Members of the muscarinic acetylcholine receptor family (M1-M5) have central roles in the regulation of many fundamental physiological functions. Identifying the specific receptor subtype(s) that mediate the diverse muscarinic actions of acetylcholine is of considerable therapeutic interest, but has proved difficult primarily because of a lack of subtype-selective ligands. Here we show that mice deficient in the M3 muscarinic receptor (M3R-/- mice) display a significant decrease in food intake, reduced body weight and peripheral fat deposits, and very low levels of serum leptin and insulin. Paradoxically, hypothalamic messenger RNA levels of melanin-concentrating hormone (MCH), which are normally upregulated in fasted animals leading to an increase in food intake, are significantly reduced in M3R-/- mice. Intra-cerebroventricular injection studies show that an agouti-related peptide analogue lacked orexigenic (appetite-stimulating) activity in M3R-/- mice. However, M3R-/- mice remained responsive to the orexigenic effects of MCH. Our data indicate that there may be a cholinergic pathway that involves M3-receptor-mediated facilitation of food intake at a site downstream of the hypothalamic leptin/melanocortin system and upstream of the MCH system.
Over the last eight years, the authors analyzed obstructive lymphedema of a unilateral upper extremity in a total of 27 females, comparing the use of supramicrosurgical lymphaticovenule anastomoses and/or conservative treatment. The most common cause of edema was mastectomy, with or without subsequent radiation therapy for breast cancer. As an objective assessment of the extent of edema, the circumferences of the affected and opposite normal forearms were measured at 10 cm below the olecranon of the arm. Twelve of these patients received continual bandaging. In these patients, the average excess circumference of the affected arm was 6.4 cm over that of the normal forearm; the average duration of edema before treatment was 3.5 years; the average period for conservative treatment was 10.6 months; and the average decrease in circumference was 0.8 cm (11.7 percent of the preoperative excess). Twelve patients underwent surgery and postoperative continual bandaging. In these patients, the average excess circumference was 8.9 cm; the average duration of edema before surgery was 8.2 years; the average follow-up after surgery was 2.2 years; and the average decrease in circumference was 4.1 cm (47.3 percent of the preoperative excess). These results indicated that supermicrolymphaticovenular anastomoses with postoperative bandaging have a valuable place in the treatment of obstructive lymphedema.
The antioxidant properties of three garlic preparations and organosulfur compounds in garlic have been determined. Aged garlic extract inhibited the emission of low level chemiluminescence and the early formation of thiobarbituric acid-reactive substances (TBA-RS) in liver microsomal fraction initiated by t-butyl hydroperoxide. However, the water extracts of raw and heat-treated garlic enhanced the emission of low level chemiluminescence. Among the variety of organosulfur compounds, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), the major organosulfur compounds found in aged garlic extract, showed radical scavenging activity in both chemiluminescence and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays, indicating that these compounds may play an important role in the antioxidative activity of aged garlic extract.
The superficial circumflex iliac artery perforator (SCIP) flap differs from the established groin flap in that it is nourished by only a perforator of the superficial circumflex iliac system and has a short segment (3 to 4 cm in length) of this vascular system. Three cases in which free superficial circumflex iliac artery perforator flaps were successfully transferred for coverage of soft-tissue defects in the limb are described in this article. The advantages of this flap are as follows: no need for deeper and longer dissection for the pedicle vessel, a shorter flap elevation time, possible thinning of the flap with primary defatting, the possibility of an adiposal flap with customized thickness for tissue augmentation, a concealed donor site, minimal donor-site morbidity, and the availability of a large cutaneous vein as a venous drainage system. The disadvantages are the need for dissection for a smaller perforator and an anastomosing technique for small-caliber vessels of less than 1.0 mm.
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