Cannabinoid compounds in combination with curcumin and piperine display an anti-tumorigenic effect against colon cancer cells.

Currently, use of cannabinoids is limited to improve adverse effects of chemotherapy and their palliative administration during treatment is curiously concomitant with improved prognosis and regressed progression in patients with different tumor types. Although, non-psychoactive cannabidiol (CBD) and cannabigerol (CBG) display antineoplastic effects by repressing tumor growth and angiogenesis both in cell line and animal models, their use as chemotherapeutic agents is awaiting further investigation. Both clinical and epidemiological evidence supported by experimental findings suggest that micronutrients such as curcumin and piperine may present a safer strategy in preventing tumorigenesis and its recurrence. Recent studies demonstrated that piperine potentiates curcumin's inhibitory effect on tumor progression via enhancing its delivery and therapeutic activity. In this study, we investigated a plausible therapeutic synergism of a triple combination of CBD/CBG, curcumin, and piperine in the colon adenocarcinoma using HCT116 and HT29 cell lines. Potential synergistic effects of various combinations including these compounds were tested by measuring cancer cell proliferation and apoptosis. Our findings revealed that different genetic backgrounds of HCT116 and HT29 cell lines resulted in divergent responses to the combination treatments. Triple treatment showed synergism in terms of exhibiting anti-tumorigenic effects by activating the Hippo YAP signaling pathway in the HCT116 cell line.

Impact of silencing eEF2K expression on the malignant properties of chordoma.

BACKGROUND: Eukaryotic elongation factor 2 kinase (eukaryotic elongation factor 2 kinase, eEF2K) is a calcium calmodulin dependent protein kinase that keeps the highest energy consuming cellular process of protein synthesis under check through negative regulation. eEF2K pauses global protein synthesis rates at the translational elongation step by phosphorylating its only kown substrate elongation factor 2 (eEF2), a unique translocase activity in ekaryotic cells enabling the polypeptide chain elongation. Therefore, eEF2K is thought to preserve cellular energy pools particularly upon acute development of cellular stress conditions such as nutrient deprivation, hypoxia, or infections. Recently, high expression of this enzyme has been associated with poor prognosis in an array of solid tumor types. Therefore, in a growing number of studies tremendous effort is being directed to the development of treatment methods aiming to suppress eEF2K as a novel therapeutic approach in the fight against cancer. METHODS: In our study, we aimed to investigate the changes in the tumorigenicity of chordoma cells in presence of gene silencing for eEF2K. Taking a transient gene silencing approach using siRNA particles, eEF2K gene expression was suppressed in chordoma cells. RESULTS: Silencing eEF2K expression was associated with a slight increase in cellular proliferation and a decrease in death rates. Furthermore, no alteration in the sensitivity of chordoma cells to chemotherapy was detected in response to the decrease in eEF2K expression which intriguingly promoted suppression of cell migratory and invasion related properties. CONCLUSION: Our findings indicate that the loss of eEF2K expression in chordoma cell lines results in the reduction of metastatic capacity.

A Novel Virtue in Stem Cell Research: Exosomes and Their Role in Differentiation.

In the past decade a number of different stem cell types have entered the clinical applications increasingly as a therapeutic option, due to their tissue maintenance capacity at the site where they localize. Although it was initially thought that conferral of resilience to damaged tissue largely depends on the stem cells themselves through orchestration of signaling among the local epithelial and immune systems at the injury site, recent findings point out that the remarkable regenerative capacity of stem cells is rather due to their nanovesicular products that emerge as the new active players of tissue repair processes. Among these extracellular vesicles exosomes generated particularly by stem cells have been receiving a substantial interest both in the fields of stem cell biology and extracellular vesicles. In this chapter fundamental facts about stem cell biology, biogenesis of extracellular vesicles and exosomes, their structure, and function are summarized. Moreover, properties of both tumor-derived exosomes as well as those derived from stem cells are discussed relatively in-depth in terms of their influence on proximal and distal tissue physiology. Last but not the least, among countless studies in an exploding field, we summarize those that attempt to unravel the complex signaling networks through which stem cell-derived exosomes alter the fate of differentiating stem cells as well as the molecular make-up of exosomes released from differentiating stem cells by conducting thorough proteomic and genomic analyses with the ultimate goal of identifying effector gene products mediating exosomal cues in stem cell biology.

Hyperemesis gravidarum and its relation with maternal body fat composition.

The objective of this study was to determine if maternal body fat composition and body mass index were associated with hyperemesis gravidarum (HG) in the first trimester of pregnancy. Healthy pregnant women (n = 30) without nausea and vomiting (control group) and women with HG (n = 54; study group), all with singleton pregnancy at 6-14 weeks gestational age, were included. Body mass index was measured before and during pregnancy. Visceral adipose tissue (VAT) and subcutaneous fat thickness were measured during pregnancy. Comparison of the groups revealed that VAT and pre-pregnancy body mass index but not subcutaneous fat thickness were significantly higher in the HG group versus controls. VAT and pre-pregnancy body mass index predicted 83.8% and 67.1% of HG cases, respectively. VAT and pre-pregnancy body mass index were correlated with the development of hyperemesis gravidrum and hence could be considered as predictive markers for HG.

Sleep deprivation in the last trimester of pregnancy and inadequate vitamin D: Is there a relationship?

BACKGROUND: Disturbed sleep is a significant health issue for pregnant women. Inadequate vitamin D intake is common among pregnant women and can affect many bodily systems. The purpose of this cross-sectional study was to test the hypothesis that serum vitamin D levels are low in pregnant women who have poor sleep quality in their last trimester. METHODS: We enrolled 92 pregnant women who were admitted to the Maternity Clinic of Turgut Ozal University (Ankara, Turkey) in their last trimester. Venous blood sampling was performed to determine serum 25-hydroxyvitamin D levels. Sleep quality was measured by the Pittsburgh Sleep Questionnaire. The Student t test and Chi-square test were used to evaluate the relationships between variables. Logistic regression analysis was used to identify independent predictors of the vitamin D level. RESULTS: The median score of the Pittsburgh Sleep Questionnaire was 6.2 ± 3.3 (range, 1-17). We determined that 43.5% (40) of participants had poor sleep quality. The mean number of sleep hours at night was 8.6 ± 1 hours (range, 6.30-11 hours), and the mean sleep latency was 20.3 ± 12.7 minutes (range, 5-60 minutes). Vitamin D levels were measured for 87 participants; the median serum level of 25 (OH) vitamin D was 22.9 ± 16.2 ng/mL (range, 4.9-99 ng/mL). Among all patients, we did not determine any significance between the vitamin D-deficient group and the non-vitamin D-deficient group with regard to the Pittsburgh Sleep Questionnaire Inventory (PSQI) total score and subcomponents scores of the questionnaire (p > 0.05). Among 37 patients with poor sleep quality and for whom the vitamin D level was measured, 56.8% (21) women had vitamin D deficiency, and 81% (30) women had vitamin D insufficiency. However, we did not find any significance between participants with poor sleep and participants with good sleep quality with regard to age, occupational status, relationship with her partner, prepregnancy body mass index (BMI), weight gain during pregnancy, being primiparus, length of labor, and mode of delivery. Our findings further showed that being in a low income family was associated with poor sleep quality. CONCLUSION: Inadequate vitamin D and poor sleep quality are prevalent in pregnant women, but low levels of vitamin D are not associated with poor sleep quality. Further studies with larger sample sizes and studies that include preterm deliveries and special sleep disorders should be performed to understand this issue better.

Effect of combined oral contraceptive use on serum 25-hydroxy vitamin D levels and ultrasound parameters in patients with polycystic ovary syndrome.

PURPOSE: To investigate if there is an effect of combined oral contraceptive (COC) use on serum 25-hydroxy vitamin D [25(OH)D] levels in patients with polycystic ovary syndrome (PCOS). METHODS: PCOS was defined by the 2003 Rotterdam criteria. All patients with PCOS were treated with a COC containing 0.035 mg ethinylestradiol and 2 mg cyproterone acetate for 6 months. Serum 25(OH)D levels, HOMA-IR, ovarian volume and antral follicule count were measured before and after the treatment. RESULTS: The median 25(OH)D levels were 9.40 (range 4.40-24.50) µg/l and 7.00 (5.00-13.50) µg/l before and after COC use, respectively. Serum 25(OH)D levels decreased after the treatment; however, the difference was not statistically significant (p = 0.055). CONCLUSION: This study seems to be the first prospective trial revealing the effect of COC use on serum 25(OH)D levels in women with PCOS. Although the decrease in serum 25(OH)D levels in patients with PCOS with the use of COC alone, did not reach to statistically significance level after 6 months treatment with COC.

Is There a Relationship Between Pelvic Organ Prolapse and Tissue Fibrillin-1 Levels?

PURPOSE: Pelvic organ prolapse is a multifactorial disorder in which extracellular matrix defects are implicated. Fibrillin-1 level is reduced in stress urinary incontinence. In Marfan syndrome, which is associated with mutations in Fibrillin-1, pelvic floor disorders are commonly observed. We hypothesize that Fibrillin-1 gene expression is altered in pelvic organ prolapse. METHODS: Thirty women undergoing colporrhaphy or hysterectomy because of cystocele, rectocele, cystorectocele, or uterine prolapse were assigned to a pelvic prolapse study group, and thirty women undergone hysterectomy for nonpelvic prolapse conditions were assigned to a control group. Real-time polymerase chain reaction was conducted on vaginal tissue samples to measure the expression of Fibrillin-1. Expression levels were compared between study and control groups by Mann-Whitney U test with Bonferroni revision. RESULTS: Fibrillin-1 gene expression was not significantly lower in the study group than in the control group. Similarly, no significant correlation between Fibrillin-1 levels and grade of pelvic prolapse was found. Age over 40 years (P=0.018) and menopause (P=0.027) were both associated with reduced Fibrillin-1 levels in the pelvic prolapse group, whereas the delivery of babies weighing over 3,500 g at birth was associated with increased Fibrillin-1 expression (P=0.006). CONCLUSIONS: The results did not indicate a significant reduction in Fibrillin-1 gene expression in pelvic prolapse disorders; however, reduced Fibrillin-1 may contribute to increased pelvic organ prolapse risk with age and menopause. Increased Fibrillin-1 gene expression may be a compensatory mechanism in cases of delivery of babies with high birth weight. Further studies are needed for a better understanding of these observations.

Effects of curcumin on ovarian ischemia-reperfusion injury in a rat model.

Ischemia-reperfusion injury is a significant problem following reperfusion treatment for ovarian torsion. It is generally caused by reactive oxygen species-induced damage. Antioxidant agents, such as curcumin, may protect ovaries from this adverse effect. The aim of the present randomized, controlled study was to evaluate the short-term protective effect of curcumin on a rat model of ovarian ischemia-reperfusion injury. A total of 30 female Wistar albino rats, weighing 160-230 g, were divided into 2 groups depending upon the time of unilateral, left ovary ischemia/reperfusion (group 1, 2 h ischemia/2 h reperfusion and group 2, 4 h ischemia/4 h reperfusion). These groups were subdivided into 3 subgroups (sham, control and curcumin). The sham subgroups were not subjected to ischemia/reperfusion. Control and curcumin subgroups were performed under ischemia for 2 h plus 2 h reperfusion or 4 h ischemia plus 4 h reperfusion. Curcumin, 200 mg/kg, was intraperitoneally administered simultaneously with reperfusion to the curcumin subgroups. Serum nitric oxide (NO), NO synthase (NOS), xanthine oxidase (XO), total antioxidant status (TAS), total oxidant status (TOS) and histological scores were measured and compared between subgroups. For group 1, no significant differences were observed between NO, NOS, XO, TAS or TOS. The left ovary histological grade was significantly higher in the control and curcumin subgroups compared with the sham subgroup (P=0.036). For group 2, TOS was significantly higher in the control group compared with the sham and curcumin groups (P=0.023). However, TAS was also significantly higher in the control subgroup compared with the other 2 subgroups (P=0.005). Left ovary histological grade was significantly higher in the control and curcumin subgroups compared with the sham subgroup (P=0.038). No significant differences were observed between NO, NOS or XO between the group 2 subgroups. The results showed that curcumin exerted no major significant protective effect on ischemia-reperfusion injury in the rat ovary.

Gut satiety hormones and hyperemesis gravidarum.

UNLABELLED: Hyperemesis gravidarum (HG) is described as unexplained excessive nausea and vomiting during pregnancy. Some gut hormones that regulate appetite may have important role in etiopathogenesis of HG and weight changes during pregnancy. In this study, levels of gut satiety hormones were evaluated in pregnant women with HG. METHODS: This prospective case-control study was conducted in 30 women with HG and 30 healthy pregnant women without symptoms of HG. Fasting venous blood samples were taken from all subjects for measurement of plasma gut hormone levels; obestatin (pg/mL), peptide YY (PYY), pancreatic polypeptide (PP) and cholecystokinin (CCK). RESULTS: Plasma PYY and PP levels were significantly higher in HG group. The most important parameter in diagnosis of HG was plasma PP level. Simple use of PP level led to the diagnosis 91.1 % of HG cases correctly. The single most important parameter in the prediction of HG was also PP level. CONCLUSION: Anorexigenic gut hormones might have important role in etiopathogenesis of hyperemesis gravidarum and weight changes during pregnancy.

Effect of Hypericum perforatum on intraperitoneal adhesion formation in rats.

INTRODUCTION: The aim of this study was to evaluate the efficacy of Hypericum perforatum for prevention of adhesion formation in rats. MATERIAL AND METHODS: Twenty-four female wistar rats underwent left uterine horn adhesion model. Rats were randomised into 4 groups. Group 1 (Control): Closure of abdominal incision without any agent administration. Group 2: Closure of incision after administration of intraperitoneal (i.p.) Ringer's lactate solution. Group 3: Closure of incision after administration of i.p. olive oil (diluent of H. perforatum). Group 4: Hypericum perforatum extract (Ecodab(®)) was administered i.p. before the closure of incision. Fourteen days later, relaparatomy was performed and surgical adhesion scores, inflammation and fibrosis scores were noted. Groups were compared according to these scores. RESULTS: There was statistical significant difference between ringer's lactate group and olive oil group according to surgical adhesion score (p = 0.009). However, groups were not different according to inflammation and fibrosis scores (p > 0.05). CONCLUSIONS: Despite antiinflammatory, antioxidants and antimicrobial properties of H. perforatum, our results revealed no positive effect of H. perforatum on the prevention of intraperitoneal adhesion formation.

Does vitamin E prevent tubal damage caused by smoking? A light microscopy and animal study.

OBJECTIVE: To assess the histomorphological effects of smoking on the cilia of fallopian tubes in mice and the effect of vitamin E on the negative effects of smoke. STUDY DESIGN: Eighteen 12-14 week-old Swiss albino type female mice were randomly divided into three groups, each consisting of six mice: Group A: control group; Group B: mice exposed to cigarette smoke; Group C: mice exposed to cigarette smoke together with vitamin E. Groups B and C were exposed to cigarette smoke for 10 weeks. After 10 weeks, tubal excision was performed in all animals. Histopathologic examination of excised tubal tissue was conducted under light microscopy. RESULTS: The number of cilia was significantly lower in Group B. Although not statistically significant, the median number of cilia in Group C was measured to be higher than in Group B but lower than in Group A. CONCLUSION: Based on the results, it can be concluded that smoking decreases tubal cilia numbers. Supplementation by vitamin E may treat or at least help to slow down the decrease in number of cilia caused by smoking; therefore it could be used therapeutically in the treatment of smoking-related tubal damage.

Acne severity and the Global Acne Grading System in polycystic ovary syndrome.

OBJECTIVE: To evaluate the association between acne, quantified by the Global Acne Grading System (GAGS), and abnormal clinical and laboratory markers of androgen excess in patients with polycystic ovary syndrome (PCOS). METHODS: The retrospective study included 133 patients with PCOS. Acne severity was quantified with the GAGS score, alopecia was graded with the Ludwig classification, and hirsutism was quantified with a modified Ferriman-Gallwey (FG) score. RESULTS: The mean GAGS score was significantly greater in younger women, those with a lower BMI, and those with a higher FG score. There was no relation between the mean GAGS score and waist circumference, waist/hip ratio, androgen hormone levels (free testosterone, total testosterone, or dehydroepiandrosterone sulfate), sex-hormone-binding globulin level, or menstrual irregularity. Alopecia was significantly associated with an increased waist/hip ratio; there was no relation between alopecia and age, waist circumference, body mass index, FG score, androgen hormone levels, or menstrual irregularity. A weak positive correlation was observed between the GAGS and FG scores. CONCLUSION: The GAGS may provide more precise and comprehensive information about acne severity in obese or hirsute patients with PCOS because this grading system includes evaluation of the type (comedones, papules, pustules, nodules) and location (anatomic area) of acne lesions.

Comparison of advanced stage mucinous epithelial ovarian cancer and serous epithelial ovarian cancer with regard to chemosensitivity and survival outcome: a matched case-control study.

OBJECTIVE: The aim of this study was to compare clinicopathologic characteristics, surgery outcomes and survival outcomes of patients with stage III and IV mucinous epithelial ovarian cancer (mEOC) and serous epithelial ovarian carcinoma (sEOC). METHODS: Patients who had surgery for advanced stage (III or IV) mEOC were evaluated retrospectively and defined as the study group. Women with sEOC who were matched for age and stage of disease were randomly chosen from the database and defined as the control group. The baseline disease characteristics of patients and platinum-based chemotherapy efficacy (response rate, progression-free survival and overall survival [OS]) were compared. RESULTS: A total of 138 women were included in the study: 50 women in the mEOC group and 88 in the sEOC group. Patients in the mEOC group had significantly less grade 3 tumors and CA-125 levels and higher rate of para-aortic and pelvic lymph node metastasis. Patients in the mEOC group had significantly less platinum sensitive disease (57.9% vs. 70.8%; p=0.03) and had significantly poorer OS outcome when compared to the sEOC group (p=0.001). The risk of death for mEOC patients was significantly higher than for sEOC patients (hazard ratio, 2.14; 95% confidence interval, 1.34 to 3.42). CONCLUSION: Advanced stage mEOC patients have more platinum resistance disease and poorer survival outcome when compared to advanced stage sEOC. Therefore, novel chemotherapy strategies are warranted to improve survival outcome in patients with mEOC.

Antiadhesive role of human amniotic fluid on peritoneal adhesion formation in a rat model. Experimental study.

OBJECTIVE: To determine the role of human amniotic fluid (HAF) in preventing or reducing postoperative adhesions. STUDY DESIGN: Uterine horn adhesion model was carried out in 24 female Wistar rats. The animals were randomized into 4 groups: (1) control, (2) Ringer's lactate, (3) whole HAF, and (4) HAF depleted from cells and proteins. Adhesion grade and histologic findings of adhesion-carrying tissues were evaluated and groups were compared according to these parameters. RESULTS: Rats treated with whole HAF had less adhesion grade when compared to the control group, but the difference was not statistically significant. On the other hand, centrifuged amniotic fluid treatment significantly reduced peritoneal adhesion grade, fibrosis and inflammation (p < 0.05). CONCLUSION: Whole HAF seems to have no beneficial effect on peritoneal adhesion formation, but HAF depleted of protein and cells does have a positive effect on reducing adhesion formation.

Is meconium stained amniotic fluid related to occult myocardial injury in term low risk pregnancies?

AIM: The present study aimed to compare Troponin T (Tp T) levels of infants born with meconium stained amniotic fluid (MSAF) to those with clear amniotic fluid. STUDY DESIGN: Case-control study SUBJECTS: Thirty-five women who had delivery complicated by MSAF between 37 and 41weeks of gestation were defined as the study group and women with healthy uncomplicated pregnancies with clear amniotic fluid who were matched for age, parity, and gestational age were defined as the control group. OUTCOME MEASURES: Cord blood Tp T level, gas analysis and neonatal outcomes were compared between groups. RESULTS: Tp T levels of the study and control groups were 0.026±0.013ng/ml and 0.031±0.016ng/ml, respectively. The difference was not statistically significant (p=0.132). On the other hand, the study group had a statistically lower HCO(3) level (21.80 vs 23.60mmol/l ) and higher rate of base deficit (4.85 vs 3.25mmol/l) than the control group. CONCLUSION: The presence of meconium during labor is not related to occult myocardial injury in low-risk term pregnancies.

Cord blood S100B levels in low-risk term pregnancies with meconium-stained amniotic fluid.

OBJECTIVE: The aim of this study was to compare cord blood S100B levels and cord blood gas parameters of term infants with meconium-stained amniotic fluid (MSAF) to those infants with clear amniotic fluid. METHODS: Term pregnant women at an active phase of labor and having MSAF were defined as the study group (n = 35) and pregnant women with clear amniotic fluid, and matched for age, parity, and gestational age were defined as the control group (n = 35). Cord blood S100B levels and gas parameters were measured. RESULTS: LogS100B values of study and control groups were 2.40 ± 0.21 and 2.43 ± 0.29 pg/ml, respectively. The difference was not statistically significant (p = 0.675). LogS100B levels slightly increased as meconium thickened. (2.32 ± 0.16, 2.41 ± 0.17, and 2.44 ± 0.28 pg/ml, respectively). However, no difference was found between groups (p = 0.438). Moreover, the study group had a statistically lower HCO(3) level (21.80 vs 23.60 mmol/l) and a higher rate of base deficit (4.85 vs 3.25 mmol/l) than the control group. However, median HCO(3) and base deficit values were within normal limits in both groups. CONCLUSION: The present study showed that cord blood S100B levels of infants born through MSAF were not different from those with clear amniotic fluid. This finding suggests that MSAF, regardless of its thickness, may not be related to brain damage in low risk term pregnancies.

Effect of vitamin D on postoperative adhesion formation in a rat uterine horn adhesion model.

OBJECTIVE: To determine the role of vitamin D for preventing or reducing postoperative adhesions. STUDY DESIGN: The uterine horn adhesion model was carried out in 24 female Wistar rats. The animals were randomized into 4 groups: (1) control, (2) Ringer's lactate, (3) olive oil, and (4) vitamin D. Adhesion grade and histologic findings of adhesion-carrying tissues were evaluated, and groups were compared according to these parameters. RESULTS: Rats treated with vitamin D had less adhesion and lower inflammation grade when compared to the control and Ringer's lactate groups, and the results were statistically significant (p < 0.05). On the other hand, no difference was detected between the groups according to the fibrosis score. CONCLUSION: Vitamin D decreased postsurgical adhesion scores by both visual scores and histologic analyses in a rat model. Further experimental and clinical trials are required to confirm these results.

First-trimester reference ranges for decidual thickness and its relation to progesterone levels.

AIMS: The present study aimed to provide normal reference ranges for decidual thickness measured ultrasonographically in healthy first-trimester pregnancies and to evaluate whether there was a relationship between decidual thickness and serum progesterone levels. METHODS: Decidual thickness of 173 women with a healthy gestation between 6+0 and 9+6 weeks was measured ultrasonographically and serum progesterone concentration was determined. Distribution of decidual thickness at each gestational week and its relation with serum progesterone levels was evaluated. RESULTS: Mean decidual thickness was 6.8, 5.7, 5.5, and 6.1 mm at 6th, 7th, 8th, and 9th gestational weeks, respectively. Decidual thickness showed a mild negative correlation with gestational week (ρ=-0.207, P=0.006) and a mild positive correlation with serum progesterone concentrations (ρ=0.191, P=0.021). CONCLUSION: The present study provided normal reference ranges for decidual thickness in healthy pregnancies in the first trimester. The association found between decidual thickness and progesterone levels might shed light on further studies investigating the predictive factors of pregnancy loss and might lead to changes in the management of threatened miscarriage.

Hyperemesis gravidarum and depression in pregnancy: is there an association?

OBJECTIVE: The aim of this study was to evaluate the impact of hyperemesis gravidarum (HG) and sociodemographic parameters on depression during pregnancy. STUDY DESIGN: Between September 2010 and September 2011, 200 consecutive women with HG were defined as the study group and 200 consecutive pregnant women without any signs and symptoms of HG, and matched for age, parity, and gestational age were defined as the control group. The Beck depression inventory-II (BDI-II) questionnaire and sociodemographic questionnaire evaluating educational level, occupation, economic status, and obstetric history were given to all participants for self-completion. The forms were collected within 6 h of hospital admission. Groups were compared according to the presence of depression and predictors of depression were analyzed by regression analysis. RESULTS: Median BDI-II scores in study and control groups were 15 and 5, respectively. The difference was statistically significant (p < 0.001). In the HG group, 35.1% of patients had mild depression, 26.0% moderate, and 17.8% had severe depression, while only 5% of patients in the control group had mild depression and 95% had no depression. Multivariate analysis showed that HG, age and family relationship were related to depression during pregnancy. Moreover, depression risk was increased 76-fold in patients with HG (odds ratio = 76.000; 95% confidence interval: 36.840-156.788; p < 0.001). CONCLUSION: Depression risk is increased in patients with HG, therefore not only medical therapy of HG, but also psychiatric evaluation should be considered for these patients.