Sex differences in the aging human heart: decreased sirtuins, pro-inflammatory shift and reduced anti-oxidative defense.

Aging is associated with increased inflammation and alterations in mitochondrial biogenesis, which promote the development of cardiovascular diseases. Emerging evidence suggests a role for sirtuins, which are NAD-dependent deacetylases, in the regulation of cardiovascular inflammation and mitochondrial biogenesis. Sirtuins are regulated by sex or sex hormones and are decreased during aging in animal models.

Why the study of the effects of biological sex is important. Commentary.

Biological sex significantly affects the presentation, outcome of treatment and progression of disease. However, the role of sex has yet underestimated consequences for physiology and pathology. We put forward that a better understanding of the effects of sex in pathophysiology and the underlying mechanisms is necessary.

Effects of Chronic D-Serine Elevation on Animal Models of Depression and Anxiety-Related Behavior.

NMDA receptors are activated after binding of the agonist glutamate to the NR2 subunit along with a co-agonist, either L-glycine or D-serine, to the NR1 subunit. There is substantial evidence to suggest that D-serine is the most relevant co-agonist in forebrain regions and that alterations in D-serine levels contribute to psychiatric disorders. D-serine is produced through isomerization of L-serine by serine racemase (Srr), either in neurons or in astrocytes.

Remodeling of estrogen-dependent sympathetic nerve fibers seems to be disturbed in adenomyosis.

Objective: To investigate neuronal remodeling processes in the uterine innervation, particularly a remodeling of sympathetic nerve fibers, as well as the role of estrogen in this modulation in adenomyosis.

Design: Retrospective case-control study.

Setting: University hospital endometriosis center.

Evidence of neurotrophic events due to peritoneal endometriotic lesions.

To investigate the neurotrophic properties of endometriosis, as well as the involvement of neurotrophic factors in the development of chronic pelvic pain in patients with endometriosis, we performed a prospective clinical study. The presence of neurotrophins was investigated in the peritoneal fluid (PF) of patients with peritoneal endometriotic lesions or adenomyosis, as well as from women with non-endometriotic adhesions and from women without endometriosis/adenomyosis/adhesions. The PF from patients with peritoneal endometriotic lesions was divided in three groups: asymptomatic endometriosis, minimal pain and severe pain.

Neuroimmunomodulatory alterations in non-lesional peritoneum close to peritoneal endometriosis.

Objectives: An imbalance in the ratio of sensory to sympathetic nerve fibre (NF) density in peritoneal endometriotic lesions (pEL) has recently been demonstrated and leads to the assumption that this preponderance of the sensory pro-inflammatory milieu is a major cause of pain in endometriosis. Therefore, the density of sensory and sympathetic NFs was determined in distal unaffected peritoneum of endometriosis patients to be able to detect possible alterations in unaffected peritoneum.

Methods: In serial pEL sections (n = 40), lesional and matching unaffected peritoneum as well as healthy peritoneum (HP) from patients without endometriosis (n = 15) were immunohistochemically analysed to identify protein gene product 9.

Eutopic endometrium from women with endometriosis does not exhibit neurotrophic properties.

The role of neurotrophins in eutopic endometrium from endometriosis-patients was investigated in a prospective study using immunofluorescence-staining, Western blot and a neuronal growth assay. The nerve growth factor is expressed in primary endometrial cell culture from women with and without endometriosis. Western blot analysis of endometrial biopsies or uterine fluid from patients with and without endometriosis shows no difference in the neurotrophin expression.

High lymph vessel density and expression of lymphatic growth factors in peritoneal endometriosis.

To investigate the occurrence of lymph vessels and lymphangiogenic growth factors in peritoneal lesions, we performed immunohistochemical staining of peritoneal lesions of 37 patients with antibodies against podoplanin (D2-40), lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), prospero homeobox protein 1 (Prox-1), vascular epithelial growth factor (VEGF)-C/VEGF-D. Overall, 10 lesions were double stained against D2-40 and von Willebrand factor. The lymph vessel density in peritoneal lesion was significantly higher in comparison with healthy peritoneum.

Neurotrophin expression is not affected in uteri of women with adenomyosis.

To investigate the involvement of neurotrophins and nerve fibres in the pathogenesis of adenomyosis, we performed a retrospective, clinical study. Hysterectomy specimens from 40 patients with histologically proven adenomyosis and from 20 patients without adenomyosis or endometriosis were used for immunohistochemical analysis. In order to investigate neurotrophic properties in adenomyosis, the antibodies against nerve growth factor (NGF), neurotrophin 3 (NT-3), the high-affinity NGF receptor (TrkA), the low-affinity neurotrophin receptor (p75(NTR)), the neuronal marker S100 (for myelinated nerve fibres) and protein gene product 9.

Imbalance between sympathetic and sensory innervation in peritoneal endometriosis.

To investigate possible mechanisms of pain pathophysiology in patients with peritoneal endometriosis, a clinical study on sensory and sympathetic nerve fibre sprouting in endometriosis was performed. Peritoneal lesions (n=40) and healthy peritoneum (n=12) were immunostained and analysed with anti-protein gene product 9.5 (PGP 9.

Immunohistochemical characterization of endometriosis-associated smooth muscle cells in human peritoneal endometriotic lesions.

Background: Smooth muscle cells (SMC) are common components of endometriotic lesions. SMC have been characterized previously in peritoneal, ovarian and deep infiltrating endometriotic lesions and adenomyosis. The aim of this retrospective study was to investigate the extent of differentiation in endometriosis-associated SMC (EMaSMC) in peritoneal endometriotic lesions.

Influence of nerve growth factor in endometriosis-associated symptoms.

To investigate the role of the nerve growth factor (NGF) in the development of dysmenorrhea/pelvic pain in patients with endometriosis, we performed a prospective, clinical, blind study. Peritoneal fluids (PFs) were obtained from patients with histologically proven endometriosis. Patients with endometriosis were divided into 7 different groups depending on their preoperative pain score and symptomatology: patients with no pain, patients with minimal pain (dysmenorrhea, pelvic pain, or both), and patients with severe pain (dysmenorrhea, pelvic pain, or both) and were used for the neuronal growth assay with cultured chicken dorsal root ganglia (DRG) and for Western blot analyses.

Overexpression of nerve growth factor in peritoneal fluid from women with endometriosis may promote neurite outgrowth in endometriotic lesions.

To investigate the role of the nerve growth factor (NGF) in the endometriosis-associated innervation in the development of endometriosis-associated symptoms, 41 peritoneal fluid samples (PF) from patients with surgically and histologically proven endometriosis and 20 PF from patients with other gynecologic conditions were analyzed with Western blot and a novel in vitro model using dorsal root ganglia (DRG) to show neuronal outgrowth; endometrial cells also were analyzed. The results suggest that the PF of endometriosis patients and endometriotic lesions have neurotropic properties, because the Western blot analysis and the cell culture stainings showed NGF expression, and the neurite outgrowth of DRG treated with PF of patients with endometriosis was significantly higher than when treated with PF of patients without endometriosis. Furthermore, blocking NGF with both anti-NGF and K252a leads to a significant decrease in neurite outgrowth.