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Biomedical subjects

M Coculescu

Publications and source records attributed to M Coculescu.

At least 37 records · Page 2Linked to original sources
PubMedDate not supplied

TRH synthesis in "mute" thyrotropinomas: cause-effect or coincidence?

In the pathogenesis of thyrotropin (TSH) immunopositive pituitary adenomas, trigger mutagenetic events are well recognized. However, the way towards a clinical significant tumor is followed under the pressure of growth factors, among which the intrapituitary synthesis of releasing factors could bring a significant contribution. In this study, the production of thyrotropin releasing hormone (TRH) and beta TSH chain was evaluated at the mRNA level by in situ hybridization and end product level by immunohistochemistry, in 18 patients submitted to neurosurgery for pituitary macroadenomas. The hormonal sampling showed abnormal secretion for FSH in 5 and TSH in 4 patients. Seven cases were immunopositive for TSH, and expressed TSH beta mRNA. All but one out of these expressed also TRH mRNA. FSH immunoreactivity was documented in 12/ 18, only one of these being negative for TRH mRNA. Paracrine TRH could contribute to the pathogenesis of these "mute" adenomas.

Adolescent↗
PubMedDate not supplied

A chemical method to isolate hypothalamic nonapeptides by coupling cyst(e)in with bimane.

Vasopressin, oxytocin as well as other active nonapeptides (vasotocin, etc) are difficult to isolate from tissues. Traditionally they were identified using cumbersome biological assays or immunoassays, commercially unavailable, and with some cross reactivity. Based on the fact that all these peptides have two Cysteines in their molecules we developed a simple, sensitive and specific method to detect them by HPLC after pre-column fluorescent derivatization with monobromobimane (mBBr). The peptides were separated on a Vydac C18 column after reduction with Tris (2-carboxyethyl) phosphine (TCEP) and derivatization with mBBr for 5 minutes in dark. Using this method we were able to detect specific peaks for arginine-, lysine-vasopressin, and vasotocin at levels as low as 10 pmol. The method can be used to detect other active peptides with cyst(e)ins in their molecule, as well.

Arginine Vasopressin↗
PubMedDate not supplied

Somatotroph to thyrotroph cell transdifferentiation during experimental hypothyroidism - a light and electron-microscopy study.

Somatotroph and thyrotroph pituitary cells share a common precursor cell expressing the transcription factor Pit1 in ontogeny. Cells expressing both thyrotropin (TSH) and growth-hormone (GH) are found in adult rat pituitary and in human pituitary adenomas in acromegaly, and these tumors contain both thyrotropin-releasing hormone (TRH) and the TRH receptors (TRHR). It has been shown that stimulation of TSH expression in primary hypothyroidism promotes changes suggestive of somatotroph to thyrotroph cell transdifferentiation. We tested this hypothesis and the role of TRH in experimental primary hypothyroidism in rats. Adult female Long-Evans rats, 6 months old, were administered the antithyroid drug methimazole (0.1% w/v) in the drinking water for 42 days. Animals were sacrificed by perfusion fixation under anaesthesia at weekly intervals and pituitary tissue processed in acrylic resin for immunofluorescence and immuno-electronmicroscopy for TSH, GH and TRHR. In the hypothyroid rat pituitary immunofluorescent somatotrophs were greatly reduced in number and gradually replaced by thyrotrophs during methimazole administration. Colocalization of GH and TSH in the same cell was noted. Immunoelectronmicroscopy demonstrated the development of enlarged thyrotrophs with dilated rough endoplasmic reticulum containing an electron-dense material and intracisternal granules, both of which are immunoreactive for TSH ('thyroidectomy cells'). The somatotrophs showed reduced GH immunoreactivity and also the presence of TSH-type, small-size secretory granules. This suggests that the greatly increased number of TSH-cells in methimazole-induced-hypothyroidism is due, at least partially, to the transdifferentiation of somatotroph into thyrotroph cells. TRHR immunofluorescence was expressed in many somatotrophs in normal rat pituitary and unlike immunoreactive GH, its expression was enhanced during hypothyroidism. The number of TRHR-immunoreactive cells increased in parallel with the number of TSH-immunoreactive cells. This indicates a role for TRH stimulation in the transdifferentiation process. Taken together, these data suggest that, in addition to the cell mutation mechanism involving an early totipotential progenitor cell, transdifferentiation of existing somatotroph cells also plays a part in the pathogenesis of multihormonal GH-secreting adenomas.

Animals↗
PubMedDate not supplied

Blood-brain barrier for human growth hormone and insulin-like growth factor-I.

There is a blood-brain barrier (BBB) for GH. A certain, unknown amount of GH passes the BBB, acts on the neuronal GH receptors and directly influences the brain mechanisms serving the feedback and ultradian secretion of GH. The high density of GH receptors in the choroid plexus suggests a possible receptor-mediated transcytosis transport. The effects of GH on brain development, neuronal plasticity and neuroprotection seem to be mediated by IGFs. GH and IGFs are also synthesized in the brain. The relative contributions to brain functions of GHs produced inside and outside the BBB are unknown. The cerebrospinal fluid (CSF) space is the compartment inside the barrier accessible to clinicians. High GH levels in CSF were reported in acromegaly and also a small increase was reported after chronic administration of hGH in GH-deficiency syndromes. For the practitioner it is necessary to determine the normal range of hGH levels in CSF.

Animals↗
PubMedDate not supplied

Expression of thyrotropin-releasing hormone messenger RNA in human pituitary adenomas with follicle-stimulating hormone immunoreactivity.

OBJECTIVE: To assess the correlation between thyrotropin-releasing hormone (TRH) messenger RNA (mRNA) and the immunoreactive type of human pituitary adenomas. METHODS: Twenty-eight patients (14 to 73 years old) who had pituitary adenomas (18 nonfunctioning adenomas, 8 growth hormone-secreting adenomas, and 2 prolactinomas) underwent surgical treatment. Pituitaries removed at autopsy from four patients without evidence of pituitary disease were used as controls. Fragments of pituitary adenomas were processed for TRH mRNA by in situ hybridization (radioactive and nonradioactive) and for TRH peptide and anterior pituitary hormones (b-thyrotropin, b-follicle-stimulating hormone [FSH], bluteinizing hormone [LH], prolactin, and growth hormone) by immunohistochemistry with use of the avidinbiotin technique. Quantitative immunohistochemical studies were performed by using image analysis software. The signal was considered positive when more than 5% of the cells were stained. RESULTS: Cells expressing TRH mRNA were detected in 22 of 28 pituitary adenomas--15 of 18 nonfunctioning pituitary adenomas, 5 of 8 growth hormone-secreting adenomas, and both prolactinomas. TRH peptide was revealed in only 10 adenomas, all expressing TRH mRNA as well. All but one nonfunctioning adenoma expressing TRH mRNA in more than 5% of the cells were b-FSH immunoreactive (15 of 16 cases; P<0.005, c 2 test), whereas only 6 of 16 nonfunctioning adenomas exhibited both b-thyrotropin and TRH mRNA and only 5 of 16 were positive for both b-LH and TRH mRNA. CONCLUSION: These results confirm previous data demonstrating the presence of TRH mRNA and TRH peptide in human pituitary tumor cells. We further showed that the presence of TRH mRNA is significantly correlated with FSH immunoreactive gonadotropinomas. The release of FSH after an intravenous TRH test only in gonadotropinomas, together with local production of TRH, suggests a role for TRH in pathogenesis.

Journal Article↗
PubMedDate not supplied

Preliminary EEG study of protective effects of Tebonin in transient global cerebral ischemia in rats.

Free radicals and platelet activating factor (PAF) have been implicated as important mediators in neuronal injury after cerebral ischemia-reperfusion and, particularly, in postischemic hypoperfusion. The electroencephalography (EEG) is a real time reflection of changes in neuronal activity and metabolism. The objective of this study was to investigate the effects of preventive treatment with Ginkgo biloba extract (EGb 761--Tebonin) in cerebral global ischemia and reperfusion in rats using computerized EEG analysis. Ginkgo biloba extract, known to be, in vitro, a free radicals scavanger and a PAF--antagonist, was administrated in dose of 100 mg/kg over 24 hours, for 5 days before and 5 days after cerebral ischemia--reperfusion. The apparition of isoelectric EEG (flat-line) following 4-vessel occlusion was observed after a mean time of 25 sec. in Ginkgo biloba treated rats and after 18 sec. in control rats (p < 0.0015). Computerized spectral analysis of EEG has shown that the percentage of slow waves at 10 minutes after reperfusion was 117% higher in control group than in Ginkgo biloba group (p < 0.015) and the percentage of slow waves after 15 minutes of reperfusion was 100% higher in the control group than in the Ginkgo biloba group (p < 0.02). Five days after cerebral ischemia--reperfusion the percentage of slow waves was unsignificantly higher in the control group than in the Ginkgo biloba group (p > 0.05).

Animals↗
PubMedDate not supplied

Diagnostic traps in porphyria: case report and literature review.

Porphyrias are metabolic disorders of heme biosynthesis, which encompass a broad range of symptoms and signs, neurologic, cutaneous or mixed. Because of lack of specificity and polymorphous clinical picture, porphyrias can mimic either neuropsychiatric, dermatologic, or gastrointestinal diseases. We present the case of a 58 years old man to whom clinical presentation suspicious of Addison's disease (melanoderma, fatigue, weight loss, intermittent abdominal pain) was the disguise of porphyria cutanea tarda. A general background of porphyrias and differential diagnosis with other forms of hepatic porphyria, as well as other causes of hyperpigmentation, are given. The clinician should be aware of the protean manifestations of porphyrias and include them in clinical judgment in various situations.

Addison Disease↗
PubMedDate not supplied

[Double localization of pancreatic insulinoma. Diagnostic and therapeutic difficulties].

Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. Because most of insulinomas are less than 2 cm in size and rarely they not may be visible by CT scan or transabdominal ultrasonography. Intraoperative ultrasonography may be a solution. Although as surgical method is preferred enucleation because operative time is shorter and easier and the low frequency postoperative complications, pancreaticoduodenectomy Whipple is indicated in selected cases. We report a case of double insulinoma located in the head of the pancreas in which the diagnosis and surgical treatment presented difficulties which determined a particular clinical evolution.

Female↗
PubMedDate not supplied

Psychoneuroendocrine stress-induced syndromes.

Psychoneuroendocrine stress-induced syndromes were characterised as expression of the activity of neuroendocrine transducers. A physiopathologic classification delineated the diseases which appeared as a result of the increase of the endocrine response to acute stress, i.e., catecholamine cardiomyopathy, reactive hypercortisolism, amenorrhea, infertility, sexual dysfunction of euthyroid sick syndrome in man and immunosuppression. The clinical diseases secondary to chronic stress, together with their physiopathologic therapy, i.e., central hypocorticism and psychosocial dwarfism, are described. They are produced by active inhibition of the endocrine response mechanism called by us: dysprotection.

Endocrine System Diseases↗
PubMedDate not supplied

Tentative identification of arginine vasotocin in the bovine pineal extract prepared by in the bovine pineal extract prepared by the Milcu-Nanu method.

The bovine pineal extract prepared by the Milcu-Nanu method (BPE-MN) has frog bladder, rat antidiuretic and rat uterine activities susceptible to tryptic digestion. The ratios of these activities are characteristic of arginine vasotocin (AVT). Desalting on Amberlite CG25 and partial purification of BPE-MN by free-flow continuous electrophoresis (FFCE) allow the separation of some fractions with AVT-like biological activities and with a carrier-free electrophoretic mobility similar to the synthetic AVT. The results strongly suggest the presence of AVT in the bovine pineal extract prepared by the Milcu-Nanu method.

Animals↗
PubMedDate not supplied

LH and FSH in human cerebrospinal fluid.

LH and FSH of cerebrospinal fluid (CSF) and serum were radioimmunologically measured. Samples were obtained simultaneously from 116 subjects of the following groups: A. 22 patients with non-endocrine diseases, B. 18 patients with cranial diabetes insipidus (DI) of whom 4 with metastatic carcinomas, C. 5 patients with primary empty sella syndrome, D. one with hydatiform mole, and E. 70 patients with pituitary adenomas, i.e. growth hormone--or prolactin-secreting or "non-secreting" adenomas, of whom 38 patients with invasive and 32 with enclosed adenomas. LH and FSH are normal constituents of CSF and their CSF levels poorly correlates with the serum ones (LH r = 0.477 p less than 0.01). Enclosed adenomas with SSE showed low levels of LH in CSF. High CSF-gonadotropins concentrations (above 4.0 mIU/ml) with a low serum/CSF ratio (below 3) was frequently, but not constantly found in patients with invasive adenomas and are not indicative per se of this diagnosis. Some patients with brain metastasis from breast carcinoma and DI, or with non-tumoral diseases and DI showed similar high patterns of CSF gonadotropins though the serum levels were within normal range. This suggests that local vascular mechanisms, including the retrograde circulation of gonadotropins from the pituitary to the hypothalamus, influence the blood-brain barrier much more than the release of gonadotropins into the systemic blood circulation.

Acromegaly↗