Jeffrey H. Plochocki

Voluntary exercise induces structural remodeling in the hearts of dystrophin-deficient mice.

In this exploratory study, we test the hypothesis that voluntary exercise affects the progression of dystrophic changes in the left ventricle of the heart. Wild‐type (C57BL/10ScSn) and dystrophin‐deficient (mdx) mice, aged 7 weeks, were divided into sedentary and exercise‐treated groups and tested for differences in cardiac histomorphometry. Exercised mdx mice were found to exhibit significantly enlarged ventricles and thinner lateral ventricular walls than sedentary mdx mice (P < 0.05). Trichrome staining indicated the presence of fibrotic lesions in the left ventricular myocardium in 20% of the exercised mdx group. Fibrotic lesions were not found in control or sedentary mdx mice. No histomorphometric differences were found between treatment groups in wild‐type mice. Our findings suggest voluntary exercise may accelerate the progression of ventricular dilation and fibrosis in young mdx mice. The effects of exercise on cardiac remodeling should be considered during the treatment of cardiac disease in dystrophin‐deficient patients. Muscle Nerve 42: 881–885, 2010

Evaluation of the chondral modeling theory using fe-simulation and numeric shape optimization

The chondral modeling theory proposes that hydrostatic pressure within articular cartilage regulates joint size, shape, and congruence through regional variations in rates of tissue proliferation. The purpose of this study is to develop a computational model using a nonlinear two‐dimensional finite element analysis in conjunction with numeric shape optimization to evaluate the chondral modeling theory. The model employed in this analysis is generated from an MR image of the medial portion of the tibiofemoral joint in a subadult male. Stress‐regulated morphological changes are simulated until skeletal maturity and evaluated against the chondral modeling theory. The computed results are found to support the chondral modeling theory. The shape‐optimized model exhibits increased joint congruence, broader stress distributions in articular cartilage, and a relative decrease in joint diameter. The results for the computational model correspond well with experimental data and provide valuable insights into the mechanical determinants of joint growth. The model also provides a crucial first step toward developing a comprehensive model that can be employed to test the influence of mechanical variables on joint conformation.

Sexual Dimorphism of Anterior Sacral Curvature

Abstract:  This study assesses the predictive value of anterior sacral curvature for sex estimation from skeletonized remains. Sacra from a sample of 125 American adults of known age and sex were examined. Nine measurements describing anterior sacral curvature were used in the analysis. Statistical treatment of the data included univariate statistics and discriminant function analysis for sex classification. A bootstrap validation method was employed to assess the classification error rates. Sacral curvature was significantly greater in men than in women at the level of the S2–S3 and S3–S4 articulations (p < 0.05). Correct classification estimates for the discriminant function range from 66–72%. Although sexually dimorphic, metric observations of sacral curvature are not as reliable at predicting sex as other skeletal elements. Anterior sacral curvature should only be used for sex estimation in the absence of other, more reliable, indicators.

Genistein treatment increases bone mass in obese, hyperglycemic mice.

Background Obesity and type 2 diabetes mellitus are associated with elevated risk of limb bone fracture. Incidences of these conditions are on the rise worldwide. Genistein, a phytoestrogen, has been shown by several studies to demonstrate bone-protective properties and may improve bone health in obese type 2 diabetics. Methods In this study, we test the effects of genistein treatment on limb bone and growth plate cartilage histomorphometry in obese, hyperglycemic ob/ob mice. Six-week-old ob/ob mice were divided into control and genistein-treated groups. Genistein-treated mice were fed a diet containing 600 mg genistein/kg for a period of 4 weeks. Cross-sectional geometric and histomorphometric analyses were conducted on tibias. Results Genistein-treated mice remained obese and hyperglycemic. However, histomorphometric comparisons show that genistein-treated mice have greater tibial midshaft diameters and ratios of cortical bone to total tissue area than the controls. Genistein-treated mice also exhibit decreased growth plate thickness of the proximal tibia. Conclusion Our results indicate that genistein treatment affects bone of the tibial midshaft in the ob/ob mouse, independent of improvements in the hyperglycemic state and body weight.

A functional and clinical reinterpretation of human perineal neuromuscular anatomy: Application to sexual function and continence

Modern anatomical and surgical references illustrate perineal muscles all innervated by branches of the pudendal nerve but still organized into anatomically distinct urogenital and anal triangles with muscles inserting onto a central perineal body. However, these conflict with the anatomy commonly encountered during dissection. We used dissections of 43 human cadavers to characterize the anatomical organization of the human perineum and compare our findings to standard references. We found bulbospongiosus and the superficial portion of the external anal sphincter (EAS) were continuous anatomically with a common innervation in 92.3% of specimens. The superficial transverse perineal muscle inserted anterior and lateral to the midline, interdigitating with bulbospongiosus. The three EAS subdivisions were anatomically discontinuous. Additionally, in 89.2% of our sample the inferior rectal nerve emerged as a branch of S3 and S4 distinct from the pudendal nerve and innervated only the subcutaneous EAS. Branches of the perineal nerve innervated bulbospongiosus and the superficial EAS and nerve to levator ani innervated the deep EAS. In conclusion, we empirically demonstrate important and clinically relevant differences with perineal anatomy commonly described in standard texts. First, independent innervation to the three portions of EAS suggests the potential for functional independence. Second, neuromuscular continuity between bulbospongiosus and superficial EAS suggests the possibility of shared or overlapping function of the urogenital and anal triangles. Clin. Anat. 29:1053–1058, 2016.

A Functional and Clinical Reinterpretation of Human Perineal Neuromuscular Anatomy

Modern anatomical and surgical references illustrate perineal muscles all innervated by branches of the pudendal nerve but still organized into anatomically distinct urogenital and anal triangles with muscles inserting onto a central perineal body. However, these conflict with the anatomy commonly encountered during dissection. We used dissections of 43 human cadavers to characterize the anatomical organization of the human perineum and compare our findings to standard references. We found bulbospongiosus and the superficial portion of the external anal sphincter (EAS) were continuous anatomically with a common innervation in 92.3% of specimens. The superficial transverse perineal muscle inserted anterior and lateral to the midline, interdigitating with bulbospongiosus. The three EAS subdivisions were anatomically discontinuous. Additionally, in 89.2% of our sample the inferior rectal nerve emerged as a branch of S3 and S4 distinct from the pudendal nerve and innervated only the subcutaneous EAS. Branches of the perineal nerve innervated bulbospongiosus and the superficial EAS and nerve to levator ani innervated the deep EAS. In conclusion, we empirically demonstrate important and clinically relevant differences with perineal anatomy commonly described in standard texts. First, independent innervation to the three portions of EAS suggests the potential for functional independence. Second, neuromuscular continuity between bulbospongiosus and superficial EAS suggests the possibility of shared or overlapping function of the urogenital and anal triangles. Clin. Anat. 29:1053–1058, 2016.

Mechanically-induced osteogenesis in the cortical bone of pre- to peripubertal stage and peri- to postpubertal stage mice

BackgroundExercise during postnatal development plays a key role in determining adult bone mass and reducing the risk of fracture and osteoporosis later in life. However, the relationship between mechanically-induced osteogenesis and age is unclear. Elevated levels of estrogen during puberty may inhibit periosteal bone formation. Thus, magnitudes of mechanically-induced osteogenesis may be vary with pubertal state.MethodsThe present study uses a murine model to examine age-related changes in bone formation at the femoral midshaft with voluntary exercise. Pre- to peripubertal mice aged 3 weeks and peri- to postpubertal mice aged 7 weeks were randomly divided into sedentary and exercised groups and subjected to histomorphometric comparison after 4 weeks of treatment.ResultsResults of the experiment indicate that exercise significantly increased osteogenesis on the periosteal and endocortical surface of the mice in the older age group (P < 0.05). Exercise had no significant effect on bone formation of mice in the younger age group, although exercised mice exhibited more bone growth on average than controls. Endocortical apposition was the primary method of bone formation for all mice in the experiment; however exercised mice in the older age group were able to add more bone on the periosteal surface than age-matched controls and exercised mice in the younger age group (P < 0.05). Medullary area increased with age, but exercised mice in both age groups had smaller medullary cavities relative to overall bone area than controls.ConclusionThese findings suggest that the amount and location of mechanically-induced osteogenesis differs by age during skeletal development. Late adolescence may be the optimal time to accrue bone mass and maximize bone strength.

The Effects of Glucocorticoid and Voluntary Exercise Treatment on the Development of Thoracolumbar Kyphosis in Dystrophin- Deficient Mice

The development of spinal curvature deformities is a hallmark of muscular dystrophy. While glucocorticoid treatment has been shown to prolong muscle function in dystrophic mice, its effects on the development of dystrophinopathic spinal deformation are poorly understood. In this study, we test the effects of glucocorticoid treatment on the onset of thoracolumbar kyphosis in the dystrophin-deficient mdx mouse using voluntary running exercise to exacerbate muscle fibrosis. We measure the kyphotic index, erector spinae muscle fibrosis, and vertebral bone histomorphometry in 4-month-old mdx mice in four groups: sedentary control, exercise-treated (continuous voluntary access to an activity wheel), glucocorticoid-treated, and glucocorticoid + exercise-treated. Exercise treated mice were found to have significantly lower kyphotic index (i.e., greater kyphosis) and greater muscle fibrosis relative to controls (p < 0.05). However, the deleterious effect of exercise on KI and muscle fibrosis was prevented by glucocorticoid treatment. Some differences in bone histological parameters were observed between treatment groups, suggesting there is a complex relationship between dystrophic muscular changes and vertebral bone mass. Our findings indicate glucocorticoid treatment delays the onset of thoracodorsal spinal deformation in mdx mice.

Histological study of white rhinoceros integument

In this study, we report findings from a microscopic analysis of the white rhinoceros (Ceratotherium simum) integumentary ultrastructure. Skin samples from the cheek, shoulder, flank and rump were taken from a 46-year-old female southern white rhinoceros and examined using H&E and elastic histological stains. The epidermis was thickest in the flank (1.003 mm) followed by the rump, cheek and shoulder. The stratum corneum comprised more than half the epidermal thickness. Numerous melanin granules were found in the basal and spinosum layers. The epidermal-dermal junction was characterized by abundant papillary folds increasing surface contact between integument layers. Most of the dermal thickness consisted of organized collagen bundles with scattered elastic fibers. Collagen fiber bundles were thickest in the flank (210.9 μm) followed by shoulder, rump and cheek. Simple coiled sweat glands were present in the dermis, but hair and sebaceous glands were absent. Together, these data suggest the white rhinoceros has a unique integumentary system among large terrestrial herbivores.

The chondrogenic response to exercise in the proximal femur of normal and mdx mice

BackgroundSubmaximal exercise is used in the management of muscular dystrophy. The effects of mechanical stimulation on skeletal development are well understood, although its effects on cartilage growth have yet to be investigated in the dystrophic condition. The objective of this study was to investigate the chondrogenic response to voluntary exercise in dystrophin-deficient mice.MethodsControl and dystrophin-deficient (mdx) mice were divided into sedentary and exercise-treated groups and tested for chondral histomorphometric differences at the proximal femur.ResultsControl mice ran 7 km/week further than mdx mice on average, but this difference was not statistically significant (P > 0.05). However, exercised control mice exhibited significantly enlarged femur head diameter, articular cartilage thickness, articular cartilage tissue area, and area of calcified cartilage relative to sedentary controls and exercised mdx mice (P < 0.05). No differences were found between other treatment groups.ConclusionsMdx mice exhibit a reduced chondrogenic response to increased mechanical stimulation relative to controls. However, no significant reduction in articular dimensions was found, indicating loss of chondral tissue may not be a clinical concern with dystrophinopathy.