Comparative sensitivity to the fungicide tebuconazole of biofilm and plankton microbial communities in freshwater ecosystems.

Stream and lake ecosystems in agricultural watersheds are exposed to fungicide inputs that can threaten the structure and functioning of aquatic microbial communities. This research analyzes the impact of the triazole fungicide tebuconazole (TBZ) on natural biofilm and plankton microbial communities from sites presenting different degrees of agricultural contamination. Biofilm and plankton communities from less-polluted (LP) and polluted (P) sites were exposed to nominal concentrations of 0 (control), 2 and 20 µg TBZ L(-1) in 3-week microcosm experiments. Descriptors of microbial community structure (bacterial density and chlorophyll-a concentration) and function (bacterial respiration and production and photosynthesis) were analyzed to chart the effects of TBZ and the kinetics of TBZ attenuation in water during the experiments. The results showed TBZ-induced effects on biofilm function (inhibition of substrate-induced respiration and photosynthetic activity), especially in LP-site communities, whereas plankton communities experienced a transitory stimulation of bacterial densities in communities from both LP and P sites. TBZ attenuation was stronger in biofilm (60-75%) than plankton (15-18%) experiments, probably due to greater adsorption on biofilms. The differences between biofilm and plankton responses to TBZ were likely explained by differences in community structure (presence of extracellular polymeric substances (EPS) matrix) and microbial composition. Biofilm communities also exhibited different sensitivity levels according to their in-field pre-exposure to fungicide, with P-site communities demonstrating adaptation capacities to TBZ. This study indicates that TBZ toxicity to non-targeted aquatic microbial communities essentially composed by microalgae and bacteria was moderate, and that its effects varied between stream and lake microbial communities.

Inhibitory effect of prepro-thyrotrophin-releasing hormone (178-199) on adrenocorticotrophic hormone secretion by human corticotroph tumours.

Prepro-thyrotrophin-releasing hormone (TRH) (178-199), a 22-amino acid cleavage product of the TRH prohormone, has been postulated to act as an adrenocorticotrophin hormone (ACTH)-release inhibitor. Indeed, although in vitro evidence indicates that this peptide may inhibit basal and stimulated ACTH secretion in rodent anterior pituitary primary cultures and cell lines, not all studies concur and no study has as yet evaluated the effect of this peptide in Cushing's disease. The present study aimed to test the effect of preproTRH(178-199) in human tumoural corticotrophs. Twenty-four human ACTH-secreting pituitary tumours (13 macroadenomas, 11 microadenomas) were collected during surgery and incubated with 10 or 100 nm preproTRH(178-199). ACTH secretion was assessed after 4 and 24 h of incubation by immunometric assay and expressed relative to levels observed in control, unchallenged wells (= 100%). Parallel experiments were performed in rat anterior pituitary primary cultures. A clear inhibition of ACTH secretion at 4 and 24 h was observed in 12 specimens (for 10 nm ppTRH: 70 +/- 4% control at 4 h and 83 +/- 5% control at 24 h; for 100 nm ppTRH: 70 +/- 4% control at 4 h and 85 +/- 5% control at 24 h), whereas a mild and short-lasting stimulatory effect was observed in three tumours and no changes in ACTH secretion in the remaining nine tumoural specimens. The inhibitory effect of preproTRH(178-199) was more evident in macroadenomas and significantly correlated with sensitivity to dexamethasone inhibition. Significant inhibition of ACTH secretion by preproTRH(178-199) in rat pituitary cultures was observed after 24 h of incubation. The present study conducted in a large series of human corticotroph tumours shows that preproTRH(178-199) inhibits tumoural ACTH secretion in a sizable proportion of specimens, in close relation to the size of the tumour and its sensitivity to glucocorticoid negative feedback. This appears a promising avenue of research and further studies are warranted to explore the full scope of preproTRH(178-199) as a regulator of ACTH secretion.

Ghrelin stimulates adrenocorticotrophic hormone (ACTH) secretion by human ACTH-secreting pituitary adenomas in vitro.

Ghrelin is a brain-gut peptide with wide-ranging endocrine, metabolic, cardiovascular and neural effects. Ghrelin, like its synthetic counterparts, the growth hormone (GH) secretagogues, has been shown to markedly stimulate adrenocorticotrophic hormone (ACTH) and cortisol secretion in humans and the ACTH-releasing effect of GH secretagogues is even greater in patients with pituitary ACTH-secreting tumours. Furthermore, these tumours synthesize ghrelin itself, suggesting an intrapituitary ghrelin circuit. The aim of the present study was to evaluate the effect of ghrelin on ACTH secretion by human pituitary corticotroph tumours in vitro to test the functionality of this circuit. Nine ACTH-secreting pituitary tumours (four microadenomas, five macroadenomas) were collected during surgery and incubated with 10-100 nM human ghrelin or with 10 nM human corticotrophin-releasing hormone (CRH). Control experiments were performed in rat anterior pituitary primary cultures. ACTH secretion was assessed after 4 h and 24 h incubation by immunometric assay. After 4 h of incubation with ghrelin, medium ACTH concentrations were two- to ten-fold higher compared to ACTH concentrations in unstimulated wells. The ACTH-releasing effect of ghrelin was significantly less than the response elicited by 10 nM CRH (up to 40-fold) Similar results were obtained after 24 h of incubation and a superimposable response pattern was observed in rat anterior pituitary primary cultures. The present study demonstrates that the endogenous GH secretagogue, ghrelin, stimulates ACTH secretion directly from human tumoural corticotrophs, as well as from normal rat pituitary, and indicates that the marked ACTH release elicited by ghrelin in patients with Cushing's disease in vivo is due, at least in part, to its action on the pituitary tumour. However, the reversal of the response pattern reported in vivo, with ghrelin proving a lesser stimulant than CRH in vitro, suggests that additional, suprapituitary mechanisms are involved in the in vivo response. Moreover, these data uphold the concept of a functional intratumoural ghrelin paracrine circuit in human corticotroph adenomas.

Melatonin reduces oxidative stress in surgical neonates.

BACKGROUND/PURPOSE: Cytokines are inflammatory mediators found in the circulation after surgery. Newborns have less protection against oxidation and are very susceptible to free radical oxidative damage. Melatonin has been reported recently to reduce oxidative stress in neonates with sepsis, asphyxia, and respiratory distress. The aim of this study has been to determine if melatonin would lower interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-alpha) and nitrite/nitrate (NOx) levels and modify serum inflammation parameters, improving the clinical course of surgical neonates. METHODS: Ten newborns (group 1), 5 with surgical malformations and respiratory distress (group 1a) and 5 with isolated abdominal surgical malformations (group 1b) received a total of 10 doses of melatonin (10 mg/kg) at defined times interval for 72 hours. The treatment was started within 3 hours after the end of surgery. Ten surgical neonates (group 2), did not receive melatonin. Twenty healthy neonates (group 3) served as control. Blood samples were collected at the end of operation; before treatment with the antioxidant; and 24 hours 72 hours, and 7 days after start of treatment with melatonin or placebo, respectively. RESULTS: Postoperative value of cytokines and NOx levels of groups 1 and 2 were significantly higher than group 3. Compared with group 1b, group 2 displayed significantly higher cytokines and NOx levels at 24 hours, 72 hours, and at 7 days. In group 1a the immediate postoperative values of cytokines were significantly higher than group 1b and group 2, but a significant improvement was observed after administration of melatonin with significantly lower levels of IL-6 and IL-8 with respect to group 2. An improvement of clinical outcome was observed by progressive reduction of clinical parameters of inflammation. CONCLUSIONS: Melatonin reduces cytokines and NOx levels showing potent antioxidant properties with improvement in clinical outcome. Further studies are warranted to define, on larger numbers, the role of melatonin in surgical patients.

The loop region of the helix-loop-helix protein Id1 is critical for its dominant negative activity.

Id1, a helix-loop-helix (HLH) protein which lacks a DNA binding domain, has been shown to negatively regulate other members of the HLH family by direct protein-protein interactions, both in vitro and in vivo. In this study, we report the results of site-directed mutagenesis experiments aimed at defining the regions of Id1 which are important for its activity. We have found that the HLH domain of Id1 is necessary and nearly sufficient for its activity. In addition, we show that two amino acid residues at the amino terminus of the Id1 loop are critical for its activity, perhaps by specifying the correct dimerization partners. In this regard, replacing the first four amino acids of the loops of the basic HLH proteins E12 and E47 with the corresponding amino acids of Id1 confers Id1 dimerization specificity. These studies point to the loop region as an important structural and functional element of the Id subfamily of HLH proteins.

[Measurement of the spontaneous growth hormone increase in short children. Diagnostic significance and neuroendocrine implications]. / Valutazione dell'increzione spontanea di ormone della crescita in bambini con bassa statura. Significato diagnostico e implicazioni neuroendocrine.

The assessment of growth hormone deficiency (GHD) in children with growth retardation is frequently difficult. The diagnostic reliability of standard pharmacological GH provocative tests has been questioned and several investigators have focussed on measurement of spontaneous GH secretion at frequent intervals over periods of 12-24 hours, with mathematical analysis of resulting secretory patterns. The aim of our study was to assess GH secretion in children with growth retardation, either in prepuberal and puberal ages, in order 1) to evaluate the diagnostic relevance of spontaneous GH secretion in comparison to tests, and 2) to gain neuroendocrine interpretations of GH secretion. We investigated 58 short children (height < 5th centile), 35 males, aged 6.4-15 years, without chronic diseases or dysmorphic syndromes. All subjects were divided into 3 groups, either in prepubertal and pubertal ages: normal (normal growth rate, within -0.80 HVSDS; normal GH peak after standard clonidine test > 7 ng/ml; 15 prepubertal, 8 pubertal); slow-growing (growth rate lower than -0.80 SDS; normal GH peak to test; 13 prepubertal, 13 pubertal); GH deficit (growth rate lower than -0.80 SDS; GH peak to test < 7 ng/ml; 6 prepubertal, 3 pubertal). In all children spontaneous GH secretion was evaluated for 24-hrs, 12-hrs daily and 12-hrs overnight, sampling every 30 minutes. The results were analyzed by the PULSAR computer program to determine number, height, area and amplitude of pulses and the baseline and GH secretory areas under and over baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased S100 beta neurotrophic activity in Alzheimer's disease temporal lobe.

The confirming diagnosis of Alzheimer's disease includes an assessment of the concentration of neuritic plaques in the temporal lobe of the brain. The presence of abnormal levels of neurotrophic factors in Alzheimer's disease is one possible explanation for the increased concentration of aggregates of overgrown neurites in the neuritic plaques of Alzheimer's disease. The protein S100 beta, a neurotrophic factor produced by astroglia in the brain, induces neurite outgrowth in cerebral cortical neurons. The generation of specific S100 beta antibodies, the cloning of a full-length cDNA encoding the S100 beta mRNA, and the development of a neurite extension assay system for S100 beta allowed testing of the hypothesis that Alzheimer's disease S100 beta expression is elevated in brain temporal lobe where neuritic plaques are concentrated. The levels of S100 beta protein, mRNA, and specific neurotrophic activity were elevated 10-20-fold in extracts of temporal lobe from autopsy samples of Alzheimer's disease patients compared to those of aged control patients. The cells containing the increased S100 beta were reactive astrocytes; the neuritic plaques were surrounded by S100 beta-containing astrocytes. The elevated levels of S100 beta provides a link between the prominent reactive gliosis and neuritic plaque formation in this common disease of the elderly and raises the possibility that S100 beta contributes to Alzheimer's disease neuropathology.

[Aztreonam: monocenter microbiological study with prevention experience in surgery]. / Aztreonam: indagine microbiologica monocentrica con esperienza di profilassi in chirurgia.

Aztreonam is a monobactam antibiotic active against aerobic gram-negative bacteria. The susceptibility of 127 urinary tract isolates to aztreonam, cefotaxime, cefonicid and ceftazidime was determined. Aztreonam showed good antibacterial activity even against Pseudomonas spp. Only 7 bacterial strains were resistant to aztreonam. The clinical efficacy and pharmacokinetics of aztreonam were assessed in two patients treated for urinary tract infections. The concentrations of aztreonam in serum and urine are reported. Aztreonam safety was evaluated on 20 patients given aztreonam immediately prior to an elective abdominal, urinary or gynecological operation. The results provide support for the use of aztreonam for prophylaxis.

[Domperidone as an anti-emetic in antineoplastic chemotherapy]. / Il domperidone come antiemetico in corso di chemioterapie antiblastica.

The antiemetic effects of domperidone in patients undergoing post-surgical cytostatic treatment for stomach and colorectal carcinoma have been evaluated. The study has been performed on 3 groups of patients treated with domperidone, metoclopramide and placebo respectively. The antiemetic activity of domperidone proved to be better than that of metoclopramide. No side effects were observed in patients treated with domperidone.