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.

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.

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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-1alpha and IL-1beta, but not tumor necrosis factor alpha, enhanced IL-8 secretion from both cell types. IL-8 levels in cultures of granulosa-lutein cells from hyperstimulated in vitro fertilization cycles were not affected by either gonadotropins or steroids. These data provide evidence that ovarian IL-8 is gonadotropin and cytokine induced and may be involved in the hormonally regulated stages of follicular development and ovulation.

This study investigates the passive mechanical properties of the subscapularis muscle in children with a contracture as a result of obstetrical brachial plexus palsy. Muscle biopsies were harvested from nine children undergoing open surgery for shoulder contracture. Passive mechanical testing of single cells and muscle bundles was performed. Corresponding comparisons were made using muscle biopsies from seven healthy controls. Single muscle fibres from patients with obstetric brachial plexus palsy displayed a shorter slack sarcomere length, linear deformation of the fibre within a wider zone of sarcomere length and a greater relative increase in stiffness compared with muscle bundles. We conclude that secondary changes in muscle fibre properties will occur as a result of a longstanding lack of sufficient passive stretch, leading to compensatory changes in the extracellular matrix. These results suggest the presence of a dynamic feedback system constituting a muscle-to-extracellular matrix communication interface.