Overall, doxorubicine-congestive heart failure (CHF) (male Wistar rats and NMRI mice; 6 challenges with doxorubicine (2.5 mg/kg, i.p.) throughout 15 days and then a 4-week-rest period) is consistently deteriorating throughout next 14 days, if not reversed or ameliorated by therapy (/kg per day): a stable gastric pentadecapeptide BPC157 (GEPPPGKPADDAGLV, MW 1419, promisingly studied for inflammatory bowel disease (Pliva; PL 10, PLD-116, PL 14736)) (10 microg, 10 ng), losartan (0.7 mg), amlodipine (0.07 mg), given intragastrically (i.g.) (once daily, rats) or in drinking water (mice). Assessed were big endothelin-1 (BET-1) and plasma enzyme levels (CK, MBCK, LDH, AST, ALT) before and after 14 days of therapy and clinical status (hypotension, increased heart rate and respiratory rate, and ascites) every 2 days. Controls (distilled water (5 ml/kg, i.g., once daily) or drinking water (2 ml/mouse per day) given throughout 14 days) exhibited additionally increased BET-1 and aggravated clinical status, while enzyme values maintained their initial increase. BPC157 (10 microg/kg) and amlodipine treatment reversed the increased BET-1 (rats, mice), AST, ALT, CK (rats, mice), and LDH (mice) values. BPC157 (10 ng/kg) and losartan opposed further increase of BET-1 (rats, mice). Losartan reduces AST, ALT, CK, and LDH serum values. BPC157 (10 ng/kg) reduces AST and ALT serum values. Clinical status of CHF-rats and -mice is accordingly improved by the BPC157 regimens and amlodipine.
Cadmium and other metallic ions can act as metalloestrogens and endocrine disruptors of reproductive tissues and fetal development in mammals, including humans. The detrimental effects occur with respect to the synthesis of both steroid and polypeptide hormones in the placenta. Leptin is produced by the trophoblast and may regulate fetal organogenesis and development. In human term placentas, concentrations of toxic metals and their effects on steroidogenesis were assessed in healthy parturients (109 non-smokers and 99 smokers) in relation to tobacco smoking. Trace elements (cadmium, lead, iron, zinc and copper) were analyzed in placentas using atomic absorption spectroscopy, and steroid hormones (progesterone and estradiol) were assayed in placental samples by an enzyme-immunometric method. Cadmium concentrations were doubled in placentas of smokers as compared with non-smokers, and placental lead and zinc concentrations increased significantly. Placental concentrations of iron, copper, progesterone and estradiol did not differ. In addition, human trophoblast cells were co-cultured with 0, 5, 10 or 20 microm CdCl(2) for 96 h and leptin mRNA assessed by quantitative polymerase chain reaction. Leptin mRNA declined dose-responsively as a result of CdCl(2) exposure. Collectively, the results confirm that human placental tissue offers a unique opportunity to biomonitor cadmium exposure in both the maternal and the internal fetal environments. In addition, the results strongly suggest that cadmium may cause a decline in placental leptin synthesis, as we have previously shown for placental progesterone production. This may constitute further evidence of the endocrine-disrupting effects of cadmium, as a constituent of tobacco smoke, on reproduction in women.
Bone morphogenetic protein-7 in tendon graft integration might be successfully used in reconstructive surgery of ligaments.
Androgens have important effects on the human skeleton, and deficiency has been associated with bone loss in both males and females. The skeletal actions of androgens may be mediated directly via the androgen receptor (AR) or indirectly via the estrogen receptor after aromatization to estrogens. The presence of androgen receptors has been demonstrated in bone cells and chondrocytes in vitro, but their presence in human bone in situ has not been reported. In order to provide further evidence for a direct action of androgens on bone via androgen receptors, we have used specific monoclonal antibodies to investigate the expression of human AR in normal developing and osteophytic bone of both sexes. In the growth plates from the developing bone, androgen receptors were predominantly expressed in hypertrophic chondrocytes and in osteoblasts at sites of bone formation. They were also observed in osteocytes in the bone, and in mononuclear cells and endothelial cells of blood vessels within the bone marrow. In the osteophytes, androgen receptors were widely distributed at sites of endochondral ossification in proliferating, mature, and hypertrophic chondrocytes and at sites of bone remodeling in osteoblasts. They were also expressed in osteocytes and mononuclear cells within the bone marrow. The pattern and number of cells expressing the receptor was similar in both sexes. Our results show for the first time the presence and distribution of androgen receptors in normal developing human and osteophytic bone in situ and further provide evidence for a direct action of androgens on bone and cartilage cells.
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