A pragmatic randomized controlled trial to evaluate the effectiveness of a facilitated exercise intervention as a treatment for postnatal depression: the PAM-PeRS trial.

BACKGROUND: Postnatal depression affects about 10-15% of women in the year after giving birth. Many women and healthcare professionals would like an effective and accessible non-pharmacological treatment for postnatal depression. METHOD: Women who fulfilled the International Classification of Diseases (ICD)-10 criteria for major depression in the first 6 months postnatally were randomized to receive usual care plus a facilitated exercise intervention or usual care only. The intervention involved two face-to-face consultations and two telephone support calls with a physical activity facilitator over 6 months to support participants to engage in regular exercise. The primary outcome was symptoms of depression using the Edinburgh Postnatal Depression Scale (EPDS) at 6 months post-randomization. Secondary outcomes included EPDS score as a binary variable (recovered and improved) at 6 and 12 months post-randomization. RESULTS: A total of 146 women were potentially eligible and 94 were randomized. Of these, 34% reported thoughts of self-harming at baseline. After adjusting for baseline EPDS, analyses revealed a -2.04 mean difference in EPDS score, favouring the exercise group [95% confidence interval (CI) -4.11 to 0.03, p = 0.05]. When also adjusting for pre-specified demographic variables the effect was larger and statistically significant (mean difference = -2.26, 95% CI -4.36 to -0.16, p = 0.03). Based on EPDS score a larger proportion of the intervention group was recovered (46.5% v. 23.8%, p = 0.03) compared with usual care at 6 months follow-up. CONCLUSIONS: This trial shows that an exercise intervention that involved encouragement to exercise and to seek out social support to exercise may be an effective treatment for women with postnatal depression, including those with thoughts of self-harming.

Oscillations in soil bacterial redox reactions.

Spatial oscillations in soil contaminant concentration profiles are sometimes observed, but rarely commented on, or are attributed to noisy data. In this paper we consider a possible mechanism for the occurrence of oscillatory reactant profiles within contaminant plumes. The bioremediative reactions which occur are effected by bacteria, whose rôle is normally conceived of as being passive. Here we argue that competition, for example between heterotrophic and fermentative bacteria, can occur in the form of an activator-inhibitor system, thus promoting oscillations. We describe a simple model for the competition between two such microbial populations, and we show that in normal oligotrophic groundwater conditions, oscillatory behaviour is easily obtained. When such competition occurs in a dispersive porous medium, travelling waves can be generated, which provide a possible explanation for the observed soil column oscillations.

Modelling spatial oscillations in soil borehole bacteria.

Spatial oscillations in groundwater contaminant concentrations can be successfully explained by consideration of a competitive microbial community in conditions of poor nutrient supply, in which the effects of spatial diffusion of the nutrient sources are included. In previous work we showed that the microbial competition itself allowed oscillations to occur, and, in common with other reaction-diffusion systems, the addition of spatial diffusion transforms these temporal oscillations into travelling waves, sometimes chaotic. We therefore suggest that irregular chemical profiles sometimes found in contaminant plume borehole profiles may be a consequence of this competition.

Gene redundancy and pharmacological gene therapy: implications for X-linked adrenoleukodystrophy.

As more functional redundancy in mammalian cells is discovered, enhanced expression of genes involved in alternative pathways may become an effective form of gene therapy. X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder with impaired very-long-chain fatty acid metabolism. The X-ALD gene encodes a peroxisomal membrane protein (ALDP) that is part of a small family of related peroxisomal membrane proteins. We show that 4-phenylbutyrate treatment of cells from both X-ALD patients and X-ALD knockout mice results in decreased levels of and increased beta-oxidation of very-long-chain fatty acids; increased expression of the peroxisomal protein ALDRP; and induction of peroxisome proliferation. We also demonstrate that ALDP and ALDRP are functionally related, by ALDRP cDNA complementation of X-ALD fibroblasts. Finally, we demonstrate the in vivo efficacy of dietary 4-phenylbutyrate treatment through its production of a substantial reduction of very-long-chain fatty acid levels in the brain and adrenal glands of X-ALD mice.

Retrospective study of first episode psychosis in the Dublin Southwest Mental Health Service: demographics, clinical profile and service evaluation of treatment.

OBJECTIVE: In Ireland, National Clinical Programmes are being established to improve and standardise patient care throughout the Health Service Executive. In line with internationally recognised guidelines on the treatment of first episode psychosis the Early Intervention in Psychosis (EIP) programme is being drafted with a view to implementation by mental health services across the country. We undertook a review of patients presenting with a first episode of psychosis to the Dublin Southwest Mental Health Service before the implementation of the EIP. This baseline information will be used to measure the efficacy of our EIP programme. METHODS: Patients who presented with a first episode psychosis were retrospectively identified through case note reviews and consultation with treating teams. We gathered demographic and clinical information from patients as well as data on treatment provision over a 2-year period from the time of first presentation. Data included age at first presentation, duration of untreated psychosis, diagnosis, referral source, antipsychotic prescribing rates and dosing, rates of provision of psychological interventions and standards of physical healthcare monitoring. Outcome measures with regards to rates of admission over a 2-year period following initial presentation were also recorded. RESULTS: In total, 66 cases were identified. The majority were male, single, unemployed and living with their family or spouse. The mean age at first presentation was 31 years with a mean duration of untreated psychosis of 17 months. Just under one-third were diagnosed with schizophrenia. Approximately half of the patients had no contact with a health service before presentation. The majority of patients presented through the emergency department. Two-thirds of all patients had a hospital admission within 2 years of presentation and almost one quarter of patients had an involuntary admission. The majority of patients were prescribed antipsychotic doses within recommended British National Formulary guidelines. Most patients received individual support through their keyworker and family intervention was provided in the majority of cases. Only a small number received formal Cognitive-Behavioural Therapy. Physical healthcare monitoring was insufficiently recorded in the majority of patients. CONCLUSIONS: There is a shortage of information on the profile and treatment of patients presenting with a first episode of psychosis in Ireland. This baseline information is important in evaluating the efficacy of any new programme for this patient group. Many aspects of good practice were identified within the service in particular with regards to the appropriate prescribing of antipsychotic medication and the rates of family intervention. Deficiencies remain however in the monitoring of physical health and the provision of formal psychological interventions to patients. With the implementation of an EIP programme it is hoped that service provision would improve nationwide and to internationally recognised standards.

Early postpartum symptoms in puerperal psychosis.

OBJECTIVE: To examine the nature of the earliest reported symptoms in women who develop a bipolar affective puerperal psychosis (PP). DESIGN: A retrospective interview study. SETTING: Women were recruited for clinical and molecular genetic studies of PP from a national PP network, articles in the national press and referrals from UK specialist perinatal psychiatry services. SAMPLE: One hundred and twenty-seven women met the criteria for an episode of strictly defined bipolar affective PP developing within 4 weeks of childbirth. METHODS: Participants were interviewed using the Schedule for clinical assessment in neuropsychiatry and hospital records were reviewed. Lifetime and puerperal episode diagnoses were made according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) based on all the available information. During interview, participants were asked to describe the earliest symptoms they believed to be related to their illness onset. The day of onset for each symptom was recorded. MAIN OUTCOME MEASURES: We present subjectively experienced emotional and behavioural changes occurring within 3 days of childbirth, reported by four or more women. RESULTS: Seventy-three percent of women recalled experiencing an onset of symptoms by day 3. The most commonly recalled symptoms were feeling excited, elated or high (52%), not needing to sleep or not able to sleep (48%), feeling active or energetic (37%) and talking more or feeling very chatty (31%). CONCLUSIONS: Hypomanic symptoms are particularly characteristic of the early postpartum in women who develop PP. These types of symptoms should be carefully monitored in individuals at high risk of PP episodes.

Role of ALDP (ABCD1) and mitochondria in X-linked adrenoleukodystrophy.

Peroxisomal disorders have been associated with malfunction of peroxisomal metabolic pathways, but the pathogenesis of these disorders is largely unknown. X-linked adrenoleukodystrophy (X-ALD) is associated with elevated levels of very-long-chain fatty acids (VLCFA; C(>22:0)) that have been attributed to reduced peroxisomal VLCFA beta-oxidation activity. Previously, our laboratory and others have reported elevated VLCFA levels and reduced peroxisomal VLCFA beta-oxidation in human and mouse X-ALD fibroblasts. In this study, we found normal levels of peroxisomal VLCFA beta-oxidation in tissues from ALD mice with elevated VLCFA levels. Treatment of ALD mice with pharmacological agents resulted in decreased VLCFA levels without a change in VLCFA beta-oxidation activity. These data indicate that ALDP does not determine the rate of VLCFA beta-oxidation and that VLCFA levels are not determined by the rate of VLCFA beta-oxidation. The rate of peroxisomal VLCFA beta-oxidation in human and mouse fibroblasts in vitro is affected by the rate of mitochondrial long-chain fatty acid beta-oxidation. We hypothesize that ALDP facilitates the interaction between peroxisomes and mitochondria, resulting, when ALDP is deficient in X-ALD, in increased VLCFA accumulation despite normal peroxisomal VLCFA beta-oxidation in ALD mouse tissues. In support of this hypothesis, mitochondrial structural abnormalities were observed in adrenal cortical cells of ALD mice.

Age-related macular degeneration and mortality: the Melbourne Collaborative Cohort Study.

AimsTo assess associations between features of age-related macular degeneration (AMD) and mortality.MethodsA total of 21 129 participants from the Melbourne Collaborative Cohort Study aged 47-85 years (60% female) were assessed for AMD (2003-2007). Mortality data to December 31, 2012 were obtained through linkage with the National Death Index. Associations were assessed using Cox regression, adjusting for age, sex, smoking, region of birth, education, physical activity, diet and alcohol.ResultsLate AMD was identified in 122 (0.6%) participants, including those with choroidal neovascularisation (n=55, 0.3%), geographic atrophy (n=87, 0.4%) and reticular pseudodrusen (n=87, 0.4%). After a median follow-up period of 8.1 years, 1669 (8%) participants had died, including those from cardiovascular diseases (386), tobacco-related cancers (179), and neurodegenerative disease (157). There was evidence of an increased rate of all-cause mortality for those with choroidal neovascularisation (Hazard Ratio (HR) 1.71 95% CI 1.06-2.76) and geographic atrophy (HR 1.46 95% CI 0.99-2.16). Choroidal neovascularisation was also associated with an increased rate of cardiovascular mortality (HR 3.16 95% CI 1.62-6.15) and geographic atrophy was associated with an increased rate of death from tobacco-related cancer (HR 2.86 95% CI 1.15-7.09). Weak evidence was also present for an association between choroidal neovascularisation and death from neurodegenerative disease (HR 2.49 95% CI 0.79-7.85). Neither reticular pseudodrusen nor the earlier stages of AMD were associated with mortality.ConclusionsLate AMD is associated with an increased rate of all-cause mortality. Choroidal neovascularisation and geographic atrophy were associated with death from cardiovascular disease and tobacco-related cancer, respectively.

STAT3 activation is required for Asp(816) mutant c-Kit induced tumorigenicity.

Activating mutations of c-kit at codon 816 (Asp(816)) have been identified in variety of malignancies, including acute myeloid leukemia (AML), mastocytosis and germ cell tumors. The mutant c-Kit receptor confers cytokine independence and induces tumorigenicity. However, the molecular mechanisms, particularly the changes in the signal transduction pathways, responsible for these biological effects induced by mutant c-Kit are largely undefined. Using the human embryonic kidney cell line, 293, we show in the current report that constitutive activation of STAT3 and STAT1 is associated with D816H mutant c-Kit. Transfection of dominant negative STAT3, but not STAT1 inhibits mutant c-Kit mediated anchorage-independent growth in vitro and tumor formation in vivo. Expression of constitutively activated STAT3 restores the mutant c-Kit receptor's transforming ability in 293 cells. These results demonstrate that activation of STAT3 by Asp(816) mutant c-Kit is required for the anchorage-independent growth and tumorigenicity induced by Asp(816) mutant c-Kit.

Basic fibroblast growth factor is a testicular germ cell product which may regulate Sertoli cell function.

Previously, a proteinacious factor secreted by a mixture of rat testicular spermatocytes and round spermatids was shown to stimulate transferrin mRNA and protein levels in Sertoli cells. To identify the germ cell-secreted proteins which affect Sertoli cell functions, concentrated germ cell-conditioned medium was fractionated by reverse-phase HPLC. The fraction which eluted at 35% acetonitrile increased transferrin secretion in Sertoli cell cultures 2.4-fold above the basal level. Both the active fraction and a protein extract from cultured germ cells were positive for basic fibroblast growth factor (bFGF) as determined by Western blot analysis and immunoprecipitation. The apparent molecular sizes of the immunoreactive proteins were 30, 27, and 24 kilodaltons (kDa). By immunohistochemistry, bFGF was shown to be present in pachytene spermatocytes and Leydig cells. The bFGF receptor was also examined by immunohistochemistry and found to be present in Leydig cells, round and elongated spermatids, and Sertoli cells. The presence of receptors was more pronounced in stages I-VIII. Western blot analysis confirmed that the receptors were expressed in isolated round spermatids, elongated spermatids, and Sertoli cells. Two major receptor species with apparent molecular sizes of 120 and 145 kDa were detected in the rat testis. Germ cells contained both of these receptors, but Sertoli cells possessed only the 120-kDa receptor. From these experiments, it is evident that bFGF is a germ cell product which may regulate Sertoli cell function. The expression of bFGF and its receptor may be an important component of germ cell-Sertoli cell and/or germ cell-germ cell communication during spermatogenesis.

Alternative leader sequences in insulin-like growth factor I mRNAs modulate translational efficiency and encode multiple signal peptides.

Rat insulin-like growth factor I (IGF-I) mRNAs contain multiple 5'-untranslated regions due to the use of leader exons transcribed from several transcription initiation sites and to alternative splicing within leader exon 1. Synthetic RNAs with 5'-ends corresponding to the use of exon 1 transcription initiation sites were translated in vitro into prepro-IGF-I peptides initiated at a Met-48 codon in exon 1 or a Met-22 codon in exon 3, and RNAs with a 5'-end corresponding to the major exon 2 transcription start site were translated into a prepro-IGF-I peptide initiated at a Met-32 codon in exon 2. All forms of prepro-IGF-I were processed by canine pancreatic microsomes, suggesting that all these prepeptides function as signal peptides. The translational efficiency of IGF-I RNAs was inversely proportional to the length of the 5'-untranslated region. Mutation of the first of three upstream AUG codons in exon 1, which potentially initiates a 14-amino acid open reading frame, did not affect prepro-IGF-I translation. The other two AUG codons are immediately followed by stop codons. The absence of both upstream AUG codons in a completely spliced exon 1-derived RNA enhanced the in vitro and in vivo translatability of this RNA as compared with the full-length RNA. Mutation of the downstream initiation codon in particular increased translational efficiency in vitro and in intact cells, suggesting that an inefficient reinitiation event at the Met-48 codon contributes to the poorer translation of IGF-I mRNAs in which these upstream AUGUGA motifs occur. We conclude that IGF-I mRNAs potentially encode multiple forms of preproIGF and that specific differences in their 5'-untranslated regions provide a molecular basis for translational control of IGF-I biosynthesis.

Gonocytes of male rats resume migratory activity postnatally.

In the testis of the neonatal rat, maturation of germ cells, or gonocytes, lays the foundations for spermatogenesis which will begin later in postnatal development. One of the most critical and yet least understood of the events that occur during the immediate neonatal period is relocation of gonocytes from the more central part of the seminiferous cord, where they are surrounded by Sertoli cells, to its periphery, where they contact the basement membrane. For the current study, we examined this change in gonocyte position by identifying some of the cellular mechanism involved, with the aim of determining whether movement of gonocytes to the basement membrane in vivo and development of cellular processes by these cells in vitro represents a resumption of migratory activity similar to that displayed by their fetal ancestors and by other motile cells. First, we used either thiamine pyrophosphatase cytochemistry or the fluorescent probe nitrobenzoxadiazole ceramide to visualize the Golgi complex in gonocytes and found that (1) this organelle matures and apparently enlarges in vivo with a time course paralleling movement of gonocytes to the basement membrane and undergoes similar changes in vitro that correlate with gonocyte process formation, and (2) the Golgi complex is located in perinuclear cytoplasm facing the apparent direction of gonocyte movement in vivo and in cytoplasm near the cellular process in the great majority of elongated gonocytes in coculture. Next we used two drugs, brefeldin A and monensin, which have in common their ability to disrupt the Golgi complex, and found that both drugs prevent process formation by gonocytes in a manner that is completely reversible. We also tested the involvement of the cytoskeleton in gonocyte elongation by utilizing nocodazole to disrupt and taxol to stabilize microtubules, as verified by alpha-tubulin immunofluorescence. Inclusion of the drug abolished (taxol) or substantially diminished (nocodazole) the ability of gonocytes to elongate in a reversible manner. We also found that the Golgi complex was intact in the presence of taxol and that microtubules were intact in the presence of both Golgi complex-specific drugs. Thus, our findings indicate that (1) both the Golgi complex and microtubules are involved in development of processes by gonocytes and (2) neither structure is sufficient by itself to allow these cells to elongate. Taken together, our data provide new evidence suggesting that the cellular mechanism utilized by postnatal gonocytes in relocating to the basement membrane are those mediating active migration.(ABSTRACT TRUNCATED AT 400 WORDS)

Neonatal gonocytes co-cultured with Sertoli cells on a laminin-containing matrix resume mitosis and elongate.

We co-cultured gonocytes and Sertoli cells isolated on the day of birth and observed the appearance, 1 and 3 days after the start of culture, of gonocytes that had developed cellular processes and that were labeled by [3H]thymidine, respectively. These events occurred in the absence of hormones, etc. and with a time course very similar to that seen in vivo. In other incubations, we found that the presence of laminin in the underlying substrate was critical in promoting proliferation and elongation of gonocytes. These observations strongly suggest that interactions between gonocytes and other testicular cells/factors in the co-cultures promote maturation of these germ cells in vitro, and thus provide new evidence to support the concept that paracrine mechanisms are important during testicular development as well as in adults.

Tumor necrosis factor-alpha and X-linked adrenoleukodystrophy.

The two most common forms of X-linked adrenoleukodystrophy (X-ALD), the childhood cerebral form (CCER) and the adult form, adrenomyeloneuropathy (AMN), arise from the same mutations in the X-ALD gene at Xq28. These two forms are distinguished by the degree of cerebral inflammation. Segregation analysis suggests that an autosomal modifying gene may be a major determinant of phenotype in X-ALD. Thus, a modifying gene could be involved in initiating or promoting the inflammatory response. In this study we detected a difference in tumor necrosis factor-alpha (TNF-alpha) bioactivity, but not TNF-alpha protein levels, in serum from some advanced CCER patients. Early-stage CCER patients and AMN patients were in the normal range. Allelic differences in TNF-alpha or levels of soluble TNF receptor did not account for bioactivity differences or phenotypic heterogeneity in X-ALD.

Human leukocyte antigens and cytokine expression in cerebral inflammatory demyelinative lesions of X-linked adrenoleukodystrophy and multiple sclerosis.

The two most common forms of X-linked adrenoleukodystrophy (X-ALD) are the cerebral forms (CER) with an inflammatory demyelinating reaction that resembles multiple sclerosis, and adrenomyeloneuropathy (AMN) which involves primarily the spinal cord and in which the inflammatory reaction is mild or absent. We found no significant association between the childhood cerebral form (CCER) or AMN and the human leukocyte (HLA) class I and Class II antigens including the class II DR2 haplotypes associated with multiple sclerosis. Inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-4, interleukin-6 and interferon-gamma) gene expression was increased in multiple sclerosis brain lesions, as has been reported previously, but much less so in CER brain lesions. These findings suggest that the pathogenesis of the inflammatory response in X-ALD differs from that in multiple sclerosis.

Therapeutic developments in peroxisome biogenesis disorders.

Clinically, peroxisome biogenesis disorders (PBDs) are a group of lethal diseases with a continuum of severity of clinical symptoms ranging from the most severe form, Zellweger syndrome, to the milder forms, infantile Refsum disease and rhizomelic chondrodysplasia punctata. PBDs are characterised by a number of biochemical abnormalities including impaired degradation of peroxide, very long chain fatty acids, pipecolic acid, phytanic acid and xenobiotics and impaired synthesis of plasmalogens, bile acids, cholesterol and docosahexaenoic acid. Treatment of PBD patients as a group is problematic since a number of patients, especially those with Zellweger syndrome, have significant neocortical alterations in the brain at birth so that full recovery would be impossible even with postnatal therapy. To date, treatment of PBD patients has generally involved only supportive care and symptomatic therapy. However, the fact that some of the milder PBD patients live into the second decade has prompted research into possible treatments for these patients. A number of experimental therapies have been evaluated to determine whether or not correction of biochemical abnormalities through dietary supplementation and/or modification is of clinical benefit to PBD patients. Another approach has been pharmacological induction of peroxisomes in PBD patients to improve overall peroxisomal biochemical function. Well known rodent peroxisomal proliferators were found not to induce human peroxisomes. Recently, our laboratory demonstrated that sodium 4-phenylbutyrate induces peroxisome proliferation and improves biochemical function (very long chain fatty acid beta-oxidation rates and very long chain fatty acid and plasmalogens levels) in fibroblast cell lines from patients with milder PBD phenotypes. Dietary supplementation and/or modification and pharmacological induction of peroxisomes as treatment strategies for PBD patients will be the subject of this review.

Expression of apolipoprotein E mRNA in the epithelium and interstitium of the testis and the epididymis.

Apolipoprotein E (apo E) is an important constituent of plasma lipoproteins and is believed to be involved in the regulation of lipid transport and distribution between tissues. The production of this apolipoprotein in extra-hepatic tissues such as the testis and epididymis could facilitate specific local functions. Apo E mRNA was detected in testis, epididymis, seminal vesicles, and prostate. In the epididymis, apo E was detected using in situ hybridization in epithelial cells and in some cells in the interstitium throughout the organ (i.e., caput, corpus, and cauda). Northern blot analysis showed that apo E mRNA is present in Sertoli cells and germ cells, but not peritubular myoid cells. Interstitial cells of the testis displayed the most intense signal for apo E message using in situ hybridization. Messenger RNA for apo E was also detected in the interstitium of rat testes at 3 and 6 days after animals were treated with ethylene dimethanesulfonate (EDS) to eliminate Leydig cells. Thus, in addition to Leydig cells, other cell types within the interstitium are capable of producing apo E message. Levels of testicular apo E mRNA increased between 30 and 60 days pc during which the germ cell population is increasing. As determined by northern blot analysis of RNA from stage synchronized testes, the levels of apo E mRNA fluctuate in relation to the cycle of the seminiferous epithelium. The cells responsible for this stage-specific variation in message could not be identified by in situ hybridization. Apolipoprotein Al (apo Al) mRNA was also found to be expressed in the epididymis but not in the testis of adult rats. The role of apolipoproteins in spermatogenesis and sperm maturation has not been elucidated. The results of this study demonstrate the specific tissues and cells types which play a role in the production and possible regulation of apo E mRNA in the male reproductive tract. These data will help in the elucidation of the function of apo E in spermatogenesis and sperm maturation.

Cerebral inflammation in X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (X-ALD) is an inherited neurodegenerative disease that affects approximately 1 in 25 000 males. It is characterized by elevated levels of saturated very long chain fatty acids (VLCFA), i.e., >C22:0, particularly in ganglioside and cholesterol ester fractions of brain white matter and adrenal cortex. Failure of peroxisomal very long chain fatty acyl-CoA synthetase (VLCS) to activate these VLCFA prevents their degradation by peroxisomal beta-oxidation. X-ALD maps to Xq28 and the gene encodes a peroxisomal membrane protein and not the gene for VLCS. The two most common forms of X-ALD are the cerebral (CER) form, with an inflammatory demyelinating reaction that resembles multiple sclerosis (MS), and adrenomyeloneuropathy (AMN), which involves the spinal cord and in which the inflammatory reaction is mild or absent. Investigations into the nature of the cerebral inflammatory demyelinating reaction in X-ALD will be the subject of this review.

Endocrine and metabolic responses of intact and hypophysectomized turkey poults given a daily injection of chicken growth hormone.

Female turkey poults were hypophysectomized at 4-5 weeks of age. Beginning at 6 weeks of age, 20 hypophysectomized and 20 intact birds received a daily intramuscular injection of natural chicken growth hormone (cGH, 100 micrograms/kg body weight) or vehicle for 12 days. Blood samples were taken from each bird just before injection and 4 hr post-injection at 6 and 12 days of treatment. Hypophysectomy reduced the growth rate of turkey poults to 75% of that of intact controls, significantly reduced carcass protein and ash percentages, and significantly lower plasma concentrations of GH, insulin-like growth factor-I, triiodothyronine, thyroxine, insulin, glucose, triglycerides, and non-esterified fatty acids. Hypophysectomy was without effect on liver GH receptor binding activity, but increased liver 5'-monodeiodinase activity. Daily cGH injection had no effect on the average daily gain of either hypophysectomized or intact poults when compared to vehicle-injected controls over 12 days of treatment. Daily cGH administration increased plasma insulin-like growth factor-I levels in intact and hypophysectomized turkeys, and increased plasma triiodothyronine, insulin, glucose, and triglyceride concentrations in hypophysectomized birds, but not in intact birds. Responses of young turkeys to hypophysectomy and GH replacement were consistent with the known metabolic role of GH in other species, but the influence of GH on growth appears to be of less importance in poultry than in mammals.

Response of young broiler chickens to chronic injection of recombinant-derived human insulin-like growth factor-I.

The purpose of this study was to determine if exogenous insulin-like growth factor-I (IGF-I) would improve growth rate or body composition of young broiler chickens. Broiler cockerels were given a daily intramuscular (im) injection of sodium acetate buffer (buffer control), 100 or 200 micrograms recombinant-derived human IGF-I (rhIGF-I) per kg body weight from 11 to 24 days of age. Exogenous IGF-I did not affect the average daily gain, average daily feed consumption, or the gain-to-feed ratio of broiler chickens. Although daily injection of 200 micrograms/kg of rhIGF-I reduced (P less than 0.05) body ash content, there was no significant effect of IGF-I treatment on either body fat or protein content. Plasma GH levels were depressed (P less than 0.05) by chronic treatment with rhIGF-I. In contrast, plasma levels of T3 and T4 were not affected by rhIGF-I treatment. The half-life of rhIGF-I in plasma was determined at 25 days of age in naive control or chronically-injected chickens after a single intravenous dose of 50 micrograms rhIGF-I/kg. We found a single compartment, first-order disappearance pattern of rhIGF-I from chicken plasma. The half-life (t1/2) of rhIGF-I in plasma was similar (t1/2 = 32.5 min) for naive controls (injected once) or chronically-treated chickens which had received a daily injection of rhIGF-I (100 or 200 micrograms/kg) for 14 d. These data indicate that daily injection of IGF-I cannot be used to enhance growth performance or body composition of broiler chickens when given during the early growth period. The depression of plasma GH levels in rhIGF-I-injected chickens supports a negative-feedback role of IGF-I on pituitary GH secretion.