Disruption of endogenous tidal rhythms of larval release linked to food supply and heat stress in an intertidal barnacle

The timing of larval release may greatly affect the survivorship and distribution of pelagic stages and reveal important aspects of life history tactics in marine invertebrates. Endogenous rhythms of breeding individuals and populations are valuable indicators of selected strategies because they are free of the neutral effect of stochastic environmental variation. The high-shore intertidal barnacle Chthamalus bisinuatus exhibits endogenous tidal and tidal amplitude rhythms in a way that larval release would more likely occur during fortnightly neap periods at high tide. Such timing would minimize larval loss due to stranding and promote larval retention close to shore. This fully explains temporal patterns in populations facing the open sea and inhabiting eutrophic areas. However, rhythmic activity breaks down to an irregular pattern in a population within the São Sebastião Channel subjected to large variation of food supply around a mesotrophic average. Peaks of chl a concentration precede release events by 6 d, suggesting resource limitation for egg production within the channel. Also, extreme daily temperatures imposing mortality risk correlate to release rate just 1 d ahead, suggesting a terminal reproductive strategy. Oceanographic conditions apparently dictate whether barnacles follow a rhythmic trend of larval release supported by endogenous timing or, alternatively, respond to the stochastic variation of key environmental factors, resulting in an erratic temporal pattern.

Influenza dell'Omeostasi Idrico-Elettrolitica sul Ciclo Veglia-Sonno

During the wake sleep (W-S) cycle in mammals, the alternation of the different states, wake, NREM sleep (NREMS) and REM sleep (REMS), is associated not only with electroencephalographic or behavioural changes, but also with modifications in the physiological regulations of the organism. The most evident change is the existence of a suspension of the somatic and autonomic thermoregulatory responses during REMS. Since thermoregulation is prevalently controlled by the Preoptic Area-Anterior Hypothalamus (PO-AH), its suspension during REM sleep has been taken as a sign of an impairment of the hypothalamic integrative activity that could explain the modifications in physiological regulation observed in this sleep stage. The recent finding from our laboratory that the secretion of the antidiuretic hormone arginine-vasopressin (AVP) in response to a central osmotic stimulation is quantitatively the same throughout the different stages of the W-S cycle, has shown that hypothalamic osmoregulation is not suspended during REMS. In order to clarify the extent of the hypothalamic involvement in the regulation of the W-S cycle, we have studied the effects of three days of water deprivation and of two days of recovery during which animals were allowed a free access to water, on the architecture of the W-S cycle. The condition of water deprivation represents a severe challenge involving neuroendocrine and autonomic hypothalamic regulations. In contradiction with thermoregulatory studies, in which it has been clearly demonstrated that a thermal challenge selectively reduces REMS occurrence, the results of this study show that REMS occurrence is mildly reduced only in the third day of water deprivation. The most striking effects produced by water deprivation appear to concern NREMS, which shows a selective and significant reduction in its slow EEG activity (delta-power) but not in its duration. The recovery period is mainly characterized by a disruption of the normal circadian rhythm of REMS occurrence and by a rebound of the delta power in NREMS. Thus, an autonomic challenge different from those related to thermoregulation and an endocrine challenge as the continuous secretion of AVP show to exert different effects on the stages of the wake-sleep cycle. Also, this study demonstrates that the impairment of the hypothalamic integrative activity thought to characterize the occurrence of REMS only involves thermoregulatory structures.

Modulazione del differenziamento osteogenico di precursori mesenchimali umani per applicazioni di ingegneria tissutale

Lo scheletro è un tessuto dinamico, capace di adattarsi alle richieste funzionali grazie a fenomeni di rimodellamento ed alla peculiare proprietà rigenerativa. Tali processi avvengono attraverso l’azione coordinata di osteoclasti ed osteoblasti. Queste popolazioni cellulari cooperano allo scopo di mantenere l’ equilibrio indispensabile per garantire l’omeostasi dello scheletro. La perdita di tale equilibrio può portare ad una diminuzione della massa ossea e, ad una maggiore suscettibilità alle fratture, come avviene nel caso dell’osteoporosi. E’ noto che, nella fisiopatologia dell’osso, un ruolo cruciale è svolto da fattori endocrini e paracrini. Dati recenti suggeriscono che il rimodellamento osseo potrebbe essere influenzato dal sistema nervoso. L’ipotesi è supportata dalla presenza, nelle vicinanze dell’osso, di fibre nervose sensoriali responsabili del rilascio di alcuni neuro peptidi, tra i quali ricordiamo la sostanza P. Inoltre in modelli animali è stato dimostrato il diretto coinvolgimento del sistema nervoso nel mantenimento dell’omeostasi ossea, infatti ratti sottoposti a denervazione hanno mostrato una perdita dell’equilibrio esistente tra osteoblasti ed osteoclasti. Per tali ragioni negli ultimi anni si è andata intensificando la ricerca in questo campo cercando di comprendere il ruolo dei neuropeptidi nel processo di differenziamento dei precursori mesenchimali in senso osteogenico. Le cellule stromali mesenchimali adulte sono indifferenziate multipotenti che risiedono in maniera predominante nel midollo osseo, ma che possono anche essere isolate da tessuto adiposo, cordone ombelicale e polpa dentale. In questi distretti le MSC sono in uno stato non proliferativo fino a quando non sono richieste per processi locali di riparo e rigenerazione tessutale. MSC, opportunamente stimolate, possono differenziare in diversi tipi di tessuto connettivo quali, tessuto osseo, cartilagineo ed adiposo. L’attività di ricerca è stata finalizzata all’ottimizzazione di un protocollo di espansione ex vivo ed alla valutazione dell’influenza della sostanza P, neuropeptide presente a livello delle terminazioni sensoriali nelle vicinanze dell’osso, nel processo di commissionamento osteogenico.

Drosophila melanogaster as a model to study host-parasitoid interactions: the case of the polydnaviral protein TnBVANK1

Parasitic wasps attack a number of insect species on which they feed, either externally or internally. This requires very effective strategies for suppressing the immune response and a finely tuned interference with the host physiology that is co-opted for the developing parasitoid progeny. The wealth of physiological host alterations is mediated by virulence factors encoded by the wasp or, in some cases, by polydnaviruses (PDVs), unique viral symbionts injected into the host at oviposition along with the egg, venom and ovarian secretions. PDVs are among the most powerful immunosuppressors in nature, targeting insect defense barriers at different levels. During my PhD research program I have used Drosophila melanogaster as a model to expand the functional analysis of virulence factors encoded by PDV focusing on the molecular processes underlying the disruption of the host endocrine system. I focused my research on a member of the ankyrin (ank) gene family, an immunosuppressant found in bracovirus, which associates with the parasitic wasp Toxoneuron nigriceps. I found that ankyrin disrupts ecdysone biosynthesis by impairing the vesicular traffic of ecdysteroid precursors in the cells of the prothoracic gland and results in developmental arrest.

Effect of volume loading with 1 liter intravenous infusions of 0.9% saline, 4% succinylated gelatine (Gelofusine) and 6% hydroxyethyl starch (Voluven) on blood volume and endocrine responses: a randomized, three-way crossover study in healthy volunteers

To study the changes in blood volume and hormones controlling sodium and water homeostasis after infusions of 0.9% saline, Gelofusine (4% succinylated gelatin in 0.7% saline, weight-average molecular weight 30 kD), and Voluven (6% hydroxyethyl starch in 0.9% saline, weight-average molecular weight 130 kD) in healthy volunteers.

Pheochromocytoma in rats with multiple endocrine neoplasia (MENX) shares gene expression patterns with human pheochromocytoma

Pheochromocytomas are rare neoplasias of neural crest origin arising from chromaffin cells of the adrenal medulla and sympathetic ganglia (extra-adrenal pheochromocytoma). Pheochromocytoma that develop in rats homozygous for a loss-of-function mutation in p27Kip1 (MENX syndrome) show a clear progression from hyperplasia to tumor, offering the possibility to gain insight into tumor pathobiology. We compared the gene-expression signatures of both adrenomedullary hyperplasia and pheochromocytoma with normal rat adrenal medulla. Hyperplasia and tumor show very similar transcriptome profiles, indicating early determination of the tumorigenic signature. Overrepresentation of developmentally regulated neural genes was a feature of the rat lesions. Quantitative RT-PCR validated the up-regulation of 11 genes, including some involved in neural development: Cdkn2a, Cdkn2c, Neurod1, Gal, Bmp7, and Phox2a. Overexpression of these genes precedes histological changes in affected adrenal glands. Their presence at early stages of tumorigenesis indicates they are not acquired during progression and may be a result of the lack of functional p27Kip1. Adrenal and extra-adrenal pheochromocytoma development clearly follows diverged molecular pathways in MENX rats. To correlate these findings to human pheochromocytoma, we studied nine genes overexpressed in the rat lesions in 46 sporadic and familial human pheochromocytomas. The expression of GAL, DGKH, BMP7, PHOX2A, L1CAM, TCTE1, EBF3, SOX4, and HASH1 was up-regulated, although with different frequencies. Immunohistochemical staining detected high L1CAM expression selectively in 27 human pheochromocytomas but not in 140 nonchromaffin neuroendocrine tumors. These studies reveal clues to the molecular pathways involved in rat and human pheochromocytoma and identify previously unexplored biomarkers for clinical use.

Internal fixation of symphyseal disruption resulting from childbirth

To investigate the clinical and radiographic results after operative treatment of complete symphyseal disruption resulting from childbirth and to evaluate residual pain and implant failure in relation to the timing of surgery.

Intrapancreatic Accessory Spleen Misdiagnosed as a Nonsecreting Endocrine Tumor: Case Report and Review of the Literature

In a large series of nonselected autopsy investigations an accessory spleen was found in 10-30%. The second most common site is the pancreatic tail (17%). We report a case of intrapancreatic accessory spleen misdiagnosed as a nonsecreting neuroendocrine tumor of the pancreas. Nuclear scintigraphy may provide the definitive diagnosis of an intrapancreatic spleen and therefore prevent patients from unnecessary major surgery.

Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10

Multiple endocrine neoplasia type 2 is characterized by germline mutations in RET. For exon 10, comprehensive molecular and corresponding phenotypic data are scarce. The International RET Exon 10 Consortium, comprising 27 centers from 15 countries, analyzed patients with RET exon 10 mutations for clinical-risk profiles. Presentation, age-dependent penetrance, and stage at presentation of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism were studied. A total of 340 subjects from 103 families, age 4-86, were registered. There were 21 distinct single nucleotide germline mutations located in codons 609 (45 subjects), 611 (50), 618 (94), and 620 (151). MTC was present in 263 registrants, pheochromocytoma in 54, and hyperparathyroidism in 8 subjects. Of the patients with MTC, 53% were detected when asymptomatic, and among those with pheochromocytoma, 54%. Penetrance for MTC was 4% by age 10, 25% by 25, and 80% by 50. Codon-associated penetrance by age 50 ranged from 60% (codon 611) to 86% (620). More advanced stage and increasing risk of metastases correlated with mutation in codon position (609?620) near the juxtamembrane domain. Our data provide rigorous bases for timing of premorbid diagnosis and personalized treatment/prophylactic procedure decisions depending on specific RET exon 10 codons affected.

Functional Imaging of Pheochromocytoma with Ga-DOTATOC and C-HED in a Genetically Defined Rat Model of Multiple Endocrine Neoplasia

Rats affected by the MENX multitumor syndrome develop pheochromocytoma (100%). Pheochromocytomas are uncommon tumors and animal models are scarce, hence the interest in MENX rats to identify and preclinically evaluate novel targeted therapies. A prerequisite for such studies is a sensitive and noninvasive detection of MENXassociated pheochromocytoma. We performed positron emission tomography (PET) to determine whether rat pheochromocytomas are detected by tracers used in clinical practice, such as 68Ga-DOTATOC (somatostatin analogue) or (11)C-Hydroxyephedrine (HED), a norepinephrine analogue. We analyzed four affected and three unaffected rats. The PET scan findings were correlated to histopathology and immunophenotype of the tumors, their proliferative index, and the expression of genes coding for somatostatin receptors or the norepinephrine transporter. We observed that mean 68Ga-DOTATOC standard uptake value (SUV) in adrenals of affected animals was 23.3 ± 3.9, significantly higher than in control rats (15.4 ± 7.9; P = .03). The increase in mean tumor-to-liver ratio of (11)C-HED in the MENX-affected animals (1.6 ± 0.5) compared to controls (0.7 ± 0.1) was even more significant (P = .0016). In a unique animal model, functional imaging depicting two pathways important in pheochromocytoma biology discriminated affected animals from controls, thus providing the basis for future preclinical work with MENX rats.

Cognitive function in postmenopausal breast cancer patients one year after completing adjuvant endocrine therapy with letrozole and/or tamoxifen in the BIG 1-98 trial

Endocrine therapy for breast cancer may affect cognition. The purpose of this study was to examine whether cognitive function improves after cessation of adjuvant endocrine therapy. Change in cognitive function was assessed in 100 postmenopausal breast cancer patients in the BIG 1-98 trial, who were randomized to receive 5 years of adjuvant tamoxifen or letrozole alone or in sequence. Cognitive function was evaluated by computerized tests during the fifth year of trial treatment (Y5) and 1 year after treatment completion (Y6). Cognitive test scores were standardized according to age-specific norms and the change assessed using the Wilcoxon signed-rank test. There was significant improvement in the composite cognitive function score from Y5 to Y6 (median of change = 0.22, effect size = 0.53, P < 0.0001). This improvement was consistent in women taking either tamoxifen or letrozole at Y5 (P = 0.0006 and P = 0.0002, respectively). For postmenopausal patients who received either adjuvant letrozole or tamoxifen alone or in sequence, cognitive function improved after cessation of treatment.

Subjective cognitive complaints one year after ceasing adjuvant endocrine treatment for early-stage breast cancer

Background:In the BIG 1-98 trial objective cognitive function improved in postmenopausal women 1 year after cessation of adjuvant endocrine therapy for breast cancer. This report evaluates changes in subjective cognitive function (SCF).Methods:One hundred postmenopausal women, randomised to receive 5 years of adjuvant tamoxifen, letrozole, or a sequence of the two, completed self-reported measures on SCF, psychological distress, fatigue, and quality of life during the fifth year of trial treatment (year 5) and 1 year after treatment completion (year 6). Changes between years 5 and 6 were evaluated using the Wilcoxon signed-rank test. Subjective cognitive function and its correlates were explored.Results:Subjective cognitive function and the other patient-reported outcomes did not change significantly after cessation of endocrine therapy with the exception of improvement for hot flushes (P=0.0005). No difference in changes was found between women taking tamoxifen or letrozole. Subjective cognitive function was the only psychosocial outcome with a substantial correlation between year 5 and 6 (Spearman's R=0.80). Correlations between SCF and the other patient-reported outcomes were generally low.Conclusion:Improved objective cognitive function but not SCF occur following cessation of adjuvant endocrine therapy in the BIG 1-98 trial. The substantial correlation of SCF scores over time may represent a stable attribute.British Journal of Cancer advance online publication, 24 April 2012; doi:10.1038/bjc.2012.156 www.bjcancer.com.