Bupivacaine-induced regeneration of rat soleus muscle: ultrastructural and immunohistochemical aspects

The regeneration of soleus muscle injury induced by the bupivacaine model was studied ultrastructurally and immunohistochemically. Twenty-one young (age range 3-3.5 months) male Wistar rats were subjected to a single intramuscular injection of 1 mL of 0.5% Marcaine. The muscles were examined on biopsy days 1, 2, 3, 5, 7, 14, and 21. By day 1, mononuclear inflammatory cells had invaded the necrotic sarcoplasm. Degenerative morphological findings counted mainly for the hypercontracted fibers, dilation of sarcoplasmic reticulum, plasma membrane defects, mitochondrial alterations, and myofibril discontinuities. By day 2 proliferating myoblasts were seen with variety in shape, which fused on the day 3. Myotubes with multiple central nuclei and euchromatic nucleoli were formed by day 5. Asynchronous repair events were seen with bundles of myofilaments toward the core of the fibers, in contrast to the least mature distal growth cones, which had free myoblasts in proximity and formatted pseudopods. Chronologically asynchronous regeneration stages possibly suggested successive satellite cell activation profiles or heterogeneity in satellite cell population. In parallel with the electron microscopy, in light microscope immunocytochemistry, desmin- and vimentin-positive mononuclear cells were observed within the first 3 biopsy days, but as regeneration proceeded, desmin predominated over vimentin. Merosin immunoreactivity revealed preservation of the basal lamina, which is crucial for the stability and survival of myotubes. By day 21, fibers restored the overall control architecture.     

Lifestyle factors and forearm bone density in young Greek men

OBJECTIVE: The aim of this study was to evaluate the effects of dietary factors (calcium, proteins, alcohol, coffee and tea intake), exercise, sunlight exposure and immobilization on bone mineral content (BMC) and bone mineral density (BMD) in young men. PATIENTS AND MEASUREMENTS: We examined a group of 300 healthy men, aged 18-30. Mean weight was 80-81 kg (53-125 kg range) and height 179 cm (160-195 cm range). Distal BMC (dBMC), distal BMD (dBMD) and ultradistal BMD (udBMD) at the radius were measured by single X-ray absorptiometry (Osteometer DTX). The data concerning lifestyle factors were obtained through a questionnaire. The 300 men were divided in four groups according to calcium intake, four groups taking into account protein and three groups alcohol intake. There also were five groups of exercise level, six groups of sun exposure and two groups of duration of immobilization. RESULTS: In the group with the lowest levels of calcium intake (< 400 mg/day), dBMD and udBMD were lower than in the other groups of calcium intake (P = 0.002). dBMC and udBMD were lower (P = 0.043 and 0.015, respectively) in subjects with low physical activity (< 2 h/week), whereas dBMC and udBMD were higher (P < 0.0005) in subjects with frequent sun exposure (group labelled 'very often'). Multiple regression analysis on bone mineral density of the forearm showed that, calcium intake, exercise and sunlight were also independent predictors of bone mass. No significant correlation between the other examined factors and BMD or BMC was detected. CONCLUSIONS: Calcium intake, exercise level and sun exposure showed a statistically significant correlation with distal BMD and BMC in young adult men.     

Effects of previous antiresorptive therapy on the bone mineral density response to two years of teriparatide treatment in postmenopausal women with osteoporosis

INTRODUCTION: EUROFORS was a 2-yr prospective, randomized trial of postmenopausal women with established osteoporosis, designed to investigate various sequential treatments after teriparatide 20 microg/d for 1 yr. The present secondary analysis examined the effects of 2 yr of open-label teriparatide in women previously treated with antiresorptive drugs for at least 1 yr. METHODS: A subgroup of 245 women with osteoporosis who had 2 yr of teriparatide treatment were stratified by previous predominant antiresorptive treatment into four groups: alendronate (n=107), risedronate (n=59), etidronate (n=30), and non-bisphosphonate (n=49). Bone mineral density (BMD) at the lumbar spine and hip was determined after 6, 12, 18, and 24 months, and bone formation markers were measured after 1 and 6 months. RESULTS: Significant increases in bone formation markers occurred in all groups after 1 month of teriparatide treatment. Lumbar spine BMD increased at all visits, whereas a transient decrease in hip BMD, which was subsequently reversed, was observed in all groups. BMD responses were similar in all previous antiresorptive groups. Previous etidronate users showed a higher increase at the spine but not at the hip BMD. Duration of previous antiresorptive therapy and lag time between stopping previous therapy and starting teriparatide did not affect the BMD response at any skeletal site. Treatment-emergent adverse events were similar to those reported in treatment-naive postmenopausal women with osteoporosis treated with teriparatide. CONCLUSIONS: Teriparatide induces positive effects on BMD and markers of bone formation in postmenopausal women with established osteoporosis, regardless of previous long-term exposure to antiresorptive therapies.     

Evaluation of the chronic toxicity and oncogenicity of N,N-diethyl-m- toluamide (DEET)

Chronic toxicity and/or oncogenicity studies were conducted in rats, mice, and dogs with the insect repellent DEET. DEET was mixed in the diet and administered to CD rats for two years at concentrations that corresponded to dosage levels of 10, 30 or 100 mg/kg/day for males and 30, 100, or 400 mg/kg/day for females; to CD-1 mice for 18 months at dosage levels of 250, 500, or 1000 mg/kg/day; and to dogs for one year, via gelatin capsules, at dosage levels of 30, 100, or 400 mg/kg/day. In the rodent studies, each group consisted of 60 animals of each sex, and two concurrent independent control groups, each containing 60 animals/sex were included in each study. Each group in the dog study consisted of four male and four female dogs and one control group was included in the study. Treatment-related effects were observed at the highest dose level in all three studies. For rats, the effects included decreases in body weight and food consumption and an increase in serum cholesterol in females only. In mice, the effects observed were decreases in body weight and food consumption in both sexes. The effects observed in dogs included increased incidences of emesis and ptyalism, and levels of transient reduction in hemoglobin and hematocrit, increased alkaline phosphatase (males only), decreased cholesterol, and increased potassium. One male dog in the high-dose group also exhibited ataxia, tremors, abnormal head movements, and/or convulsions on several occasions during the study. The highest no- observed-effect levels (NO-ELs) for rats, mice and dogs were determined to be 100, 500, and 100 mg/kg/day, respectively. No specific target organ toxicity or oncogenicity was observed in any of the studies.      

Balloon-dilatable arterial banding prosthesis: experimental study

Two arterial banding prostheses were developed that could be dilated by an intraluminal balloon dilator. One prosthesis consisted of radiopaque umbilical tape with a pleat secured by four 8-0 silk sutures thinly coated with silicone type A medical adhesive. This design was used to band the main pulmonary artery in five dogs, the subclavian artery in five, and the aorta in one. The second prosthesis, a stainless steel fatigued helix encased in a siliconized shield, was used to band the main pulmonary artery in two dogs and the descending aorta in two. After a mean duration of 89 days the bands were dilated with an intraluminal balloon dilator at 6 atm (608 kPa) of pressure for 30 seconds. In all 15 experiments the bands dilated and the gradient at the band was reduced. The stainless steel helix was more successful and has technical advantages for clinical application.     

hs-CRP is a potential predictor of no-reflow in patients with AMI after emergency PCI

The paper aims to determine whether the inflammation,a powerful risk factor that has been demonstrated for the development of coronary artery disease,plays a role in no-reflow phenomenon in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).Methods We prospectively analyzed 656 patients with AMI after primary PCI.Based on post-PCI angiography data,patients were divided into two groups:the no-reflow group (TIMI=2,n =60) and the reflow group (TIMI=3,n =596).Results Our results showed that the inflammatory factors including leukocyte count (×109/L) (10.90±4.04 vs.9.12±2.98 P =0.002),hs-CRP (5.04±0.71 vs.4.70±0.75 P =0.001) and other factor platelet count (×109/L) (210.96±33.42 vs.196.41±46.06 P =0.033) in no-reflow group are significantly higher than those in reflow group,major adverse cardiac events happened in the patients with no-reflow are higher than in reflow patients no matter in hospital or at the end of follow-up.We also found the left ventricular ejection fraction (LVEF) dramatically decreased (58.65±9.34 vs.51.29±11.38,P＜0.001) and left ventricular end-diastolic dimension (LVEDD) significantly increased (49.94±6.75 mm vs.54.66±6.68mm,P＜0.001) in no-reflow patients at the end of follow-up.Conclusions Our results suggest that inflammation factors function in no-reflow phenomenon,and no-reflow is a serious complication after primary PCI which predicts poor left ventricular systolic functional recovery and mortality in patients with AMI.(J Geriatr Cardiol 2008;5:217-222)     

Impaired prenatal and postnatal growth in Dutch patients with phenylketonuria. The National PKU Steering Committee

OBJECTIVE: To assess whether physical growth is affected in early treated Dutch patients with phenylketonuria (PKU). METHODS: The birth weights of all 137 early detected patients with PKU born in the period from 1974 to 1988 in the Netherlands were compared with reference values. Height, head circumference, and weight were measured at the age at which treatment started (commonly about 2-3 weeks), at 6 months of age, and yearly from the child's first birthday up to the age of 10 years. These measurements were compared with reference values. RESULTS: The adjusted birth weight in patients with PKU was 141 g (95% confidence interval (CI) 66 to 216 g) less than Dutch reference values by Kloosterman and 103 g (95% CI 9 to 196 g) less compared with the birth weight of another reference group. At the age at which treatment started, z scores of patients for height by age were -0.23 (95% CI -0.44 to -0.02) and z scores for head circumference by the age were -0.25 (95% CI -0.44 to -0.06). From the age at which treatment started up to the age of 3 years z scores for height by age further decreased to -0.74 (95% confidence interval -0.93 to -0.56), after which no additional decrease occurred. In contrast, z scores for head circumference increased from -0.25 at the first visit to 0.08 (95% CI -0.14 to 0.30) at the age of 1 year, after which they remained close to zero. Weight by height was close to the expected centiles for all ages. CONCLUSION: Patients with PKU are growth retarded at birth and have smaller head circumferences than the normal population. In Dutch patients further growth retardation occurs in the first three years of life.     

The effects of calcitonin on acute bone loss after pertrochanteric fractures. A prospective, randomised trial

We investigated the effect of calcitonin in the prevention of acute bone loss after a pertrochanteric fracture and its ability to reduce the incidence of further fractures in the same patient. Fifty women aged between 70 and 80 years who had a pertrochanteric fracture of the hip were randomly allocated to group A (200 IU of nasal salmon calcitonin daily for three months) or group B (placebo). Patients in group A showed a significantly higher level of total alkaline phosphatase and osteocalcin on the 15th day after injury and a significantly higher level of bone alkaline phosphatase on the 90th day after surgery. These patients also had significantly lower levels of urinary C-telopeptide (CrossLaps) on the 15th, 45th and 90th days after injury and lower levels of urinary hydroxyproline on the 15th and 45th days after injury. Patients in group A had significantly higher bone mineral density at all recorded sites except the greater trochanter at three months and one year after operation. After a four-year period of clinical observation, five patients (24%) in group B sustained a new fracture, in four of whom (20%) it was of the contralateral hip. Our findings show that calcitonin reduces acute bone loss in patients with pertrochanteric fractures and may prevent the occurrence of new fractures of the contralateral hip in the elderly.