Estimates of Environmental Exposure to Radiofrequency Electromagnetic Fields and Risk of Lymphoma Subtypes.

We investigated the association between environmental exposure to radiofrequency electromagnetic fields (RF-EMF) and risk of lymphoma subtypes in a case-control study comprised of 322 patients and 444 individuals serving as controls in Sardinia, Italy in 1998-2004. Questionnaire information included the self-reported distance of the three longest held residential addresses from fixed radio-television transmitters and mobile phone base stations. We georeferenced the residential addresses of all study subjects and obtained the spatial coordinates of mobile phone base stations. For each address within a 500-meter radius from a mobile phone base station, we estimated the RF-EMF intensity using predictions from spatial models, and we performed RF-EMF measurements at the door in the subset of the longest held addresses within a 250-meter radius. We calculated risk of lymphoma and its major subtypes associated with the RF-EMF exposure metrics with unconditional logistic regression, adjusting by age, gender and years of education. In the analysis of self-reported data, risk associated with residence in proximity (within 50 meters) to fixed radio-television transmitters was likewise elevated for lymphoma overall [odds ratio = 2.7, 95% confidence interval = 1.5-4.6], and for the major lymphoma subtypes. With reference to mobile phone base stations, we did not observe an association with either the self-reported, or the geocoded distance from mobile phone base stations. RF-EMF measurements did not vary by case-control status. By comparing the self-reports to the geocoded data, we discovered that the cases tended to underestimate the distance from mobile phone base stations differentially from the controls ( P = 0.073). The interpretation of our findings is compromised by the limited study size, particularly in the analysis of the individual lymphoma subtypes, and the unavailability of the spatial coordinates of radio-television transmitters. Nonetheless, our results do not support the hypothesis of a link between environmental exposure to RF-EMF from mobile phone base stations and risk of lymphoma subtypes.

Morphology, Morphometry and Spatial Distribution of Secondary Osteons in Equine Femur.

A high number of differences exist in bone histological features depending on the species, breed, age and bone. Moreover, osteon distribution may vary in the different sides of a bone as a consequence of different biomechanical strains. The aim of this work was to study the distribution and morphology of osteons in different sides of the equine femoral diaphysis with the attempt to correlate them to the main strains operating on them. The following parameters of secondary osteons and Haversian canals were measured in the transverse sections of diaphyses: perimeter, area, minimum and maximum diameter, eccentricity and osteon population density. A typical Haversian tissue was observed with elliptic secondary osteons consisting in about 10 well-defined lamellae surrounding a circular Haversian canal. Quantitative analysis displays a different population density of secondary osteons depending on the side. The caudal and medial sides, where compression strains are higher, have more secondary osteons in comparison with the cranial and lateral sides, where tension strains are prevalent. These data suggest that secondary osteon population density may depend on the predominant strains. Even the elliptical shape of secondary osteons may be related to biomechanical strains, as their major axes are oriented cranio-caudally parallel to prevalent strains.

Characterization of an established endothelial cell line from primary cultures of fetal sheep hypothalamus.

Immortalized cell lines from fetal brain are an experimental model for studying the in vitro molecular pathways regulating neural cell differentiation and the development of neural networks. The procedures are described to obtain an established cell line from the 90-day old fetal sheep hypothalamus. Viral oncogene LT-SV40 transformation was used to isolate a stable cell line (ENOS-01) that was characterized immunocytochemically. Immortalized cells can be classified as an endothelial cell line of hypothalamic microvasculature. Furthermore, mRNA expression and immunocytochemical of estrogen receptors α and ß were also evaluated. Since it is known that cerebral vessels are directly targeted by sex steroids, our established cell line represents an alternative system to study estradiol/receptor interactions during brain development. Our in vitro model can provide a tool to investigate the complex relationships among the cell types forming the blood-brain barrier, which is known to be involved in the pathogenesis of sheep transmissible neurological diseases.

Neuropeptides and enzymes are targets for the action of endocrine disrupting chemicals in the vertebrate brain.

Endocrine-disrupting chemicals (EDC) are molecules that interfere with endocrine signaling pathways and produce adverse consequences on animal and human physiology, such as infertility or behavioral alterations. Some EDC act through binding to androgen or/and estrogen receptors primarily operating through a genomic mechanism regulating gene expression. This mechanism of action may induce profound developmental adverse effects, and the major targets of the EDC action are the gene products, i.e., mRNAs inducing the synthesis of various peptidic molecules, which include neuropeptides and enzymes related to neurotransmitters syntheses. Available immunohistochemical data on some of the systems that are affected by EDC in lower and higher vertebrates are detailed in this review.

Beta-amyloid: a disease target or a synaptic regulator affecting age-related neurotransmitter changes?

The amyloid cascade hypothesis sustains that beta-amyloid (Abeta) is the main pathogenetic factor of Alzheimer's Disease (AD). Although the direct and indirect neurotoxic role of Abeta are unchallenged, recent findings suggest that the peptide may have so far unforeseen physiological roles. In this regard, the observations showing the ability of Abeta to exert synaptic activities in absence of neurotoxicity are very intriguing. In particular, the peptide is able to affect synaptic transmission of different neurotransmitter systems in key brain areas that regulate executive and cognitive functions, an observation that points Abeta as a new neuromodulator. However, in a pathological context, Abeta may drive functional alterations of several neurotransmitter systems in the early phases of the disease, in turn producing subtle cognitive and behavioural disturbances in addition and before the well known neurodegenerative events. On the other hand, advancing age is the most significant risk factor for the development of AD. In fact, during aging increased Abeta levels have been reported. Moreover, several neurotransmitter systems undergo age-related changes in parallel to a decline of cognitive functions. However, the putative neuromodulatory role of Abeta in the context of aging is nowadays unknown. For these reasons, future studies about the spectrum of action of Abeta (brain areas and neurotransmitter systems affected) are particularly interesting since may suggest new therapeutic targets in order to sustain those functions which may be altered during aging.

Specific inhibitory effect of amyloid-beta on presynaptic muscarinic receptor subtypes modulating neurotransmitter release in the rat nucleus accumbens.

In this study we investigate on the effect of amyloid-beta1-40 (A beta 1-40) on the oxotremorine (OXO)-induced release of [(3)H] dopamine (DA), [(3)H]GABA and [(3)H]acetylcholine (ACh) from synaptosomes in the rat nucleus accumbens (NAc). OXO in presence of himbacine (HIMBA) was able to increase the basal release of [(3)H]GABA. The OXO-elicited [(3)H]GABA overflow was significantly antagonized by atropine (A; 94%), by the M3 antagonists DAU5884 (96%) and 4-DAMP (70%), and by A beta 1-40 (65%). Exposure of NAc synaptosomes to OXO produced a dose-dependent increase of [(3)H]DA overflow which was antagonized by A, partially inhibited by A beta 1-40 (100 nM) but unaffected by DAU5884 and 4-DAMP. The K(+)-evoked [(3)H]ACh overflow was inhibited by OXO. This effect was counteracted by the M2 antagonist AFDX-116 but not by the selective M4 antagonist mamba toxin 3 (MT3). The K(+)-evoked [(3)H]GABA overflow was also inhibited by OXO but conversely, this effect was counteracted by MT3 and not by AFDX-116. A beta 1-40 (100 nM) did not modify the inhibitory effect of OXO both on the K(+)-evoked [(3)H]ACh and [(3)H]GABA overflow. The results show that in the rat NAc, A beta 1-40 selectively inhibits the function of the muscarinic subtypes which stimulate neurotransmitter release and not those which modulate negatively the stimulated release.

Effects of xenoestrogens on the differentiation of behaviorally relevant neural circuits in higher vertebrates.

Several environmental chemicals have the capability of impacting endocrine function (endocrine disrupting chemicals [EDCs]), and therefore they may have long-term consequences, especially if exposure occurs during embryonic development. In this study we present data relative to two widely used animal models: the Japanese quail and the mouse. These two species have been used to understand neural, neuroendocrine, and behavioral components of reproduction and are optimal models to understand how these components are altered by precocious exposure to EDCs. In particular, we discuss the effects of embryonic exposure to diethylstilbestrol, genistein, or ethylene,1,1-dichloro-2,2-bis(p-chlorophenyl) on the sexually dimorphic parvocellular vasotocin system and male copulatory behavior in quail and the effects of bisphenol A on the nitrinergic and kisspeptin systems and their behavioral impact in the mouse. In both models the exposure to EDCs during the critical period (early embryonic period in birds, perinatal period in rodents) alters the differentiation of relevant sexually dimorphic pathways, often inducing the appearance of a sex-reversed neurochemical phenotype that is the most probable cause of the final alteration of sexually differentiated behaviors in the adult animal. In conclusion, the data presented here should stimulate a critical reanalysis of the way to determine the "safe" exposure levels to EDCs for wild species and humans, considering behavior and related neural circuits among the factors to be analyzed.

Effects of xenoestrogens on the differentiation of behaviorally-relevant neural circuits.

It has become increasingly clear that environmental chemicals have the capability of impacting endocrine function. Moreover, these endocrine disrupting chemicals (EDCs) have long term consequences on adult reproductive function, especially if exposure occurs during embryonic development thereby affecting sexual differentiation. Of the EDCs, most of the research has been conducted on the effects of estrogen active compounds. Although androgen active compounds are also present in the environment, much less information is available about their action. However, in the case of xenoestrogens, there is mounting evidence for long-term consequences of early exposure at a range of doses. In this review, we present data relative to two widely used animal models: the mouse and the Japanese quail. These two species long have been used to understand neural, neuroendocrine, and behavioral components of reproduction and are therefore optimal models to understand how these components are altered by precocious exposure to EDCs. In particular we discuss effects of bisphenol A and methoxychlor on the dopaminergic and noradrenergic systems in rodents and the impact of these alterations. In addition, the effects of embryonic exposure to diethylstilbestrol, genistein or ethylene,1,1-dichloro-2,2-bis(p-chlorophenyl) is reviewed relative to behavioral impairment and associated alterations in the sexually dimorphic parvocellular vasotocin system in quail. We point out how sexually dimorphic behaviors are particularly useful to verify adverse developmental consequences produced by chemicals with endocrine disrupting properties, by examining either reproductive or non-reproductive behaviors.

Polyfunctionalized cage compounds by pericyclic domino processes of 4,5-dicyanopyridazine with dienes: applications and limits

The title compound 1 was found to behave as an attractive masked bis-diene to give 4-oxatricyclo[4.3.1.0(3,7)]dec-8-ene, 5-aza- and 5-silatricyclo[5.3.1.0(3,8)]undec-9-ene, tricyclo[3.2.1.0(2, 7)]oct-3-ene, and tricyclo[5.3.1.0(3,8)]undec-9-ene derivatives through purely pericyclic, three-step homodomino processes with diverse bis-dienophiles; whereas the reaction with myrcene (21) was characterized by a complete sitoselectivity affording compound 25, treatment of 1 with (R)-(-)-beta-citronellene (26a) gave a 3:1 mixture of the homochiral diastereomers 30a and 31a. Some limits of this methodology, mainly arising from competitive side reactions upon the key cyclohexa-1,3-diene intermediates, are emphasized. The structures of the new compounds were established on the basis of spectral data.

[Neuroendocrine carcinoma of the skin]. / Il carcinoma neuroendocrino della cute.

Merkel cell carcinoma is an unusual neuroendocrine tumour that arises in the derm. The case reported seemed to deserve the author's attention because of the clinical features, pathological findings and natural history (local recurrence, regional lymph node metachronous metastases, distant metastases). The authors believe that a differential diagnosis between Merkel cell carcinoma and other tumours located in the subcutaneous tissue is mandatory, in order to perform specific immunohistochemical and ultrastructural study.

Primary T cell CD30-positive anaplastic large-cell lymphoma associated with adult-onset celiac disease and presenting with skin lesions.

We report the case of a 52-year-old woman with primary CD30+ anaplastic large-cell lymphoma of T cell phenotype with skin involvement, stage IVB, fulfilling almost all the clinical, histopathologic and immunophenotypic criteria for this disease, associated with adult-onset celiac disease. The diagnoses of malignancy and celiac disease were made during the same clinical episode. The clinical course of the patient has been extremely favorable and she is in complete remission, 15 months after finishing consolidation therapy.

CCK-containing paraneurons in human adenomatous prostate.

The presence of CCK-containing neuroendocrine cells in human adenomatous prostates, and the colocalization of CCK together with serotonin in the same cell, have been demonstrated by means of an immunohistochemical technique and by a double labeling immunofluorescent staining. CCK-containing neuroendocrine cells had a focal distribution in the prostates and sometimes showed dendrite-like cytoplasmic processes. The major part of CCK (96.55%) colocalized with serotonin. CCK probably stimulates muscle contraction and endocrine/exocrine secretions in the urogenital tract.

Distribution of substance P-like immunoreactive nervous structures in the duck gut during development.

The ontogeny and distribution of nerve cell bodies and fibers which are substance P-like (SPL) immunoreactive have been studied in the duck gastrointestinal tract by means of immunohistochemistry. The appearance of SPL immunoreactivity was observed in cell bodies of the oesophagus, proventriculus, gizzard and antrum region at 6 days of incubation. At 9 days of incubation SPL immunoreactive nervous structures were observed in the whole length of the intestine. In each area of the gut, SPL immunoreactivity was initially observed in cell bodies of the myenteric plexus and then of the submucous plexus. Successively, immunoreactive fibers appeared in the same plexuses and also in the circular muscle, longitudinal muscle and muscularis mucosae plexus. Only around hatching were SPL immunoreactive nervous structures seen in the mucous plexus. It was observed that in adult ducks, immunoreactive nerve cell perikarya were less numerous than in embryos and in newly-hatched ducks. The pattern of distribution of SPL immunoreactivity in adult ducks was rather similar to that of the chick and other vertebrate species.

VIP-immunoreactive nerve structures of the gastrointestinal tract in the developing and adult domestic duck.

The first appearance and distribution of VIP-containing nerve structures were studied in the gut of embryonal, newly hatched and adult domestic ducks. Immunoreactive structures appeared in the mesenchyme of the gizzard-duodenum junction (antrum) at 5 days of incubation, and soon after diffused both cranially and caudally. Early in development, VIP-positive cell bodies were more numerous than positive fibres, appearing 3 days before the latter. Later on, the positive cell bodies decreased in number while the fibres increased. In the foregut, VIP-positive structures firstly appeared in the myenteric plexus while in the mid- and hindgut they appeared simultaneously in the myenteric and submucous-plexuses. The gastrointestinal VIP-innervation in newly hatched ducks differed from that of the adult because of the incomplete development of its mucosal component. The findings obtained indicated following: The time interval from 13 to 17 days of incubation seems critical for the growth of the gastrointestinal VIP-containing neurons. The molecular factors regulating the appearance of neuronal phenotypes are probably synthesized early in the avian gizzard development. VIP is widely diffused in the rectum where it may play important roles in regulating the onset and synchronism of peristaltic and anti-peristaltic movements.

[Anaplastic carcinoma of the thyroid. Our experience]. / Il carcinoma anaplastico della tiroide. Nostra esperienza.

Nineteen patients, 12 females and 7 males, with mean age of 66 years, with anaplastic carcinoma of the thyroid, were treated between 1976 and 1990. At diagnosis, in 4 patients disease presented as intraglandular mass, in 11 as infiltration of the adjacent structures and as distant metastases in 4 cases. A preceding history of goiter was found in 7 patients. Total thyroidectomy was performed in 9 patients, subtotal thyroidectomy in 1 and a diagnostic biopsy only in 4 cases. All patients received external radiotherapy (4000-6000 rads). Median global survival was 6 months with no difference between patients receiving thyroidectomy plus RT or biopsy plus RT. All patients died of tumor except 1 who is alive and free of disease at 120 months. Combination modality treatment of anaplastic carcinoma of the thyroid represent, at times, a rational palliative therapeutic approach, even if, in selected patients with early intraglandular disease, total surgery may represent a curative therapy.

Immunocytochemistry of paraneurons in the female urethra of the horse, cattle, sheep, and pig.

The aim of this study is to describe the presence of neuroendocrine (NE) cells (paraneurons), producing biogenic amines and/or peptidergic hormones, in the female urethra of cattle, sheep, pigs, and horses, by means of histochemical and double labeling immunofluorescent techniques. 5-Hydroxy-tryptamine-, chromogranin A-, cholecystokinin- and somatostatin-containing NE cells are present in the urethral epithelium of all the species studied, with the unique exception of the lack of somatostatin cells in the horse. Paraneurons containing 5-hydroxytryptamine colocalized with chromogranin A or cholecystokinin were also found in all subjects. Such active substances are hypothesized to play a role in the contraction of the urethral musculature, emission of urogenital fluids, and inhibition of endocrine and exocrine secretions.

[Hürthle-cell tumors of the thyroid]. / I tumori della tiroide a cellule di Hurthle.

In the last 10 years 20 patients with Hürthle tumors were observed at Institute of Surgery and Oncology of Cagliari University. 17 were females and 3 males with a median age of 42 years. Tumors were malignant in 7 cases and benign in 13. A total thyroidectomy was performed in all patients with carcinoma and in 2 with adenoma because of concurrent goiter. The remaining patients were treated with a less extensive surgery. Two patients with carcinoma had a cervical node metastases at 12 and 67 months, treated by surgery (followed by radioiodine therapy in one). All patients are alive and disease free at 72 months of median follow-up. None of patients with benign adenomas recurred at 47 months of median follow-up. A longer-term follow-up is necessary in order to evaluate the benignity of adenomas.

Vasoactive intestinal polypeptidergic innervation and gastroenteropancreatic system: an immunocytochemical study in the hedgehog Erinaceus europaeus.

The pattern of the digestive vasoactive intestinal polypeptide (VIP)-ergic innervation is described immunohistochemically in the hedgehog Erinaceus europaeus. This animal is a small-sized, wild, nocturnal, lower eutherian mammal whose gastrointestinal tract shows some similarities with the avian gut. The myenteric plexus of the stomach, the mucosa of the small intestine and the circular muscle layer of the large intestine are the best VIP-innervated structures. The pattern of the positive innervation is similar to that described in other mammals and in some bird species. The widespread diffusion of the neuropeptide in the gut is probably due to the importance of its functions in the digestive physiology.

[Short near-fainting in children with or without loss of conscience]. / Malesseri fugaci del bambino con o senza perdita di coscienza.

Short near-faints with or without loss of consciousness have different etiologies and pathogenesis and, according to these, they recur with various frequency. This subject was reported on several publications and here is again examined with the contribute of personal experience and the description of distinct cases. The following causes were examined: vagal hypertonia, digestive troubles (gastroesophageal reflux), metabolic troubles (cyclic ketosis, hypoglycemia and hypocalcemia with peculiar clinic manifestations). Among the neurological causes were examined: epilepsy, benign paroxysmal vertigos and, particularly, the so called breath-holding spells and the migraine, about that were reported a few examples of "migraine accompagnée". Among the cardiovascular causes (ischaemic cerebral crisis), -particular attention was dedicated to orthostatic hypotension syncope. A short hint about hysteria ends the exposition of psychical causes of short near-faints.

Serotonin-, somatostatin- and chromogranin A-containing cells of the urethro-prostatic complex in the sheep. An immunocytochemical and immunofluorescent study.

The urethral and prostatic epithelial of the sheep contain a large number of amine- and/or peptide-producing neuroendocrine cells (NE), also called paraneurons. Four different cell types have been immunohistochemically recognised among them. The first contains the amine serotonin, the second the protein chromogranin A, the third the amine and the protein together and the fourth the hormone somatostatin. Serotonin-producing cells are elongated in shape and often show cytoplasmic dendrite-like processes directed towards the basal membrane and/or the lumen. Chromogranin A-containing cells are polymorphic and constitute the more numerous NE subpopulation. Cells containing both the bioactive substances seem to be less numerous than the chromogranin A cells and slightly more frequent than the serotonin cells. All these cell types are diffused along the whole urethro-prostatic complex and show their highest density in the collicular zone. Somatostatin-containing cells often show a unique cytoplasmic extension directed towards the basal membrane and are rare. It is supposed that the presence of serotonin in the urogenital tract is functionally correlated with the emission of urine and/or semen, while somatostatin is associated with the inhibition of local exocrine and/or endocrine secretions.