Coexistence of bone and vascular disturbances in patients with endogenous glucocorticoid excess.

Purpose: Bone and vascular diseases are considered to share pathogenic mechanisms. Excess glucocorticoids, key regulators of cardiovascular and metabolic homeostasis, may promote both diseases simultaneously. We used endogenous Cushing's syndrome (CS) to investigate whether glucocorticoid excess underlies coexisting bone and vascular diseases. Methods: We included 194 patients with adrenal tumors (ATs): autonomous cortisol secretion (ACS, n = 97) and non-functional AT (n = 97). ACS was further classified into overt CS (n = 17) and subclinical CS (SCS, n = 80). Arterial stiffness was defined as a brachial-ankle pulse wave velocity (baPWV) ≥ 1800 cm/s. Results: Patients with ACS had higher coexistence rates of vertebral fracture and arterial stiffness (23 % vs. 2 %; p < 0.001) and vertebral fracture and abdominal aortic calcification (22 % vs. 1 %; p < 0.001) than those with non-functional AT. In patients with ACS, baPWV was negatively correlated with trabecular bone score (TBS, r = -0.33; p = 0.002), but not with bone mineral density, and vertebral fracture was associated with arterial stiffness in the logistic regression analysis. In the multivariate analysis of variance, the degree of cortisol excess (defined as CS, SCS, and non-functional AT) determined the correlation between TBS and baPWV (partial η2 = 0.07; p < 0.001). In the analysis of covariance, patients with coexisting vertebral fracture and arterial stiffness had higher levels of serum cortisol after the 1-mg dexamethasone suppression test than those without. Conclusion: In endogenous glucocorticoid excess, bone and vascular diseases frequently coexisted, and deteriorated bone quality, not bone loss, was related to arterial stiffness. Thus, glucocorticoid excess may perturb the bone-vascular axis.

Association between cortisol and left ventricular diastolic dysfunction in patients with diabetes mellitus.

AIMS/INTRODUCTION: Diabetes mellitus is a major risk factor for the development of cardiovascular diseases. Heart failure with preserved ejection fraction is characterized by left ventricular diastolic dysfunction (LVDD). It has been reported that excess cortisol found in patients with Cushing's syndrome was associated with the development of LVDD. However, the relationship between cortisol concentration and LVDD in patients with diabetes mellitus has not been addressed. MATERIALS AND METHODS: We enrolled 109 patients with diabetes mellitus and 104 patients without diabetes mellitus who had undergone echocardiographic examination at Kyushu University Hospital, Fukuoka, Japan, between November 2016 and March 2019. Left ventricular function was evaluated and the ratio of early diastolic velocity from transmitral inflow to early diastolic velocity (E/e') was used as an index of diastolic function. Plasma cortisol concentrations, glycemic control, lipid profiles, treatment with antidiabetic drugs and other clinical characteristics were evaluated, and their associations with E/e' were determined using univariate and multivariate analyses. RESULTS: Multivariate linear regression analysis showed that log E/e' was positively correlated with age (P = 0.017), log systolic blood pressure (P = 0.004) and cortisol (P = 0.037), and negatively correlated with estimated glomerular filtration rate (P = 0.016) and the use of sodium-glucose cotransporter 2 inhibitors (P = 0.042) in patients with diabetes mellitus. Multivariate analysis showed that cortisol was positively correlated with age (P = 0.016) and glycated hemoglobin (P = 0.011). There was no association between E/e' and cortisol in patients without diabetes mellitus. CONCLUSIONS: Increased cortisol levels might increase the risk of developing LVDD in diabetes mellitus patients.

Solubilization of poorly water-soluble bioactive molecules in neutral aqueous media by complexation with renatured ß-1,3-1,6-glucan nanoparticles.

The design of scaffolds for solubilizing/dispersing poorly water-soluble bioactive molecules in neutral aqueous media is a major challenge of functional food, pharmaceuticals, and cosmetics development, as highlighted by the plethora of corresponding solubilization/dispersion strategies. Herein, renatured ß-1,3-1,6-glucan (r-glucan) nanoparticles prepared by neutralization of alkali-denatured ß-1,3-1,6-glucan and subsequent centrifugation are used as a host to disperse water-insoluble bioactive molecules (curcumin, all-trans-retinoic acid, and rebamipide) by simple mixing of host and guest solutions. Curcumin in the r-glucan cavity is found to be stacked in the form of J-aggregates and twisted along the helix, and is demonstrated to be retained for significantly longer than curcumin in the corresponding γ-cyclodextrin (γ-CD) complex. Specifically, curcumin incorporated in γ-CD is released within 5.5 hours, whereas that in the r-glucan complex is released very slowly, with 12% of curcumin in the latter complex retained after 31-day incubation at 37°C. Thus, inclusion protocol simplicity and slow release ability make r-glucan nanoparticles a potential carrier scaffold for various applications.

Repeated collection of conjoined oocytes from a patient with polycystic ovary syndrome, resulting in one successful live birth from frozen thawed blastocyst transfer: a case report.

Few cases have been reported in which the aspiration of a single follicle led to the recovery of two conjoined oocytes surrounded by a single zona pellucida. This report describes a successful embryo transfer with subsequent live birth derived from conjoined oocytes, and a later pair of conjoined oocytes in the same patient. After oocyte retrieval from a patient with polycystic ovary syndrome, two pairs of conjoined oocytes were collected. One oocyte was fertilized using in vitro fertilization (IVF) and developed to the blastocyst stage. This blastocyst was cryopreserved and later transferred to the uterus after separating the unfertilized conjoined oocyte. A successful pregnancy and healthy live birth was achieved. Two years later, the patient returned for a second IVF; one pair of conjoined oocytes was detected. One of the pair was fertilized and developed to a blastocyst, but was not transferred. We demonstrate that selective fertilization of a mature oocyte from conjoined oocytes by IVF can lead to the development of a blastocyst and subsequent pregnancy and live birth. To our knowledge, this is the second case report of successful live birth from conjoined oocytes. It may be the first case of repeated fertile conjoined oocytes from the same patient.

Chemical zona pellucida thinning with acidified Tyrode's solution: comparison between partial and circumferential techniques.

PURPOSE: To compare effectiveness of two different chemical zona thinning techniques. METHOD: We studied 163 patients who had experienced IVF or ICSI failures in two or more cycles. Patients were assigned to one of three groups: zona intact (n=72), partial thinning (n=59), or circumferential thinning (n=73). Before transfer, the zonae pellucidae of embryos were thinned partially or circumferentially using acidified Tyrode's solution. RESULTS: Implantation rates were 8.9% in the intact zona group, 17.6% in the partial thinning group, and 11.9% in the circumferential thinning group: respective clinical pregnancy rates were 16.7% (12/72), 32.2% (19/59), and 27.4% (20/73). Both rates were significantly higher in the partial thinning group than the intact zona group. For circumferential thinning versus zona intact groups, differences fell short of significance. CONCLUSIONS: Following embryo transfer failure, partial thinning would be recommended over circumferential thinning for successful assisted hatching.

Assisted hatching using a 1.48-µm diode laser: Evaluation of zona opening and zona thinning techniques in human embryos.

Aim: We assessed the effectiveness of assisted hatching using a 1.48-µm diode laser in human embryos, comparing zona opening and zona thinning techniques. Methods: A total of 56 day 3 embryos were assigned randomly to a zona opening group, a zona thinning group, or a control group. We then carried out assisted hatching using the OCTAX Laser Shot system (MTG Medical Technology, Altdorf, Germany) in the first two groups. In the zona opening group, the inner membrane of the zona pellucida was broken to create a full-thickness opening. In the zona thinning group, the inner membrane of the zona pellucida was not breached. After the laser procedure, embryos were cultured to the hatched blastocyst stage. Results: Blastocyst development rates did not differ significantly between the three groups. In the zona opening group, blastocysts were significantly more likely to hatch than those in the control group (P ≤ 0.05) and no arrested hatching of blastocysts was observed. Conclusions: Assisted hatching using a 1.48-µm diode laser in the zona opening technique increases the likelihood of blastocyst hatching in human embryos and does not adversely effect subsequent embryo development. (Reprod Med Biol 2006; 5: 221-226).