An implantable colloid osmometer. Measurements in subcutis and skeletal muscle of rats.

An implantable colloid osmometer has been developed for measurement of interstitial fluid colloid osmotic pressure (COP_i). Amicon hollow fibres with a cutoff at MW 10,000 were used as a semipermeable membrane. The osmometer has a length of 10–15 mm, an outer diameter of 0.35 mm, and is connected to a pressure transducer via a PE 20 catheter. The equlibration time was about 10 min. In vitro comparison to an ordinary membrane osmometer showed a coefficient of correlation of 0.99. When the osmometer is implanted in tissue, the pressure transducer read the sum of -COP_i (COP measured as a negative hydrostatic pressure, but defined as positive) and interstitial fluid hydrostatic pressure (P_i, positive or negative). In other words, the sum of the “interstitial Starling pressures” is measured directly. After perforation of the membrane, only P_i will be recorded. With intact membrane, implantation in rat subcutis (18 measurements in 8 rats) gave an average pressure of −10.8 (SD, 1.4) mm Hg. In skeletal muscle (17 measurements in 7 rats), the average pressure was −8.6 (SD, 2.1) mm Hg. With perforated membrane, pressures between −1 and 0 were obtained in both tissues, giving a COP_i of about 10 mm Hg in subcutis and 8 mm Hg in muscle. An increased pressure (less negative) could be recorded continuously or by reimplantation, while furosemide diuresis reduced the pressure.     

An acute increase in skeletal muscle carnitine content alters fuel metabolism in resting human skeletal muscle

CONTEXT: Carnitine plays an essential role in the integration of fat and carbohydrate oxidation in skeletal muscle, which is impaired in obesity and type 2 diabetes. OBJECTIVE: The aim of the present study was to investigate the effect of an increase in skeletal muscle total carnitine (TC) content on muscle fuel metabolism. DESIGN: A 5-h iv infusion of saline (control) or l-carnitine was administered while serum insulin was maintained at a physiologically high concentration during two randomized visits. PARTICIPANTS: Seven healthy, nonvegetarian young men (body mass index, 26.1 +/- 1.6 kg/m2) participated in the present study at the University of Nottingham. MAIN OUTCOME MEASURES: Skeletal muscle pyruvate dehydrogenase complex (PDC) activity and associated muscle metabolites were measured. RESULTS: The combination of hypercarnitinemia (600 micromol/liter) and hyperinsulinemia (160 mU/liter) increased muscle TC content by 15% (P < 0.01) and was associated with decreased pyruvate dehydrogenase complex activity (P < 0.05) and muscle lactate content (P < 0.05) by 30 and 40%, respectively, and an overnight increase in muscle glycogen (P < 0.01) and long-chain acyl-coenzyme A content (P < 0.05) by 30 and 40%, respectively, compared with control. CONCLUSIONS: These results suggest that an acute increase in human skeletal muscle TC content results in an inhibition of carbohydrate oxidation in conditions of high carbohydrate availability, possibly due to a carnitine-mediated increase in fat oxidation. These novel findings may have important implications for our understanding of the regulation of muscle fat oxidation, particularly during exercise, when carnitine availability may limit fat oxidation, and in obesity and type 2 diabetes where it is known to be impaired.     

Geometry of the capillary network in skeletal muscle.

The capillary branching pattern and the dimensions of the capillary network were studied in M. sartorius in frogs (Rana pipiens) after filling the microvasculature with the silicone elastomer “Microfil.” In contrast to a simple, binary-branching system, the arteriolar-capillary-venular system diverges immediately at the terminal arteriole and passes, via parallel interconnecting pathways to the venule, leading to a compact network without areas of insufficient supply. The mean value of total length for the capillary paths (3.58 ± 1.64 SD; n = 238) is governed by the distance between distributing artery and collecting vein, and the frequency distribution is Gaussian. Most paths branch repeatedly, forming one to nine segments; the number of branch points per path follows a Poisson distribution and, as would therefore be expected, the segment length distribution is exponential (mean = 0.85 mm ± 0.64 SD; n = 620). This suggests that, during growth of the network, branching occurs on a random basis along the vessel length. Possible reasons for capillary interconnections are considered. Measurements were made, for each successive order of branch point, of the number of capillaries arising, frequency of convergent and divergent branchings, and the percentage of rejoined vessels. By means of such data the geometry of the capillary network in different striated muscles could be compared, in a search for the general concepts underlying microvascular architecture.     

Microcirculation of the skeletal muscle

There are certain claudications deriving from over-intense or over-prolonged muscular activity, caused by excessive tissular pressure in the fascial cavity of the leg, anterior rather than lateral. This usually occurs in young subjects who are athletic, sportive, or soldiers. The clinical symptom is a sudden jab, like a whip-crack, both painful and paretic. The direct measurement of tissular pressure, using the needle method, confirms the excess of pressure already high when the patient is resting; it rises manifestly with muscular effort and slowly falls again after it. The pressure-gradient calls for fasciotomy in hyperalgetic cases from a certain tissular pressure-gradient onwards. Phlebography has shown the venous collapse and clinical attention is often in these cases to the presence of "muscular hernia" in the leg. Clinical data are self-explanatory and Reneman recently recalled this with a case of capillaro-venular stasis, followed by an excess of permeability and the formation of interstitial oedema which has a restraining effect. Structures and functions of the microcirculation of the skeletal muscle enable us to understand the phenomena.     

Hepatic imaging. An overview

For optimal detection and characterization of focal or diffuse liver disease, it is essential to obtain the most appropriate imaging test in the correct clinical setting. Access to clinical information and medical history is, therefore, essential. Moreover, familiarity with currently available modalities for imaging the liver [figure: see text] allows the optimal use of the technical advances in ultrasound imaging, CT scanning, MR imaging, and nuclear scintigraphy technology and contributes to improved diagnostic accuracy.     

Hepatocellular carcinoma. An overview

Hepatocellular carcinoma is a common malignancy affecting approximately one million people around the world every year. The incidence is low in the occidental world and high in locations such as Southeast Asia and sub-Saharan Africa. Hepatocellular carcinoma primarily affects old people, reaching its highest prevalence among those aged 65 to 69 years old. Chronic infection by the hepatitis B virus is the most common cause of this disease. Other important causes are cirrhosis, chronic viral hepatitis (hepatitis C virus, and hepatitis B plus D viruses), alcohol abuse, obesity, hemochromatosis, alfa1-antitripsin deficiency, and toxins similar to aflatoxin. In most cases, hepatocellular carcinoma is asymptomatic and has a low life expectancy. This article presents a review of the most important epidemiological, diagnostic and treatment data about this disease.     

Proof of the effect of testosterone on skeletal muscle.

In spite of the widespread abuse of androgenic steroids by athletes and recreational body-builders, the effects of these agents on athletic performance and physical function remain poorly understood. Experimentally induced androgen deficiency is associated with a loss of fat-free mass; conversely, physiologic testosterone replacement of healthy, androgen-deficient men increases fat-free mass and muscle protein synthesis. Testosterone supplementation of HIV-infected men with low testosterone levels and of older men with normally low testosterone concentrations also increases muscle mass. However, we do not know whether physiologic testosterone replacement can improve physical function and health-related quality of life, and reduce the risk of falls and disability in older men or those with chronic illness. Testosterone increases maximal voluntary strength in a dose-dependent manner and thus might improve performance in power-lifting events. However, testosterone has not been shown to improve performance in endurance events. The mechanisms by which testosterone increases muscle mass are not known, but probably involve alterations in the expression of multiple muscle growth regulators.     

Age-related alterations in the arterial microvasculature of skeletal muscle.

This study investigated the possibility that the aging process results in alterations in the structure and/or functional reactivity of the microvessels that could contribute to increased resistance to blood flow in working skeletal muscle. Initially, latex casts were made of the cremaster muscle microvasculature in adult (12 mo) and senescent (24 mo) male Fischer 344 rats. Although the average diameter was not different between age groups, segmental length (distance between adjacent branches) increased significantly (3rd order) during aging. Additionally, in vivo experiments were performed to determine the response of the vessels to the topical application of norepinephrine and adenosine. There was no increase in vasoconstriction produced by norepinephrine; however, the vasodilation in response to adenosine declined dramatically (1st and 2nd order) with advancing age. It can be concluded that the increase in skeletal muscle vascular resistance during contraction in aged male rats could be explained by morphological changes and/or the diminished vasodilation elicited by adenosine.     

Proteolysis and structure of skeletal muscle actin.

Under standard conditions, G-actin has been submitted to nine proteases of varying specificity, and in each case the pattern of fragments produced has been studied by NaDodSO4 gel electrophoresis. The results suggest that the actin monomer consists of a large region (ca. 33 kilodaltons) and a small, easily degraded region (ca. 9 kilodaltons). The COOH terminus is in the large region. Consideration of primary sequence homologies, medium resolution maps of actin crystals, and certain reactions of actin suggests that the NH2 terminus is in the small region, as is the negative sequence to which a divalent metal cation is normally chelated, but that the nucleotide-binding site is on the large region near the junction between the regions. From analysis of these results, numerous properties of actin are understandable.     

Protection of the ischemic skeletal muscle

This report (1) summarizes our current understanding of the nature of the revascularization syndrome and defines the patients most vulnerable to such damage, (2) details the principles for avoiding the revascularization syndrome evolving from our experimental work in the field of ischemic and reperfused skeletal muscle, (3) presents the clinical applicability of controlled reperfusion in skeletal muscle and our initial experience in patients, and (4) points to unresolved problems in the field of skeletal muscle protection.     

Evidence-based endocrinology. Finding the current best research evidence for practice in endocrinology.

New medical information is accumulating at an astonishing rate. It is available in many forms and flavors, and information seekers benefit from being discriminating in searches for answers to clinical problems. Few problems can be addressed satisfactorily simply by entering some relevant content terms into Medline. Such a search, unless the problem is rare, usually results in a flood of citations with no arrangement according to quality, and the user must determine painstakingly which citations are relevant and clinically useful. Fortunately, evidence-based information services are catching up with the growth of the medical literature. Such services organize and provide access to the current best evidence at the point of need. We have described a "4 S" hierarchy of evidence-based resources to help focus a practitioner's information seeking strategies, with systems at the highest level of organization, followed by synopses, syntheses, and studies. Practitioners should become familiar with the best access routes for regularly updated services of relevance to their interests and direct their inquiries initially to the highest level of organization of information that exists for their interests. Evidence-based resources continue to be created and evolve, so keeping an eye out for new resources and examining their pedigrees according to the "4 S" approach permit practitioners to assemble and organize an ever-improving personal evidence-based library for endocrinology.     

Imaging of skeletal muscle

Various diagnostic imaging techniques such as sonography, computed tomography, scintigraphy, radiography, and magnetic resonance imaging (MRI) have made possible the noninvasive evaluation of skeletal muscle injury and disease. Although these different modalities have roles to play, MRI is especially sensitive in the diagnosis of muscle disorders and injury and has proved to be useful in determining the extent of disease, in directing interventions, and in monitoring the response to therapies. This article describes how magnetic resonance images are formed and how the signal intensities in T1- and T2-weighted images may be used for diagnosis of the above-mentioned conditions and injuries.     

On the origin of the contractile force in skeletal muscle.

Analysis of the early tension responses after abrupt step changes in the length of isometrically contracting skeletal muscle shows that the magnitude of the recovery tension (T2) and the time dependence of this process at various step displacements give a good correlation with the behavior expected for a helix-coil transition in the subfragment-2 (S-2) region of myosin. The "instantaneous" tension response (to T1) after the step change in length appears to have its origin in compliance within the coil region of S-2, which is formed through helix melting at the moment of force generation.     

Sexuality and aging. An overview

To summarize our ramblings, we want to highlight the following points as you deal with the topic of sexuality and aging: 1. Sexuality, the mix of physical and relational behaviors that gives us both parenting and bonding, is lifelong, extending well beyond the reproductive years, and a normal factor in self-esteem and satisfaction. 2. Aged individuals need sexually and medically what people in general want and need, and the idea of an acceptable decline into a sexless state is insulting. 3. An immense amount of information is available to assist seniors in dealing with physical and emotional problems relating to sexuality, and much can be done by showing sensitivity and by breaking down the habits of concealing problems or attributing them to the demon of age. 4. In sexuality, as well as in all other areas, we need to recognize that older individuals will be present at society's table in increasing numbers and with increasing expectations, and it is up to society to make them welcome--now, because they include our parents, and in the future, because they will include ourselves.