BACKGROUND: Endothelial dysfunction, the initial pathogenic factor in atherosclerosis, can be alleviated via transient limb ischemia. We observed the effects of regular transient limb ischemia (RTLI) on atherosclerosis in hypercholesterolemic rabbits. METHODS: Twenty-eight rabbits were randomized to control, cholesterol, sham, ischemia groups (n = 7 each) between October 2010 and March 2011. They were fed a normal diet in the control group and hypercholesterolemic diet in other groups for 12 weeks. Six cycles of RTLI were performed once per day on the ischemia group. Serum samples were prepared to measure the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) before the experiment (W0), at the end of weeks 4, 8, 12 (W4, W8, W12). The whole aorta was harvested at W12 and stained using Sudan IV to identify the plaque. The plaque area was measured using Image J. Results were analyzed by analysis of variance or rank sum test. RESULTS: Concentrations of TC in the cholesterol group were higher than those in the control group at W4 (29.60 [23.75, 39.30] vs. 1.00 [0.80, 1.55], Z = -2.745, P = 0.006), W8 (41.78 [28.08, 47.37] vs. 0.35 [0.10, 0.68], Z = -2.739, P = 0.006), W12 (48.32 [40.04, 48.95] vs. 0.61 [0.50, 0.86], Z = -2.739, P = 0.006). Similar results were obtained for HDL-C and LDL-C. Serum concentrations of TC, HDL-C, and LDL-C in the hypercholesterolemic groups had no differences (all P > 0.05). The percentage of plaque area in the cholesterol group was higher than that in the control group (47.22 ± 23.89% vs. 0, Z = -2.986, P = 0.003). Square root of the percentage of plaque area was smaller in the ischemia group than that in the cholesterol (0.44 ± 0.13 vs. 0.67 ± 0.18, P = 0.014) or sham groups (0.44 ± 0.13 vs. 0.61 ± 0.12, P = 0.049). CONCLUSION In hypercholesterolemic rabbits, RTLI might prevent atherosclerosis progression by reducing the percentage of plaque area.
Animals ; Atherosclerosis ; blood ; prevention & control ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Extremities ; pathology ; Hypercholesterolemia ; blood ; Ischemic Attack, Transient ; blood ; Ischemic Postconditioning ; methods ; Male ; Rabbits ; Triglycerides ; blood

Ossification of the posterior longitudinal ligament (OPLL) can be defined as an ectopic ossification in the tissues of spinal ligament showing a hyperostotic condition. OPLL is developed mostly in the cervical spine and clinical presentations of OPLL are majorly myelopathy and/or radiculopathy, with serious neurological pathology resulting in paralysis of extremities and disturbances of motility lowering the quality of life. OPLL is known to be an idiopathic and multifactorial disease, which genetic factors and non-genetic factors including diet, obesity, physical strain on the posterior longitudinal ligament, age, and diabetes mellitus, are involved into the pathogenesis. Up to now, surgical management by decompressing the spinal cord is regarded as standard treatment for OPLL, although there might be the risk of development of reprogression of ossification. The molecular pathogenesis and efficient therapeutic strategy, especially pharmacotherapy and/or preventive intervention, of OPLL has not been clearly elucidated and suggested. Therefore, in this review, we tried to give an overview to the present research results on OPLL, in order to shed light on the potential pharmacotherapy based on molecular pathophysiologic aspect of OPLL, especially on the genetic/genomic factors involved into the etiology of OPLL.
Diabetes Mellitus ; Diet ; Drug Therapy ; Extremities ; Ligaments ; Longitudinal Ligaments ; Obesity ; Ossification, Heterotopic ; Paralysis ; Pathology ; Quality of Life ; Radiculopathy ; Spinal Cord ; Spinal Cord Diseases ; Spine

BACKGROUND AND PURPOSE: GNE myopathy is a rare progressive myopathy caused by biallelic mutations in the GNE gene, and frequently accompanied by rimmed vacuoles in muscle pathology. The initial symptom of foot drop or hip-girdle weakness eventually spreads to all limbs over a period of decades. Recent advances in pathophysiologic research have facilitated therapeutic trials aimed at resolving the core biochemical defect. However, there remains unsettled heterogeneity in its natural course, which confounds the analysis of therapeutic outcomes. We performed the first large-scale study of Korean patients with GNE myopathy. METHODS: We gathered the genetic and clinical profiles of 44 Korean patients with genetically confirmed GNE myopathy. The clinical progression was estimated retrospectively based on a patient-reported questionnaire on the status of the functional joint sets and daily activities. RESULTS: The wrist and neck were the last joints to lose antigravity functionality irrespective of whether the weakness started from the ankle or hip. Two-thirds of the patients could walk either independently or with an aid. The order of losing daily activities could be sorted from standing to eating. Patients with limb-girdle phenotype showed an earlier age at onset than those with foot-drop onset. Patients with biallelic kinase domain mutations tended to progress more rapidly than those with epimerase and kinase domain mutations. CONCLUSIONS: The reported data can guide the clinical management of GNE myopathy, as well as provide perspective to help the development of clinical trials.
Age of Onset ; Ankle ; Disease Progression ; Eating ; Extremities ; Foot ; Hip ; Humans ; Joints ; Muscular Diseases ; Muscular Dystrophies, Limb-Girdle ; Neck ; Pathology ; Phenotype ; Phosphotransferases ; Population Characteristics ; Retrospective Studies ; Surveys and Questionnaires ; Vacuoles ; Wrist

Aged ; Biopsy ; methods ; Diagnosis, Differential ; Erythema ; diagnosis ; etiology ; Extremities ; pathology ; Fever ; complications ; Humans ; Immunoglobulin A ; analysis ; Male ; Purpura ; diagnosis ; etiology ; Skin ; diagnostic imaging ; pathology ; Vasculitis ; complications ; immunology

BACKGROUND: Stroke involving the cerebral white matter (WM) has increased in prevalence, but most experimental studies have focused on ischemic injury of the gray matter. This study was performed to investigate the WM in a unique rat model of photothrombotic infarct targeting the posterior limb of internal capsule (PLIC), focusing on the identification of the most vulnerable structure in WM by ischemic injury, subsequent glial reaction to the injury, and the fundamental histopathologic feature causing different neurologic outcomes. METHODS: Light microscopy with immunohistochemical stains and electron microscopic examinations of the lesion were performed between 3 hours and 21 days post-ischemic injury. RESULTS: Initial pathological change develops in myelinated axon, concomitantly with reactive change of astrocytes. The first pathology to present is nodular loosening to separate the myelin sheath with axonal wrinkling. Subsequent pathologies include rupture of the myelin sheath with extrusion of axonal organelles, progressive necrosis, oligodendrocyte degeneration and death, and reactive gliosis. Increase of glial fibrillary acidic protein (GFAP) immunoreactivity is an early event in the ischemic lesion. WM pathologies result in motor dysfunction. Motor function recovery after the infarct was correlated to the extent of PLIC injury proper rather than the infarct volume. CONCLUSIONS: Pathologic changes indicate that the cerebral WM, independent of cortical neurons, is highly vulnerable to the effects of focal ischemia, among which myelin sheath is first damaged. Early increase of GFAP immunoreactivity indicates that astrocyte response initially begins with myelinated axonal injury, and supports the biologic role related to WM injury or plasticity. The reaction of astrocytes in the experimental model might be important for the study of pathogenesis and treatment of the WM stroke.
Astrocytes ; Axons ; Coloring Agents ; Extremities ; Glial Fibrillary Acidic Protein ; Gliosis ; Gray Matter ; Internal Capsule* ; Ischemia ; Microscopy ; Models, Animal ; Models, Theoretical ; Myelin Sheath ; Necrosis ; Neurons ; Oligodendroglia ; Organelles ; Pathology ; Plastics ; Prevalence ; Recovery of Function ; Rupture ; Stroke ; White Matter

Cap myopathy is pathologically characterized by cap structures comprising well-demarcated areas under the sarcolemma and containing deranged myofibrils and scattered Z-disks. Clinically it presents with slowly progressive muscle weakness, myopathic face, and frequent respiratory insufficiency. Four genes have been reported to be associated with the disease: TPM2, TPM3, ACTA1, and NEB. Here we describe that a patient presenting with mild limb weakness with facial affection showed cap structures on muscle pathology and carried a heterozygous TPM3 mutation.
Extremities ; Humans ; Muscle Weakness ; Muscular Diseases* ; Mutation, Missense* ; Myofibrils ; Pathology ; Respiratory Insufficiency ; Sarcolemma ; Tropomyosin

OBJECTIVE: To map the progression of osteoporosis following spinal cord injury in mice in specific areas and analyze changes in parathyroid hormone (PTH) and ion levels which could be responsible for overall bone loss. SUMMARY OF BACKGROUND DATA: Spinal cord injury rapidly induces severe bone loss compared to other conditions, yet the cause of this bone loss has not been identified. Studies suggest the bone loss after injury is not solely due to disuse. METHODS: To quantify bone loss we weighed individual bones and measured bone mineral density using dual energy X-ray absorptiometry at acute (1 week) and chronic (4 week) time points following a T9 contusion. An ELISA was used to measure blood PTH levels at 1 and 4 weeks after injury. Calcium and phosphate levels were also analyzed at 4 weeks following injury at the University of Miami pathology core. RESULTS: We observed a significant decrease in bone mineral density in hind limbs after an acute injury, and found this bone loss to progress over time. Furthermore, following chronic injury a decrease in bone mineral density is also observed in bones above the level of injury and in the total bone mineral density. We observed a significant decrease in parathyroid hormone levels in injured mice at the chronic time point, but not at the acute time point which suggests this could be involved in the global bone loss following injury. We also observed a significant increase in serum calcium levels following injury which could account for the imbalance of PTH levels.
Absorptiometry, Photon ; Animals ; Bone Density ; Calcium ; Contusions ; Enzyme-Linked Immunosorbent Assay ; Extremities ; Mice* ; Osteoporosis ; Parathyroid Hormone ; Pathology ; Spinal Cord Injuries* ; Spinal Cord*

OBJECTIVETo determine the effective dosage and formulation of agkistrodon in collagen-induced arthritis (CIA) rats.

METHODSCIA was induced by injection of collagen in complete/incomplete Freund's adjuvant. Agkistrodon decoction, agkistrodon powder, and agkistrodon wine were administered daily starting from the onset of arthritis. Paw swelling degree was measured by using a volume-measuring instrument every 7 days after primary immunization. Arthritis index was measured and calculated using the "five scoring method" every 7 days. The levels of serum interleukin-1ß (IL-1ß) and type II collagen IgG antibodies were detected by enzyme-linked immunosorbent assay. Finally, all ankles were removed, and X-ray radiography was performed with In-vivo Imaging System FX. Samples were counterstained with hematoxylin and eosin for analysis.

RESULTSAmong the various dosage formulations of agkistrodon, high-dose powder, which was equivalent to an amount of 6 g/day in adults, showed better effects on the inhibition of joint swelling and reduction of arthritis index score. The relatively low levels of serum IL-1 and anti-type II collagen IgG antibodies, as well as the X-ray radiography and pathology results, further proved the superiority of the high-dose powder over the other formulations. The effect of decoction on inhibiting joint swelling was inversely proportional to the dosage. Other effects, such as reduction of arthritis index score and the levels of serum IL-1 and anti-type II collagen IgG antibodies, were directly proportional to the dosage. While the use of large dose agkistrodon wine led to negative effects.

CONCLUSIONThese data highlight the potential function of high-dose agkistrodon powder, which was equivalent to an amount of 6 g/day in adults. The powder can quickly relieve the symptoms of rheumatoid arthritis and prevent aggravation of disease, especially during the early period.

Agkistrodon ; metabolism ; Animals ; Antibodies ; blood ; Arthritis, Experimental ; blood ; chemically induced ; drug therapy ; Collagen Type II ; immunology ; Dosage Forms ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay ; Extremities ; diagnostic imaging ; pathology ; Female ; Interleukin-1beta ; blood ; Medicine, Chinese Traditional ; Rats, Wistar

Ablation Techniques ; adverse effects ; Animals ; Bone and Bones ; pathology ; Disease Models, Animal ; Extremities ; Swine

OBJECTIVETo observe the clinical efficacy of negative pressure wound therapy (NPWT) in combination with porcine acellular dermal matrix (ADM) dressing for repairing deep burn wounds in limbs of patients with non-surgical treatment.

METHODSThirty-two patients with deep partial-thickness burn to full-thickness burn on the limbs admitted to our ward from June 2012 to December 2015, conforming to the inclusion criteria, were divided into group NPWT (n=10, treated with interval negative pressure drainage at -16.6 kPa), group ADM (n=7, treated with porcine ADM dressing), and group NPWT+ ADM (n=15, treated with interval negative pressure drainage and porcine ADM dressing as above) according to the random number table and patient's consent. After being treated for 21 d, residual wounds were cured by routine dressing change using sulfadiazine silver. On post treatment day (PTD) 7, 14, and 21, wound gross observation was conducted, wound drainage fluid volume was recorded, and wound healing rate was calculated. Wound secretion was collected for bacterial culture before treatment and on PTD 21, and bacterial clearance effect was recorded. The wound healing time was also recorded. Measurement data were processed with analysis of variance for repeated measurement, one-way analysis of variance, and LSD test. Eenumeration data were processed with chi-square test or Fisher's exact test.

RESULTS(1) On PTD 7, the wounds of patients in group NPWT and group NPWT+ ADM were significantly shrinked as compared with those before treatment. Skin paddle scattered on the wounds of patients in group NPWT+ ADM on PTD 7. The wounds of patients in group ADM were slightly shrinked on PTD 7 as compared with those before treatment. On PTD 14, the wounds of patients in group NPWT were slightly shrinked as compared with those on PTD 7, while those in group NPWT+ ADM were significantly shrinked as compared with those on PTD 7. Skin paddle on the wounds of patients in group NPWT+ ADM on PTD 14 were increased and fused. The wounds of patients in group ADM were significantly shrinked on PTD 14 as compared with those on PTD 7. On PTD 21, partial wounds of patients in group NPWT were healed, while the wounds of patients in group ADM were slightly shrinked in comparison with those on PTD 14 and most of wounds were not healed. Most of wounds of patients in group NPWT+ ADM were healed. (2) On PTD 7, the wound drainage fluid volumes of patients in group NPWT and group NPWT+ ADM were obviously more than the wound drainage fluid volume of patients in group ADM (with P values below 0.01). On PTD 14, the wound drainage fluid volume of patients in group NPWT was significantly more than that in group ADM (P<0.01); while that between group ADM and group NPWT+ ADM was close (P>0.05). On PTD 21, the wound drainage fluid volume of patients in group NPWT and group NPWT+ ADM was significantly less than that in group ADM (with P values below 0.01). From PTD 7 to 21, the wound drainage fluid volumes of patients in group NPWT+ ADM were significantly reduced as compared with those in group NPWT (with P values below 0.01). (3) On PTD 7, the wound healing rates of patients in group ADM and group NPWT+ ADM were significantly lower than the wound healing rate of patients in group NPWT (P<0.05 or P<0.01), and the wound healing rate of patients in group NPWT+ ADM was significantly higher than that in group ADM (P<0.01). On PTD 14 and 21, the wound healing rates of patients in group NPWT+ ADM were significantly higher than those in group NPWT and group ADM (with P values below 0.01), and the wound healing rates of patients in group NPWT were significantly higher than those in group ADM (with P values below 0.01). (4) Before treatment, the bacteria were respectively detected in 18, 11, and 23 wounds of patients in group NPWT, group ADM, and group NPWT+ ADM. On PTD 21, the bacteria were respectively detected in 2, 8, and 2 wounds of patients in group NPWT, group ADM, and group NPWT+ ADM. The bacterial clearance of wounds of patients in group NPWT and group NPWT+ ADM was significantly better than that of patients in group ADM (with P values below 0.01). The bacterial clearance of wounds of patients in group NPWT+ ADM was close to that in group NPWT (P=1.00). (5) The wound healing time of patients in group NPWT+ ADM was (18.7±1.2) d, which was significantly shorter than that in group NPWT [(23.9±1.5) d] and group ADM [(28.4±1.8) d], with P values below 0.01. The wound healing time of patients in group NPWT was significantly shorter than that in group ADM (P<0.01).

CONCLUSIONSNPWT combined with porcine ADM dressing can effectively remove wound bacteria, reduce wound exudation, and promote wound healing in repairing deep partial-thickness burn wounds and full-thickness burn wounds. Its clinical effect is better than NPWT or porcine ADM dressing alone, and this method may be suitable for patients with non-surgical treatment.

Acellular Dermis ; Animals ; Bandages ; Burns ; therapy ; Extremities ; pathology ; Humans ; Negative-Pressure Wound Therapy ; Swine ; Treatment Outcome ; Wound Healing