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Hypoxia can affect various fish populations, including yellow perch Perca flavescens, which is an economically and ecologically important species in Lake Erie, a freshwater system that often experiences hypoxia in the hypolimnetic part of the lake. Fish, similarly to mammals, possess molecular oxygen sensor-hypoxia-inducible factor-1 (HIF-1), a transcription factor that can affect expression of many downstream genes related to animal growth and locomotion, protein synthesis, as well as ATP and amino acid metabolism. HIF-1 is a heterodimer, which consists of two subunits: oxygen-sensitive and oxygen-insensitive subunits, α and β, respectively. In this study, we report first on the molecular cloning and sequencing of P. flavescens HIF-1α. The full-length complementary DNA (cDNA) was isolated and submitted to the GenBank with accession number KT783483. It consists of 3529 base pairs (bp) carrying a single open-reading frame that encompasses 2250 bp of the coding region, 247 bp of the 5' untranslated region (UTR), and 1032 bp of the 3' UTR. The "de novo" prediction of the 3D structure of HIF-1α protein, which consists of 749 amino acids, is presented, too. We then utilized One-Step Taqman® real-time RT-PCR technology to monitor changes in HIF-1α messenger RNA (mRNA) copies in response to chronic hypoxic stress. An experiment was conducted using 14-day post-swim-up stage yellow perch larvae with uninflated swim bladders. This experiment included three treatment groups: hypoxia, mid-hypoxia, and normoxia, in four replicates (four tanks per treatment) with the following dissolved oxygen levels: 3, 4, and >7 mg O 2 /L, respectively. At the end (2 weeks) and in the middle (1 week) of the experiment, fish from each tank were sampled for body measurements and molecular biology analysis. The results showed no differences in survival (∼90%) between treatment groups. Oxygen concentration was lowered to 3.02 ± 0.15 (mean ± SE) mg O 2 /L with no adverse effect on fish survival. The highest growth rate was observed in the normoxic group. A similar trend was observed with fish body length. The growth rate of fish declined with decreasing water-dissolved oxygen. The number of HIF-1α mRNA copies was not significantly different between hypoxic, mid-hypoxic, and normoxic conditions, and this was true for fish obtained in the middle and at the end of the experiment. Graphical abstract.

The objective of the present study was to examine the effect of diets with descending fish meal (FM) inclusion levels and the addition of salt to the diet containing the lowest FM level on growth performances, feed conversion ratio, and intestinal solute carrier family 6 member 19 (SLC6A19) and oligopeptide transporter 1 (PEPT1) transcript levels, in freshwater-adapted European sea bass (Dicentrarchus labrax). We first isolated by molecular cloning and sequenced a full-length cDNA representing the neutral amino acid transporter SLC6A19 in sea bass. The cDNA sequence was deposited in GenBank database (accession no. KC812315). The twelve transmembrane domains and the 'de novo' prediction of the three-dimensional structure of SLC6A19 protein (634 amino acids) are presented. We then analysed diet-induced changes in the mRNA copies of SLC6A19 and PEPT1 genes in different portions of sea bass intestine using real-time RT-PCR. Sea bass were fed for 6 weeks on different diets, with ascending levels of fat or descending levels of FM, which was replaced with vegetable meal. The salt-enriched diet was prepared by adding 3 % NaCl to the diet containing 10 % FM. SLC6A19 mRNA in the anterior and posterior intestine of sea bass were not modulated by dietary protein sources and salt supplementation. Conversely, including salt in a diet containing a low FM percentage up-regulated the mRNA copies of PEPT1 in the hindgut. Fish growth correlated positively with the content of FM in the diets. Interestingly, the addition of salt to the diet containing 10 % FM improved feed intake, as well as specific growth rate and feed conversion ratio.

The increasing use of commercially available acellular dermis matrices for postmastectomy breast reconstruction seems to have simplified the surgical procedure and enhanced the outcome. These materials, generally considered to be highly safe or with only minor contraindications due to the necessary manipulation in preparatory phases, allow an easier one-phase surgical procedure, in comparison with autologous flaps, offering a high patient satisfaction. Unfortunately, the claim for a higher rate of complications associated with irradiation at the implant site, especially when the radiation therapy was given before the reconstructive surgery, suggested a careful behaviour when this technique is preferred. However, this hypothesis was never submitted to a crucial test, and data supporting it are often discordant or incomplete. To provide a comprehensive analysis of the field, we searched and systematically reviewed papers published after year 2005 and registered clinical trials. On the basis of a meta-analysis of data, we conclude that the negative effect of the radiotherapy on the breast reconstruction seems to be evident even in the case of acellular dermis matrices aided surgery. However, more trials are needed to make solid conclusions and clarify the poor comprehension of all the factors negatively influencing outcome.

Atg1 is a Serine/Threonine protein kinase that plays a pivotal role in autophagy. A complete coding sequence of ATG1 is not available for the silkworm, Bombyx mori which is a good model for studying the autophagic process. In the present study we isolated two full-length cDNAs of 2175 (transcript variant A) and 2271 (transcript variant B) bases representing ATG1 in the silkworm. Phylogenetic analysis indicated that BmATG1 was closely related to orthologs of other insects. The encoded BmAtg1 proteins shared extensive homology with orthologs from yeast to mammals, showing high conservation at the N-terminal region where the catalytic domain and ATP- and Mg-binding sites are located. A de novo prediction of the three-dimensional structure for each protein is presented. We used real-time RT-PCR to quantify dynamic changes in mRNA copy number of BmATG1 in the midgut and fat body of fifth instar larvae undergoing starvation, as well as in other tissues of silkworm at the end of last larval instar. Our qPCR results revealed that BmATG1 expression levels at the end of larval life were comparable in the midgut, fat body and Malpighian tubules, while these were higher in the gonads; moreover, the mRNA copy number of ATG1 was very different among the anterior, middle and posterior silk glands. Real-time PCR analysis also showed that starvation significantly influenced BmATG1 mRNA copy number in the fat body of silkworm, inducing an upregulation 24h after food withdrawal, with only a slight effect in the midgut. Low expression levels of BmATG1 were observed in both tissues of control animals up to the second day of spinning phase., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: In comparison to higher vertebrates, fish are thought to rely heavily on innate immune system for initial protection against pathogen invasion because their acquired immune system displays a considerably poor immunological memory, and short-lived secondary response. The endogenous antimicrobial polypeptides (AMPPs) directly and rapidly killing pathogens such as bacteria, fungi, parasites, and viruses are included within the realm of innate defenses. In addition to piscidins, AMPPs that in recent years have been shown to be commonly linked to innate defense, are histones and their polypeptide fragments, and peptides derived from the respiratory protein hemoglobin. There is evidence that a number of stresses lead to significant regulation of AMPPs and thus their monitoring could be a highly sensitive measure of health status and risk of an infectious disease outbreak, which is a major impediment to the continued success of virtually all aquaculture enterprises and is often the most significant cause of economic losses., Results: We firstly isolated and deposited in Genbank database the cDNA sequences encoding for hemoglobin-β-like protein (Hb-LP) [GeneBank: JN410659], H2B histone-like protein 1 (HLP1) GenBank: JN410660], and HLP2 [GenBank: JN410661]. The "de novo" prediction of the three-dimensional structures for each protein is presented. Phylogenetic trees were constructed on Hb-LP, HLP1, and HLP2 sequences of sea bass and those of other teleost, avian, reptiles, amphibian and mammalian species. We then used real time RT-PCR technology to monitor for the first time in sea bass, dynamic changes in mRNA copy number of Hb-LP, HLP1, HLP2, and dicentracin in gills, skin, eyes, stomach and proximal intestine in response to acute crowding/confinement stress. We showed that acute crowding stress induces an increase in the expression levels of the aforementioned genes, in gills and skin of sea bass, but not in other tissues, and that this expression patterns are not always rapidly reversed upon re-exposure to normal conditions., Conclusion: The higher expression of the four target genes in gills and skin of sea bass suggests that this AMPP represents a first and immediate line of defense in combating pathogens and stressors since these tissues constitute the first physiological barriers of the animal.

Nanotechnology is expected to be promising in many fields of medical applications, mainly in cancer treatment. While a large number of very attractive exploitations open up for the clinics, regulatory agencies are very careful in admitting new nanomaterials for human use because of their potential toxicity. The very active research on new nanomaterials that are potentially useful in medicine has not been counterbalanced by an adequate knowledge of their pharmacokinetics and toxicity. The different nanocarriers used to transport and release the active molecules to the target tissues should be treated as additives, with potential side effects of themselves or by virtue of their dissolution or aggregation inside the body. Only recently has a systematic classification of nanomaterials been proposed, posing the basis for dedicated modeling at the nanoscale level. The use of in silico methods, such as nano-QSAR and PSAR, while highly desirable to expedite and rationalize the following stages of toxicological research, are not an alternative, but an introduction to mandatory experimental work., (2010 John Wiley & Sons, Ltd.)

Brain-derived neurotrophic factor (BDNF) belongs to neurotrophin family, a class of molecules playing key roles in neuronal development, survival and regeneration, neurite growth and plasticity: memory processes are mainly affected, and mutations of the human BDNF gene are associated to cognitive and behavioural disturbances. All neurotrophins contain a highly conserved C-terminal domain and bind to the same receptor family. Both correct folding and post-translational processing of the entire preproprotein are pivotal for sorting to the extracellular space, dimerization and receptor binding. Evolutionary studies conducted so far demonstrate that a single ancestor gene underwent two independent duplication events at an early stage of vertebrate evolution, leading to the formation of the current neurotrophins. However, works focusing on BDNF evolution are scarce and fragmentary, mainly in lower vertebrates. In this work, we report cloning of eight DNA sequences from amphibians and teleosts, and analysis of the entire coding regions (cDNA sequences) of BDNF from 35 organisms, from teleosts to mammals. A phylogenetic tree was constructed and the analysis of non-synonymous-synonymous substitution rates performed for the different branches. Our results suggest that natural selection is acting on mammals, separating them from other classes. Since preproprotein cleavage and 3D structure of mature protein are important for functional activity of BDNF, we also propose a de novo prediction of the 3D structure of translates in at least one species for each class, in order to get hints about the functional constraints of the protein.

Blue Fin Tuna (BFT), Thunnus thynnus, has been seriously endangered by global massive overfishing and by the pollution of marine environment. Feeding and fattening of caught tuna in marine cages is a recent resource, but the development of a self-sustained aquaculture activity, being independent from the supply of wild fish, is required from both industrial and conservation perspectives. At this scope, several technical problems have to be solved and the control of reproduction is the cardinal one. Beside the technological developments of farming facilities and protocols, a molecular approach seems promising for the studies of appropriate nutritional strategies, reproduction physiology and animal welfare, as well as lifestyle and response to endocrine disruptor pollutants. In this context, we have started an EST project on this species sequencing 2743, 2907, and 3014 clones from expression libraries of ovary, testis and liver, respectively, and 1499 clones from an ovary normalized library. Thanks to this project, we have identified several sequences with known function in other organisms, but not previously described in this species. Among the new genes, 712 were found only in the expression library of the ovary, 613 in that of the testis and 318 in that of the liver, while 324 additional genes were shared by two or more expression libraries; other 127 genes not found in the expression libraries were obtained from the ovary normalized library. This represents a contribution to the knowledge of the molecular basis of BFT and a necessary step for facilitating further molecular studies on this species. Accession numbers: EC 091633 to EC 093160; EG 629962 to EG 631176; EC 917676 to EC 919417; EG 999340 to EG 999999; EH 000001 to EH 000505; EH 667253 to EH 668984; EL 610526 to EL 611807; EC 42144 to EC 422414; and EH 379568 to EH 380065.

Perch are promising species for freshwater aquaculture and, differently from other fish, have not yet been domesticated through artificial selection; therefore, they show a wide genetic variability that is undesirable for aquaculture. In addition to the more traditional methods of aquatic biotechnology, the most recently developed molecular biological techniques can augment the overall efficiency of aquaculture. To help these new molecular techniques find their place in the everyday management of fish farming, we should make an effort to reduce the gap in genomic resources that separates farming species from "model organisms." We performed single-pass sequencing on 1237 randomly selected clones from a perch liver cDNA expression library, 350 clones of a brain-minus-liver, and 639 clones of a liver-minus-brain subtraction library. The sequences were deposited in the NCBI Expressed Sequence Tags database (www.ncbi.nlm.nih.gov/projects/dbEST). In the three libraries we identified 108, 46, and 104 genes, respectively. EST cataloguing and profiling of perch will provide a basis for functional genomic research in this species, but will also promote studies in comparative and environmental genomics, for identifying polymorphic markers that are useful, for example, to survey the disease resistance of fish and for discovering of new molecular markers of exposure. Using these genomic resources, micro- and macroarrays can be produced that will give immediate and practical benefits in the field of aquaculture, allowing early diagnosis of the fish conditions and helping in the generation of new mechanistic data on the nature of fish responses to different farming conditions.

Chemical oxidation of the chlorosomes from Chloroflexus aurantiacus and Chlorobium tepidum green bacteria produces bacteriochlorophyll radicals, which are characterized by an anomalously narrow EPR signal compared to in vitro monomeric BChl c (.+) [Van Noort PI, Zhu Y, LoBrutto R and Blankenship RE (1997) Biophys J 72: 316-325]. We have performed oxidant concentration and temperature-dependent X-band EPR measurements in order to elucidate the line narrowing mechanism. The linewidth decreases as the oxidant concentration is increased only for Chloroflexus indicating that for this system Heisenberg spin exchange is at least partially responsible for the EPR spectra narrowing. For both species the linewidth is decreasing on increasing the temperature. This indicates that temperature-activated electron transfer is the main narrowing mechanism for BChl radicals in chlorosomes. The extent of the electron transfer process among different BChl molecules has been evaluated and a comparison between the two species representative of the two green bacteria families has been made. In parallel, high frequency EPR experiments have been performed on the oxidized chlorosomes of Chloroflexus and Chlorobium at 110 and 330 GHz in the full temperature range investigated at X-band. The g-tensor components obtained from the simulation of the 330 GHz EPR spectrum from Chlorobium show the same anisotropy as those of monomeric Chl a (.+) [Bratt PJ, Poluektov OG, Thurnauer MC, Krzystek J, Brunel LC, Schrier J, Hsiao YW, Zerner M and Angerhofer A (2000) J Phys Chem B 104: 6973-6977]. The spectrum of Chloroflexus has a nearly axial g-tensor with reduced anisotropy compared to Chlorobium and monomeric Chl a in vitro. g-tensor values and temperature dependence of the linewidth have been discussed in terms of the differences in the local structure of the chlorosomes of the two families.

The data concerning the cephalic phase of insulin secretion (CPIS) in human obesity are controversial. We investigated the effect of a variety of sensory challenges on CPIS in 17 non-diabetic obese patients (four males, 13 females, mean age 41.1 years, mean BMI 38.7). Water, saccharin, and lemon juice were used as oral stimuli, and a complete meal was simply presented as visual and olfactory stimulations. Twelve healthy normal-weight subjects (four men, eight women, mean age 39.9, mean BMI 22.5) also underwent oral stimulation as controls, and the patients who underwent the sight and smell stimulations were also tested for pancreatic polypeptide (PP) changes in order to verify the occurrence of truly cephalic reflex during the test. Insulin levels were measured before and after each stimulation (every min for the first 5 min, and then after 10, 20, and 30 min). None of the stimuli (saccharin, lemon juice or water retained in the mouth for 2 min and were then spat out; the combined and separate sight and smell of a meal for 2 min) led to a significant increase in insulin in the obese patients (except in the case of one woman after oral stimulation). The oral stimuli led to a variable CPIS in one female and three male controls. Despite the absence of CPIS, the five obese patients undergoing all three sensory stimulations related to the meal (combined sight and smell, sight alone and smell alone) showed an early and significant increase in plasma PP concentrations within the first 3 min; this was more pronounced after the combined than after the separate exposure. Although only preliminary, these results underline the variability but substantial lack of CPIS in obese patients, thus suggesting that it can be considered a relatively rare and unrelevant event even in the presence of a true brain-mediated reflex revealed by the rapid and consistent increase in PP found in our experiments.

Eight obese patients (4 male, 4 female; mean age = 35.9 years) before [mean body mass index (BMI) = 37.1] and after (mean BMI = 31.4) weight loss by means of a mixed hypocaloric diet were compared with 8 lean subjects (4 male, 4 female; mean age = 37.1 years, mean BMI = 22.3) in a study of their nocturnal sleep patterns and sleep-related growth hormone (GH) secretions. Although no sleep disorders (in particular, sleep apnea and hypersomnia) were observed, GH secretion was markedly altered in obese patients that showed no sleep-related GH peaks. After weight loss, the sleep architecture in obese subjects was unchanged. On the contrary, GH peak appeared to be only partially restored and delayed until after stage III-IV of non-REM sleep. Our study on obese subjects suggests that the altered nocturnal GH secretion, probably related to a hypothalamic dysfunction, may be the result of the obesity per se.

This study has been planned to investigate some aspects of the interaction between acetylsalicylic acid (ASA) and tolbutamide on insulin secretion. In healthy subjects, oral administration of 3.2 g daily of ASA for 3 days significantly enhanced a) basal insulin levels (p less than 0.01), b) arginine-stimulated insulin secretion (25 g i.v. over 30 min) (p less than 0.01) and c) tolbutamide-stimulated insulin secretion (1 g or 0.25 g i.v. as a bolus) (areas under curves: p less than 0.02). Corresponding decreases in glycemia were observed. Tolbutamide binding to serum proteins was significantly reduced after ASA treatment (p less than 0.02). We conclude that, in case of tolbutamide test, interferences between ASA and tolbutamide on insulin secretion might be dependent, at least in part, on enhancement of free-tolbutamide percentage in plasma and not only on a direct or synergic action of ASA on pancreatic B-cell. Therefore, acute stimulation of insulin secretion by tolbutamide appears not to be completely comparable to other traditional stimuli, when ASA effects are studied.

Lipolytic rate in basal conditions and after adrenergic stimulation with norepinephrine (NE, 8.87 microM) from suspensions of differently sized human adipocytes has been tested. Adipocytes were intra surgically provide for obese (OB) and normal-weight (NW) individuals. Total volume of cells was constant in all samples, being 4% in the incubation system. Glycerol released in the buffer at the end of one hour incubation was measured and results expressed by three different features, i.e. related to: A) total volume of cells (nmol glycerol/40 microliters/h); B) cell number (nmol/cell x 10(4)/h), or C) cell surface unit (nmol/mm2/h). No statistically significant differences between OB and NW have been found, nor between histometrical parameters or between lipolytic rates. A positive, significant correlation between lipolytic rate B and Mean Cell Volume (MCV) or total Cell Surface (TCS 10(4)) has been found (rs from 0.90 to 0.94, p less than 0.01) both in basal conditions and after stimulation. A significant, positive correlation between stimulated lipolytic rate C and MCV (r = 0.67, p less than 0.05) has also been observed. Our results suggest that lipolytic rate appears to be correlated to cell volume. While the expression of lipolytic rate with relation to total volume of cells in the sample (rate A) may be more convenient to minimize the effect of different size of cells in different samples, data expressed as glycerol released per number of cells (rate B) or per surface unit (rate C) appears however to be more suitable form main experimental purposes in metabolic studies of adipocytes.

The role of alpha-adrenoceptors in the regulation of glucose-induced insulin release (GIR) was investigated in islets of normal and neonatally streptozotocin-injected non-insulin-dependent diabetic rats (STZ). In normal islets GIR was suppressed to approximately 50% by 10(-8) M of the alpha 2-adrenergic agonist UK 14304, whereas 10(-9) M of the agonist induced a similar inhibition in STZ islets. In normal islets, suppression of GIR by UK 14304 (10(-8) M) was totally antagonized by 10(6) M idazoxan (alpha 2-antagonist) or 10(6) M phentolamine (alpha 1 + alpha 2-antagonist). In STZ islets, the inhibitory effect of UK 14304 (10(-9) M) was entirely reversed by 10(-5) M idazoxan or 10(-6) M phentolamine. The alpha 1-antagonist prazosin (10(-7)-10(-5) M) was without effect on insulin release suppressed by UK 14304 in normal and STZ islets. Insulin release at 3.3, 8.3, or 16.7 mM glucose was augmented by phentolamine but not by idazoxan. It is concluded that the inhibitory effect of catecholamines on insulin release is mediated by alpha 2-receptors in normal and STZ islets. Phentolamine augments basal and glucose-induced insulin release by a mechanism that does not involve alpha 2-adrenoceptors.

Effects of long-term antiepileptic therapy on the hypothalamic-pituitary axis were evaluated from the basal and stimulated plasma levels of growth hormone (GH) and prolactin (PRL) and from circadian adrenocorticotropic hormone (ACTH)/cortisol rhythms. Data for patients with well-controlled epilepsy of mild-to-moderate severity were compared with those for normal healthy volunteers. Analysis of the effects of each antiepileptic drug (AED) and of combined AEDs revealed minor abnormalities of stimulated GH secretion in all treated patients. In epileptic men, all individual AEDs (except valproate) and AED polytherapy increased both basal and stimulated plasma levels of PRL. In epileptic women, this effect was more variable and less marked, probably because of early depletion of PRL reserves. Each AED and combined AEDs did not significantly change circadian ACTH/cortisol rhythms in epileptic patients. The effects observed seem not to be related to epilepsy per se. Clinical implications, pathways, and neurotransmitters involved and possible mechanisms of the neuroendocrine effects of long-term AED therapy are discussed.

In the present study bone mineral content (BMC) was measured at 1/3 and 1/10 the length of the radius from the distal end in 100 adult diabetic subjects (55 females, 45 males, 54 insulin-dependent [IDD], 46 non-insulin-dependent [NIDD]), using single photon absorptiometry. Each individual BMC value in the diabetics was first compared to normal BMC values for age obtained in our laboratory from 500 non-diabetic subjects. BMC in the diabetics was within the normal range (M +/- 2 SD) with respect to sex and age. Data from IDD and NIDD males, under and over 50 years of age, and of IDD and NIDD females, pre- and postmenopausal, were compared with the respective control group data after matching each diabetic subject to a non-diabetic one of identical age and menstrual history and of comparable body mass index. In each group BMC in the diabetic subjects was found not to be statistically different from BMC in the control ones. Correlation analysis was carried out between BMC and endocrine or metabolic parameters obtained in 52 of the diabetic patients. BMC in diabetic subjects was not correlated with plasma levels of hormones (thyroid hormones, cortisol, 17-beta-estradiol, testosterone), Ca, P or alkaline phosphatase activity. It was inversely correlated with urinary Ca and P in NIDD women and with urinary Ca in NIDD men. No relationship was found between BMC and the metabolic control of diabetes (evaluated by basal glycemia, 2h-post-prandial glycemia and glycosylated hemoglobin).

The effect of controlled long-term oral trial with 2 g/die of acetylsalicylic acid (ASA) in addition to diet in 14 patients suffering from impaired glucose tolerance (according to WHO criteria) was compared to diet alone plus placebo (PL). All patients were randomly assigned to ASA or PL, and then submitted to cross-over scheduling procedure (30 + 30 days). Plasma glucose levels observed after an oral glucose tolerance test (OGTT, 100 g) became normal in patients receiving ASA for 30 days (p less than 0.01 at x2 analysis). No change of abnormal OGTT data was observed when patients were treated with PL. Insulin secretin after OGTT and after i.v. glucose tolerance test (IVGTT, 5 g) was unmodified by ASA. Basal glucose levels and plasma glucose disappearance rate after IVGTT also remained unchanged after ASA. Only two subjects had to stop ASA treatment because of gastric discomfort. The oral administration of 2 g of ASA might possibly interfere with intestinal glucose absorption. The well known influence of ASA on prostaglandin synthesis and on insulin secretion could not be relevant in our own pharmacological approach.

Left ventricular function (LVF) was studied in 25 obese patients (four males and 21 females) by serial poligraphic measurements, namely systolic time intervals (STI), during a short period of dieting (2721 kJ/day (650 kcal/day) as single daily meal regimen). In the same period, all the patients underwent also three standardized exercise tests at the cycloergometer. At the end of the study (20th day), statistically significant differences were obtained in weight loss (P less than 0.001); two main parameters of STI, namely pre-ejection period index (PEPI) and PEP/LVET ratio were lowered (P less than 0.001): furthermore, peak and recovery systolic blood pressure (SBP) and heart rate (HR) during exercising, were also significantly reduced. These data suggest that an improvement of LVF and cardiac performance are present since the early phases of caloric restriction in obesity.

The effects of short-term oral treatments with prostaglandin (PG) synthesis inhibitors, acetylsalicylic acid (ASA), or diclofenac (DCF), on basal and stimulated growth hormone (GH) and prolactin (PRL) secretion were studied in 23 healthy volunteers. Before and after 4 days on ASA (3.2 g daily) or DCF (75 mg daily), subjects were given cimetidine or metoclopramide to evaluate PRL reserve. Arginine infusion test (for GH and PRL response) was performed only in ASA-treated subjects. Arginine-induced GH and PRL release was abolished and enhanced, respectively, by ASA pre-treatment. PRL response to cimetidine was greater than that observed in basal conditions when ASA was given, but remained unchanged after DCF administration. Neither ASA nor DCF was capable of modifying the PRL response to metoclopramide. Basal GH and PRL levels were not influenced by ASA or DCF. In conclusion, some PG may play an important role in the regulation of GH and PRL secretion, and some PG inhibitors (like ASA) may significantly interfere with some dynamic tests for pituitary reserve.

We have studied the effects of short-term treatment with lithium carbonate (900-1,200 mg/day for 4 days) on insulin secretion and blood glucose levels of 28 healthy volunteers (8 females and 20 males, aged 23-29 years) who underwent the following stimulations: two intravenous glucose loads of 25 and 5 g (IVGTT25; IVGTT5); arginine infusion (25 g over 30 min); tolbutamide test (0.25 g i.v.). Seven subjects for each group were tested. A placebo treatment was also performed. Short-term lithium treatment significantly reduced the insulin response to IVGTT25, arginine and tolbutamide. No differences were observed in blood glucose levels during all stimuli. Serum electrolyte levels and thyroid function were not affected by the treatment. In conclusion, these findings suggest, in healthy subjects, a good peripheral glucose utilization after brief-term lithium administration, in spite of impaired insulin response to various stimuli.