Adipose zinc-α2-glycoprotein is a catabolic marker in cancer and noncancerous states.

OBJECTIVE: Zinc-α2-glycoprotein (ZAG) has been proposed as a tumour-derived cancer cachexia factor. However, ZAG is produced by some normal tissues, including white adipose tissue (WAT), and high serum ZAG levels are present in nonmalignant conditions. We determined whether human WAT contributes to serum ZAG levels and how serum and WAT-secreted ZAG levels correlate with catabolism in patients with cancer and in obese subjects undergoing a very low-calorie diet (VLCD) for 11 days. DESIGN/SUBJECTS: ZAG levels in serum and in conditioned medium from WAT/adipocytes were determined by enzyme-linked immunosorbent assay. ZAG release from WAT in vivo was determined in 10 healthy subjects. The correlation between ZAG and cachexia was studied in 34 patients with newly diagnosed gastrointestinal cancer. The impact of a VLCD on ZAG release and serum levels was assessed in 10 obese women. RESULTS: ZAG was released from abdominal WAT and adipocytes in vitro. However, the arteriovenous differences in vivo showed that there was no significant contribution of WAT to the circulating levels. WAT-secreted but not serum ZAG correlated positively with poor nutritional status but not with fat mass (or body mass index) in patients with gastrointestinal cancer. In obese subjects on a VLCD, ZAG secretion from WAT increased significantly whereas serum levels remained unaltered. CONCLUSIONS: ZAG is released from human WAT, but this tissue does not contribute significantly to the circulating levels. WAT-secreted ZAG correlates with nutritional status but not with fat mass in both cancer and nonmalignant conditions. Adipose ZAG is therefore a local factor activated primarily by the catabolic state per se.

Adipose tissue pathways involved in weight loss of cancer cachexia.

BACKGROUND: The regulatory gene pathways that accompany loss of adipose tissue in cancer cachexia are unknown and were explored using pangenomic transcriptome profiling. METHODS: Global gene expression profiles of abdominal subcutaneous adipose tissue were studied in gastrointestinal cancer patients with (n=13) or without (n=14) cachexia. RESULTS: Cachexia was accompanied by preferential loss of adipose tissue and decreased fat cell volume, but not number. Adipose tissue pathways regulating energy turnover were upregulated, whereas genes in pathways related to cell and tissue structure (cellular adhesion, extracellular matrix and actin cytoskeleton) were downregulated in cachectic patients. Transcriptional response elements for hepatic nuclear factor-4 (HNF4) were overrepresented in the promoters of extracellular matrix and adhesion molecule genes, and adipose HNF4 mRNA was downregulated in cachexia. CONCLUSIONS: Cancer cachexia is characterised by preferential loss of adipose tissue; muscle mass is less affected. Loss of adipose tissue is secondary to a decrease in adipocyte lipid content and associates with changes in the expression of genes that regulate energy turnover, cytoskeleton and extracellular matrix, which suggest high tissue remodelling. Changes in gene expression in cachexia are reciprocal to those observed in obesity, suggesting that regulation of fat mass at least partly corresponds to two sides of the same coin.

Intra-arterial injection of prolactin-releasing peptide elevates prolactin gene expression and plasma prolactin levels in rainbow trout.

Prolactin-releasing peptide (PrRP), recently isolated from the brain of mammals and teleosts, is a strong candidate for being a stimulatory hormone of pituitary prolactin secretion. The present study examined whether or not PrRP is capable of inducing prolactin gene expression and elevating plasma prolactin levels in vivo in cannulated rainbow trout. Following a single intra-arterial injection of chum salmon PrRP (40 nmol kg(-1)) through a dorsal aorta catheter, plasma prolactin levels increased (P<0.05) rapidly (2 min and 30 min), and prolactin mRNA levels were elevated (P<0.05) in pituitaries sampled 8 h after the injection. In contrast, plasma levels of somatolactin were decreased (P<0.05) and growth hormone and somatolactin mRNA levels were not significantly affected by PrRP. Thus, PrRP appears to be a potent prolactin secretagogue as well as prolactin transcription inducer in vivo in the rainbow trout.

Growth hormone endocrinology of Atlantic salmon (Salmo salar): pituitary gene expression, hormone storage, secretion and plasma levels during parr-smolt transformation.

A number of studies on the Atlantic salmon (Salmo salar), have reported changes in plasma GH during parr-smolt transformation, but there is a lack of information about the endocrinology of the GH system during this process. In order to elucidate the mechanisms underlying these changes in plasma GH levels during the parr-smolt transformation of Atlantic salmon, GH mRNA expression in the pituitary was studied together with total pituitary GH content, in vitro GH secretion rate and plasma GH and IGF-I levels. Atlantic salmon were kept in outside tanks, under natural condition from early February until late June. Approximately three times a month fish were killed and pituitaries and blood were sampled for investigation. Further, pituitaries were moved to the laboratory for in vitro GH secretion studies. The results show that the GH system is first activated by an increase in GH secretion rate, which leads to an increase in plasma GH levels and causes a drop in the total GH content of the pituitary. This drop in pituitary GH content is later reversed by an increased GH synthesis seen as an increase in GH mRNA expression. Maximal activation of the GH system is seen to occur in early May, when plasma IGF-I levels reach highest levels, after which a certain deactivation of the GH system takes place. The data show that plasma levels of GH are to a large extent regulated by the secretion rate from the pituitary, although changes in the GH clearance rate are also likely to take place and influence the plasma GH levels. The study further underlines the significant role that the GH-IGF-I axis plays in the parr-smolt transformation of the Atlantic salmon.

[A mutation detection in a transcription factor for adipocyte development in children with severe obesity.].

OBJECTIVE: A substantial proportion of human obesity may be explained by genetic variability. Researchers have tried to identify the important genes in obesity with little sucsess. PPARg2 (peroxisome proliferator activated receptor g 2) is a transcription factor of the nuclear hormone receptor superfamily. It plays a key role in the developement and differentiation of adipocytes. Recently the mutation Pro115Gln in the PPARg2 gene was identified and shown to have a significant correlation with severe obesity. The actual prevalence and distribution of this mutation is not known. The aim of this study was to look for this mutation among Icelandic children suffering from severe obesity. MATERIAL AND METHODS: Thirty-five children and adolescents, aged 4-18, who have been diagnosed with severe obesity participated in the study. Eight parents and siblings aged 19-41 also participated. All study subjects had been obese since early childhood. Body mass index (BMI) was used to describe the phenotype of the subjects. The participants had a BMI of 28.0 to 52.2 kg/m(2). Genomic DNA was extracted from leucocytes. A 131 bp segment was amplified using polymerase chain reaction. The amplified product was digested with the restriction enzyme Hinc II, resolved on agarose gel and visualized under ultraviolet illumination after staining with ethidium bromide. To examine other mutations on the same 131 bp segment enzymatic mutation detection (EMD) was used. Finally the segments giving variable results using EMD were sequenced using the classic Sanger s method. RESULTS: The mutation Pro115Gln was not found in any of the specimens after analysis of the restriction fragment length polymorphism. The results of EMD indicated mutations or polymorphisms in three of the subjects but DNA sequencing failed to confirm these results. CONCLUSIONS: The mutation Pro115Gln or other genetic alternations within the exon examined do not appear to have a significant role in severe early - onset obesity in Icelandic children.

Dopaminergic innervation of the rainbow trout pituitary and stimulatory effect of dopamine on growth hormone secretion in vitro.

To elucidate which factors regulate growth hormone (GH) secretion in rainbow trout, dopaminergic innervation of the rainbow trout pituitary along with the action of dopamine in vitro, were studied. Brains with attached pituitaries were double-labeled for putative dopaminergic neuronal fibers and somatotropes, using fluorescence immunohistochemistry. A direct dopaminergic innervation to the proximal pars distalis (PPD) with dopaminergic fibers terminating adjacent to somatotropes was demonstrated. Growth hormone secretion from whole pituitaries was measured in perifusate using a homologous GH-RIA. Dopamine (DA; 10(-7)-2x10(-6) g ml(-1)) increased basal GH secretion, with the GH secretion normalizing again after the DA exposure was halted. When pituitaries were pre-treated with somatostatin-14 (SRIF-14; 10(-12)-10(-9) g ml(-1)), before being exposed to different doses of DA, there was an inhibition of GH secretion which was not reversed after treatment of SRIF-14 was halted, unless DA was added. It is concluded that dopamine can function as a GH secretagogue in the rainbow trout pituitary gland.

Growth hormone inhibits growth hormone secretion from the rainbow trout pituitary in vitro.

Growth hormone (GH) secretion in salmonids and other fish is under the control of a number of hypothalamic factors, but negative feed-back regulation by circulating hormones can also be of importance for the regulation of GH secretion. Mammalian studies show that GH has a negative feed-back effect on its own secretion. In order to elucidate if GH levels present a direct ultra-short negative feedback loop at the pituitary level GH secretion was studied in intact pituitaries from 50 g fish in an in vitro perifusion system. Following an initial equilibrium period pituitaries were exposed to five increasing concentrations (1-1,000 ng ml(-1)) of ovine GH (oGH) in 20-min steps, before being returned to a GH-free perifusion. Ovine GH caused a significant dose-dependent inhibition of GH secretion and it is concluded that GH can exert a direct negative feedback control on GH secretion at the pituitary level.

[Thirty years of intensive care. Clinical experience at Reykjavik Hospital.].

OBJECTIVE: Reykjavik Hospital has been the main trauma center in Iceland. The Intensive Care Unit (ICU) was founded in 1970 and has been in operation since then. The aim of this study was to review its clinical experience these 30 years. MATERIAL AND METHODS: A retrospective study of patient records was conducted for all admissions to the ICU between 1970 and the end of 1999. Data was collected pertaining to the annual rate of admission, proportion of patients requiring ventilator treatment, mortality rate, age distribution, reasons for admission and medical speciality. RESULTS: A total of 13,154 patients were admitted to the ICU between 1970 and the end of 1999. A steady increase in the rate of admissions was observed during the study period, reaching 550-600 patients for the ICU annually. There was a statistically significant increase in the proportion of patients requiring ventilator treatment over the study period, reaching 38% of ICU admissions by the end of the study. During the study period only one statistically significant change was observed in age distribution. The annual rate of admission to the ICU for patients over 60 years of age increased significantly between the periods 1985-1989 and 1990-1999. The proportion of surgical patients increased (70% of patients by the end of the study) and the proportion of medical patients decreased (ending at 30% of patients). During the last decade a significant increase was seen in patients admitted after major surgery. The observed mortality rate in the final years of the study was observed to be significantly less than it had been in previous years. The observed mortality rate from 1970 to 1989 was 11.7% of patients, decreasing to 8.6% from 1990 to 1998. The average length of stay was also observed to decline. CONCLUSIONS: The decline in mortality occurred in spite of an increased rate of admission and an increased workload. This change is attributed to improvement in the care of critically ill patients over the study period.

Obstetric outcome of natural and assisted conception twin pregnancies is similar.

BACKGROUND: The risk of obstetric intervention and adverse fetal or neonatal outcome is considerably higher in multiple gestation than in singleton pregnancy. How assisted conception influences obstetric management and outcome in twin pregnancies has not been evaluated. METHODS: A survey of all twin pregnancies in Iceland and the Tayside Region, Scotland for a four year period, 1990-93, comparing twins after assisted fertilization with natural conception. RESULTS: The total number of twin pregnancies was 522, of which 453 were natural conceptions and 69 assisted. The twin rate was 1:75 among natural conceptions, but 1:5 in women having assisted fertilization. Mean gestational age in both groups was 36 weeks. Elective Cesarean section was used more often in the assisted conception group (odds ratio 2.57; p = 0.003). Induction rates did not differ to any significant degree and once labor commenced, no difference was seen between assisted and natural conception twins in the mode of delivery or neonatal short term morbidity. Birthweight, gestational length and perinatal mortality rates by conventional and extended classification were not different. CONCLUSION: After allowing for more frequent elective Cesarean section in the obstetric care of the assisted conception pregnancies, there was no major difference in obstetric and neonatal management or outcome between twins resulting from natural and assisted conception.

[Obstetric outcome among naturally and IVF conceived twins.].

Pregnancy and delivery are generally perceived to be more hazardous among twins compared to singletons. Assisted conception techniques have increased the number of twins, but the effect on obstetric management and outcome is not well known. During 1990-1993 there were 254 twin pregnancies of 5? 16 weeks gestation in Iceland, of which 52 (20.5%) were after IVF; - a twin rate of 1:73 deliveries. The natural rate was 1:90. IVF women were on average 3 years older but of equal height and smoking habits as the natural mothers. Mean gestational age was 36 +/-3.68 (SD) weeks for both IVF and natural twins. In 61.9% labour commenced spontaneously after natural conception, compared to 51.9% after IVF (N.S.) and 64.4% of natural and 58.8% of IVF twins were delivered normally (N.S.). Caesarean section rates were almost equal, but there were twice as many forceps and ventouse deliveries of IVF babies (p<0.02). There appeared to be a minor tendency for more frequent elective Cesarean section in IVF pregnancies, but emergency section was more prevalent among those who conceived naturally. IVF twins were on average 64g lighter (mean birthweight 2552g) than natural twins (mean birthweight 2616g), which was unaffected by smoking habits and gestional length. The sex ratio was higher among IVF twins. IVF twins were more often admitted to neonatal intensive care, but remained there a shorter time. This suggests a lower threshold for admission of twins conceived following IVF treatment. Perinatal mortality was not different among natural compared to IVF twins; 20/1000 by conventional criteria. However when total perinatal wastage was calculated, the figure was 46.5/1000, suggesting excess deaths early in pregnancy and beyond the first week of life in twin pregnancies in general.