Physical activity and bone mass: exercises in futility?

Growing bone responds to low or moderate exercise through significant additions of new bone in both cortical and trabecular moieties and results in adaptation through periosteal expansion and endocortical contraction. Intracortical activation frequency declines in growing bone in response to exercise, reducing porosity and the remodelling space. These adaptations can be maintained into and throughout adulthood. Young bones have a greater potential for periosteal expansion than aging bone, allowing them to adapt more rapidly and efficiently to an acute need for increased strength, but a threshold level of activity exists above which some bones respond negatively by suppressing normal growth and modelling activity, reducing geometric, mechanical and material properties in cortical and trabecular bone. From cross-sectional studies, differences in bone mass between exercising and non-exercising adults are generally less than 10%, but do not account for exercise history which may be very important, and often fail to consider important confounding variables. There is sufficient longitudinal data to demonstrate that moderate to intensive training can bring about modest increases of about 1-3% in bone mineral content (BMC) of men and premenopausal women. In young adults very strenuous training may increase BMC of the tibia up to 11% and its bone density (BD) by 7%, but may represent periosteal woven bone formation in response to excessive strain. Some evidence shows that exercise can also add bone mass to the post-menopausal skeleton, although the amounts are site-specific and relatively modest. Increases as high as 5-8% can be found after 1-2 years of intensive exercise, but additions of bone to the femur and radius are generally less than 2%, well within the range of the remodelling space and measurement precision. Although increases in bone mass of the post-menopausal skeleton may be extremely modest, physical activity is important to preserve bone mass and muscle function. Detraining reduces any bone mass increase to pre-existing values so that long-term benefits are only retained with continuing exercise. Most importantly, the amount of bone gain that can be achieved appears dependent primarily on the initial bone mass suggesting that individuals with extremely low initial bone mass may have more to gain from exercise than those with moderately reduced bone mass.     

Electron transfer reactions in RB90745, a bioreductive drug having both aromatic N-oxide and nitroarene moieties

This study defines the current modes of treatment of patients with uterine fibromas with a review of the literature. Progesterone treatments appear to be principally used in cases of minor functional symptomatology and we discuss recent studies of mifepristone. GnRH agonists are particularly effective in preoperative treatment for conservative surgery. The indications and results of hysteroscopic resection and laparoscopic myomectomy are compared to those of classic myomectomy and hysterectomy. The indications for myolysis are discussed.     

Postischemic hyperglycemia worsens neurologic outcome after spinal cord ischemia

PURPOSE: The neurologic effect of induced hyperglycemia in the postischemic period was investigated with a rat aortic occlusion model. METHODS: Sprague-Dawley rats weighing 200 to 350 gm were anesthetized, intubated, and ventilated with 1% to 1.5% halothane. Temperature was continuously monitored and maintained at 37 degrees +/- 0.5 degrees C. The chest was opened, the thymus excised, and the aortic arch exposed. Snares were placed around the aorta distal to the left subclavian artery and the right and left subclavian arteries. The three vessels thus isolated were occluded for 8 minutes. With snare release and withdrawal, the rats received an intraperitoneal injection of 5% dextrose in water (2 gm/kg) or an equivalent volume of 0.9% saline solution. In a second group of rats the administration of glucose or saline solution was delayed until 30 minutes after snare release. Blood samples for blood glucose determination were obtained before operation, before occlusion, immediately after occlusion, and 15, 30, 45, 60, and 240 minutes after occlusion. A neurologic deficit score was assigned at 1, 4, 18, and 24 hours after occlusion to quantify hindlimb neurologic deficit based on 15-point scale (0 = normal, 15 = severe deficit). Sham-operated rats received the same operation and injection, but the snares were only manipulated and not made occlusive. RESULTS: The rats that were administered glucose immediately after snare release showed a statistically significant exacerbation of lower extremity neurologic deficit at 24 hours after occlusion (p < or = 0.05, Mann-Whitney U test). The sham-operated rats were normal (0 score) at 24 hours. Significant elevation of blood glucose (321 +/- 33 mg/dl) was seen in the glucose-injected rats at 15 minutes and continued for up to 4 hours after occlusion (p = 0.040 and 0.014, respectively; Student's t test). CONCLUSION: Postischemic hyperglycemia immediately after a standard spinal cord ischemic stress worsens neurologic outcome.     

Interactions between normal and tumoral tissues at the boundary of human anterior pituitary adenomas. An immunohistochemical study

Previously, the species complex Oncomelania hupensis, individuals of which act as intermediate hosts for the human bloodfluke Schistosoma japonicum, has been characterised by morphological and isoenzyme criteria. We have examined genetic variation between and within three subspecies of Oncomelania hupensis, i.e. O. h. hupensis (China), O. h. quadrasi (Philippines) and O. h. nosophora (Japan), by direct means using a PCR-based RFLP method. The subspecies of O. hupensis were readily distinguished by their characteristic restriction patterns, supporting isoenzyme data which suggests these may warrant species-specific status. No genetic variation was observed between O. h. quadrasi from different islands within the Philippines. In contrast, geographical isolates of O. h. hupensis differed markedly by this method indicating several genetically distinct populations of O. h. hupensis occur in China.     

Protein adsorption onto poly(ether urethane ureas) containing Methacrol 2138F: a surface-active amphiphilic additive

Surface characterization and protein adsorption studies were carried out on a series of additive dispersed and additive coated poly(ether urethane ureas), PEUUs, to characterize early events in the blood compatibility of these materials. A hypothesis that is based on surface hydrophilicity, surface flexibility, and adsorption media has been developed to understand the modulated adsorption of plasma proteins by PEUU additives. Electron spectroscopy for chemical analysis (ESCA) and contact angle analysis were performed on two PEUU formulation as well as on PEUU formulations modified with Methacrol 2138F (co[diisopropylaminoethyl methacrylate (DIPAM)/decyl methacrylate (DM)][3/1]) or acrylate or methacrylate polymer or copolymer analogs of Methacrol 2138F. Methacrol 2138F is a commercially used amphiphilic copolymethacrylate. ESCA showed that the PEUUs loaded with Methacrol 2138F or with its hydrophilic component, homopoly (DIPAM) (h-(DIPAM)), had a higher percentage of nitrogen at their surfaces than did the base PEUUs. Contact angle analysis also showed that the air side of PEUU formulations loaded with Methacrol 2138F were more hydrophobic than was the air side of base PEUUs when films were cast from dimethylacetamide. However, during contact angle testing, the air side of PEUU films loaded with Methacrol 2138F rapidly became more hydrophilic than did the air side of the base PEUU films. A radioimmunoassay and whole or diluted human plasma were also used to characterize the presence of the proteins fibrinogen, immunoglobulin G, factor VIII/von Willebrand factor, Hageman factor (factor XII), and albumin, on the surface of the same PEUUs as analyzed by ESCA and contact angle. The protein adsorption assay showed that PEUU films loaded or coated with Methacrol 2138F, with a copolyacrylate analog of Methacrol 2138F (co(diisopropylaminoethyl acrylate [DIPAA]/decyl acrylate [DA]) [3/1]), or with the hydrophilic polyacrylate or polymethacrylate component analogs of Methacrol 2138F (h-DIPAM or h-DIPAA) adsorbed significantly lower amounts of the proteins than did either the base PEUU formulations or the homopoly(decyl methacrylate) (h-DM) or homopoly(decyl acrylate) (h-DA) coated or loaded PEUUs.     

Targeted overexpression of protein kinase C beta2 isoform in myocardium causes cardiomyopathy

Increased cardiovascular mortality occurs in diabetic patients with or without coronary artery disease and is attributed to the presence of diabetic cardiomyopathy. One potential mechanism is hyperglycemia that has been reported to activate protein kinase C (PKC), preferentially the beta isoform, which has been associated with the development of micro- and macrovascular pathologies in diabetes mellitus. To establish that the activation of the PKCbeta isoform can cause cardiac dysfunctions, we have established lines of transgenic mice with the specific overexpression of PKCbeta2 isoform in the myocardium. These mice overexpressed the PKCbeta2 isoform transgene by 2- to 10-fold as measured by mRNA, and proteins exhibited left ventricular hypertrophy, cardiac myocyte necrosis, multifocal fibrosis, and decreased left ventricular performance without vascular lesions. The severity of the phenotypes exhibited gene dose-dependence. Up-regulation of mRNAs for fetal type myosin heavy chain, atrial natriuretic factor, c-fos, transforming growth factor, and collagens was also observed. Moreover, treatment with a PKCbeta-specific inhibitor resulted in functional and histological improvement. These findings have firmly established that the activation of the PKCbeta2 isoform can cause specific cardiac cellular and functional changes leading to cardiomyopathy of diabetic or nondiabetic etiology.     

Abnormal carnitine distribution in the muscles of patients with idiopathic inflammatory myopathy

OBJECTIVE: To analyze the levels of free carnitine and carnitine esters in the muscles of patients with inflammatory myopathies. METHODS: Six men and 7 women with inflammatory myopathy and 25 age-matched healthy controls were studied. Free carnitine and carnitine esters in muscle homogenates were measured by a radiochemical procedure. Muscle histochemical staining and measurement of respiratory chain enzyme activity were also performed. RESULTS: Eleven patients had muscle carnitine insufficiency. Five of them had subsarcolemmal oxidative accumulations, 5 had lipid droplets, and 4 had defects of the respiratory chain enzyme complexes. CONCLUSION: Abnormal distribution of muscle carnitine is present in patients with inflammatory myopathies and could impair muscle function. Coexistent mitochondrial dysfunction may contribute to carnitine insufficiency.     

Evidence for a catabolic role of glucagon during an amino acid load

Despite the strong association between protein catabolic conditions and hyperglucagonemia, and enhanced glucagon secretion by amino acids (AA), glucagon's effects on protein metabolism remain less clear than on glucose metabolism. To clearly define glucagon's catabolic effect on protein metabolism during AA load, we studied the effects of glucagon on circulating AA and protein dynamics in six healthy subjects. Five protocols were performed in each subject using somatostatin to inhibit the secretion of insulin, glucagon, and growth hormone (GH) and selectively replacing these hormones in different protocols. Total AA concentration was the highest when glucagon, insulin, and GH were low. Selective increase of glucagon levels prevented this increment in AA. Addition of high levels of insulin and GH to high glucagon had no effect on total AA levels, although branched chain AA levels declined. Glucagon mostly decreased glucogenic AA and enhanced glucose production. Endogenous leucine flux, reflecting proteolysis, decreased while leucine oxidation increased in protocols where AA were infused and these changes were unaffected by the hormones. Nonoxidative leucine flux reflecting protein synthesis was stimulated by AA, but high glucagon attenuated this effect. Addition of GH and insulin partially reversed the inhibitory effect of glucagon on protein synthesis. We conclude that glucagon is the pivotal hormone in amino acid disposal during an AA load and, by reducing the availability of AA, glucagon inhibits protein synthesis stimulated by AA. These data provide further support for a catabolic role of glucagon at physiological concentrations.     

Early and intensive physiotherapy accelerates recovery postarthroscopic meniscectomy: results of a randomized controlled study

The efficacy of an early, intensive, supervised rehabilitation program to accelerate knee strength recovery in the first 3 weeks postmeniscectomy by arthroscopy was evaluated using a randomized controlled trial design. The maximal voluntary isokinetic strength of 31 men, randomly allocated to either a treatment (EXP) or a control (CTL) group, was measured twice by a blind rater: preoperatively (pretest) and 3 weeks postsurgery (posttest), using a computer-controlled Kin-Com dynamometer (Chattecx Corporation, Chattanooga, TN). Strength deficits of the operated leg at the pretest and posttest were established in percent of the values obtained for the sound leg at the pretest. In the interval between the surgery and the posttest, the patients of the EXP group (n = 15) received nine supervised treatments combined to home exercises whereas patients of the control group (n = 16) had no specific physiotherapy treatment but were given instructions in postsurgical management and prescribed exercises by the orthopedic surgeons. Patients of the EXP group had better knee extensor strength recovery than patients of the CTL group (ANCOVA, p < 0.001). The size of the strength difference (3 weeks postsurgery) between EXP and CTL subgroups (n = 8) matched according to preoperative deficits was as large as 26% and the residual deficits of the untreated patients were two to three times larger than those of the treated patients. The results of this study highlight the importance of instituting an early intensive and supervised rehabilitation program, especially for workers returning to a strenuous job requiring good knee extensor muscle function.