aim of this study was to investigate the findings of ultrasound that could predict the metabolic syndrome (MetS) which may develop in polycystic ovary syndrome (PCOS) patients. A total of 96 consecutive PCOS patients, who were scheduled for any gynaecologic examination from January 2015 to January 2016 and who were eligible for the study, were prospectively enrolled in it. About 15.6% of PCOS patients were diagnosed with MetS. The mean age of the MetS patients and the non-MetS patients were 25.8 and 23.3, respectively (p = .056). The mean ovary volume was calculated as being 11.7 mL in the MetS patients and as 9.6 mL in the non-MetS patients (p = .027). The Doppler and the other ultrasound findings were compared between the groups and no significant difference was observed. When a receiver operator characteristic curve analysis was conducted for the ovarian volume to predict MetS, the area under curve was 0.67 (95% CI, 0.52-0.81). The optimum cut-off point for OV was determined at 9.2 mL, with the sensitivity and specificity of 80.0% and 50.6%, respectively. The risk of developing MetS appears to be higher in PCOS patients with higher OV values. Impact statement What is already known on this subject? Metabolic syndrome is not rare in PCOS patients. There are several studies to specify a predictor for MetS development in PCOS. Most are biochemical predictors, such as hyperandrogenemia, a visceral adiposity index, lipid accumulation product, adiponectin index and a leptin-to-adiponectin ratio. What do the results of this study add? The ultrasound markers to predict the insulin resistance at PCOS is already used, but are new for predicting MetS. What are the implications of these findings for clinical practice and/or further research? Ultrasound is an available tool in most clinics and predicting MetS is important for the future health problems of PCOS patients.

Effects of 900-MHz electromagnetic fields exposure throughout middle/late adolescence on the kidney morphology and biochemistry of the female rat.

The effect of the electromagnetic field (EMF) established when cell phones are in use on human health, and particularly the head, has been the subject of major scientific research. Phones are usually carried near the lumbar region when not in use, and the kidneys will also inevitably be affected by such fields. We investigated the effects on the kidneys of female rats exposed to a continuous 900-megahertz (MHz) EMF for 1 h daily in mid-late adolescence. Control, sham, and EMF groups were established. The EMF was applied to the application group rats daily on postnatal days 35-59. A pseudo-megahertz effect was applied to sham group rats. All animals were euthanized on postnatal day 60. Right kidney tissues were subjected to routine procedures. Malondialdehyde, total antioxidant status, and total oxidant status (TOS) were investigated in left kidneys, and the oxidative stress index (OSI) was also calculated from these. Histopathological analysis revealed no pathology in either the control or sham groups. However, findings including hemorrhage in glomerulus, vacuolization and irregularity in the proximal and distal tubular epithelium, diffuse glomerular degeneration and edema, occasional degeneration in Bowman capsules, hemorrhage in the medullary region, disturbed nucleus location and morphology, and tubular edema in the cortex were observed in the EMF groups. TOS and OSI values were lower in the EMF group (9.4316 ± 1.0211 and 0.8461 ± 0.0826, respectively) and the sham group (8.2171 ± 0.6437 and 0.7358 ± 0.0545, respectively) than in the control group (11.1522 ± 1.3389 and 1.0085 ± 0.1174, respectively) ( p < 0.05). In conclusion, exposure to a continuous 900-MHz EMF for 1 h daily during middle and late adolescence may cause various changes in the female rat kidney at postnatal day 60.

A Comparison of the Effects of Grayanotoxin-Containing Honey (Mad Honey), Normal Honey, and Propolis on Fracture Healing.

OBJECTIVES: Delayed healing and non-union of fractures have a significant effect upon patient morbidity. Studies have therefore largely concentrated on accelerating fracture healing. This study was intended to compare the effect of "mad honey" and propolis on fracture healing using radiological and histopathological analysis. SUBJECTS AND METHODS: Femur fracture was surgically performed on 48 rats, followed by fixation. Animals were then divided into 8 groups: 2 control groups (15- and 30-day) and 6 treatment groups (15- and 30-day normal honey, 15- and 30-day "mad honey," and 15- and 30-day propolis). Rats were sacrificed at the end of these periods, and radiological and histological examinations were performed. RESULTS: Radiological healing in the propolis group after 15-day therapy was statistically better than in the control (p = 0.004) and normal honey (p = 0.006) groups. After 30-day therapy, healing in the propolis group (p = 0.005) and grayanotoxin-containing "mad honey" group (p = 0.007) were significantly better than in the control group. Histologically, there was a statistically significant difference between the 15-day propolis group and the other groups (control, honey, mad honey: p = 0.003, p = 0.003, and p = 0.002, respectively). We also found a statistically significant difference when the 30-day propolis group (p = 0.005) and "mad honey" group (p = 0.007) were compared to the control group. CONCLUSIONS: This study shows that grayanotoxin-containing "mad honey" and propolis can accelerate fracture healing.

Peripapillary retinal nerve fiber layer and ganglion cell-inner plexiform layer thickness in adult-onset familial Mediterranean fever.

OBJECTIVE: The purpose of the present study was to evaluate the thickness of the peripapillary retinal nerve fiber layer (RNFL) and retinal ganglion cell-inner plexiform layer (GCIPL) in adult-onset familial Mediterranean fever (FMF). METHODS: Forty two adult-onset FMF patients and forty two healthy controls were included in the present study. Detailed ocular examination was performed, and then the thickness of the peripapillary RNFL and GCIPL was measured by Spectral domain optical coherence tomography. The patients were divided into two groups according to their disease severity score, M694V gene mutation, colchicine dosage used per day, colchicine usage time period and number of FMF attacks per year. RESULTS: There were no statistically significant differences in peripapillary RNFL and retinal GCIPL thickness in patients with adult-onset FMF and controls. CONCLUSION: According to our study, it looks like that neither adult-onset FMF nor colchicine has any effect on the RNFL and GCIPL thicknesses. Further studies with a large sample size are needed.