In a healthy body, ROS (reactive oxygen species) and antioxidants remain in balance When the balance is disrupted towards an overabundance of ROS, oxidative stress (OS) occurs OS influences the entire reproductive lifespan of a woman and even thereafter (ie menopause) OS results from an imbalance between prooxidants (free radical species) and the body's scavenging ability (antioxidants) ROS are a double-edged sword – they serve as key signal molecules in physiological processes but also have a role in pathological processes involving the female reproductive tract ROS affect multiple physiological processes from oocyte maturation to fertilization, embryo development and pregnancy It has been suggested that OS modulates the age-related decline in fertility It plays a role during pregnancy and normal parturition and in initiation of preterm labor Most ovarian cancers appear in the surface epithelium, and repetitive ovulation has been thought to be a causative factor Ovulation-induced oxidative base damage and damage to DNA of the ovarian epithelium can be prevented by antioxidants There is growing literature on the effects of OS in female reproduction with involvement in the pathophsiology of preeclampsia, hydatidiform mole, free radical-induced birth defects and other situations such as abortions Numerous studies have shown that OS plays a role in the pathoysiology of infertility and assisted fertility There is some evidence of its role in endometriosis, tubal and peritoneal factor infertility and unexplained infertility This article reviews the role OS plays in normal cycling ovaries, follicular development and cyclical endometrial changes It also discusses OS-related female infertility and how it influences the outcomes of assisted reproductive techniques The review comprehensively explores the literature for evidence of the role of oxidative stress in conditions such as abortions, preeclampsia, hydatidiform mole, fetal embryopathies, preterm labour and preeclampsia and gestational diabetes The review also addresses the growing literature on the role of nitric oxide species in female reproduction The involvement of nitric oxide species in regulation of endometrial and ovarian function, etiopathogenesis of endometriosis, and maintenance of uterine quiescence, initiation of labour and ripening of cervix at parturition is discussed Complex interplay between cytokines and oxidative stress in the etiology of female reproductive disorders is discussed Oxidant status of the cell modulates angiogenesis, which is critical for follicular growth, corpus luteum formation endometrial differentiation and embryonic growth is also highlighted in the review Strategies to overcome oxidative stress and enhance fertility, both natural and assisted are delineated Early interventions being investigated for prevention of preeclampsia are enumerated Trials investigating combination intervention strategy of vitamin E and vitamin C supplementation in preventing preeclampsia are highlighted Antioxidants are powerful and there are few trials investigating antioxidant supplementation in female reproduction However, before clinicians recommend antioxidants, randomized controlled trials with sufficient power are necessary to prove the efficacy of antioxidant supplementation in disorders of female reproduction Serial measurement of oxidative stress biomarkers in longitudinal studies may help delineate the etiology of some of the diosorders in female reproduction such as preeclampsia

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Role of oxidative stress in female reproduction

The skeletal muscle extracellular matrix (ECM) plays an important role in muscle fiber force transmission, maintenance, and repair. In both injured and diseased states, ECM adapts dramatically, a property thathas clinical manifestations and alters muscle function. Here, we review the structure, composition, and mechanical properties of skeletal muscle ECM, describe the cells that contribute to the maintenance of the ECM and, finally, overview changes that occur with pathology. New scanning electron micrographs of ECM structure are also presented with hypotheses about ECM structure-function relationships. Detailed structure-function relationships of the ECM have yet to be defined and, as a result, we propose areas for future studies.

Structure and function of the skeletal muscle extracellular matrix

A 66-year-old man was suddenly unable to speak, follow directions, or move his right arm and leg. He received tissue plasminogen activator within 90 minutes. Four days later, his speech was limited to effortful answers of yes or no. He could not walk or use his right arm, and self-care tasks required maximal assistance. What advice would you offer him and his family regarding rehabilitation for his disabilities?

https://www.nejm.org/doi/pdf/10.1056/NEJMcp043511

Rehabilitation after Stroke

Interleukin-8 and human cancer biology.

Summary Rehabilitation after hemiplegic stroke has typically relied on the training of patients in compensatory strategies. The translation of neuroscientific research into care has led to new approaches and renewed promise for better outcomes. Improved motor control can progress with task-specific training incorporating increased use of proximal and distal movements during intensive practice of real-world activities. Functional gains are incorrectly said to plateau by 3–6 months. Many patients retain latent sensorimotor function that can be realised any time after stroke with a pulse of goal-directed therapy. The amount of practice probably best determines gains for a given level of residual movement ability. Clinicians should encourage patients to build greater strength, speed, endurance, and precision of multijoint movements on tasks that increase independence and enrich daily activity. Imaging tools may help clinicians determine the capacity of residual networks to respond to a therapeutic approach and help establish optimal doseresponse curves for training. Promising adjunct approaches include practice with robotic devices or in a virtual environment, electrical stimulation to increase cortical excitability during training, and drugs to optimise molecular mechanisms for learning. Biological strategies for neural repair may augment rehabilitation in the next decade.

/pdf/strategies-for-stroke-rehabilitation-19ij3gyrkd.pdf

Strategies for stroke rehabilitation

The passive mechanical properties of small muscle fiber bundles obtained from surgical patients with spasticity (n = 9) and patients without neuromuscular disorders (n = 21) were measured in order to determine the relative influence of intracellular and extracellular components. For both types of patient, tangent modulus was significantly greater in bundles compared to identical tests performed on isolated single cells (P < 0.05). However, the relative difference between bundles and single cells was much greater in normal tissue than spastic tissue. The tangent modulus of normal bundles (462.5 +/- 99.6 MPa) was 16 times greater than normal single cells (28.2 +/- 3.3 MPa), whereas the tangent modulus of spastic bundles (111.2 +/- 35.5 MPa) was only twice that of spastic muscle cells (55.0 +/- 6.6 MPa). This relatively small influence of the extracellular matrix (ECM) in spastic muscle was even more surprising because spastic muscle cells occupied a significantly smaller fraction of the total specimen area (38.5 +/- 13.6%) compared to normal muscle (95.0 +/- 8.8%). Based on these data, normal muscle ECM is calculated to have a modulus of 8.7 GPa, and the ECM from spastic muscle of only 0.20 GPa. These data indicate that spastic muscle, although composed of cells that are stiffer compared to normal muscle, contains an ECM of inferior mechanical strength. The present findings illustrate some of the profound changes that occur in skeletal muscle secondary to spasticity. The surgical implications of these results are discussed.

Inferior mechanical properties of spastic muscle bundles due to hypertrophic but compromised extracellular matrix material.

Mammalian ovulation has several similarities to local inflammatory reactions, involving participation of leukocytes and inflammatory mediators. In response to a preovulatory luteinizing hormone surge, there is an influx of leukocytes into the preovulatory follicle and uncharacterized chemotactic activity towards these cells has previously been reported in follicular fluid of several species, including the human. In the present study, we have investigated the presence and local production of interleukin-8 (IL-8), a potent leukocyte-chemotactic and neutrophil-activating cytokine, in the human preovulatory follicle. Immunoreactive IL-8 was present in the follicular fluid in all of 12 in-vitro fertilization (IVF) patients investigated. IL-8 concentrations in follicular fluid (1269 +/- 245 pg/ml) were approximately 30-fold higher than in plasma (41 +/- 14 pg/ml). Isolated granulosa cells in culture secreted large amounts of IL-8 protein. Basal secretion of IL-8 was dose-dependently enhanced by the presence of fetal calf serum and was further stimulated by the addition of the ovulation-associated cytokine IL-1 beta. Messenger RNA for IL-8 was detected by reverse transcription/polymerase chain reaction (RT-PCR) in all tested samples of granulosa cells of IVF patients (n = 8) and in all biopsies from preovulatory follicle walls obtained in natural cycles (n = 6). This is the first demonstration of IL-8 in the mammalian ovary. Local production, combined with high follicular fluid concentrations, suggests that this cytokine plays a role in cyclic ovarian events, such as ovulation.

/pdf/endocrinology-and-paracrinology-the-human-preovulatory-3glyiq2xo8.pdf

Endocrinology and Paracrinology The human preovulatory follicle is a source of the chemotactic cytokine interleukin-8

https://www.gynecologiconcology-online.net/article/S0090-8258(98)95198-8/pdf

The Chemotactic Cytokine Interleukin-8—A Cyst Fluid Marker for Malignant Epithelial Ovarian Cancer?

Interleukin 8 (IL-8) is a chemotactic cytokine involved in the recruitment and activation of neutrophils as well as in cell proliferation and angiogenesis. Because these events are essential components of folliculogenesis, ovulation, and subsequent repair of the ruptured follicle, the presence and regulation of IL-8 in the human follicle of the menstrual cycle was investigated. The concentrations of IL-8 were higher in follicular fluids from dominant follicles of late follicular/ovulatory phase compared with those of midfollicular phase. IL-8 was detected in the media from cultured granulosa and theca cells, with 10-fold higher levels in the theca cell cultures. Exposure to FSH and LH increased the IL-8 secretion from granulosa cells, but no effect was seen in theca cell cultures. Estradiol and progesterone did not affect IL-8 secretion from any cell type. The cytokines IL-1α and IL-1β, but not tumor necrosis factor α, enhanced IL-8 secretion from both cell types. IL-8 levels in cultures of granulosa-lute...

Gonadotropin- and cytokine-regulated expression of the chemokine interleukin 8 in the human preovulatory follicle of the menstrual cycle.

The aims of the present study were to characterize the expression and cellular localization of isoforms of nitric oxide synthase (NOS) in the human corpus luteum (CL) and to determine the effects of nitric oxide (NO) on CL steroidogenesis. Immunoblotting analyses revealed that endothelial NOS (eNOS) is the most abundant isoform in human CL with highest values during the late luteal phase. Immunoreactive eNOS was localized predominantely in the theca lutein layer, being particularly abundant in endothelial cells, but with positive staining also in some steroidogenic cells. Immunoreactive inducible NOS (iNOS) was also detected, but to lesser degree, and did not display apparent phase-specific changes. The effect of NO on CL steroid synthesis was examined using human chorionic gonadotrophin (HCG)-stimulated dispersed CL cells cultured in vitro. Progesterone production was significantly decreased (P < 0.05) by the NO donor spermine NONOate (10(-5) mol/l) in cells of the late, but not mid-, luteal phase. To investigate a potential link between NO and the local prostaglandins (PG), concentrations of PGF(2alpha) and PGE(2) were measured in culture medium. NO significantly increased (P < 0.05) concentrations of both PGF(2alpha) and PGE(2) during the late luteal phase. It is concluded that NO may be luteolytic in the human CL of menstruation.

Eva Runesson

Papers

Inferior mechanical properties of spastic muscle bundles due to hypertrophic but compromised extracellular matrix material.

Endocrinology and Paracrinology The human preovulatory follicle is a source of the chemotactic cytokine interleukin-8

The Chemotactic Cytokine Interleukin-8—A Cyst Fluid Marker for Malignant Epithelial Ovarian Cancer?

Gonadotropin- and cytokine-regulated expression of the chemokine interleukin 8 in the human preovulatory follicle of the menstrual cycle.

Evidence for nitric oxide acting as a luteolytic factor in the human corpus luteum.