Somatostatin receptor subtype 2 and 5 in human GH-secreting pituitary adenomas: analysis of gene sequence and mRNA expression.

The role of somatostatin receptor subtypes 2 and 5 (SSTR2 and SSTR5) in determining the secretory and proliferative phenotype as well as the sensitivity to somatostatin analogue treatment is not clearly established. We quantified the expression of SSTR2 and SSTR5 mRNA using a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 19 human growth hormone (GH) -secreting adenomas. Tumour characteristics and in vivo sensitivity to somatostatin analogues were assessed; tumours were screened for Gsalpha gene mutations.

The expression of the antiproliferative gene ZAC is lost or highly reduced in nonfunctioning pituitary adenomas.

The ZAC gene encodes a new zinc-finger protein that concomitantly induces apoptosis and cell cycle arrest and localizes to chromosome 6q24-q25, a well-known hot spot related to cancer. ZAC is highly expressed in the anterior pituitary gland, and its ablation by antisense targeting promotes pituitary cell proliferation. Here we investigate ZAC status in pituitary tumors to evaluate its role in pituitary tumorigenesis.

Proliferation index of nonfunctioning pituitary adenomas: correlations with clinical characteristics and long-term follow-up results.

Objective: The recurrence of nonfunctioning pituitary adenomas (NFPAs) after surgical removal is common. The aim of our study was to investigate and correlate the growth fraction of NFPAs with clinical characteristics and long-term follow-up results.

Methods: Tumor specimens were obtained from 101 consecutive patients with NFPAs (48 female patients and 53 male patients; mean age, 52.

Surgical management of thyrotropin-secreting pituitary adenomas.

The reported cases of hyperthyroidism due to a TSH-secreting pituitary adenoma have steadily increased in previous years; however, information about the results and long term outcome after pituitary surgery is scanty. Twenty-four patients with a TSH-secreting adenoma underwent pituitary surgery at our department in the last 15 years. Hypersecretion of other pituitary hormones was diagnosed in 7 patients.

The desmopressin test in the differential diagnosis between Cushing's disease and pseudo-Cushing states.

Differentiating Cushing's disease (CD) from pseudo-Cushing (PC) states may still be difficult in current practice. Because desmopressin (1-deamino-8D-arginine vasopressin, DDAVP), a vasopressin analogue, stimulates ACTH release in patients with CD but not in the majority of normal, obese, and depressed subjects, we investigated its ability to discriminate CD from PC states. One hundred seventy-three subjects (76 with active CD, 30 with PC, 36 with simple obesity, and 31 healthy volunteers) were tested with an iv bolus of 10 microg DDAVP.

Interleukin-6 is inhibited by glucocorticoids and stimulates ACTH secretion and POMC expression in human corticotroph pituitary adenomas.

Interleukins and their receptors are expressed intrinsically in the anterior pituitary and regulate hormone production and cell proliferation. It has previously been shown that interleukin-6 (IL-6) regulates hormone secretion in normal pituitary cells and cell lines. Here we examined the effects of IL-6 on propiomelanocortin (POMC) expression and ACTH production in corticotroph adenoma cells in vitro.

Acromegaly associated with a granular cell tumor of the neurohypophysis: a clinical and histological study. Case report.

Acromegaly is usually caused by a growth hormone (GH)-secreting pituitary adenoma, and hypersecretion of GH-releasing hormone (GHRH) from a hypothalamic or neuroendocrine tumor accounts for other cases. The authors report on the unusual association of acromegaly with a granular cell tumor of the neurohypophysis. A 42-year-old woman with a 10-year history of acral enlargement, headache, and menstrual abnormalities was referred to our department for a suspected GH-secreting pituitary adenoma.

New antiherpetic 1,3-phenylene derivatives, inhibitors of the interaction of the HSV-1 origin binding protein (OBP) with DNA.

The synthesis of new 1,3-phenylene derivatives and their preliminary evaluation as antivirals (Herpes simplex 1, HSV-1) whose antiherpetic activity can be related with the inhibition of the interaction of the origin binding protein (OBP) with the DNA are presented. The new compounds are adjusted to a previously defined common structural model, consisting of a central aromatic system, which presents two side chains of different lengths in relative position 1, 3; these chains are made up of atomic groups characterized by the alternation of positive and negative centers, situating differently substituted rings, preferably aromatic, at the ends of both chains. Some of these derivatives, such as N,N''-(4-methoxy-1,3-phenylene)bis[N'-(4-nitrophenyl)urea] (2c) or (1,3-phenylene)bis[N-(p-tolyl)aminosulfonyl] (11b), show antiherpetic activity related to the proposed mechanism.

Non-random trisomies of chromosomes 5, 8 and 12 in the prolactinoma sub-type of pituitary adenomas: conventional cytogenetics and interphase FISH study.

Specimens from 53 pituitary adenomas (PAs), including 17 NFPA, 16 PRL-, 9 ACTH-, 9 GH- and 2 TSH-secreting tumors, underwent cytogenetic analysis by the direct and short-term culture methods. Only 8 tumors (15%) appeared to have an abnormal karyotype. To increase the resolution of cytogenetic analysis, direct preparations from 31 PAs were investigated by interphase FISH with probes specific for chromosomes 5, 8, 12 and X, for which gain in pituitary tumors has been reported.

Glycosaminoglycans treatment increases IGF-I muscle levels and counteracts motor neuron death: A novel nonanticoagulant action.

The present study shows that sciatic nerve crush in 2-day-old rats causes extensor digitorum longus (EDL) muscle atrophy and motor neuron loss and that treatment with glycosaminoglycans (GAGs) promotes muscle reinnervation, motor neuron survival, and markedly increases insulin-like growth factor-I (IGF-I) content in the denervated muscles. EDL muscle denervation-induced atrophy in saline-treated rats is progressive and reaches the greatest extent at 42 days after birth, which correlates with reduced EDL weight growth. There is also a partial reinnervation as shown by the number of reinnervated EDL muscle fibers (65.

Comprehensive critical incident monitoring in a neonatal-pediatric intensive care unit: experience with the system approach.

Objective: To examine the occurrence of critical incidents (CIs) in order to improve quality of care.

Design: Prospective survey.

Setting: Multidisciplinary, neonatal-pediatric intensive care unit (ICU) of a non-university, teaching children's hospital.

Determination of the proliferation and apoptotic index in adrenocorticotropin-secreting pituitary tumors : comparison between micro- and macroadenomas.

We investigated the growth fraction and cell loss fraction in a large group of patients with Cushing's disease subdivided according to tumor size. Fifty-one patients, 8 males and 43 females, aged 12 through 61 years (mean age 34.6 +/- 1.

Glycosaminoglycans boost insulin-like growth factor-I-promoted neuroprotection: blockade of motor neuron death in the wobbler mouse.

Wobbler mice display forelimb weakness, altered paw positioning, reduced running speed, muscle atrophy and motor neuron loss; co-treatment with glycosaminoglycans and insulin-like growth factor-I counteracts the progression of the disease. Reportedly, treatment with glycosaminoglycans or insulin-like growth factor-I slows the early stages of progressive forelimb dysfunction in wobbler mice. Our aim was to study whether the combination of these two drugs would result in greater neuroprotective effects.

Galanin is released by adrenocorticotropin-secreting pituitary adenomas in vivo and in vitro.

Galanin, a brain-gut peptide, is also synthesized and released by the pituitary. In man, galanin-like immunoreactivity and galanin messenger RNA have been detected specifically in normal and tumoral corticotropes, but little is known about the production and release of galanin by the human pituitary. We evaluated galanin release by 5 ACTH-secreting pituitary adenomas in culture and plasma galanin concentrations in the inferior petrosal sinuses (IPSs) of 15 patients with Cushing's disease before and after CRH administration.

The control on growth hormone release by free fatty acids is maintained in acromegaly.

Free fatty acids (FFA) physiologically regulate GH release via a negative feedback. The aim of this study was to examine whether such feedback is preserved in acromegaly, a condition in which alterations in other regulatory mechanisms of GH release occur. Eight acromegalic patients (group 1: five women and three men, 43.

Growth hormone and prolactin responses to corticotrophin-releasing-hormone in patients with Cushing's disease: a paracrine action of the adenomatous corticotrophic cells?

Objective: In patients with Cushing's disease multihormonal responses to ovine corticotrophin releasing hormone (oCRH) have been detected in blood from inferior petrosal sinuses. This finding has been explained by co-secretion of other hormones, in addition to ACTH, by the pituitary adenoma itself or by paracrine effects exerted by the adenoma on normal periadenomatous pituitary cells. To assess these hypotheses we compared the presence of a CRH induced GH and/or PRL response during inferior petrosal sinus sampling to the immunohistochemical detection of PRL and GH in adenomatous tissue removed from patients with Cushing's disease.

Systemic administration of insulin-like growth factor decreases motor neuron cell death and promotes muscle reinnervation.

Neonatal sciatic nerve axotomy causes motoneuron death and muscle denervation atrophy. The aim of the present study was to determine whether insulin-like growth factor-I (IGF-I) administration promotes muscle reinnervation and counteracts motor neuron loss after such an injury. Six weeks after sciatic nerve axotomy performed in 2-day-old pups, the number of motor neurons, as assessed by retrograde transport of horseradish peroxidase injected into the extensor digitorum longus (EDL) muscle, was reduced from 52 +/- 3 to 26 +/- 3.

Dry lung syndrome: complete airway collapse mimicking pulmonary hypoplasia?

Unlabelled: We observed a premature baby born after severe oligohydramnios who could not be ventilated efficiently even with very high pressures immediately after birth, but who, after cessation of resuscitation attempts, recovered spontaneous sufficient breathing during the following hour. After this experience we searched our case records for other newborns with dry lung syndrome using the following definition: (1) premature birth after prolonged leakage of amniotic fluid, (2) very high ventilatory requirement after birth, (3) dramatic improvement during the first 24 to 36 h and (4) respiratory distress syndrome and infection excluded. Among 93 prematures with rupture of membranes for 4 days or more we found 3, including the index case, matching this definition.

Usefulness of markers of cell proliferation in the management of pituitary adenomas.

1. Pituitary adenomas are benign and slow-growing tumours whose clinical manifestations depend mainly on the secretory activity of the adenomatous cells. Except for prolactinomas, surgical removal of the tumour is the therapy of choice.

Constitutively active Gs alpha is associated with an increased phosphodiesterase activity in human growth hormone-secreting adenomas.

Because phosphodiesterase (PDE) expression and activity are controlled by cAMP, we investigated whether activating mutations of Gs alpha gene that occur in human GH-secreting adenomas are associated with increased PDE activity. We studied 10 adenomas with wild-type Gs alpha (gsp-) and 8 with mutant Gs alpha (gsp+). Although, in the absence of PDE inhibitors, intracellular cAMP levels were similar in gsp+ e gsp- adenomas, the PDE blockade with 3-isobutyl-1-methylxanthine induced a marked increase in cAMP in all but one gsp+ adenoma (% increase: from 77 to 2900) and a slight rise in only 2 gsp-.

Laparoscopic bilateral adrenalectomy for persistent Cushing's disease after transsphenoidal surgery.

Background: We performed bilateral laparoscopic adrenalectomies on four patients (three women and one man) with Cushing's disease (pituitary-dependent Cushing's syndrome) showing persistent hypercortisolism after transsphenoidal surgery.

Methods: The technique for bilateral transperitoneal laparoscopic adrenalectomy was derived from the one previously adopted by our group for unilateral adrenalectomy and previously described. Eight trocars were used, of which two were used for both left and right adrenalectomy.

[Combined neuronal and endocrine tumors of the sellar region].

Gangliocytomas or gangliogliomas of the sellar region are very rare tumors. In a great proportion of those cases an adenoma of the anterior pituitary develops from the cell type that is hyperstimulated by the releasing hormone produced from the gangliocytoma. Five GHRH secreting gangliocytomas are reported.