Alkaline phosphatase (ALP, EC 3.1.3.1) is a membrane-bound metalloenzyme that consists of a group of true isoenzymes, all glycoproteins, encoded for by at least four different gene loci: tissue-nonspecific, intestinal, placental, and germ-cell ALP. Through posttranslational modifications of the tissue-nonspecific gene, for example, through differences in carbohydrate composition, bone and liver ALP are formed. Nowadays, most commercially available methods for separating or measuring ALP isoenzymes are easy to perform and sensitive and allow for reproducible and quantitative results. As more isoenzymes and isoforms have been characterized, confusion has arisen due to the many different names they were given. For the sake of simplicity and because of structural analogies, we propose an alternative nomenclature for the ALP isoenzymes and isoforms based on their structural characteristics: soluble, dimeric (Sol), anchor-bearing (Anch), and membrane-bound (Mem) liver, bone, intestinal, and placental ALP. Together with lipoprotein-bound liver ALP and immunoglobulin-bound ALP, these names largely fit the many forms of ALP one can encounter in human serum and tissues. The clinically relevant isoenzymes are sol-liver, Mem-liver, lipoprotein-bound liver, and Sol-intestinal ALP in liver diseases, and Sol-bone and Anch-bone ALP in bone diseases. Many different isoenzyme patterns can be found in malignancies and renal diseases. This test provides the clinician with valuable information for diagnostic purposes as well as for follow-up of patients and monitoring of treatment. However, ALP isoenzyme determination will only provide clinically useful information if the patterns are correctly interpreted. In this respect, care should be taken to use the proper reference ranges, taking into account the age and sex of the patient. A normal total ALP activity does not rule out the presence of an abnormal isoenzyme pattern, particularly in children. Separating ALP into its isoenzymes adds considerable value to the mere assay of total ALP activity.

Background-Adiponectin is an antiinflammatory, insulin-sensitizing, and antiatherogenic adipocytokine that plays a fundamental role in energy homeostasis. In patients with chronic heart failure (CHF), high circulating adiponectin levels are associated with inverse outcome. Recently, adiponectin expression has been identified in human skeletal muscle fibers. We investigated the expression of adiponectin, the adiponectin receptors, and genes involved in the downstream lipid and glucose metabolism in the skeletal muscle of patients with CHF. Methods and Results-Muscle biopsies (vastus lateralis muscle) were obtained from 13 patients with CHF and 10 healthy subjects. mRNA transcript levels of adiponectin, adiponectin receptors (AdipoR1 and AdipoR2), and downstream adiponectin-related enzymes were quantified by real-time reverse transcriptase polymerase chain reaction. Adiponectin expression in the skeletal muscle of patients with CHF was 5-fold higher than in healthy subjects (PϽ0.001), whereas AdipoR1 was downregulated (Pϭ0.005). In addition, the expression of the main genes involved in downstream pathway (peroxisome proliferator-activated receptor-␣ [PPAR-␣] and both AMP-activated protein kinase-␣1 and -␣2 subunits) as well as their target genes in lipid (acyl-coenzyme A dehydrogenase C-14 to C-12 straight chain) and glucose metabolism (hexokinase-2) were significantly reduced in CHF. The strong positive correlation found between AdipoR1 and PPAR-␣/AMP-activated protein kinase gene expression was confirmed in PPAR-␣ null mice, suggesting a cause-and-effect relationship. Immunohistochemical staining confirmed the presence of adiponectin in the skeletal muscle. Conclusions-Despite increased adiponectin expression in the skeletal muscle, patients with CHF are characterized by downregulation of AdipoR1 that is most probably linked to deactivation of the PPAR-␣/AMP-activated protein kinase pathway. These facts suggest functional adiponectin resistance at the level of the skeletal muscle in CHF. (Circ Heart Fail. 2010;3:185-194.)

In view of the relative easy and accurate methodology for bone alkaline phosphatase determination, the closer physiological link with osteoblast function and the lesser expense for its determination we suggest that this marker is a useful tool in the non-invasive diagnosis of the adynamic type of bone disease in the individual patient.

Four months of combined endurance/resistance training significantly reduced circulating levels of NT-proBNP in patients with CHF, without evidence of adverse remodelling. Exercise training might offer additional non-pharmacological modulation of the activated neurohormonal pathways in the setting of CHF.