Presence of growth/differentiation factor-15 cytokine in human follicular fluid,granulosa cells,and oocytes

Purpose

The purpose of the study was to determine whether the GDF-15 is present in follicular fluid; to evaluate if there is a relation between follicular and serum levels of GDF-15 and fertility status of study subjects; and to test whether granulosa cells, oocytes, or both produce GDF-15.

Methods

This study used follicular fluid (FF, serum, and oocytes obtained under informed consent from women undergoing oocyte retrieval for in vitro fertilization. It also used ovaries from deceased preterm newborns. Collection of FF and blood at the time of oocyte retrieval, ELISA and western blot were performed to determine levels and forms of GDF-15. Concentrations of GDF-15 in FF and serum, its expression in ovarian tissue, and secretion from granulosa cells were analyzed.

Results

GDF-15 concentration in FF ranged from 35 to 572 ng/ml, as determined by ELISA. Western blot analysis revealed the GDF-15 pro-dimer only in FF. Both normal healthy and cancerous granulosa cells secreted GDF-15 into culture media. Primary oocytes displayed cytoplasmic GDF-15 positivity in immunostained newborn ovaries, and its expression was also observed in fully grown human oocytes.

Conclusions

To the best of our knowledge, this is the first documentation of cytokine GDF-15 presence in follicular fluid. Its concentration was not associated with donor/patient fertility status. Our data also show that GDF-15 is expressed and inducible in both normal healthy and cancerous granulosa cells, as well as in oocytes.

     

Comparison of and correlation between anterior and posterior corneal elevation maps in normal eyes and keratoconus-suspect eyes

PURPOSE: To compare the anterior and posterior corneal elevation maps between keratoconus-suspect eyes and normal eyes. SETTING: Rothschild Foundation, AP-HP, University Paris VII, H?pital Bichat Claude Bernard, Paris, France. METHODS: The anterior and posterior corneal surface elevations were analyzed and compared in 60 normal myopic patients and 48 keratoconus-suspect patients. The anterior and posterior best-fit sphere radii, central and thinnest corneal pachymetries, anterior and posterior aconic shape parameters (aconic radius, aconic asphericity, aconic toricity), and anterior and posterior elevation in the 1.0 mm radius zone were analyzed. The correlations between elevation and aconic shape parameters between the anterior and posterior surfaces were compared. RESULTS: The mean central and thinnest pachymetry values were significantly lower in keratoconus-suspect eyes (P<.0001). Compared with normal eyes, keratoconus-suspect eyes had significantly increased anterior toricity (P = .0002) and posterior toricity (P<.0001), more negative asphericity (P = .042), and higher posterior elevation (P<.0001). The correlation between aconic toricity and the anterior and posterior corneal surfaces was better in keratoconus-suspect eyes than in normal eyes. Aconic asphericity and apical curvature were less correlated in keratoconus-suspect eyes than in normal eyes. CONCLUSIONS: The posterior corneal elevation and the corneal thickness values were different in keratoconus-suspect eyes. The correlation between the anterior and posterior corneal aconic shapes was between keratoconus-suspect eyes and normal eyes.     

Renin–angiotensin system blockade alone or combined with ETA receptor blockade: effects on the course of chronic kidney disease in 5/6 nephrectomized Ren-2 transgenic hypertensive rats

Background: Early addition of endothelin (ET) type A (ET_A) receptor blockade to complex renin–angiotensin system (RAS) blockade has previously been shown to provide better renoprotection against progression of chronic kidney disease (CKD) in Ren-2 transgenic hypertensive rats (TGR) after 5/6 renal ablation (5/6 NX). In this study, we examined if additional protection is provided when ET_A blockade is applied in rats with already developed CKD. Methods: For complex RAS inhibition, an angiotensin-converting enzyme inhibitor along with angiotensin II type 1 receptor blocker was used. Alternatively, ET_A receptor blocker was added to the RAS blockade. The treatments were initiated 6 weeks after 5/6 NX and the follow-up period was 50 weeks. Results: When applied in established CKD, addition of ET_A receptor blockade to the complex RAS blockade brought no further improvement of the survival rate (30% in both groups); surprisingly, aggravated albuminuria (588 ± 47 vs. 245 ± 38 mg/24 h, p < 0.05) did not reduce renal glomerular injury index (1.25 ± 0.29 vs. 1.44 ± 0.26), did not prevent the decrease in creatinine clearance (203 ± 21 vs. 253 ± 17 µl/min/100 g body weight), and did not attenuate cardiac hypertrophy to a greater extent than observed in 5/6 NX TGR treated with complex RAS blockade alone. Conclusions: When applied in the advanced phase of CKD, addition of ET_A receptor blockade to the complex RAS blockade brings no further beneficial renoprotective effects on the CKD progression in 5/6 NX TGR, in addition to those seen with RAS blockade alone.     

Progression of hypertension and kidney disease in aging fawn-hooded rats is mediated by enhanced influence of renin–angiotensin system and suppression of nitric oxide system and epoxyeicosanoids

The fawn-hooded hypertensive (FHH) rat serves as a genetic model of spontaneous hypertension associated with glomerular hyperfiltration and proteinuria. However, the knowledge of the natural course of hypertension and kidney disease in FHH rats remains fragmentary and the underlying pathophysiological mechanisms are unclear. In this study, over the animals’ lifetime, we followed the survival rate, blood pressure (telemetry), indices of kidney damage, the activity of renin–angiotensin (RAS) and nitric oxide (NO) systems, and CYP450-epoxygenase products (EETs). Compared to normotensive controls, no elevation of plasma and renal RAS was observed in prehypertensive and hypertensive FHH rats; however, RAS inhibition significantly reduced systolic blood pressure (137 ± 9 to 116 ± 8, and 159 ± 8 to 126 ± 4 mmHg, respectively) and proteinuria (62 ± 2 to 37 ± 3, and 132 ± 8 to 87 ± 5 mg/day, respectively). Moreover, pharmacological RAS inhibition reduced angiotensin (ANG) II and increased ANG 1–7 in the kidney and thereby may have delayed the progression of kidney disease. Furthermore, renal NO and EETs declined in the aging FHH rats but not in the control strain. The present results, especially the demonstration of exaggerated vascular responsiveness to ANG II, indicate that RAS may contribute to the development of hypertension and kidney disease in FHH rats. The activity of factors opposing the development of hypertension and protecting the kidney declined with age in this model. Therefore, therapeutic enhancement of this activity besides RAS inhibition could be attempted in the therapy of human hypertension associated with kidney disease.     

Mood changes,depression and suicide risk during isotretinoin treatment: a prospective study

Background Depression and mood changes appear as potentional side effects of isotretinoin in the Summary of Product Characteristics. There have been many studies treating this topic but in most cases not identifying any significant depression or suicide risk. To further investigate this issue, we conducted a prospective, uncontrolled study to evaluate mood changes and suicidal ideations in patients receiving isotretinoin therapy. Methods One‐hundred patients were included in our single center, no‐blind, and no controlled prospective study. All patients completed the Beck’s Depression Inventory, Version II (BDI‐II) before the treatment, following the first month of the treatment and then every third month until finishing the isotretinoin therapy. All questionnaires were checked by a psychiatrist. Suicidal ideations were monitored. Statistical analysis of BDI‐II scores was performed. Results All patients completed the study. Before the treatment, six percent of the patients had suffered from depressive symptoms. During the isotretinoin treatment, we did not find any deterioration of depression problems in any of these patients. On the contrary, in most patients the depressive symptoms disappeared. Symptoms of depression occurred in two patients, in which case coexisting situational factors were found to be the cause. No occurrence of suicidal ideations was found. Conclusions We did not find any depressive symptoms or suicide risk caused by isotretinoin. On the contrary, a statistically significant improvement of BDI‐II scores was found. In our opinion, patients have to be informed about the risk of depression but emphasizing the fact that it is very rare.     

Mucosal maxillary cysts: long-term subjective outcomes after surgical treatment

Mucosal maxillary cysts (MMCs) are usually asymptomatic and are often diagnosed as an incidental finding. The aim of this study is to assess clinical significance of MMCs and the long-term effect of surgical treatment on the symptoms initially addressed to MMCs. The study included a retrospective analysis of 64 patients who had undergone surgery for MMC using a questionnaire focused mainly on the effect surgery had on symptoms. Mean time of follow-up was 79 months. Patients were also divided and compared according to the presence of rhinitic symptoms. Twenty-six patients (63.4 %) reported complete disappearance of symptoms, 8 (19.5 %) reported improvement, 4 (9.7 %) reported no change in symptoms following surgery and 3 (7.3 %) reported that symptoms reappeared. Significantly (p = 0.0365) better results were achieved in patients without preexisting rhinitic symptoms. This study supports the opinion that in some cases, MMCs are involved in the development of sinonasal symptoms. Surgical treatment leads, in most patients, to disappearance or improvement of symptoms and the effect is better in patients without rhinitic symptoms.     

Supplementation with n-3 polyunsaturated fatty acids to lipopolysaccharide-induced rats improved inflammation and functional properties of renal Na,K-ATPase

Measurements of enzyme kinetics of renal Na,K-ATPase were used for characterization of ATP- and Na⁺-binding sites in rats that were subjected to 10 days of moderate inflammation that was induced by a single dose of Escherichia coli lipopolysaccharides (LPSs) at a dose of 1 mg kg⁻¹ body weight. We hypothesized that LPSs might initiate a malfunction of renal Na,K-ATPase, which is a key enzyme involved in regulation of sodium homeostasis in the organism. We also investigated the potential effect that fish oil (FO) has in the prevention of Na,K-ATPase alterations by administering FO daily at a dose of 30 mg kg⁻¹. Alone, LPS elevated the level of C-reactive protein by more than 500% and free radicals by 36% in plasma, as indicated by an increased level of malondialdehyde. The Na,K-ATPase was slightly altered in the vicinity of the ATP-binding site as suggested by the 9% increase of the concentration of ATP necessary for half-maximal activation of the enzyme, thus indicating a deteriorated binding of ATP as a consequence of inflammation. Daily supplementation of FO partly attenuated LPS-induced injury, as observed by a significant decrease in the plasma levels of C-reactive protein and free radicals, hence maintaining the activity of renal Na,K-ATPase to the level of healthy control animals. In conclusion, our findings showed that FO prevented an excessive malondialdehyde production in LPS-treated animals and stabilized renal Na,K-ATPase.     

Chronic Exposure to Arsenic and Markers of Cardiometabolic Risk: A Cross-Sectional Study in Chihuahua,Mexico

Background

Exposure to arsenic (As) concentrations in drinking water > 150 μg/L has been associated with risk of diabetes and cardiovascular disease, but little is known about the effects of lower exposures.

Objective

This study aimed to examine whether moderate As exposure, or indicators of individual As metabolism at these levels of exposure, are associated with cardiometabolic risk.

Methods

We analyzed cross-sectional associations between arsenic exposure and multiple markers of cardiometabolic risk using drinking-water As measurements and urinary As species data obtained from 1,160 adults in Chihuahua, Mexico, who were recruited in 2008–2013. Fasting blood glucose and lipid levels, the results of an oral glucose tolerance test, and blood pressure were used to characterize cardiometabolic risk. Multivariable logistic, multinomial, and linear regression were used to assess associations between cardiometabolic outcomes and water As or the sum of inorganic and methylated As species in urine.

Results

After multivariable adjustment, concentrations in the second quartile of water As (25.5 to < 47.9 μg/L) and concentrations of total speciated urinary As (< 55.8 μg/L) below the median were significantly associated with elevated triglycerides, high total cholesterol, and diabetes. However, moderate water and urinary As levels were also positively associated with HDL cholesterol. Associations between arsenic exposure and both dysglycemia and triglyceridemia were higher among individuals with higher proportions of dimethylarsenic in urine.

Conclusions

Moderate exposure to As may increase cardiometabolic risk, particularly in individuals with high proportions of urinary dimethylarsenic. In this cohort, As exposure was associated with several markers of increased cardiometabolic risk (diabetes, triglyceridemia, and cholesterolemia), but exposure was also associated with higher rather than lower HDL cholesterol.

Citation

Mendez MA, González-Horta C, Sánchez-Ramírez B, Ballinas-Casarrubias L, Hernández Cerón R, Viniegra Morales D, Baeza Terrazas FA, Ishida MC, Gutiérrez-Torres DS, Saunders RJ, Drobná Z, Fry RC, Buse JB, Loomis D, García-Vargas GG, Del Razo LM, Stýblo M. 2016. Chronic exposure to arsenic and markers of cardiometabolic risk: a cross-sectional study in Chihuahua, Mexico. Environ Health Perspect 124:104–111; http://dx.doi.org/10.1289/ehp.1408742